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Background: The purpose of this study was to study the relationships among Hp infection, secretion of gastrointestinal hormones and contraction of colon muscles of Sprague Dawley rats. Helicobacter pylori (Hp) is proved to be a chief criminal of gastric diseases. It can even be detected outside upper digestive tract like lung and kidney. Scientists found that Hp might modulate hormone secretion by influencing brain-gut axis. However, the specific relationships among Hp infection, hormone secretion and colonic motility are still undefined., Materials and Methods: Hp infection procedures were completed by intragastric administration to male Sprague Dawley rats. All model groups' rats were confirmed of Hp infection by rapid urease test and gastric mucosa biopsy. Plasma hormones were determined using Enzyme Immunoassay Kits after Hp infection. Colonic motility was assessed by counting numbers of fecal pellet output and recording contractions of isolated colonic strips through isometric force transducer., Results: Hp infection groups significantly increased fecal pellet output compared with negative Hp infection groups (P < 0.05). The Hp infection groups' mean tension of spontaneous contraction of colon smooth muscle was significantly greater than the negative Hp infection groups' (P < 0.05). Significant differences can be found between Hp infection groups and negative Hp infection groups, concerning the concentration of gastrin, cholecystokinin and substance P (P < 0.05)., Conclusions: Hp infection probably activate the regulation of brain-gut peptides and gastrointestinal hormones, which could interact with associated receptors in smooth muscle cells, leading to increased count of fecal pellet output and increased colon motility of smooth muscles., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Numerous diagnostic tests are available to detect Helicobactor pylori (H. pylori). There has been no single test available to detect H. pylori infection reliably. We evaluated the accuracy of a new fluorescence quantitative PCR (fqPCR) for H. pylori detection in children., Methods: Gastric biopsy specimens from 138 children with gastritis were sent for routine histology exam, rapid urease test (RUT) and fqPCR. 13C-urea breath test (13C-UBT) was carried out prior to endoscopic procedure. Gastric fluids and dental plaques were also collected for fqPCR analysis., Results: 38 children (27.5%) were considered positive for H. pylori infection by gold standard (concordant positive results on 2 or more tests). The remaining 100 children (72.5%) were considered negative for H. pylori. Gastric mucosa fqPCR not only detected all 38 H. pylori positive patients but also detected 8 (8%) of the 100 gold standard-negative children or 11 (10.7%) of the 103 routine histology-negative samples. Therefore, gastric mucosa fqPCR identified 46 children (33.3%) with H. pylori infection, significantly higher than gold standard or routine histology (P<0.01). Both gastric fluid and dental plaque fqPCR only detected 32 (23.2%) and 30 (21.7%) children with H. pylori infection respectively and was significantly less sensitive than mucosa fqPCR (P<0.05) but was as sensitive as non-invasive UBT., Conclusions: Gastric mucosa fqPCR was more sensitive than routine histology, RUT, 13C-UBT alone or in combination to detect H. pylori infection in children with chronic gastritis. Either gastric fluid or dental plaque PCR is as reliable as 13C-UBT for H. pylori detection.

Background: The incidence of 'true' re-infection with Helicobacter pylori after successful eradication remains uncertain., Aim: To determine the worldwide rates, risk factors and clinical implications of 'true' re-infection of Helicobacter pylori. 'True' re-infection of H. pylori is defined as the situation where tests for H. pylori infection, which were negative for 12 months after eradication, become positive again at a later stage., Results: Thirty six studies were identified through a literature search to be able to produce annual rates of 'true' re-infection, and data from 33 original articles were considered reliable and adequate in the further review. Generally, the reported rates varied from 0% to 23.4% in adults and from 1.9% to 9.6% in children. Most studies from developed countries reported rates of less than 1%, whereas relatively higher rates were reported in most of the developing countries. Small sample sizes included in the studies appeared to be associated with increased re-infection rates. Interfamilial transmission is the major cause of re-infection, although iatrogenic re-infection through contaminated endoscopic equipment has been reported., Conclusion: Helicobacter pylori re-infection is not a concern in a clinical setting, especially in the developed world; however, caution must be exercised in most developing countries.

Aim: To determine the antibiotic susceptibility of Helicobacter pylori and evaluate the efficacy of a clarithromycin-based triple therapy in relation to antibiotic resistance., Methods: Consecutive patients referred for upper endoscopy due to dyspeptic symptoms were recruited. Gastric biopsies were obtained for the CLO test, histology and culture. Antibiotic susceptibility was assessed by the E-test. Patients with H. pylori infection received rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily for 7 days., Results: Of 234 patients recruited, 124 were H. pylori-positive and culture was successful in 102 patients. The updated prevalences of resistance to clarithromycin, amoxicillin and metronidazole were 7.8, 0 and 39.2%, respectively. A total of 86 patients received 1-week triple therapy with rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1,000 mg, all twice daily, and 81 patients attended the follow-up test. Eradication rates by per-protocol and intention-to-treat analysis were 92.6 and 87.2%, respectively. The eradication rate by per protocol was significantly higher in patients with clarithromycin-susceptible strains than in those with clarithromycin-resistant strains (98.6 vs. 28.6%, p < 0.001)., Conclusion: Clarithromycin resistance reduces the clinical efficacy of clarithromycin-based triple therapy. However, due to the low prevalence of clarithromycin resistance, clarithromycin-based therapy is still the first choice for clinical use., (Copyright 2006 S. Karger AG, Basel.)

Background: Peptic ulcer disease is mainly caused by Helicobacter pylori infection and the use of non-steroidal anti-inflammatory drugs., Aim: To investigate the trends in the prevalence of peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use in uninvestigated dyspeptic patients over recent years in Hong Kong., Methods: Data from consecutive patients with uninvestigated dyspeptic symptoms referred by family physicians for open access upper endoscopy during 1997 and 2003 were analysed in relation to peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use., Results: Among 2700 patients included, 405 (15%) had peptic ulcer disease and 14 (0.5%) had gastric cancer. There was a reduced trend from 1997 to 2003 in the prevalence of peptic ulcer disease (17, 20, 14, 16, 13, 14 and 14%, respectively, chi2 = 5.80, P = 0.016) (mainly because of decrease in duodenal ulcers), H. pylori infection (44, 50, 49, 44, 40, 40, 36 and 43%, respectively, chi2 = 13.55, P < 0.001) and non-steroidal anti-inflammatory drug use (13, 5, 5, 6, 3, 4, 4 and 5% respectively, chi2 = 13.61, P < 0.001). The prevalence of peptic ulcer disease, H. pylori infection and non-steroidal anti-inflammatory drug use between 2001 and 2003 were significantly lower than that between 1997 and 2000 (17% vs. 13%, OR = 0.78, 95% CI: 0.63-0.96, P = 0.020 for peptic ulcer disease; 47% vs. 39%, OR =0.72, 95% CI: 0.60-0.86, P < 0.001 for H. pylori infection; and 6% vs. 4%, OR = 0.56, 95% CI: 0.39-0.82, P = 0.002 for non-steroidal anti-inflammatory drug use). H. pylori infection was associated with both duodenal ulcer (OR = 15.87, 95% CI: 10.60-23.76, P < 0.001) and gastric ulcer (OR = 3.12, 95% CI: 2.15-4.53, P < 0.001) whereas non-steroidal anti-inflammatory drug use was only associated with gastric ulcer (OR = 2.97, 95% CI: 1.70-5.20, P < 0.001)., Conclusions: The prevalence of peptic ulcer disease, mainly duodenal ulcers, was reduced in association with a decreasing trend in the prevalence of H. pylori infection and non-steroidal anti-inflammatory drug use from 1997 to 2003.

Background: The performance of commercial Helicobacter pylori diagnostic kits developed for particular geographic regions has often been found to be of poor diagnostic value when applied to other regions, possibly because of infections being caused by different H. pylori strains in different regions., Aim: To evaluate the performance of an IgG2 anti-H. pylori enzyme-linked immunoassay test (Helirad Alert) for detection of H. pylori infection in both Australian and Hong Kong (Chinese) subjects., Methods: Serum samples were tested for H. pylori specific IgG2 and IgG antibodies by enzyme-linked immunoassay kits using identical antigen preparation in 168 Australian and 160 Hong Kong (Chinese) subjects diagnosed with dyspepsia., Results: Using a cut-off value determined by analysis of H. pylori-negative Australian samples, the sensitivity, specificity and accuracy of the IgG2 assay were 77.8, 97.4 and 91.1%, respectively, for the Australian samples and 96.3, 83.8 and 90% for Hong Kong samples. For the IgG assay, sensitivity, specificity and accuracy were 87.0, 99.1 and 95.2% for Australian samples and 97.5, 75 and 86.3% for Hong Kong samples respectively. Receiver-operating characteristic analysis showed better discrimination of H. pylori status when the IgG2 assay was applied to Hong Kong samples, while the IgG assay was better in the Australian samples., Conclusion: These data demonstrate that the Helirad Alert enzyme-linked immunoassay could provide a reliable method for screening H. pylori infection in both western and Chinese populations.

Background: Recent studies suggest that the Helicobacter pylori eradication rate in patients with non-ulcer dyspepsia is lower when compared to patients with peptic ulcer diseases., Aim: The aim of this study was to study the efficacy of triple therapy for H. pylori infection in patients with duodenal ulcer vs. patients with non-ulcer dyspepsia., Methods: A total of 582 Chinese patients with proven H. pylori infection were recruited to receive: omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg all given twice daily for 7 days (OCA regime). Endoscopy with rapid urease test, histology and culture were performed before treatment. Post-treatment H. pylori status was determined by (13)C-urea breath test. Metronidazole, clarithromycin and amoxicillin resistance was defined as minimum inhibitory concentration (MIC) of >8 microg/mL, >1 microg/mL and >1 microg/mL, respectively., Results: A significantly higher (intention-to-treat/per-protocol) eradication rate was found in patients with duodenal ulcer than those with non-ulcer dyspepsia (91/94% vs. 84/88% respectively, P = 0.011 and P = 0.016). Clarithromycin resistance rate was higher in patients with non-ulcer dyspepsia than those with duodenal ulcer (14% vs. 6%, P = 0.015). Clarithromycin resistance (40% vs. 5%, P < 0.001, OR 12, 95% CI: 5.7-24.3) and the diagnosis of non-ulcer dyspepsia (91% vs. 84%, P = 0.011, OR 2.0, 95% CI: 1.2-3.3) significantly affected the success of H. pylori eradication., Conclusion: Clarithromycin resistance accounts for the significantly lower and suboptimal H. pylori eradication rate of OCA regimen in Chinese patients with non-ulcer dyspepsia compared to those with duodenal ulcer.

Background: We previously reported that aspirin inhibited Helicobacter pylori growth and suppressed the mutagenic effect of metronidazole., Aim: To determine the effects of a cyclo-oxygenase (COX)-2-specific inhibitor, SC-236, and a non-selective COX inhibitor, indometacin, on the growth, urease activity and antimicrobial susceptibility of H. pylori., Methods: Three H. pylori reference strains, and 18 clinical isolates were treated with SC-236 or indometacin for 24 and 48 h. Growth, urease activity and susceptibility to clarithromycin and metronidazole of the bacteria were assessed by viable colony counting, spectrophotometry and E-test respectively., Results: SC-236 and indometacin inhibited H. pylori growth in a dose-dependent manner with the lowest inhibitory concentrations of 0.03 and 0.1 mm, and the lethal concentrations of 0.09 and 0.3 mm, respectively. The numbers of CFU/mL in Brucella broth containing 0.09 mm SC-236 were 2 log lower at 24 h, and even 3 log lower at 48 h than that at 0 h (P = 0.035, compared with the vehicle control). Treatment of 0.3 mm indometacin reduced the number of CFU/mL by 1 log at 24 h compared with that at 0 h (P = 0.037 compared with the vehicle control). Helicobacter pylori urease activity began to decrease with 0.06 mm SC-236 at 24 h (P = 0.016), and 0.3 mm indometacin at 48 h (P = 0.025). MICs of metronidazole and clarithromycin against H. pylori were decreased significantly in the presence of 0.03 mm SC-236 or 0.1 mm indometacin (all P < 0.001)., Conclusion: Both SC-236 and indometacin suppressed the growth and urease activity of H. pylori in a dose-dependent manner, and increased its susceptibility to the antibiotics.

Aims: To determine gastric expression of trefoil family factor 2 (TFF2) and MUC6 in Helicobacter pylori positive and negative subjects, and its association with antralisation at the gastric incisura., Methods: Gastric biopsies from the antrum, incisura, and body of 76 dyspeptic patients without ulcers were used for the determination of H. pylori infection, histological changes, and epithelial TFF2 and MUC6 expression., Results: In the foveola, the rates of TFF2 and MUC6 immunostaining were greater in H. pylori infected (n = 27) than in uninfected patients (n = 49) at the antrum (59.3% v 4.1% for TFF2 and 63.0% v 4.1% for MUC6; both p < 0.001) and incisura (44.4% v 2.0% for TFF2 and 48.1% v 0% for MUC6; both p < 0.001). In the deeper glands, the rates were also greater in H. pylori infected than in uninfected patients at the incisura (85.2% v 22.4% for both TFF2 and MUC6; p < 0.001). Antral-type mucosa was present at the incisura in 28 of the 76 patients. TFF2 and MUC6 expression in the foveola and deeper glands was significantly associated with antral-type mucosa, independent of H. pylori status., Conclusions: Helicobacter pylori infection increases the expression of TFF2 and MUC6 in the gastric epithelium. Aberrant TFF2 and MUC6 expression is associated with antralisation of gastric incisura.

Aim: To determine whether pre-treatment antibody response to Helicobacter pylori virulence factors predicts eradication success and symptom relief 12 months after triple therapy in non-ulcer dyspepsia., Methods: H. pylori-positive patients with non-ulcer dyspepsia received 1-week omeprazole-based triple therapy, or omeprazole plus placebos. Symptoms were assessed using a validated Likert scale. Gastric biopsies taken before and 12 months after treatment were used for histological examination. Pre-treatment blood samples were used for the detection of anti-H. pylori immunoglobulin G (IgG) antibodies, and specific IgG antibodies to 19.5-, 26.5-, 30-, 35-, 89- (VacA) and 116-kDa (CagA) antigens of H. pylori., Results: IgG antibodies to the six antigens were detected in 62%, 96%, 88%, 47%, 54% and 78% of patients, respectively. The presence of antibody to 19.5-, 26.5- or 30-kDa antigen was associated with an increased anti-H. pylori IgG absorbance index. IgG absorbance indices were greater in those with H. pylori eradication (vs. persistent infection). The prevalence of antibodies to the six antigens was not significantly different between those with symptom relief vs. those without. The 19.5-kDa antigen (P = 0.018) and VacA (P = 0.001) were independent risk factors for body gastritis., Conclusions: An increased pre-treatment anti-H. pylori IgG absorbance index may be a useful predictor of the success of eradication therapy. Although the 19.5-kDa antigen and VacA were associated with body gastritis, none of the six antigens tested predicted symptom relief after triple therapy.

Aim: To test the efficacy of rabeprazole, levofloxacin and rifabutin triple therapy vs. quadruple therapy for the second-line treatment of Helicobacter pylori infection., Methods: One hundred and nine patients who had failed previous H. pylori eradication were randomized to receive: (i) rabeprazole, 20 mg b.d., rifabutin, 300 mg once daily, and levofloxacin, 500 mg once daily, for 7 days (triple therapy); or (ii) rabeprazole, 20 mg b.d., metronidazole, 400 mg t.d.s., bismuth subcitrate, 120 mg q.d.s., and tetracycline, 500 mg q.d.s., for 7 days (quadruple therapy). Endoscopy and culture were performed before treatment., Results: The clarithromycin (79% vs. 21%, P < 0.001) and metronidazole (89% vs. 40%, P < 0.001) resistance rates were significantly higher in patients with previous exposure than in those with no previous exposure. The intention-to-treat and per protocol eradication rates were 91%/91% for the triple therapy group and 91%/92% for the quadruple therapy group. For patients with double resistance to metronidazole and clarithromycin, the eradication rates were 85% (17/20) in the triple therapy group and 87% (13/15) in the quadruple therapy group. Compliance was greater than 95% for both regimens., Conclusion: Rabeprazole, levofloxacin and rifabutin-based triple therapy and quadruple therapy were equally effective as second-line treatments for H. pylori infection.

Background/aims: Helicobacter pylori induces the apoptosis of gastric epithelial cells in vivo and in vitro. However, the molecular mechanism has not been clarified. The aim of this study was to investigate the effect of H pylori on the apoptosis of gastric epithelial cells and the expression of apoptosis related genes in vitro., Methods: Human gastric adenocarcinoma SGC-7901 cells were co-cultured with a cytotoxic H pylori strain, NCTC 11637, at various densities ranging from 3.2 x 10(4) to 1.0 x 10(8) colony forming units (CFU)/ml for 48 hours. Apoptosis in gastric cells was determined by transmission electron microscopy, Hoechst 33258 fluorochrome staining, and flow cytometry. The expression of apoptosis related proteins, Bcl-2, Bax, and c-Myc, was measured by an immunohistochemical method, and c-Myc mRNA expression was determined by the reverse transcription-polymerase chain reaction., Results: Helicobacter pylori induces morphological changes typical of apoptosis. Both fluorochrome staining and flow cytometry showed that the apoptotic index began to increase when H pylori were at a density of > 1.6 x 10(4) CFU/ml, and in a density dependent manner (p < 0.01; one way ANOVA). The expression of the Bax and c-Myc proteins and of c-Myc mRNA was increased, whereas Bcl-2 expression was decreased after co-culture for 48 hours., Conclusions: Helicobacter pylori induced apoptosis in gastric epithelial cells is mediated by altered expression of the products of the Bcl-2, Bax, and c-Myc genes.

Background: Recently, a rapid-release 100-mg 13C-urea tablet with citrate supplement (Diabact UBT) showed excellent performance in a European population., Aim: To investigate the accuracy of a 50-mg tablet-based 13C-urea breath test protocol., Methods: : Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C-Urea breath test was performed using a 50-mg 13C-urea tablet (Diabact UBT) and compared with the gold standard (rapid urease test and histology). Baseline, 10-min, 20-min and 30-min breath samples were collected in all cases. The cut-off values at each measurement interval were determined by three standard deviations above the mean excess delta 13CO2 excretion of Helicobacter pylori-negative patients., Results: Two hundred patients (150 before therapy and 50 after therapy) were available for analysis, with a mean age of 48.4 years, and 99 patients (50%) were H. pylori positive. The sensitivity and specificity of the 50-mg tablet-based 13C-urea breath test at 10 min, 20 min and 30 min were 100% and 98%, 100% and 100%, and 100% and 98%, respectively., Conclusion: A 20-min, 50-mg tablet-based 13C-urea breath test (Diabact UBT) protocol is highly accurate for the diagnosis of H. pylori infection.

Background: We have previously shown that ranitidine bismuth citrate-based, clarithromycin-containing triple therapy achieves a higher eradication rate than proton pump inhibitor-based regimens in areas with a high prevalence of metronidazole resistance., Aim: To evaluate whether this higher efficacy of ranitidine bismuth citrate over proton pump inhibitor can be extended to non-clarithromycin-containing regimens., Methods: Helicobacter pylori-positive dyspeptic patients were randomized to receive either ranitidine bismuth citrate, 400 mg, amoxicillin, 1000 mg, and metronidazole, 400 mg, or omeprazole, 20 mg, amoxicillin, 1000 mg, and metronidazole, 400 mg, each given twice daily for 1 week. H. pylori eradication was confirmed by 13C-urea breath test 5 weeks later. The side-effects of the treatments were documented., Results: Two hundred and twenty-nine patients were eligible for analysis. By intention-to-treat and per protocol analysis, the eradication rates were 77% and 79%, respectively, in the ranitidine bismuth citrate-amoxicillin-metronidazole group and 77% and 82%, respectively, in the omeprazole-amoxicillin-metronidazole group (P = 0.58 and P = 0.65). However, patients in the omeprazole-amoxicillin-metronidazole group reported a significantly higher incidence of minor side-effects when compared to those in the ranitidine bismuth citrate-amoxicillin-metronidazole group (P = 0.001)., Conclusions: Ranitidine bismuth citrate-amoxicillin-metronidazole was equally as effective as omeprazole-amoxicillin-metronidazole triple therapy, and may be considered as an alternative non-clarithromycin-based regimen in the Chinese population.

Background: Helicobacter pylori infection has been associated with growth restriction in young children., Aim: To determine whether there is an association between H. pylori infection and intrauterine growth restriction., Methods: Four hundred and forty-eight consecutive pregnant women (aged 15-44 years), attending for routine examinations in the third trimester, were enrolled. Clinical, demographic and previous obstetric data, as well as smoking history, were collected. At delivery, the weight, height, gender and status of the neonate were recorded; intrauterine growth restriction was defined if the birth weight was below the 10th percentile according to the gestational age for infants born in Australia., Results: Eighty-nine (20%) women were seropositive for H. pylori. The prevalence of H. pylori was significantly lower in Caucasians (17%) vs. non-Caucasians (42%, P < 0.0001). There were 34 (7.5%) cases of intrauterine growth restriction (7% Caucasians, 16% Asians, 12% Aborigines and 0% Pacific Islanders). Intrauterine growth restriction was more common in H. pylori-seropositive women than in H. pylori-seronegative women [13.5% vs. 6%; odds ratio (OR) = 2.41; 95% confidence interval (CI), 1.14-5.08; P = 0.018]. A multiple logistic regression model revealed that smoking (OR = 3.55; 95% CI, 1.62-7.79; P = 0.002), maternal height (OR = 0.48; 95% CI, 0.28-0.80; P = 0.005) and H. pylori seropositivity (OR = 2.59; 95% CI, 1.12-5.95; P = 0.025) were all independent risk factors for intrauterine growth restriction., Conclusions: H. pylori infection in pregnant women may affect foetal intrauterine growth.

Aim: To test the efficacy of omeprazole, furazolidone and amoxicillin triple therapy for the treatment of Helicobacter pylori infection after failure of standard first-line therapy recommended by the Asia-Pacific Consensus on the management of H. pylori infection., Methods: Patients with failed H. pylori eradication received omeprazole, 20 mg, furazolidone, 100 mg, and amoxicillin, 1 g, all twice daily for 1 week. Endoscopy (CLO test, histology and culture) was performed before treatment. Post-treatment H. pylori status was determined by 13C-urea breath test 6 weeks later., Results: Fifty patients were recruited. Resistance to metronidazole, clarithromycin and both drugs was in the range of 50-64%, 60-75% and 40-50%, respectively, after failure of first-line therapy. Amoxicillin resistance was not found. The intention-to-treat and per protocol H. pylori eradication rates were 52% and 53%, respectively. Patients with double resistance to metronidazole and clarithromycin showed the lowest eradication rate (38%), which was significantly lower than that of patients with sensitive strains (88%). Side-effects were minimal and compliance was excellent (98%)., Conclusions: One-week omeprazole, furazolidone and amoxicillin rescue therapy achieved a high eradication rate in strains sensitive to metronidazole and clarithromycin. This is a cheap and safe rescue regimen when guided by pre-treatment sensitivity testing.

Background: A new rapid urine test was developed to detect anti-Helicobacter pylori antibody in urine using the principle of immunochromatography. The accuracy of this test in the Chinese population remains to be defined., Aim: To evaluate a new rapid urine test for the diagnosis of H. pylori infection in the Chinese population., Methods: Eligible patients without previous treatment of H. pylori were recruited. In-house rapid urease test and histology were used as the gold standard. The rapid urine test (RAPIRUN H. pylori antibody) was performed and the results were compared with the gold standard., Results: One hundred and twenty-three patients were eligible for analysis and 61 (50%) were H. pylori positive by the gold standard. The rapid urine test showed a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 96.7%, 95.2%, 95.2%, 96.7% and 95.9%, respectively. Results were obtained within 20 min and no special laboratory support was required., Conclusions: The rapid urine test by immunochromatography is highly accurate for the diagnosis of H. pylori infection in untreated Chinese patients.

Background: Numerous serological tests for the detection of Helicobacter pylori infection have been developed. However, many perform poorly when evaluated in the Chinese population., Aim: To search for optimal serological tests for the detection of H. pylori infection in Chinese patients., Methods: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, gastric biopsies were taken for the CLOtest and histological examination. Patients were then given a 13C-urea breath test. Sera were used to test for H. pylori infection, employing three commercial enzyme-linked immunosorbent assay kits (pylori DTect, HP IgG and GAP IgG). Results were compared with the gold standard defined by the CLOtest, histology and 13C-urea breath test., Results: Among the 142 patients (47 male, 95 female; mean age, 49 years) recruited, 81 (57%) were H. pylori-positive, 57 (40%) were H. pylori-negative and four (3%) were defined to be indeterminate. Using a self-defined cut-off value after calculation, the best accuracies for the pylori DTect, HP IgG and GAP IgG tests were 97%, 91% and 80%, respectively., Conclusions: The pylori DTect test is an optimal serological test for the detection of H. pylori infection in Hong Kong Chinese patients. The HP IgG test may be used as an alternative.

We aimed to determine if changes in the patterns of upper gastrointestinal diseases at endoscopy have occurred over the past decade. Retrospectively, 917 consecutive patients were selected based on upper endoscopy between June 1 and August 31, in 1990 (n = 217), 1994 (n = 270), and 1998 (n = 430). Demographic, clinical, endoscopic, and histological information were extracted from the medical records on a standardized case record form. Over the eight-year period, follow-up of peptic ulcer (15%, 5%, and 5%, respectively, in 1990, 1994, and 1998, df = 2, P < 0.001), bleeding (22%, 14%, and 13%, P = 0.008), and nausea/vomiting (15%, 16%, and 10%, df = 2, P = 0.003) had become less frequent, but reflux (21%, 19%, and 34%, df = 2, P < 0.001) and dyspepsia (24%, 43%, and 32%, df = 2, P < 0.001) more frequent indications for upper endoscopy. The prevalence of peptic ulcer disease decreased (22%, 15%, and 13%, df = 2, P = 0.025), but the prevalence of reflux esophagitis increased significantly (29%, 30%, and 39%, df = 2, P = 0.010). The prevalence of both the use of nonsteroidal antiinflammatory drugs (NSAIDs) (18%, 20%, and 11%, respectively, in 1990, 1994, and 1998, df = 2, P = 0.004) and H. pylori infection (39% in 1994 and 30% in 1998, df = 1, P = 0.032) decreased. Overall, NSAID use was independently associated with gastric ulcers (OR = 2.39, 95% CI 1.21-4.73, chi2 = 6.31, df = 1, P = 0.012), but not esophagitis. H. pylori infection was independently associated with duodenal ulcers (OR = 4.74, 95% CI 2.30-9.77, chi2 = 17.8, df = 1, P < 0.001), histologically chronic (OR = 166.8, 95% CI 76.1-365.4, chi2 = 313.0, df = 1, P < 0.001) and active (OR = 30.1, 95% CI 17.0-53.5, chi2 = 189.7, df = 1, P < 0.001) gastritis and lymphoid aggregates (OR = 5.49, 95% CI 3.02-9.97, chi2 = 36.3, df = 1, P < 0.001). In conclusion, the prevalence of peptic ulcer disease appears to have been decreasing, whereas reflux esophagitis has been increasing over the past decade in Western Sydney. The decreased use of NSAIDs and decline of H. pylori infection have likely both contributed to the reduction of peptic ulcer disease, but the increase in reflux esophagitis remains to be fully explained.

Background: There is a substantial genetic heterogeneity among Helicobacter pylori strains, and certain genotypes have been suggested to be associated with the virulence of this pathogen. The aim of this study was to investigate the distribution of H. pylori vacA, cagA and iceA genotypes and their association with duodenal ulcer disease in Hong Kong., Materials and Methods: Gastric biopsies of 72 H. pylori infected patients were analyzed by specific polymerase chain reactions., Results: Of the 72 cases, 69 (95.8%) had vacA signal sequence s1c strains, and three (4.2%) had s1a strains. vacA middle region sequences, m1b and m2, were detected in 23 (31.9%) and 46 (63.9%), respectively. Six (8.3%) cases contained multiple vacA subtypes. vacA s2 allele was only observed in three (4.3%) cases, which were also infected with s1c subtype. cagA was present in 64 (88.9%) of 72 patients, and iceA1 subtype was detected in 46 (63.9%) cases. Neither cagA nor vacA and iceA were associated with duodenal ulcer disease., Conclusion: The distribution of vacA, cagA and iceA alleles in H. pylori strains in Hong Kong is similar to that in east Asia. There is a difference in the distribution of genotypes between strains in Hong Kong and those in mainland China, although strains in the two regions exhibit a very close relation. The association of these virulence genes and duodenal ulcer disease needs reappraisal, particularly under geographic considerations.

Background: The proportion of duodenal ulcers not associated with Helicobacter pylori infection or the use of non-steroidal anti-inflammatory drugs (NSAIDs) is increasing., Aim: To identify the clinical and endoscopic characteristics of non-H. pylori, non-NSAID duodenal ulcers., Methods: Clinical and endoscopic data and H. pylori status were prospectively collected from consecutive patients who underwent upper endoscopy from 1997 to 1999. Patients with duodenal ulcers were identified, and those with non-H. pylori, non-NSAID duodenal ulcers were analysed further., Results: A total of 11 717 upper endoscopies were performed in 8344 patients. Of these, 1153 (14%) had duodenal ulcers. Of 599 patients with active ulcers and known H. pylori status, 104 (17%) had ulcers not associated with H. pylori or the use of NSAIDs, 393 (66%) had ulcers associated with H. pylori alone, 51 (8.5%) had ulcers associated with the use of NSAIDs alone and 51 (8.5%) had ulcers associated with both. Multivariate logistic regression analysis revealed that the presence of concomitant diseases (odds ratio=15.0; 95% confidence interval, 8.64-25.9; P < 0.001) and the absence of epigastric pain/discomfort (odds ratio=0.52; 95% confidence interval, 0.29-0.91; P=0.022) were independent predictors for non-H. pylori, non-NSAID duodenal ulcers., Conclusions: Non-H. pylori, non-NSAID duodenal ulcers exhibit certain distinct clinical and endoscopic characteristics. The presence of concomitant diseases is an important predictive factor.

Background: We have previously shown that the 75 mg 13C-urea breath test without citrate test meal is highly accurate for the diagnosis of Helicobacter pylori infection in Chinese subjects. A lower dose 50 mg 13C-urea breath test protocol with a sampling time at 20 min has not been validated previously., Aim: To investigate the accuracy of a 20-min 50 mg 13C-urea breath test protocol in Chinese subjects., Methods: Consecutive dyspeptic patients referred for upper endoscopy were recruited. 13C-urea breath test was performed using (a) 75 mg and 50 mg of 13C-urea on two separate days without a test meal, and (b) 50 mg of 13C-urea with 2.4 g citrate as test meal, and compared with the gold standard [rapid urease test (CLO test) and histology]. Baseline, 20-min and 30-min breath samples were collected in all cases., Results: Two hundred and six patients were tested. The accuracy of the 50 mg 13C-urea breath test (no citrate) at 20 min and 30 min was 98%, comparable to that of the 50 mg 13C-urea breath test with citrate (99.1%) and the 75 mg 13C-urea breath test without citrate (100%)., Conclusions: A 20-min 50 mg 13C-urea breath test without citrate produced highly accurate results for the diagnosis of Helicobacter pylori infection and is more economical and convenient for the Chinese population.

Objective: The association between Helicobacter pylori (H. pylori) infection and diabetes mellitus is controversial. We aimed to determine the prevalence of H. pylori infection in patients with diabetes and nondiabetic controls, and assess whether H. pylori infection was associated with upper gastrointestinal (GI) symptoms in diabetes mellitus., Methods: A total of 429 patients with type 1 (n = 49) or type 2 (n = 380) diabetes mellitus (48.6% women, mean age 60.7 yr) and 170 nondiabetic controls (34.7% women, mean age 60.4 yr) were evaluated. All subjects completed a validated questionnaire (the Diabetes Bowel Symptom Questionnaire) to determine upper GI symptoms, and a blood sample was tested for H. pylori infection using a validated ELISA kit (sensitivity 96%, specificity 94%)., Results: Seroprevalence of H. pylori was 33% and 32%, respectively, in patients with diabetes and controls (NS). In both groups, the seroprevalence was significantly higher in men than in women; 39% vs 25% (p = 0.002) in diabetic patients, and 40% vs 20% (p = 0.01) in controls. Patients with diabetes had a significantly higher prevalence of early satiety (OR = 2.30), fullness (OR = 3.15), and bloating (OR = 1.50) compared with controls. Upper GI symptoms were present in 49% of H. pylori-positive and 53% of H. pylori-negative patients with diabetes (OR = 0.87, 95% CI 0.58-1.31, p = 0.56). H. pylori infection was also not associated with any of the individual upper GI symptoms before or after adjustment for potential confounding factors. However, patient age and female gender were identified as independent risk factors for upper GI symptoms. Smoking was a risk factor for bloating and early satiety., Conclusions: H. pylori infection appears not to be associated with diabetes mellitus or upper GI symptoms in diabetes mellitus.

Helicobacter pylori infection, which is present in 30 - 60% of the population in developed countries and in more than 60% in developing countries, is established to be a major cause of gastritis, peptic ulcer disease and gastric cancer. Eradication therapy has been incorporated into clinical practice over the past 15 years. Treatment regimens include a 2 week bismuth-based triple therapy (a bismuth compound plus metronidazole, tetracycline or amoxycillin), a 1 week proton-pump inhibitor (PPI)-based triple therapy and a 1 week ranitidine bismuth citrate (RBC)-based triple therapy (a PPI or RBC plus any two of the three antibiotics, metronidazole, amoxycillin and clarithromycin). These regimens achieve eradication rates of >> 80%. H. pylori resistance to metronidazole and clarithromycin decreases the clinical efficacy of most regimens, despite the high eradication rates for resistant strains achieved by the RBC-triple therapy in some recent trials. The dose of antibiotics (especially clarithromycin) and the duration of treatment may also influence the eradication rate. Doctors' beliefs impact on clinical practice and, thus, influence the clinical application of eradication therapy. Whereas peptic ulcer disease and primary gastric low-grade B-cell mucosa-associated lymphoid tissue lymphoma (MALToma) have become established as definite indications for eradication therapy, there remain controversies surrounding non-ulcer dyspepsia, gastro-oesophageal reflux disease, atrophic gastritis, intestinal metaplasia, use of non-steroidal anti-inflammatory drugs (NSAIDs) and H. pylori-related extradigestive diseases.

Objectives: Helicobacter pylori is an identified carcinogen for gastric cancer, however, the underlying mechanisms remain to be defined. In this review, we sought to elucidate the role of apoptosis in gastric carcinogenesis, to determine the influence of H. pylori infection on apoptosis, and finally to provide insights into the mechanisms by which H. pylori may lead to gastric carcinogenesis., Methods: A broad-based MEDLINE and Current Contents literature search was performed to identify relevant publications between 1966 and March 2000 addressing H. pylori infection, apoptosis, cell proliferation, gastric carcinoma, oncogenes, and tumor suppressor genes, as well as the products of these genes. Abstracts from recent major conferences that provided adequate additional data were also included., Results: Apoptotic cells are rare in the glandular neck region (the generative cell zone) of normal gastric mucosa. With progression of atrophic gastritis, the generative cell zone shifts downward and a relatively large number of apoptotic cells occur. In intestinalized glands, both apoptotic cells and proliferative cells are present in deeper portions of the glands, corresponding to the generative zone. A higher frequency of apoptosis has been observed in gastric dysplasia than in coexisting gastric carcinomas, whereas the number of proliferative cells is significantly higher in gastric carcinoma than in dysplasia. Upregulation of oncogene bcl-2 in premalignant lesions and "downregulation" of the gene after malignant change is probably a common event. Accumulation of p53 protein is first detected in dysplasia, although mutation of the pS3 gene may occur in intestinal metaplasia. H. pylori infection induces apoptosis in gastric epithelial cells, which returns to normal after eradication of the infection. Numerous molecules produced by H. pylori including cytotoxin (VacA), lipopolysaccharide, monochloramine, and nitric oxide may directly induce apoptosis. Moreover, H. pylori-stimulated host inflammatory/immune responses lead to release of a large amount of cytokines. Cytokines produced by type 1 T helper cells, such as TNF-alpha and IFN-gamma, markedly potentiate apoptosis. Gastric cell proliferation is significantly higher in patients with H. pylori infection than in normal controls, and eradication of the infection leads to a reduction in cell proliferation. Apoptosis and cell proliferation are also increased in precancerous lesions such as gastric atrophy, intestinal metaplasia, and dysplasia in the presence of H. pylori infection. However, H. pylori-induced apoptosis may no longer be cell cycle-dependent in these lesions because of the occurrence of alterations and mutations of apoptosis-regulating genes, resulting in a loss of balance between apoptosis and cell proliferation., Conclusions: It is hypothesized that H. pylori-induced apoptosis may play a key role in gastric carcinogenesis by increasing cell proliferation and/or resulting in gastric atrophy.

Objective: To identify demographic and endoscopic characteristics of patients with Helicobacter pylori positive and negative chronic peptic ulcer disease., Design: Cross-sectional study of peptic ulcer disease in prospectively recruited PATIENTS undergoing gastroscopy., Patients: 277 consecutive patients referred for gastroscopy in 1996-1998., Main Outcome Measures: Rapid urease test, culture and histological examination for H. pylori infection; anti-H. pylori IgG antibodies in serum; demographic data, intake of non-steroidal anti-inflammatory drugs (NSAIDs) in the preceding 3 months, and size, number and location of ulcers., Results: 54 patients (19%) had evidence of peptic ulcer disease (34 gastric ulcer, 14 duodenal ulcer and 6 both gastric and duodenal ulcer); 45 had active chronic peptic ulcer disease and were analysed in detail. H. pylori was present in 25 (56%) of these patients; 10 (22%) had used NSAIDs and 7 of the NSAID group also had H. pylori infection. Of the patients with gastric ulcers, those with non-H. pylori, non-NSAID ulcers were significantly younger than both those with H. pylori-associated ulcers (mean age, 48 v. 65 years, P = 0.02) and those with NSAID-associated ulcers (mean age, 48 v 68 years, P = 0.02). The average size and number of gastric ulcers did not differ between patients with and without H. pylori infection. Of patients with duodenal ulcers, those with H. pylori infection had significantly fewer ulcers (1.1 v. 1.8, P = 0.04), although ulcer size was similar in the infected and uninfected groups., Conclusions: Gastric ulcers may now be more common than duodenal ulcers. Gastric ulcers associated with H. pylori infection and/or NSAID use occurred mostly in older people, while non-H. pylori, non-NSAID gastric ulcers were more common in younger patients. In the duodenum, single ulcers were associated with H. pylori infection, and multiple ulcers were more frequent in the non-H. pylori, non-NSAID group.

Background: Helicobacter pylori infection and associated peptic ulcer disease (PUD) has become less common in some countries., Aim: To determine if H. pylori serology alone or combined with a history of ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) and an age threshold can be used as an indirect ulcer test., Methods: Two hundred and fifty-two consecutive Australian patients (121 males, mean age 52 years) referred for endoscopy were enrolled. Blood was tested by a validated ELISA. At endoscopy, eight biopsies were taken for CLO-testing, culture and histology. NSAID use over the prior 3 months was recorded., Results: One hundred and six (42%) patients were seropositive for H. pylori, 48 (19%) patients had PUD and 30 (12%) used NSAIDs. Serology alone had a sensitivity of 52% and a specificity of 60% for identifying PUD; the sensitivity and specificity were 60% and 55%, respectively, when combined with a history of NSAID use. Serology, regardless of NSAID use, would have saved 23% in endoscopy workload but would have missed 17% of PUD cases if an age threshold of < 45 years was chosen for omitting endoscopy., Conclusions: Serology was a poor ulcer test despite an excellent performance for detecting H. pylori. A strategy combining serology and an age threshold with a history of NSAID use to reduce endoscopy workloads may not always be appropriate.

A number of commercial ELISA kits are now available for detection of Helicobacter pylori infection. Generally, whereas the manufacturers have claimed high sensitivity and specificity, independent studies have often failed to confirm the results. The aim of this study was to independently evaluate the pylori DTect ELISA, a commercial kit for detection of H. pylori infection, in Australian patients with dyspepsia and reflux symptoms. Two hundred and nine consecutive patients (102 males and 107 females, mean age 52.8 years) who were referred for endoscopy due to upper gastrointestinal symptoms, but had not received anti-H. pylori therapy were enrolled. A 10 mL blood sample was obtained from each subject and used to evaluate the kit. The absorbance index (AI) was calculated from the mean of two readings of optical density (OD) of each serum sample. Eight biopsies from the gastric antrum (x3), body (x2), fundus (x2), and incisura (x1) were obtained from each patient for CLO-testing (x1), culture (x3), and histological examination (x4) for H. pylori. Overall, 84 (40.2%) patients were infected with H. pylori as determined by the biopsy-based "gold standard." The AIs ranged from 0 to 1.86; 0.12 to 1.86 in H. pylori positive patients and 0 to 1.49 in negative patients. The pylori DTect ELISA obtained an accuracy of 94 to 95% under AI ranges between 0.20 to 0.40, with the highest accuracy being 95% under AIs of 0.25 and 0.35. An AI of 0.25 was recommended as the best cut-off AI, with a sensitivity of 96.4%, specificity of 93.6%, positive predictive value of 91% and negative predictive value of 97.5%. It is concluded that the pylori DTect ELISA is accurate for detecting H. pylori infection in patients with dyspepsia and reflux symptoms in Australia, when an AI of 0.25 is taken as the cut-off value.

Objectives: Helicobacter pylori is a carcinogen; gastric carcinoma involves a multistep process from chronic gastritis to atrophy, intestinal metaplasia, and dysplasia. The aims of this study were to determine the types of mucosa at different gastric sites in H. pylori-infected and uninfected patients, and whether the presence of antral-type mucosa in the incisura, body, and fundus is associated with gastric atrophy and intestinal metaplasia., Methods: Two hundred and sixty-eight patients with dyspepsia were enrolled. Eight biopsies (i.e., antrum x3, body x2, fundus x2, and incisura x1) were obtained. One antral biopsy was used for the CLO-test. Three (each from the antrum, body, and fundus) were cultured. The remaining biopsies were examined histologically according to the updated Sydney System after staining with hematoxylin and eosin and Giemsa. A validated serological test was also applied., Results: Overall, 113 (42%) patients were infected with H. pylori. At the incisura, antral-type mucosa was more prevalent in infected than in uninfected patients (84% vs. 18%; odds ratio [OR] = 23.9, 95% confidence interval [CI] 12.5-45.8; p<0.001). Atrophic gastritis and intestinal metaplasia at the incisura was present in 19.5% and 13.3%, respectively, of infected, and 4.5% and 3.2%, respectively, of uninfected patients (both p<0.01). Moreover, atrophic gastritis at the incisura was associated with the presence of antral-type mucosa at the site (termed antralization); the prevalence of atrophic gastritis was 19.5% (24/123) in the presence of antralization, whereas the rate was 2.1% (3/145) without antralization (OR = 11.4, 95% CI 3.4-39.2; p<0.001). Similarly, at the incisura, 16.3% (20/123) of "antralized" cases and 1.4% (2/145) of "unantralized" cases had intestinal metaplasia (OR = 13.8, 95% CI, 3.2-60.7; p<0.001). The association between antralization at gastric body and fundus also appeared to be associated with atrophic gastritis and intestinal metaplasia at these sites., Conclusions: Atrophic gastritis and intestinal metaplasia occurs predominantly at the gastric antrum and incisura with H. pylori infection. Antralization of the gastric incisura is a common event in H. pylori-infected patients, and appears to be associated with an increased risk of atrophic gastritis and intestinal metaplasia.

Background: Cell culture assay is an accurate test for detecting Helicobacter pylori cytotoxicity., Aims: To evaluate McCoy cells for detecting Helicobacter pylori cytotoxicity by comparing with HeLa cells, and determine the association of cytotoxic strains with endoscopic and histological findings., Methods: Helicobacter pylori isolates from 68 dyspeptic patients and 11 asymptomatic volunteers were tested. 180 microl (1.8 x 10(4) cells) of grown McCoy or HeLa cell suspension was seeded into each well of a 96-well microtitre tray and the medium was replaced once after 24 hours. Sonicate (20 microl) of each isolate was then added to the wells, in duplicate. After 24 and 48 hours incubation, intracellular vacuolation was assessed by inverted light microscopy., Results: Using McCoy cells 57% of isolates showed cytotoxicity (23% weak and 34% strong), while using HeLa cells 30% of isolates showed strong cytotoxicity. All isolates toxic in HeLa cells were also toxic in McCoy cells. The prevalence of cytotoxic strains was not significantly different between the endoscopic findings; 50% in normal endoscopy, 60% in non-ulcer dyspepsia and 59% in peptic ulcer disease. However, cytotoxic strains were more common in subjects with severe histological gastritis than in those with normal mucosa or mild gastritis (66% vs 30%, p<0.01). Similarly, the prevalence of cytotoxic strains was also higher in subjects with active gastritis than in those without (64% vs 23%, p<0.01)., Conclusions: McCoy cells are more sensitive than HeLa cells for detecting Helicobacter pylori cytotoxicity in vitro. There is an association between cytotoxic strains and the severity and activity of histological gastritis.

Epidemiological and pathophysiological studies, as well as clinical trials, attempting to identify a relationship between Helicobacter pylori infection and non-ulcer dyspepsia (NUD), or a subset of NUD, have produced inconsistent and confusing results. While it is possible that H. pylori eradication may be beneficial for symptom relief in a small proportion of patients, routine H. pylori testing and treatment in documented NUD is not currently widely accepted. Despite the lack of convincing evidence, the European Helicobacter pylori Study Group, an Asian Pacific Consensus Meeting, the American Digestive Health Foundation and the American Gastroenterology Association have all recommended considering H. pylori eradication in patients with NUD on a patient-by-patient basis. Recently, large prospective, randomised, double-blind, controlled clinical trials applying highly effective antimicrobial therapy have been conducted with 12 months follow-up. Although these well-designed studies have reached differing conclusions, the results have been largely negative. H. pylori eradication therapy in NUD will fail to relieve symptoms in most patients in the long term.

Objective: As conflicting studies have recently been published, we aimed to determine if Helicobacter pylori (H. pylori) infection is associated with gastric adenocarcinoma., Methods: This was a meta-analysis of observational epidemiological studies., Results: A total of 42 studies met the selection criteria and were categorized by the type of study design: eight cohort and 34 case-control studies. The pooled odds ratio for H. pylori in relation to gastric carcinoma was 2.04 (95% CI: 1.69-2.45). Both patient age (OR 0.77, 95% CI: 0.68-0.89) and intestinal type cancers (OR 1.14, 95% CI: 1.05-1.25) were independent effect modifiers. Analysis of other effect modifiers showed no relationship with female gender (OR 0.76, 95% CI: 0.64-0.89), stage of cancer (advanced %) (OR 1.12, 95% CI: 0.88-1.43), anatomical location (cardia %) (OR 1.54, 95% CI: 0.32-7.39) or cohort (nested case-control) studies (OR 1.72, 95% CI: 0.32-9.17). There was significant heterogeneity among the studies (tau2 = 149; p < 0.001). The quality of the studies varied considerably, with the majority of excellent studies producing positive results and the very poor to moderate studies producing mixed results., Conclusions: H. pylori infection is associated with a 2-fold increased risk of developing gastric adenocarcinoma.

It is unknown whether antibiotic susceptibility testing of antral isolates alone is representative of Helicobacter pylori susceptibility. We aimed to determine: (i) the prevalence of metronidazole- and clarithromycin-resistant strains in infected dyspeptic patients; and (ii) whether there is consistency in the susceptibility to metronidazole and clarithromycin among isolates cultured from different gastric sites. Antral, body and fundus biopsies were taken from 242 consecutive patients and cultured on blood agar under micro-aerophilic conditions for 5-7 days. Isolates from 66 patients (13 had one, 15 had two and 38 had three isolates) were tested for susceptibility to metronidazole and clarithromycin using previously validated disc diffusion tests. Of the 66 patients, 42 (64%) had strains resistant to metronidazole while four (6.1%) had clarithromycin-resistant strains. The prevalence of metronidazole resistance was not significantly different between men and women (65% vs 60%) or across different age groups. In five (9.4%) of the 53 patients with multiple isolates, discrepant results for metronidazole susceptibility were observed: susceptible antral and body isolates but resistant fundus isolates in two cases and susceptible antral isolates but resistant body and fundus isolates in the others. Clarithromycin susceptibilities were consistent among the isolates cultured from different gastric sites in all patients. It is concluded that metronidazole-resistant strains of H. pylori are common while clarithromycin-resistant strains are rare. Metronidazole susceptibility testing of antral isolates does not appear to be representative of isolates from the body and fundus in a subset of patients.

Background: The relationship between Helicobacter pylori infection and symptoms remains controversial. We aimed to determine if an association exists between unexplained dyspepsia (pain or discomfort centered in the upper part of the abdomen) and H pylori., Methods: A validated questionnaire was completed by 592 healthy blood donors. Helicobacter pylori serologic values (via enzyme-linked immunosorbent assay), blood group status, and Rh status were measured; 4.9% of subjects who had a history of peptic ulcer disease were excluded from the analyses., Results: The prevalence of dyspepsia and no ulcer history was 11% (95% confidence interval [CI], 8.6%-13.8%); 15.4% of subjects with dyspepsia had H pylori while 14.6% of subjects without dyspepsia were infected (P=.90). The mean dyspepsia impact scores (combining frequency and severity) in those with and without H pylori were 4.7 and 5.4, respectively (P=.20). The median H pylori optical density values in dyspepsia vs no dyspepsia were not significantly different (P=.30). Independent risk factors for dyspepsia were the use of aspirin (odds ratio [OR], 2.2; 95% CI, 1.3-3.7) and smoking (OR, 2.1; 95% CI, 1.3-3.6) but not age, sex, marital status, educational level, income, or the use of alcohol, coffee, or nonsteroidal anti-inflammatory drugs. Independent risk factors for H pylori were increasing age (OR, 1.8 per decade; 95% CI, 1.5-2.3), male sex (OR, 2.1; 95% CI, 1.3-3.4), and net family income (OR, 1.8; 95% CI, 1.2-3.3)., Conclusion: Dyspepsia in the community is linked to smoking and aspirin use, but not to H pylori infection.

Background: Rapid whole blood tests for Helicobacter pylori infection were developed to assist in the management of patients with dyspepsia in general practice. However, they have not been extensively tested in this setting., Aim: To investigate the test characteristics of the BM-Test (Helisal Quick Test) when used in general practice., Method: One hundred and ten dyspeptic patients attending local general practitioners were recruited into the study. The BM-Test was administered by the general practitioner at the screening visit according to standard instructions supplied with the test kit. The patient was then referred to Nepean or Mornington Peninsula Hospitals for further assessment. including a 14C-urea breath test. The test kit was forwarded to the appropriate hospital centre for an independent, blinded reading. The sensitivity and specificity of the BM-Test were evaluated against the results of the 14C-UBT., Results: Based on general practitioner readings, the BM-Test had a sensitivity of 59.3% and a specificity of 90.2%. The positive and negative predictive values were 87.5% and 65.7%, respectively. When based on independent readings, sensitivity rose to 71.2% and specificity fell to 88.2%. The BM-Test was more sensitive for older patients than for younger patients when based on both the general practitioner and independent readings., Conclusion: The BM-Test performs below the generally recommended sensitivity and specificity of 90% required for clinical practice.

Objective: H. pylori causes chronic gastritis, which may progress to peptic ulcer, gastric atrophy, or gastric cancer. However, little is known about the role of H. pylori infection in reflux esophagitis and the relationship between reflux esophagitis and atrophic gastritis needs to be clarified. We sought to identify the possible interrelationships among Helicobacter pylori infection, reflux esophagitis, and atrophic gastritis, to signal areas in which researchers should consider focusing their attention., Methods: A broad-based Medline search was performed to identify all related publications addressing H. pylori infection, atrophic gastritis, gastroesophageal reflux disease (GERD), secretion of gastric acid, and gastric motility published between 1966 and July 1997., Results: Whereas some studies have shown no significant association between H. pylori infection and reflux esophagitis, others have observed that the prevalence of H. pylori infection was lower in patients with GERD, implying a protective role. Eradication of H. pylori leads to occurrence of reflux esophagitis in some cases, but the mechanisms inducing posteradication reflux esophagitis are unknown. H. pylori infection may lead to atrophic gastritis (and hence hypochlorhydia) through both bacterial and host factors, although gastric atrophy and subsequent intestinal metaplasia are hostile to H. pylori because of hypochlorhydria. Although it has been reported that long-term proton pump inhibitor therapy for refractory reflux esophagitis may induce or enhance the development of gastric atrophy in H. pylori-infected patients, this relationship has been disputed., Conclusions: H. pylori infection may be negatively associated with reflux esophagitis, but this requires confirmation. Research then needs to focus on whether this is explained through motility- or acid-related mechanisms. The potential costs of maintenance antireflux therapy may need to be taken into account when evaluating the cost effectiveness of anti-H. pylori therapy.

Epidemiological, pathophysiological and therapeutic studies have been carried out in order to try and establish whether an association between H. pylori infection and non-ulcer dyspepsia exists. A meta-analysis of pooled data showed that the prevalence of H. pylori infection in dyspepsia was higher than in controls (odds ratio 2.3), but this may be explained by selection bias. No convincing symptom profiles have been found to be associated with the infection, and there have been no consistent observations regarding the effects of the infection on gastroduodenal motility or sensation. Clinical trials in adults have been equivocal. Although a recent meta-analysis identified an overall benefit of H. pylori therapy, only selected trials could be included. Some studies have suggested that significant symptom improvement requires up to 12 months follow-up to be documentable. Little relevant paediatric clinical trial data are available. While it is possible that H. pylori may be responsible for symptoms in a small proportion of patients with non-ulcer dyspepsia and in some of these cases anti-H. pylori therapy may be beneficial, this remains to be established.

Objectives: The natural history of Helicobacter pylori infection in humans is not well established. We aimed to systematically review the literature on the natural acquisition and spontaneous elimination of the infection and its clinical consequences., Methods: A broad-based MEDLINE and Current Contents search was performed to identify all related publications between 1986 and 1996. Abstracts from recent major conferences that provided adequate data were also included., Results: The prevalence of H. pylori infection increases with age, the rates being significantly lower in developed countries than in developing countries. However, the overall prevalence is decreasing in both developing and developed countries, which probably is responsible for the steep decline of gastric cancer in some industrialized countries. The natural acquisition of H. pylori infection occurs, for the most part, in childhood, and it appears that the incidence is currently slightly higher in developing countries than in industrialized countries. Spontaneous elimination of the infection also occurs, especially in young children and the elderly. The route of transmission continues to be uncertain, with the best evidence favoring both the gastro-oral and fecal-oral routes. Low socioeconomic status is a major risk factor for acquisition of the infection. Genetics probably plays a role in the acquisition or clearance of H. pylori infection in individuals., Conclusions: Low rates of natural acquisition and elimination of the infection in adults suggest that it is worthwhile to eradicate the organism from adults, but there should be further evaluation of the need for eradication of H. pylori in children.

Recurrence of Helicobacter pylori infection after successful eradication occurs and is associated with relapse of gastroduodenal diseases. The aims of this paper were to assess the incidence and identify the nature and possible causes of recurrence of the infection. A broad-based Medline search was performed to identify all related publications addressing recurrence of the infection between 1986 and 1995. The 12-month recurrence rate varied among the different studies from 0 to 41.5%. A few studies showed 18- to 24-month recurrence rates, which ranged between 0 and 21.4%. Limited data, obtained using molecular fingerprinting techniques, have shown that in most cases recurrence is due to recrudescence of the original strain; a few cases appear to be due to reinfection with a new strain. Recrudescence is most likely during the first 12 months after apparent eradication. Despite the high sensitivity and specificity of the available individual tests for detecting H. pylori infection in untreated patients, no technique alone is sensitive enough to monitor eradication when the four-week-rule definition for eradication is used. A combination of two or more techniques increases sensitivity. Sensitivity and specificity are increased when biopsies are taken from both gastric antrum and corpus. The best treatments have the lowest recurrence rates and recurrence is rare when the eradication rate is over 90%. Individual susceptibility and reexposure to H. pylori are suggested as two major causes of reinfection.

The ability of oligonucleotide probes containing short repetitive sequence motifs to differentiate between isolates of Helicobacter pylori was investigated. Genomic DNA preparations from H. pylori were digested with the restriction enzyme HindIII, electrophoresed in agarose gels and transferred to nylon filters. Five separate oligonucleotide probes were tested for hybridization sequentially to fingerprint the digested DNA from a panel of 29 clinical isolates and one type strain of H. pylori, and their relative discriminatory abilities were assessed. Four probes, (GACA)4, (GT)8, (GTG)5 and (GGAT)4, were each shown to yield highly informative hybridization band profiles allowing differentiation of H. pylori isolates. The DNA fingerprints of individual isolates obtained with each probe were distinct and reproducible. Direct comparison with ribotyping revealed that oligonucleotide fingerprinting had far superior discriminatory power. Computer-assisted similarity analysis of (GGAT)4-generated hybridization profiles of pairwise combinations of H. pylori isolates revealed that there was no correlation between ribotype and oligonucleotide fingerprint patterns. The results of this study demonstrate that oligonucleotide probes containing microsatellite sequences provide a new and powerful tool for isolate discrimination of H. pylori.

Susceptibilities to clarithromycin and metronidazole of 444 Helicobacter pylori isolates cultured from antral biopsies of 444 dyspeptic patients were determined by disc diffusion tests (15 mu g disc for clarithromycin, 5 mu g disc for metronidazole). Susceptibility of 46 of these isolates to erythromycin (5 mu g disc) was also tested. Minimal inhibitory concentrations (MICs) of clarithromycin for 42 selected isolates were determined by a plate dilution method. A zone diameter of 30 mm was defined as a 'cut-off' size differentiating susceptibility and resistance of the organism to clarithromycin, by comparing results obtained with the two methods. Of the 444 isolates, 424 (95.5%) were highly sensitive to clarithromycin, with zone diameters ranging from 30 to 98 mm. Twenty isolates (4.5%) were defined as resistant to clarithromycin, with zone diameters ranging between 6 and 28 mm. The incidence of clarithromycin resistance was similar in men and women and in different age groups, and was not significantly different between patients with peptic ulcer and non-ulcer dyspepsia. Among the 444 isolates, 168 (37.8%) were metronidazole resistant. There was cross resistance between clarithromycin and erythromycin, but not between clarithromycin and metronidazole. Stability of clarithromycin resistance was evaluated by the disc diffusion test and confirmed by the plate dilution method. Among the 20 clarithromycin-resistant isolates, nine (45%) reverted to be sensitive after 25 subcultures on drug-free agar. The findings in this study indicate that the incidence of clarithromycin-resistant H. pylori in untreated dyspeptic patients is low. Cross-resistance occurs between macrolides and resistance to clarithromycin in some strains is reversible.

The direct and indirect effects of helicobacter pylori on cell kinetics of gastric epithelial cell line AGS were investigated by flow cytometric analysis of Ki-67 positive cells and by MTT assay. Flow cytometric analysis of Ki-67 positivity permits detection of cells that are in S-phase, whereas the MTT assay is a colometric measure of the number of viable cells. In the absence of added stimulants, 23.06 (4.88)% mean (SD) of AGS cells were Ki-67 positive. When cells were preincubated in the presence of H pylori, there was a significant increase in Ki-67 positivity (66.20 (7.89)%, p < 0.001). This increase was not seen in cells cultured in the presence of Campylobacter jejuni (24.63 (8.11)% or Escherichia coli (21.66 (9.78)%). Pre-incubation of AGS cells with supernatants from both H pylori and mitogen activated peripheral blood lymphocytes also increased the per cent of cells that were Ki-67 positive (72.93 (8.68) and 69.96 (12.35)%; p, 0.001) respectively. Similar results were also found in MTT assay. These data show that both H pylori directly and the immune/inflammatory response to H pylori indirectly can influence the rate of epithelial cell proliferation, suggesting this bacterium may be an initiating step in gastric carcinogenesis and an important co-carcinogenic factor in H pylori positive subjects.

Interaction between lymphocytes and epithelial cells may play a key role in Helicobacter pylori (H. pylori)-associated gastric mucosal inflammation. This interaction process is at least partially mediated by various cell adhesion molecules. The aims of the present study were to assess using flow cytometric analysis whether H. pylori directly or supernatants from H. pylori-activated peripheral blood mononuclear cells (PBMC) can affect the expression of adhesion molecules on the gastric epithelial cell line AGS in vitro. The results showed that resting AGS cells expressed CD44 and ICAM-1. Co-culture of AGS with H. pylori or cytokine-rich supernatants from H. pylori-activated PBMC resulted in up-regulation of expression of CD44 and ICAM-1 on AGS cells. These data suggest that H. pylori directly and indirectly through inflammatory cytokines may contribute to alternations in adhesion molecule expression on gastric epithelial cells. This may be of pathological significance in H. pylori-associated gastric mucosal inflammation and carcinogenesis.

Helicobacter pylori infection has been linked with gastric carcinoma. Epithelial cell proliferation is an indicator of cancer risk. The aim of this study was to assess gastric epithelial cell proliferation before and after eradication therapy and to assess the efficacy of treatment of H. pylori infection using lanzoprazole and clarithromycin. Twenty-three patients with H. pylori-associated gastritis were treated with lanzoprazole 30 mg daily for four weeks and clarithromycin 500 mg three times a day for two weeks. Antral mucosal biopsies were taken for gastric epithelial cell proliferation analysis using the in vitro bromodeoxyuridine (BrdU) immunohistochemical technique before and four weeks after eradication therapy. Labeling index percent (LI%) was calculated as the percent ratio of proliferating cells to the total number of cells in the gastric pit. Efficacy of treatment was assessed in 16 subjects. Eight were negative for H. pylori infection 28 days after therapy and in eight patients H. pylori infection was not eradicated. The eradication rate for the regime was 50%. Cell kinetics were assessed in 19 subjects who completed treatment. Patients with H. pylori infection had a significantly higher LI% compared to normal (N = 19, LI%: 5.01 +/- 0.3 vs 3.2 +/- 0.2, N = 29). Eradication of H. pylori infection significantly reduced epithelial cell proliferation (N = 9, LI%: 5.2 +/- 0.4 to 3.2 +/- 0.8, P < 0.001), whereas it was unaltered in those whose infection was not eradicated (N = 10, LI%: 4.8 +/- 0.4 to 5.5 +/- 0.5, P = 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To determine the 12-month posttherapy recurrence (recrudescence) of Helicobacter pylori in patients with healed duodenal ulcer after apparent eradication of the organism with anti-H. pylori treatment. The influence of original anti-H. pylori treatment regimens on the recrudescence was also evaluated., Methods: One hundred and ninety patients who had duodenal ulcer healed and H. pylori eradicated (as assessed by four routine techniques 4 wk after the end of anti-H. pylori therapy) with one of five regimens were studied. The five regimens were: 1) colloidal bismuth subcitrate (CBS) 120 mg; 2) CBS plus amoxicillin (500 mg); 3) CBS plus metronidazole (400 mg); 4) CBS plus metronidazole and amoxicillin; and 5) CBS plus metronidazole and tetracycline (500 mg). CBS was taken four times daily for 4 wk, and antibiotics were taken three times daily for the first week. The patients were re-endoscoped, and the status of H. pylori, duodenal ulcer, and gastritis was assessed after a period of follow-up (mean 14 months after commencement of treatment)., Results: H. pylori infection recurred in 36 (18.9%) of these patients. Recrudescence rate with monotherapy was 47.1%, with dual therapy 29.2-35% and with triple therapy 9.2-14.3%. Nineteen (52.7%) of the 36 patients with recrudescent infection had ulcer relapse, and the rate for H. pylori-negative patients was 3.2% (5/154)., Conclusion: Recrudescence of H. pylori infection after apparent eradication can occur, but it could be that the treatment was only suppressing the organism. The definition of eradication of H. pylori infection may need to be revised, and more sensitive techniques to assess eradication of H. pylori are required.

The aim of this study was to find out if reinfection or recrudescence accounted for the recurrence of Helicobacter pylori infections after apparent eradication of the bacterium. Three hundred and twenty patients were treated with colloidal bismuth subcitrate (120 mg four times daily for four weeks), metronidazole and tetracycline (400 mg and 500 mg, respectively, thrice daily for the first week). H pylori was eradicated four weeks after the end of treatment as assessed by the rapid urease test, histological examination, Gram staining, and culture. However, the infection recurred in 29 (9.1%) of the patients one year after apparent eradication. Pre and posteradication isolates from five patients were available. DNA was extracted and used for restriction endonuclease analysis with Hind III and Hae III, and for polymerase chain reaction (PCR) based randomly amplified polymorphic DNA fingerprinting with a combination of two 10 nucleotide primers. Sodium dodecyl sulphate polyacrylamide gel electrophoretic analysis was performed also. Randomly amplified polymorphic DNA fingerprinting was unique in that it yielded highly discriminatory fingerprints, which showed that the pretreatment and recurrent isolates obtained from each of the five patients were indistinguishable from one another. This shows that recurrence of H pylori infection is probably caused by recrudescence and that the discriminatory power of randomly amplified polymorphic DNA fingerprinting is a practicable and discriminatory typing scheme for H pylori.

Cultures of Helicobacter pylori on chocolate agar slants in bijou bottles and on chocolate agar plates inside BBL Campy Pouches were mailed from Dublin to Galway, Ireland; Bordeaux, France; and Beijing, China. Both systems maintained viability of H. pylori for at least 4 days under mailing conditions. Ninety percent of the isolates on the slants survived for 6 days, but only 30% of the isolates in the pouches survived. When the slants were stored at 4 degrees C after arrival, 50% of the isolates were recoverable 10 days after mailing. Failure of recovery was due to coccoid formation by the organisms. Contamination was not a problem in either system. Chocolate agar slants are considered the more suitable system for transporting H. pylori cultures, especially when transport time longer than 4 days is expected.