Antibody-secreting cells in the stomachs of symptomatic and asymptomatic Helicobacter pylori-infected subjects

In this study we analyzed whether infection with Helicobacter pylori gives rise to specific B-cell responses against a number of putative virulence factors of H. pylori, e.g., urease, flagellin, and different bacterial surface antigens, locally in the gastric mucosa. This was studied in antrum and corpus biopsies collected from 11 H. pylori-infected patients with duodenal ulcers, 11 asymptomatic H. pylori carriers, and 13 noninfected, healthy controls. Mononuclear cells were isolated from the biopsies and assayed for frequencies of total and H. pylori-specific antibody-secreting cells (ASCs) by means of the enzyme-linked immunospot technique. The H. pylori-infected subjects had remarkably higher frequencies of total immunoglobulin A (IgA)- and IgM-secreting cells than the noninfected subjects, while the frequencies of IgG-secreting cells were virtually the same in the different groups. In addition, most of the infected subjects had IgA ASCs reacting with H. pylori membrane proteins, flagellin, and urease, while none of the noninfected subjects had any detectable H. pylori-reactive ASCs. Furthermore, half of the infected subjects also had ASCs reacting with a Helicobacter-specific 26-kDa protein, while only a few of them had ASCs reacting with neutrophil-activating protein, the neuraminyllactose-binding hemagglutinin HpaA, or lipopolysaccharides purified from different H. pylori strains. The frequencies of H. pylori-specific ASCs in the antrum and corpus were almost identical, and no differences in either antigen specificity or magnitude of the B-cell response in the stomach could be detected between the ulcer patients and the asymptomatic H. pylori carriers. This study demonstrates that H. pylori infection induces strong antibody responses in the human gastric mucosa, both in asymptomatic carriers and in duodenal ulcer patients. However, the outcome of infection could not be explained by differences in the local B-cell response to any of the antigens used in this study.     

Platelet-derived growth factor BB mediated regulation of 12-lipoxygenase in porcine aortic smooth muscle cells

BACKGROUND & AIMS: Recently, we postulated a new concept of duodenal ulcer pathogenesis suggesting that antral Helicobacter pylori infection blocks inhibitory pathways to the gastrin and parietal cells, resulting in an increased and prolonged postprandial acid secretion. the aim of this study was to examine duodenal acid load and duodenal bulb pH after a meal before and after eradication of H. pylori. METHODS: Using a marker-dilution method and a pH electrode in the duodenal bulb, gastric emptying, acid secretion, gastrin release, duodenal acid load, and duodenal bulb pH were studied during 2 hours after peptone meals of pH 7.0 and 2.0 in 8 H. pylori-negative controls and 8 H. pylori-infected subjects before and 6 months after eradication. RESULTS: The H. pylori-infected subjects had an increased gastric emptying, gastrin release, and acid secretion, higher duodenal acid load, and lower duodenal bulb pH after the meals. These responses were normalized after eradication. CONCLUSIONS: H. pylori-infected subjects have an increased and prolonged postprandial acid secretion, partly caused by an impaired low pH inhibition of acid secretion, gastrin release, and gastric emptying, resulting in an increased duodenal acid load and a prolongation of low pH in the duodenal bulb, as a general prerequisite for the development of duodenal ulcer disease.     

Human antibody response to Helicobacter pylori lipopolysaccharide: presence of an immunodominant epitope in the polysaccharide chain of lipopolysaccharide

We have examined the antibody response to Helicobacter pylori lipopolysaccharides (LPS) in humans. We used sera from patients with gastroduodenal diseases and healthy adults infected or not infected with H. pylori. Data from the experiments for antibody binding to LPS suggested that the polysaccharide chains from many H. pylori strains showed high immunogenicity in humans. Sera from most (above 70%) H. pylori-infected individuals contained immunoglobulin G (IgG) antibodies against the polysaccharide region highly immunogenic H. pylori LPS. The IgG titers of individual serum samples that reacted strongly with highly immunogenic LPS were quite similar (r2 = 0.84 to 0.98). The results suggest wide distribution among H. pylori strains of a highly antigenic epitope in the polysaccharide moieties of their LPS. Also, the similarity in the titers of individual serum samples against highly immunogenic LPS points to the existence of epitopes sharing a common structural motif. However, some strains showed low antigenicity, even those with polysaccharide-carrying LPS. The dominant subclass of IgG that reacted with the highly immunogenic LPS was IgG2, which was preferentially raised against polysaccharide antigens. Recently, a structure that mimics that of the Lewis antigens was identified in the O-polysaccharide fraction of H. pylori LPS; however, no correlation between antigenicity of the polysaccharide chain in humans and the presence of Lewis antigens was found. The IgA and IgM titers against H. pylori LPS seemed to be mostly nonspecific and directed against lipid A. In a few cases, however, sera from individuals infected with H. pylori gave strong IgA and IgM titers against the highly immunogenic polysaccharide. In conclusion, the LPS of many H. pylori strains possess an antigenic epitope in their polysaccharide regions that is immunogenic in humans. However, our results show that the antigenic epitope is unlikely to be immunologically related to structures mimicking Lewis antigens.     

Local cytokine response in Helicobacter pylori-infected subjects

The host immune response to Helicobacter pylori infection might be of importance with regard to the outcome of infection by this organism, e.g., to explain why only a proportion of infected subjects develop peptic ulcers. In this study we have analyzed the local response of different cytokines-i.e., the proinflammatory interleukin-1beta, (IL-1beta), IL-6, tumor necrosis factor alpha, and IL-8; the immunoregulatory gamma interferon (IFN-gamma); and IL-4; and the anti-inflammatory transforming growth factor beta (TGF-beta)-in antral biopsy specimens from H. pylori-infected duodenal ulcer (DU) patients and asymptomatic (AS) carriers (i.e., with chronic gastritis only). For comparison, biopsy specimens from uninfected healthy individuals were also analyzed. An immunohistochemical technique was used to allow quantification of the cytokine responses as well as identification of the cell types associated with the cytokine expression. We found that the levels of all of the studied cytokines except IL-4 were increased in the H. pylori-infected subjects compared to the levels in the healthy individuals. Our results indicate that the antral cytokine response is of the Th1 type since IFN-gamma, but not IL-4, was up-regulated both in H. pylori-infected DU patients and in AS carriers. However, there were no significant differences in either proinflammatory or immunoregulatory cytokine levels when H. pylori-infected subjects with and without peptic ulcers were compared. Some of the cytokines, particularly IL-1beta and TGF-beta, were also found in the gastric mucosae of healthy, uninfected subjects. We also showed that the gastric epithelium contributes substantially to the antral cytokine response of the proinflammatory cytokines IL-1beta and IL-6 in addition to IL-8.     

Helicobacter pylori infection in patients with chronic pancreatitis and duodenal ulcer

BACKGROUND: The prevalence of duodenal ulcer is high in patients with chronic pancreatitis. Patients with simple duodenal ulcer without chronic pancreatitis are mostly Helicobacter pylori-infected, and the prevalence of IgG seropositivity is > 95%. The prevalence of H. pylori infection in patients with chronic pancreatitis is not known. METHODS: IgG antibodies against H. pylori were measured in a cross-sectional survey of consecutive patients who had their exocrine pancreas function examined with a Lundh meal test in the period 1988-95 and in a control group of patients with simple duodenal ulcer. RESULTS: Twenty-seven per cent of the patients with chronic pancreatitis had duodenal ulcer during the observation period. The prevalence of IgG antibodies against H. pylori was 22% in patients with chronic pancreatitis without duodenal ulcer as compared with 27% with non-organic abdominal pain. The prevalence of IgG antibodies against H. pylori was 60% in patients with chronic pancreatitis complicated by duodenal ulcer as compared with 86% in controls with simple duodenal ulcer. CONCLUSIONS: H. pylori infection contributes but may not be the only cause of duodenal ulcer in patients with chronic pancreatitis.     

Helicobacter pylori infection and duodenal ulcer in children and adolescents

To investigate the relationship between H. pylori infection and duodenal ulcer in children and adolescents, the markers of H. pylori infection were studied in 22 children and adolescents who had duodenal ulcers and were followed prospectively (Group A). Another 36 patients with gastrointestinal symptoms, but without ulcer, were also studied for comparison (Group B). Antral and duodenal tissues were biopsied and analyzed for the presence of H. pylori using three standard methods: urease test, culture and histology. The specific IgG antibody against H. pylori positivity using the ELISA method were also analysed. By these three methods, H. pylori positivity in the antral tissues, chronic active antral gastritis, and seroprevalence rate were found to be much higher in Group A than Group B. However, a similar trend was not found in the duodenal tissues. H. pylori was found in four of five patients during postoperative follow-up for duodenal ulcer. Among the four patients, no duodenal ulcer but chronic active gastritis was detected endoscopically in three who received vagotomy. Only the one who received simple closure of the perforated duodenal ulcer had a recurrent duodenal ulcer. It was concluded that a close relationship among duodenal ulcer, chronic active gastritis and H. pylori is present in children and adolescents.     

Search for putative virulence factors of Helicobacter pylori: the low-molecular-weight (33-35 K) antigen

Early studies suggested that two Helicobacter pylori proteins, CagA and VacA, were virulence factors. Support for that hypothesis has been undermined by geographic differences in prevalence of these antigens. To identify other possible putative virulence factors by establishing a relationship between antigens and different H. pylori diseases, two commercial available immunoblot assay kits, HelicoBlot 2.0 (Genelabs Diagnostics, Singapore) and RIDA Blot Helicobacter (R-Biopharm GmbH, Darmstadt, Germany), were used to investigate the prevalence of various specific antigen seropositivity in 80 H. pylori-infected Japanese (20 each with gastritis, duodenal ulcer, gastric ulcer, or gastric cancer). The production of interleukin-8 (IL-8) in biopsy specimens was also measured by enzyme-linked immunosorbent assay (ELISA). Both assays had 100% sensitivity; specificity was 90% for HB2.0 and 80% for RIDA-BH. With the exception of the 33-35 K antigen, there was no relationship between antigens, endoscopic diagnoses, histological findings, or mucosal IL-8 levels. The 33-35 K antigen was present in 97.5% (39 of 40) patients with gastric or duodenal ulcer compared to 70% (14 of 20) those with chronic gastritis (P < 0.006). The mean IL-8 levels in the corpus was significantly higher in those with antibody to the 33-35 K antigen compared to those without (105.4+/-22 pg/mg vs 10.2+/-8.8 pg/mg) (P=0.015). There was no relationship between other antigens including CagA and production of IL-8. In conclusion, the low-molecular-weight 33-35 K antigen may play an important role in the pathogenesis of H. pylori-related disease.     

Parietal cells in the duodenal bulb and their relation to Helicobacter pylori infection

AIM: To investigate the prevalence, and relation to Helicobacter pylori, of parietal cells in the duodenal bulb using a monoclonal antibody directed against H+,K(+)-ATPase (HK12.18). METHODS: Twenty six patients with duodenal ulcer disease and 16 healthy controls were studied. H pylori status was determined by gastric histology and culture and by the 13C-urea breath test. Four biopsy specimens were taken from the duodenal bulb and stained with HK12.18. The presence/absence and number of parietal cells in the duodenal bulb were assessed blindly by a histopathologist. RESULTS: The overall prevalence of parietal cells in the duodenal bulb was 31% (13/42) and was similar in patients with duodenal ulcer and in controls, and in H pylori positive and negative subjects. The median (range) number of parietal cells in the duodenal bulb was 7.5 (4-20) parietal cells/subject, and was similar in all four groups. CONCLUSIONS: The prevalence of parietal cells in the duodenal bulb (31%) is notably higher than previously reported in endoscopic studies, and is in keeping with reports from studies on necropsy/operative specimens. There was no difference in the prevalence or number of parietal cells in the duodenal bulb between patients with duodenal ulcer and controls, regardless of H pylori status. These findings suggest that parietal cells in the duodenal bulb do not contribute to the pathogenesis of duodenal ulcer.     

Helicobacter pylori CagA antigen antibodies

BACKGROUND: CagA antigen of Helicobacter pylori is highly immunogenic in humans. There is an increasing evidence that infection with CagA-positive strains is related to the development of peptic ulcer disease, atrophic gastritis, or gastric cancer. The aim of our study was to assess seropositivity to CagA in a group of 95 clinically symptomatic adults who underwent gastroduodenoscopy and to correlate results to their disease characteristics. METHODS AND RESULTS: Serum immunoglobulin G antibodies to CagA detected by ELISA kit (Helicobacter p120, Viva Diagnostika, Germany) were compared to standard IgG specific antibodies against a pool of H. pylori antigens Synelisa Pin plate, ELIAS, Germany). Immunoglobulin G antibodies to CagA were present in 5/31 (16%) serum samples from H. pylori negative persons and 10/28 (36%) serum samples from H. pylori positive patients without peptic ulcer disease compared with 8/11 (73%) H. pylori positive patients with peptic ulcer disease in the past, 11/13 (85%) H. pylori positive patients with duodenal ulcers or duodenitis and 4/5 (80%) H. pylori positive (1/7, 14% H. pylori negative) serum samples from patients with gastric resection for peptic ulcers in the past. Serum levels of antibodies to CagA in the groups of patients with peptic ulcer disease in the past, with present duodenal ulcers of duodenitis and in H. pylori infected patients with gastric resection were significantly higher then those of H. pylori infected patients without peptic ulcer disease (P < 0.05). On the other hand, there was no significant difference in the presence of the specific antibodies against at pool of H. pylori antigens between these four groups. CONCLUSIONS: These data suggest that serologic response to the CagA antigen is more prevalent in H. pylori positive persons with present or past peptic ulceration than among infected persons without peptic ulcer disease. The presence of antibodies to CagA in H. pylori positive persons may be useful for the identification of patients with higher risk or more severe disease.     

Helicobacter pylori infection in a randomly selected population, healthy volunteers, and patients with gastric ulcer and gastric adenocarcinoma. A seroprevalence study in Taiwan

To investigate the association of Helicobacter pylori and gastric ulcer and adenocarcinoma, IgG antibodies against H. pylori were examined in 823 randomly selected subjects, 92 healthy volunteers, 117 patients with gastric ulcer, and 148 with gastric adenocarcinomas in Taiwan, where the prevalence of gastric adenocarcinoma is high. The seropositivity of this population in Taiwan was 54.4%. Gastric ulcer patients had a higher seropositivity (83.8%) than healthy volunteers (62.0%) and gastric adenocarcinoma patients (62.2%) (P < 0.001). Gender difference, blood type, and habit of smoking were not associated with the seroprevalence in any study groups. Gastric ulcer coexistent with duodenal ulcer had a higher seropositivity (94.7%) (P < 0.05). The seropositivity of H. pylori in gastric adenocarcinoma patients was higher than in healthy volunteers only in younger age and was not associated with histologic type, invasion, and location of major tumors. The results reemphasize the association of H. pylori infection with gastric ulcer but not with gastric adenocarcinoma in Taiwan.     

Enhanced levels of C-X-C chemokine, human GROalpha, in Helicobacter pylori-associated gastric disease

C-X-C Chemokines play an important role for neutrophil extravasation through microvessels. Although the level of interleukin (IL)-8 is known to increase in the Helicobacter pylori-infected gastric mucosa, another C-X-C chemokine, GROalpha, has not been evaluated in the H. pylori-associated gastric mucosal injury. The present study was designed to investigate gastric contents of GROalpha in relation to those of IL-8 in the gastric mucosa of H. pylori-infected peptic ulcer patients. Thirty-eight patients with gastric ulcer and 41 with gastritis underwent endoscopy with informed consent and 49 were found to be H. pylori positive and 30 H. pylori negative. Biopsies from the gastric corpus were performed in each patient to examine the H. pylori colonization by bacterial culture, the rapid urease test and histological specimens as well as measurement of the contents of human GROalpha and IL-8. Helicobacter pylori infection was eradicated in 21 patients by triple therapy (lansoprazole 30 mg, amoxycillin 2.0 g, clarithromycin 600 mg; 2 weeks). The samples for GROalpha and IL-8 assay were homogenized in 0.02% aprotinin containing phosphate-buffered solution and the mucosal contents of GROalpha and IL-8 in the supernatants were quantified by sandwich enzyme immunoassay methods. The levels of GROalpha and IL-8 in H. pylori-positive gastric mucosa were significantly higher than those in the H. pylori-negative mucosa. There was a significant linear correlation between the levels of GROalpha and IL-8 (r = 0.798, P < 0.01). After the eradication of H. pylori by the triple therapy, the levels of GROalpha and IL-8 were significantly decreased. The GROalpha showed an increase in the H. pylori-positive gastric mucosa in a similar fashion as IL-8 contents, suggesting a pathogenetic role for GROalpha in H. pylori-associated gastric mucosal injury.     

The Trp64Arg mutation of the beta3-adrenergic receptor is associated with hyperglycemia and current body mass index in Jamaican women

Helicobacter pylori is a major etiologic agent in gastroduodenal disorders. In this study, immunoglobulin A (IgA) antibodies to H. pylori antigens were evaluated in serum and gastric juice specimens obtained from patients with gastritis or peptic ulcers by utilizing antibody capture enzyme-linked immunosorbent assays (ACELISAs). Urease alpha subunit (UA), urease beta subunit (UB), the 66-kDa heat shock protein (HSP), and the 25-kDa protein (25K) were used as antigens for the ACELISAs. The antibody titers of the ACELISAs reflect the ratio of H. pylori-specific IgA to total IgA. The ratio is stable, although the antibody concentration fluctuates in gastric juice. By using ACELISAs it was possible to evaluate quantitatively not only serum IgA antibodies but also gastric juice secretory IgA (S-IgA) antibodies. In both serum IgA and gastric juice S-IgA ACELISAs, the titers of antibody to HSP and 25K were remarkably correlated with the histologic grade of gastritis, whereas those to UA and UB were not strongly correlated with histologic grade. Thus, it is useful for estimating the histologic grade of gastritis to quantify serum IgA and gastric juice S-IgA antibodies to HSP and 25K.     

Quantitative noninvasive testing for Helicobacter pylori does not predict gastroduodenal ulcer disease

BACKGROUND: Helicobacter pylori is strongly associated with gastric and duodenal ulcer disease. However, the diagnosis of gastroduodenal ulcers requires an endoscopic or radiographic examination. In this study, we attempted to establish a relationship between the magnitude of [13C]urea breath test results or serum H. pylori IgG levels and endoscopic findings in H. pylori-infected individuals. METHODS: Patients who had undergone endoscopy and had a positive [13C]urea breath test and/or positive H. pylori IgG serology were identified. Endoscopic diagnoses included duodenal ulcer, gastric ulcer, nonulcer dyspepsia, and others. Results of 6% or greater on the [13C]urea breath test was defined as positive for H. pylori infection. H. pylori IgG serology was determined by an enzyme linked immunosorbent assay with values of greater than or equal to 1.0 being seropositive. RESULTS: One hundred seventy-five patients were seropositive (mean = 3.01 +/- 1.58). One hundred sixty-eight patients had a positive [13C]urea breath test (mean = 25.43 +/- 16.90). One hundred fifty-five patients were common to both the groups. Statistical analysis did not reveal any relationship between quantitative [13C]urea breath test results or H. pylori IgG values and endoscopic diagnoses. CONCLUSION: The magnitude of [13C]urea breath test or H. pylori IgG serology cannot be used to predict the presence or absence of gastroduodenal ulcer disease.     

Recommendations for the molecular diagnosis of familial adenomatous polyposis

OBJECTIVES: We investigated the relationships between gastric metaplasia occurring during the healing and scarring stages of duodenal ulcers and Helicobacter pylori by examining the course of gastric metaplasia in H. pylori-eradicated and non-eradicated patients. METHODS: One hundred and six H. pylori-positive patients with active duodenal ulcers were assigned to either a non-eradication group or an eradication group. The non-eradication group received lansoprazole for 6 wk, followed by an H2-receptor antagonist. The eradication group also received amoxicillin and metronidazole for 1 wk, in addition to lansoprazole, after initial endoscopic examination. In both groups, biopsy specimens were obtained from the ulcer margin in the active stage and from the center of the scar in the scarring stage. Specimens were examined microscopically as well as by rapid urease test to assess the extent of gastric metaplasia and to detect the presence of H. pylori. RESULTS: The extent of gastric metaplasia increased as the ulcers healed. The extent of gastric metaplasia was of a lesser degree in the non-eradication group than in the eradication group at the time of healing, and this tendency became increasingly apparent in the course of follow-up, resulting in reduced defense mechanisms against acidity to promote the recurrence of ulcers. In the eradication group, among those in whom eradication was successful, gastric metaplasia presented a well-developed appearance with abundant intracellular mucus and remained in this condition for a prolonged period, resulting in adequate defense mechanisms against acidity to prevent the recurrence of ulcers. CONCLUSION: By the eradication of H. pylori, gastric metaplasia becomes well-developed and remains so for a prolonged period. Thus, the eradication of H. pylori appears to play a role in the prevention of ulcer recurrences by developing adequate defenses against acidity.     

Utilization of proteinase K-treated cells as lipopolysaccharide antigens for the serodiagnosis of Helicobacter pylori infections

We have evaluated the use of proteinase K (PK)-treated cells isolated from Helicobacter pylori as lipopolysaccharide (LPS) antigens in an immunoblot assay and an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of H. pylori infection. The sera from patients with chronic gastritis, gastric ulcer, duodenal ulcer or gastric cancer, and from healthy adults with or without H. pylori infection were assayed with three commercial serodiagnostic kits (HM-CAP, Helico-G, and G.A.P. II) and novel methods relying on the use of PK-treated cells. The PK-treated cells used in these assays were selected on the basis of their possibility to possess a common epitope in the O-polysaccharides of H. pylori, which is known to be highly immunogenic in humans. Of the sera from these patients, 71-94% were positive with the commercial kits, 97% with immunoblot assay, and 90% with ELISA. On the other hand, of the healthy adults infected with H. pylori, 72-97% were positive with the commercial kits, 86% with immunoblot assay, and 72% with ELISA. PK-treated cells that did not contain the common epitope were unsuitable as an antigen for immunoblot assay or ELISA. Furthermore, the reactivity of these sera reacted specifically with H. pylori PK-treated cells but not with LPSs from other gram-negative bacteria, such as Campylobacter, Proteus, Bordetella, and Salmonella. These results demonstrate that the serological assays relying on the use of H. pylori PK-treated cells possessing a highly antigenic epitope are potentially useful as a serodiagnostic test for H. pylori infection.     

Circadian gastric acidity in Helicobacter pylori positive ulcer patients with and without gastric metaplasia in the duodenum

BACKGROUND: The presence of gastric metaplasia allows helicobacter pylori to colonise the duodenum and this condition is thought to be acquired as a response to acid hypersecretion. This functional disorder, however, is present only in a subgroup of duodenal ulcer patients and, in addition, surface gastric metaplasia has been frequently found in the proximal duodenum of normal subjects and patients with non-ulcer dyspepsia, who cannot be certainly considered as acid hypersecretors. AIMS: To clarify the role of acid in inducing gastric type epithelium in the duodenum. This study aimed at assessing whether the pattern of circadian gastric acidity differs between H pylori positive duodenal ulcer patients with and without duodenal gastric metaplasia. PATIENTS: Seventy one patients with duodenal ulcer confirmed by endoscopy and who were found to be positive for H pylori infection by histology on antrum biopsy specimens were enrolled into this study. METHODS: Gastric type epithelium in the duodenum was found in 49 of 71 ulcer patients (69%). Continuous 24 hour gastric pH metry was performed in 50 healthy subjects and in the two subgroups of duodenal ulcer patients with and without gastric metaplasia in the duodenum. Gastric acidity was calculated for 24 hours (1700-1659), night (2000-0759) and day-time (0800-1959). RESULTS: Ulcer patients without gastric metaplasia showed a significantly higher gastric acidity (p < 0.001) than controls for every time interval considered, while the ulcer subgroup with gastric metaplasia was more acid than healthy subjects (p < 0.001) during the whole 24 hour period and the daytime. There was no difference between the two subgroups of duodenal ulcer patients with and without gastric metaplasia during the various time segments analysed. CONCLUSION: The findings confirm that the circadian gastric acidity of duodenal ulcer patients is higher than that of controls. As there is no difference in gastric pH between duodenal ulcer patients with and without gastric metaplasia, gastric hyperacidity is not specific to patients with duodenal gastric metaplasia. It is probable that this histological change is a non-specific response to mucosal injury resulting from various factors and not exclusively to acid.     

p53 expression is of independent predictive value in lymph node-negative breast carcinoma

OBJECTIVES: To compare the diagnostic accuracy of the most widely available tests for diagnosis of Helicobacter pylori infection after antibiotic treatment. METHODS: A total of 59 H. pylori-positive, duodenal ulcer patients (mean age, 40.7 +/- 11.7 yr; 40 male and 19 female) were treated for 2 wk with either amoxicillin-metronidazole (n = 36) or omeprazole-amoxicillin-tinidazole (n = 23), and after 4 wk, were tested for H. pylori infection by [14C]urea breath test (UBT), serum IgG antibody level, and multiple antral biopsies for rapid urease testing, histology, Warthin-Starry stain, and polymerase chain reaction to detect H. pylori DNA. Infection status was established by a concordance of test results. RESULTS: H. pylori was eradicated in 47 patients (80%). UBT and rapid urease testing had the best sensitivity and specificity, although not statistically different to Warthin-Starry stain and polymerase chain reaction. Serology and histology had little diagnostic value in this setting due to high proportion of false-positive results. CONCLUSIONS: Noninvasive UBT is as accurate in predicting H. pylori status after antibiotic treatment as rapid urease testing and Warthin-Starry stain. Especially for duodenal ulcer patients, UBT could be considered the gold standard to confirm eradication of H. pylori.     

Helicobacter pylori and gastroduodenal lesions in 547 symptomatic young adults

OBJECTIVES: Helicobacter pylori (H. pylori) is involved in the pathogenesis of gastric inflammatory disorders. Both antral chronic gastritis and H. pylori infection prevalence increase with age. The aim of the study was to assess the prevalence of H. pylori infection in young adults and to study the relationship between endoscopical and histological features and H. pylori infection. METHODS: The study concerned 547 young patients (age: 18-25 years), undergoing endoscopy for upper gastrointestinal symptoms. The severity and the activity of chronic gastritis was graded by histological examination of antral biopsies. The diagnosis of H. pylori infection was based on histology and culture or urease test. RESULTS: Fifty-three percent of the patients had a normal endoscopy; 44 ulcers were found: 34 duodenal ulcers and 10 gastric ulcers. H. pylori infection was detected in 34% of cases. The prevalence of H. pylori infection was 29.8% in non-ulcer patients, 50% in gastric ulcers and 91% in duodenal ulcers (P < 0.01). Duodenal ulcer, aspect of antral mosaic mucosa and nodular gastritis, were closely related to the presence of H. pylori. There was a significant relationship between H. pylori infection and both the severity (P < 0.01) and the activity (P < 0.01) of the antral chronic gastritis. The prevalence of follicular gastritis was 22% : it was present in 60% of H. pylori positive patients and 2.4% of H. pylori negative patients. H. pylori infection was more frequent in patients from Africa than in Europeans (P < 0.01). There was no significant association between H. pylori infection and different types of diets, settlements (rural vs urban) or symptoms. CONCLUSION: These results show that in the young population studied, duodenal ulcer, nodular gastritis, antral mosaic mucosa, active chronic gastric and follicular gastritis are closely related to H. pylori infection. They suggest that in the subgroup of non ulcer symptomatic patients, H. pylori prevalence is higher than in the general population.     

Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases

The CagA protein of Helicobacter pylori is an immunogenic antigen of variable size and unknown function that has been associated with increased virulence as well as two mutually exclusive diseases, duodenal ulcer and gastric carcinoma. The 3' region of the cagA gene contains repeated sequences. To determine whether there are structural changes in the 3' region of cagA that predict outcome of H. pylori infection, we examined 155 cagA gene-positive H. pylori isolates from Japanese patients including 50 patients with simple gastritis, 40 with gastric ulcer, 35 with duodenal ulcer, and 30 with gastric cancer. The 3' region of the cagA gene was amplified by PCR followed by sequencing. CagA proteins were detected by immunoblotting using a polyclonal antibody against recombinant CagA. One hundred forty-five strains yielded PCR products of 642 to 651 bp; 10 strains had products of 756 to 813 bp. The sequence of the 3' region of the cagA gene in Japan differs markedly from the primary sequence of cagA genes from Western isolates. Sequence analysis of the PCR products showed four types of primary gene structure (designated types A, B, C, and D) depending on the type and number of repeats. Six of the seven type C strains were found in patients with gastric cancer (P < 0.01 in comparison to noncancer patients). Comparison of type A and type C strains from patients with gastric cancer showed that type C was associated with higher levels of CagA antibody and more severe degrees of atrophy. Differences in cagA genotype may be useful for molecular epidemiology and may provide a marker for differences in virulence among cagA-positive H. pylori strains.     

Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin

BACKGROUND: Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication. AIM: To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies. METHODS: Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14-17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site). RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal. CONCLUSION: An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.