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Gastric infection with Helicobacter pylori is common throughout the world. Usually acquired in childhood, this infection causes a chronic active gastritis. Chronic infection is usually asymptomatic, but its presence predisposes infected individuals to peptic ulcer disease. 1 Unlike gastropathies associated with nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, which are erosive and hemorrhagic, H pylori gastritis is nonerosive and nonhemorrhagic, 2 the pathology of which is not visible through an endoscope. Thus, H pylori gastritis would not be considered a satisfactory explanation for chronic gastrointestinal blood loss or iron deficiency. However, in this issue, Yip et al 3 report in a cross-sectional study of Alaskan Yupik Eskimos (Yupiks) a high prevalence of See also p 1135. erosive-hemorrhagic gastritis, gastrointestinal bleeding, iron deficiency, and gastric H pylori infection. Is erosive-hemorrhagic gastritis with chronic gastric bleeding leading to iron deficiency another consequence of chronic H pylori infection? If so, is this manifestation unique

Summary Experimental carcinogenesis has discovered and analyzed the inductive effect for one type of cancer, of single factors in given animal strains. Human carcinogenesis analyses the effect of associated factors on one cancer type incidence. It does not find any direct correlation and finds a lot of intermediary effects and mechanism between the factor and established carcinogenesis. Regarding Helicobacter pylori (HP), one realizes there is no statistical correlation between gastric infection and carcinoma. The only data which sustain its role is its possible effect in promoting atrophic gastritis with intestinal metaplasia, via the serum pepsinogen 1 reduction due to anti-HP immunoglobulin A (IgA) antibody. Intestinal metaplasia of the stomach is a condition increasing cell proliferation.

Infection of Helicobacter pylori causes chronic gastritis and plays an important role in the pathogenesis of gastroduodenal ulceration. H. pylori has also been suggested to be involved in the genesis of adenocarcincoma and MALT lymphoma of the stomach. H. pylori infection is associated with increased gastric epithelial proliferation, which can be reversed by a successful eradication of the organism. Although the mechanisms of increased gastric epithelial proliferation is not known, the enhanced epithelial proliferation is important in developing gastric carcinoma. Whether or not H. pylori de nove stimulates gastric epithelial proliferation is controversial, but gastric infection with H. pylori activates a mucosal inflammatory response by consisting of large numbers of polymorphonuclear and mononuclear cells, that also includes expression of various cytokines including interleukin-8. We review the mechanisms of H. pylori in enhanced gastric epithelial cell proliferation and cytokines in patients with H. pylori infection.

Ménétrier's disease is a rare protein-losing gastropathy characterized by hypertrophic gastric fold, foveolar hyperplasia, and hypoproteinemia with resulting peripheral edema. It is clinically evident as nonspecific gastrointestinal symptoms, including abdominal discomfort, nausea and vomiting, abdominal pain, weight loss, diarrhea, and edema. Pediatric Ménétrier's disease usually has an insidious onset and progressive, chronic clinical course and it spontaneously resolves in weeks or months. The pathogenesis of Ménétrier's disease is not clearly understood. Ménétrier's disease is thought to be associated with some gastric infections. But the cause of Ménétrier's disease is unknown, an association with cytomegalovirus (CMV) and Helicobacter pylori has been suggested. In Korea, We present the first a case of pediatric Ménétrier's disease with positive evidence of CMV and H. pylori.

Tolerance has been shown to develop in duodenal ulcer patients receiving H2-receptor antagonists, particularly with increased doses. Development of tolerance to ranitidine and its possible consequences for oesophageal acid load in patients with gastro-oesophageal reflux disease has still to be established.Eighteen patients with reflux oesophagitis grade 1 were treated with 300 mg ranitidine twice daily for 3 months and examined with two-channel 23-h pH-metry in the distal oesophagus and gastric body at base line and after 3 days and 3 months. Gastric infection with Helicobacter pylori was assessed with the 14C urea breath test.Median 23-h gastric pH increased significantly from 1.5 at base line to 3.7 on day 3 and 2.8 after 3 months but decrease significantly from day 3 to month 3 of therapy. Median 23-h acid reflux time was reduced significantly by therapy, from 12.6% at base line to 6.2% on day 3 and 7.2% after 3 months, and there was no significant difference between day 3 and month 3. Although there was no significant change in commonly used indicators of gastro-oesophageal reflux, interindividual variation was great, and multiple linear regression analysis indicated that tolerance, expressed as change in median gastric pH, was related to individual changes in 23-h acid reflux time with a correlation coefficient of -0.43. Infection with H. pylori was diagnosed in 44% of patients and was negatively related to tolerance.Our group of patients developed tolerance to the effect of ranitidine on gastric acidity. While gastro-oesophageal reflux did not change significantly in the group, tolerance may seen to contribute to increased gastro-oesophageal reflux in individual patients.

Laboratory studies of arenaviruses have been limited to parenteral routes of infection; however, recent epidemiological studies implicate virus ingestion as a natural route of infection. Accordingly, we developed a model for oral and gastric infection with lymphocytic choriomeningitis virus to enable studies of mucosal transmission and vaccination by this additional route.

Trypanosoma cruzi is an intracellular parasite transmitted from a reduviid insect vector to humans by exposure of mucosal surfaces to infected insect excreta. We have used an oral challenge murine model that mimics vector-borne transmission to study T. cruzi mucosal infection. Although gastric secretions have microbicidal activity against most infectious pathogens, we demonstrate that T. cruzi can invade and replicate in the gastric mucosal epithelium. In addition, gastric mucosal invasion appears to be the unique portal of entry for systemic T. cruzi infection after oral challenge. The mucosal immune responses stimulated by T. cruzi gastric infection are protective against a secondary mucosal parasite challenge. This protective mucosal immunity is associated with increased numbers of lymphocytes that secrete parasite-specific immunoglobulin A. Our results document the first example of systemic microbial invasion through gastric mucosa and suggest the feasibility of a mucosal vaccine designed to prevent infection with this important human pathogen.

Colonization of human gastric mucosa with Helicobacter pylori leads to chronic active gastritis and induces the occurrence of an acquired mucosa-associated lymphoid tissue (MALT) in the stomach. This remodelling of the gastric mucosa together with chronic antigen persistence may induce autoimmune reactions. The aim of this study was to investigate humoral autoimmune reactions to human gastric mucosa in H. pylori gastritis and their clinical relevance. Sera from patients with dyspeptic symptoms were tested for presence of IgG immunoglobulins against H. pylori. Gastric infection with H. pylori and alterations of gastric mucosa were demonstrated by histological examination of gastric biopsy specimens. All sera were tested for reactivity against human gastric mucosa by immunohistochemistry. Two different in-situ binding sites of antigastric autoantibodies were observed. Binding to canalicular structures within parietal cells was significantly correlated with antibodies to H. pylori, elevated basal gastrin levels and atrophy of gastric corpus glands. Our data indicate that autoimmune reactions to antigens in the human gastric mucosa occur in H. pylori gastritis and that they may play a role in the pathogenesis of the disease.

Helicobacter pylori is a spiral to helical, Gram-negative, microaerophilic bacterium that has been shown to be responsible for chronic active gastritis1. H. pylori infection is a necessary but not sufficient factor in gastric ulcer disease, duodenal ulcer disease and gastric adenocarcinoma1,2. H. pylori also provides the antigens that drive the development of gastric B cell MALT lymphomas3.

The relationship between gastric inflammation caused byHelicobacter pyloriinfection and symptoms of dyspepsia remains controversial (1). Using a murine model of gastric infection, Bercik et al provide new insights into the mechanism underlying such interactions. Gastric sections from Balb/c mice infected withH pylori, strain SS-1, were used for both histological evaluation and studies of neuromuscular physiology. Acute infection (two weeks) caused an antral-predominant polymorphonuclear cell infiltrate that was superceded by a corpus-predominant mononuclear and macrophage infiltrate in chronic infection (three to 16 months).

SUMMARY Aim: To study the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on gastric cell turnover using an in vitro immunohistochemical method of bromodeoxyuridine (BrDU) uptake. Methods: Thirty patients undergoing routine upper gastrointestinal endoscopy were studied. Sixteen had taken NSAIDs daily for more than 3 months and there were 14 age-matched controls. Endoscopic gastric antral biopsies were obtained and stained immediately using the BrDU technique. Cell proliferation was expressed as a labelling index percentage (LI%) defined as the number of BrDU-labelled nuclei in 10 gastric glands, expressed as a percentage of the total cells in the gastric gland. Results: Gastric infection with Helicobacter pylori was excluded in all patients. Of the 16 patients on NSAIDs, four had gastritis, four had erosions or ulceration and eight had a normal examination. Endoscopy was normal in all patients in the control group. The LI% (mean ± S.E.M.) in the entire NSAID group was 4.09 ± 0.29 and in the control group 3.57 ± 0.29. No significant difference was observed. In the NSAID patients with gastritis and erosions or ulceration, the LI% was 4.99 ± 0.61 and 3.07 ± 0.32, respectively. There was no significant difference in LI % between the endoscopic subgroups of patients on NSAIDs or between patients on NSAIDs who had normal endoscopy and the control patients. Conclusion: These results provide evidence that refutes the hypothesis that the prevalence of NSAID gastropathy is due to an effect on gastric cell turnover.

We determined the seroepizootiology of Helicobacter pylori infection in rhesus monkeys. Plasma was obtained from 196 animals (age range, 1 to 22 years) that were housed in social environments, either in indoor gang cages, in outdoor corrals, or in free-ranging forested conditions. Plasma immunoglobulin G levels were determined with a specific enzyme-linked immunosorbent assay, and the cutoff immunoglobulin G value for H. pylori seropositivity was determined from a study of 25 monkeys whose infection status was assessed by light microscopy and culture. One-year-old animals of both genders in all housing conditions had the lowest rate of positivity (60% in monkeys 1 year old versus 81% in monkeys 2 to 10 years old, P = 0.026). In addition, females tended to have higher rates of positivity than males. Seroconversion during a 1-year observation period occurred in 7 (28%) of 25 seronegative animals. Seroreversion occurred in 3 (4%) of the 78 positive animals; all 3 of these animals had received antimicrobial agents during the year. These observations demonstrate that the epizootiology of H. pylori infection in rhesus monkeys may serve as a model for human infection.

Gastric infection with Helicobacter pylori activates a mucosal inflammatory response by mononuclear cells and neutrophils that includes expression of cytokines interleukin-1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha, and IL-8. In this study, we analyzed the IL-8 response of human gastric cancer cell lines (Kato III, AGS, and MKN28) to H. pylori infection in vitro. IL-8 mRNA expression was detected by reverse transcription-PCR amplification of RNA extracted from epithelial cells after incubation with different H. pylori wild-type and mutant strains, and IL-8 secretion was measured by an enzyme-linked immunosorbent assay. Exposure to viable H. pylori induced IL-8 mRNA and protein synthesis in all three gastric cell lines but not in nongastric epithelial cell lines. Heat-killed H. pylori and a crude cytotoxin preparation did not induce significant IL-8 secretion. IL-8 mRNA peaked between 2 and 4 h postinfection, and IL-8 protein production was maximal 24 h postinfection. Exposure of gastric carcinoma cells to other gastrointestinal bacteria, such as Pseudomonas aeruginosa, Campylobacter jejuni, and Escherichia coli, but not Campylobacter fetus, induced IL-8 synthesis. Wild-type strains that expressed the vacuolating cytotoxin (Tox+) and a cytotoxin-associated gene (cagA) product (CagA+) induced significantly more IL-8 than did CagA- Tox- strains. However, there was no decrease in IL-8 induction by isogenic mutants of CagA-, Tox-, or Cag- Tox- strains or by a mutant lacking the urease subunits. These results indicate that exposure to H. pylori and other gram-negative organisms that do not colonize the gastric mucosa induces IL-8 production by gastric carcinoma cells in vitro. Although the CagA+ Tox+ phenotype of H. pylori is associated with enhanced IL-8 production by gastric cell lines, other bacterial constituents are clearly essential.

A low natural humoral immune response to Thomsen-Friedenreich antigen (TFA) is a general phenomenon in patients with cancer, including gastric cancer, and in some premalignant conditions. It has been also shown that Helicobacter pylori infection is associated with increased risk of gastric cancer. The possible link between the TFA immune response and H. pylori infection was investigated.Enzyme-linked immunosorbent assay with H. pylori cell surface glycine extract as antigen and microhemagglutination of neuraminidase-treated blood group O donor erythrocytes were used for evaluation of IgG H. pylori antibody and TFA agglutinin levels in sera from patients with gastric cancer (n = 39) or ulcer of the stomach (n = 36) and controls (n = 49).The tendency to an inverse relationship between the two events was found in all groups studied, including cancer. H. pylori-seronegative persons had higher TFA natural antibody titer than the related H. pylori-seropositive groups. When log2 of TFA antibody titer4 for strong TFA responders and H. pylori relative antibody activity25 for H. pylori-seropositive persons were chosen as cut-off limits, the association was statistically significant (p0.02). TFA antibody level was decreased in cancer patients as compared with controls (p0.002). No relation to age, stage of the disease, or tumor morphology was noted.The data suggest that the TFA natural immune response, which is known to participate in tumor-host relationships, is also involved in H. pylori-host interactions, probably as a natural factor of resistance against H. pylori infection.

Introduction: Helicobacter pylori (H. pylori) infection affects about 30-50% of adults in developed countries and causes persistent gastric infection and chronic inflammation. H. pylori infection is a major cause of gastric ulcer disease and gastric cancer. Diagnostic tests include histology, rapid urease test (RUT), breath tests and stool antigen tests. Previously, we have introduced a new electrochemical device for rapid H. pylori detection. Aims: To prospectively evaluate the newly developed electrochemical device for H. pylori detection in the clinical setting. Material & Methods: Seventy consecutive patients (43 female, 27 male; mean age 65 years, range 26-85 years) were included. The electrochemical device for H. pylori detection consists of a working and reference electrode between which a biopsy sample was administered. Acquired voltage-values between both electrodes were analysed for characteristics typical forH. pylori infection (ammonia). According to Sydney classification, biopsies were taken from gastric antrum and corpus for electrochemical H. pylori detection, RUT and immunohistochemistry (IHC). RUT results were evaluated after 24 hours. Every patient received 13C-urea breath test. Detection rates for H. pylori were analysed blinded to IHC results, which was designated as the gold standard of H. pylori diagnosis. Results: IHC had a sensitivity, specificity and accuracy of 100%. RUT analysis and 13C-urea breath test received both a sensitivity of 100% and a specificity of 92% and 95%, respectively. Accuracy of RUT was 93% and 96% for 13C-urea breath test. The new electrochemical H. pylori detection method showed a sensitivity of 100%, specificity of 94% and accuracy of 94%, respectively. Definitive results for H. pylori detection with the new device were available within 10 seconds. Conclusion: The new developed electrochemical H. pylori detection method allows rapid and accurate detection of the infection and has therefore the potential to improve H. pylori diagnosis and treatment.

Background/Aims: There is no generally accepted model for Helicobacter pylori infection in humans. The aim of this study was to examine the natural history and effect of treatment in rhesus monkeys and sequentially define the immune response to H. pylori in relation to treatment. Methods: Infection and gastritis were graded blindly by histological analysis and culture of biopsy specimens harvested during gastroduodenoscopies in 26 anesthetized colony-bred monkeys. Plasma H. pylori -specific immunoglobulin (Ig) G levels were determined by enzyme-linked immunosorbent assay. Results: H. pylori and Gastrospirilum hominis -like organisms were present in 13 and 9 monkeys, respectively; 3 animals harbored both organisms, whereas 4 monkeys were not infected. Gastritis score was ≤1.5 in animals uninfected or infected only with G. hominis -like organisms and ≥2.0 in all H. pylori -infected animals. IgG ratios were ≥0.5 in 12 of 13 H. pylori -infected animals and in 2 of 13 H. pylori -negative animals ( P H. pylori during the observation period, with concurrent increase of gastritis and plasma IgG levels. In untreated animals, infection, gastritis, and plasma IgG levels remained unchanged over 7–15 months. Triple therapy eradicated H. pylori at 6 months in 4 of 6 animals while suppressing gastritis and plasma IgG levels. Conclusions: Rhesus monkeys harboring H. pylori are persistently infected and have gastritis and elevated specific IgG levels, all of which may respond to appropriate therapy, whereas G. hominis infection is associated with little inflammation.

Gastric infection with Helicobacter pylori (HP), which causes chronic gastritis, is characterised by neutrophil infiltration. Whilst HP derived neutrophil chemotactic factors have been identified, little is known of the potential of the gastric mucosa to produce chemotactic cytokines. Using in vitro organ culture techniques, this study has investigated 1) IL-8 production by human antral endoscopic biopsies and 2) gastric secretion of autoantibodies to IL-8. 24 hour IL-8 secretion in HP+ patients with active gastritis (i.e. intraepithelial neutrophil infiltration) (mean ± SEM, 89.1 ± 12.7 ng/mg biopsy protein, n = 17) was greater than patients with inactive gastritis (28.8 ± 8.01, n = 10, p < 0.002) (8/10 HP+) and HP negative subjects with normal mucosa (21.7 ± 4.1, n = 19, p < 0.0001) or reactive gastritis (19.1 ± 6.7, n = 4, p < 0.01). IgA autoantibodies to IL-8 were present in 19 patients (13 active gastritis, 4 inactive gastritis) and concentrations were correlated with IL-8 production (p < 0.001, r = 0.51, n = 50). Immunolocalisation demonstrated that IL-8 was present in the epithelium of histologically normal antral mucosa (n = 7) and that HP infection was associated with increased epithelial and lamina propria IL-8 expression. The local synthesis of IL-8 is likely to be an important factor in regulating mucosal neutrophil infiltration and activation in patients with HP infection. The pathological significance of mucosal IL-8 IgA autoantibodies and the expression of this cytokine in gastric epithelium requires further investigation. The IgA anti-IL-8 antibodies may however represent a down-regulatory response of the host to limit damage associated with a chronic bacterial infection.

It is worldwide accepted that Helicobacter pylori (HP) gastric infection is one of the main causes of chronic antral gastritis: starting from the lamina propria lymphocites and polymorphs infiltrate the interfoveolar space [3, 7, 10]. Treatment of HP can rapidly cause disappearance of the organism and reversion of the abnormalities. However, if the treatment fails to eradicate the organism totally, the improvement will be temporary [12].

Helicobacter pylori (HP), known to cause active chronic gastritis, has primarily been found in gastric-type mucosa. Even in the duodenum, the organism was detected in islands of metaplastic gastric mucosa. HP has also been found in gastric metaplasia of Barrett's esophagus in 15–50%. The aim of our study was to determine: (1) the frequency with which HP is found on histopathological sections of heterotopic gastric mucosa (HGM) patch(es) at the upper esophagus, as compared to that of the stomach proper, and (2) the histopathological significance of infection in the HGM patches. From 63 patients with HGM patches at the upper esophagus, 48 patients were found to have concurrent adequate specimen from the stomach for modified Steiner's stain. In 22 patients (45.8%), pair sections from HGM and stomach were negative for HP. Of 26 patients (54.1%) HP-positive on sections from the antrum and/or body (both in 21 cases) nine patients (18.7%) demonstrated HP in the HGM patches. Whereas focal acute inflammatory changes on the H&E section of HGM was present in six patients, HP was detected in HGM only in one. Chronic inflammatory cell infiltration was detected in all nine HP-positive HGM patches and in 37 of 39 HP-negative patches. A mixed acute and chronic inflammatory cell infiltration was found in five of these 37 patients. Our data demonstrate that HP infection of HGM patches at the upper esophagus is part of the HP gastritis and an independent colonization of HGM patches without gastric infection does not occur. No correlation was found between the presence of acute and chronic inflammatory changes in H&E-stained section and positivity of HP in modified Steiner's section of HGM.

Background: An association between Helicobacter pylori (H.pylori) infection and iron deficiency anemia has been reported recently in children. Aim: To investigate a causal aβociation between H. pylori infection and iron deficiency anemia. Methods: Four patients, boys aged between 6 and 14 years, were admitted for severe pale without gastrointestinal symptoms. An extensive initial work-up was ordered that included the hematologic profile, multiple stool examinations for parasites and H.pylori antibody. Endoscopy was performed and antral biopsy specimens were taken for rapid urease test and histology. Eradication therapy was administered for 2 weeks. Oral iron therapy was prescribed after eradication. The hematologic profile were aβeβed after the iron therapy. Results: We present four patients with iron deficiency anemia and poor nutritional iron intake, gastrointestinal bleeding, chronic inflammation were excluded on the basis of specific tests. Iron deficiency anemia was defined as a hemoglobin concentration of leβ than 12 g/dl (6.3-7.0 g/dl), serum iron concentration leβ than 6.6 μmol/L (3.4- 4 μmol/L), a serum ferritin concentration leβ than 20 ng/ml (10-17 ng/ml). IgG antibody titer to H.pylori was positive in all the patients. Upper gastrointestinal endoscopy revealed a marked antral nodularity. A rapid urease test result was positive. Histopathology revealed chronic gastritis. H. pylori was succeβfully eradicated. Oral iron therapy was prescribed and 3 months later hematologic profile normalized. Conclusions: A diagnosis of H. pylori infection should be taken in children with iron deficiency anemia even in the absence of gastrointestinal symptoms. H. pylori infection is a risk factor for iron deficiency anemia.

Introduction Gastric infection with Helicobacter in transgenic hypergastrinaemic INS-GAS mice has been shown to accelerate the development of gastric cancer. Both H pylori and gastrin transactivate the EGF receptor (EGFR) in an autocrine or paracrine manner, respectively. The aims of the study were to examine the effects of treatment with an EGFR inhibitor in H felis infected INS-GAS mice. Methods Male INS-GAS mice were orally infected with H felis. Six weeks post-infection, infected and uninfected controls were fed either control, or EKB-569 (EGF inhibitor) supplemented food. Mice were sacrificed at 9 months post-infection. At post mortem gastric tissue was taken for pathology, analysis of RNA, proteins and DNA. Mucosal thickness and gastric epithelial cell proliferation (Mib1), apoptosis (active caspase 3), parietal cell density (H+K+ ATPase), B cell density (CD20) and Aicda (activation-induced cytidine deaminase, a DNA editing enzyme) were assessed immunohistologically. Gene expression was determined by quantitative RT-PCR. Results H felis infection resulted in significant increases in corpus mucosal thickness, Mib1 positive epithelial cells, active caspase 3 positive epithelial cells, and reduced number of parietal cells relative to uninfected controls. EKB-569 had no effect on epithelial proliferation, apoptosis, parietal cell number and mucosal thickness. Infection was associated with increased levels of transcripts for Cox-2, Egfr, Hb-egf, γ-Ifn (1.5–3.5-fold increase, p Conclusion In this study, EKB-569 did not affect gastric pathology, but markedly reduced Helicobacter induced aberrant expression of Aicda, a DNA editing enzyme, shown to induce TP53 mutations in human gastric epithelial cells in vitro.

Helicobacter mustelae, isolated from the stomachs of adult ferrets, appears to have a world-wide distribution. Ferrets are colonized with H. mustelae at a young age, usually 5-6 weeks; in our experience 100% of adult ferrets are colonized in both the antrum and the fundus. Gastric infection correlates with elevation of serum IgG antibodies to H. mustelae. In the oxyntic mucosa the presence of superficial gastritis coincides closely with the presence of H. mustelae. In the distal antrum the organism is associated with chronic inflammation occupying the full thickness of the mucosa. In addition to lesions seen in the distal antrum, focal glandular atrophy and regeneration are noted in the proximal antrum and transitional mucosa. Antibiotics used to eradicate Helicobacter pylori in humans are also effective in eliminating H. mustelae from ferrets. H. mustelae-free ferrets do not become colonized with H. pylori when challenged orally; however, sparse colonization follows oral inoculation with a related gastric organism, "Helicobacter felis." Controlled studies of the pathophysiology of gastroduodenal disease induced by Helicobacter species can be performed in H. mustelae-infected ferrets and their H. mustelae-negative counterparts.

Endoscopic, histologic, and microbiologic evaluations of 21 cynomolgus and 34 rhesus monkeys for naturally occurring Helicobacter pylori infection were done. H. pylori was never isolated from any cynomolgus monkey, but was found in 12 rhesus monkeys. A general correlation existed between a positive culture and a gastric inflammatory response. Inoculation challenges were then undertaken. Four cynomolgus and five rhesus monkeys received two different H. pylori strains isolated from humans. Five rhesus monkeys received an isolate obtained from rhesus monkeys. Evaluation of the cynomolgus monkeys 7 and 14 days later revealed no H. pylori. Endoscopies of the rhesus monkeys were done 7, 14, 21, 28, and 56 days later. One rhesus monkey, which received the isolate from humans, became H. pylori positive at day 21 and remained positive through day 56. Restriction enzyme analysis of genomic DNA at day 56 revealed that the isolate was not identical to the challenge strain isolated from humans. All five rhesus monkeys that received the strain isolated from rhesus monkeys became H. pylori positive by day 14 and remained positive through day 56 Antral inflammation developed in all monkeys. Restriction enzyme analysis of genomic DNA on day 56 confirmed that four of five isolates were identical to the challenge strain isolated from rhesus monkeys. DNA hybridization documented homology between the challenge strains isolated from humans and rhesus monkeys plus those isolated at day 56. In this study, we showed that the rhesus monkey, if given a strain of H. pylori isolated from rhesus monkeys, develops a gastric infection with accompanying histological changes, making this model suitable for further development.

Gastric actinomycosis constitutes a rare but treatable cause of gastric outlet obstruction. When encountered clinically, it is a difficult diagnosis to make before obtaining a surgical specimen, as exemplified by the following case. A 49-year-old Egyptian male with a history of hypertension and ventral hernia repair presented to the emergency room with a complaint of postprandial vomiting for 6 months that progressed from a coffee-ground appearance to bilious. The patient also reported a 45-pound weight loss during this time. He denied any use of nonsteroidal anti-inflammatory drugs. He had been incarcerated for 3 months in a federal penitentiary. On physical exam, the patient was afebrile with stable vital signs. Physical exam was significant for the presence of normal bowel sounds with mild epigastric tenderness on palpation. His abdomen was nondistended with no guarding, rebound, or hepatosplenomegaly. There was no stool in the vault on rectal exam. The remainder of his exam was unremarkable. Laboratory studies showed a white blood cell count of 6,900 cells per microliter with 55% segmented cells and hemoglobin of 17.4 g per deciliter. Chemistries showed evidence of metabolic alkalosis, mild prerenal azotemia, and normal liver studies. Abdominal radiograph was normal. Computed tomography of the abdomen and pelvis with contrast revealed a dilated stomach with the remaining bowel loops normal in caliber. An upper endoscopy performed the day following admission showed a thickened gastric outlet possibly secondary to edema versus a mass. Biopsies were obtained that showed intestinal metaplasia and chronic gastritis. The patient was initially treated conservatively with a clear liquid diet and a proton pump inhibitor twice a day. When his symptoms did not improve, he again underwent upper endoscopy with an unsuccessful balloon dilatation of the pyloric channel. Following 2 more weeks with little clinical improvement, the patient underwent a distal gastrectomy with Bilroth I reconstruction. Pathology of the surgical specimen showed necrosis, abscess, and sulfur granules consistent with Actinomyces infection. The patient was started on 24 million units of intravenous penicillin every day for 6 weeks, to be followed by a planned course of 10 months of oral penicillin. The patient9s symptoms had resolved by the end of his intravenous penicillin course. This case illustrates both the diagnostic difficulties and the effective response to therapy of this rare gastric infection. An extensive review of the literature revealed 28 other cases of gastric actinomycosis, with numerous reports of infection throughout other regions of the gastrointestinal tract. Less than 10% of the reviewed cases included a diagnosis of actinomycosis made pre-operatively. In both our case and the reviewed cases, the diagnosis was only made with histopathologic evaluation of a surgical specimen. Although this diagnosis is typically delayed, the recognition of actinomycosis is crucial as this is a directly treatable cause of gastric outlet obstruction.

H pylori gastric infection is one of the most prevalent infectious diseases worldwide. The discovery that most upper gastrointestinal diseases are related to H pylori infection and therefore can be treated with antibiotics is an important medical advance. Currently, a first-line triple therapy based on proton pump inhibitor (PPI) or ranitidine bismuth citrate (RBC) plus two antibiotics (clarithromycin and amo-xicillin or nitroimidazole) is recommended by all consensus conferences and guidelines. Even with the correct use of this drug combination, infection can not be eradicated in up to 23% of patients. Therefore, several second line therapies have been recommended. A 7 d quadruple therapy based on PPI, bismuth, tetracycline and metronidazole is the more frequently accepted. However, with second-line therapy, bacterial eradication may fail in up to 40% of cases. When H pylori eradication is strictly indicated the choice of further treatment is controversial. Currently, a standard third-line therapy is lacking and various protocols have been proposed. Even after two consecutive failures, the most recent literature data have demonstrated that H pylori eradication can be achieved in almost all patients, even when antibiotic susceptibility is not tested. Different possibilities of empirical treatment exist and the available third-line strategies are herein reviewed.

Purpose: According to the recent studies, it is shown that the polymorphism of Interleukin gene is associated with the incidence of gastric cancer caused by the Helicobacter pylori infection. Interleukin is a cytokine markedly inhibiting gastric acid secretion. Interleukin production associated with Helicobacter pylori gastric infection may exacerbate mucosal damage including chronic gastritis and atrophic gastritis, may induce eventual neoplasia. Among these Interleukin gene polymorphisms, polymorphisms at -31 portion and -511 portion may associated with these processes, eventually increase the risk of gastric cancer. We investigated the risk of gastric cancer according to the Helicobacter pylori infection and genetic polymorphism of Interleukin in gastric cancer patients. Materials and Methods: 176 individuals with gastric cancer and 40 healthy controls were analyzed. Each group was divided into two groups whether they infected with Helicobacter pylori or not. DNA was extracted from the peripheral blood in all groups. The PCR-RFLP method was used for investigating the distribution of genotype of C/C, C/T, T/T at -31 portion and -511 portion. Results: T/T genotype at -511 portion was in gastric cancer cases and in controls, which was statistically significant. (P=0.0432) The risk of gastric cancer was increased 4.86 () in group which had T/T genotype. In gastric cancer cases, C/C genotype at 31 portion was in group with Helicobacter pylori infection and in group without infection, which was statistically significant. (P=0.0047) The risk of gastric cancer was increased 4.82 () in group which had C/C genotype. Conclusion: T genotype at -511 portion among the Interleukin genetic polymorphisms may be the risk factor of gastric cancer. And, with Helicobacter pylori infection, C genotype at -31 portion may be the risk factor of gastric cancer.

Strongyloides stercoralis ordinarily matures in the human proximal small intestine and embeds in the small intestine mucosal wall where eggs are produced. Although Strongyloides may infect many sites in hyperinfection syndromes, reports of gastric involvement are rare. We report a patient taking prednisone and an H2 blocker who developed hyperinfection syndrome, with mucosal Strongyloides larvae seen in a gastric biopsy.

AIM: The widespread use of antibacterial therapy has been suggested to be the cause for the decline in the prevalence of Helicobacter pylori infection. This study examine the serial changes of urea breath test results in a group of hospitalized patients who were given antibacterial therapy for non-gastric infections. METHODS: Thirty-five hospitalized patients who were given antibacterial therapy for clinical infections, predominantly chest and urinary infections, were studied. Most (91 %) patients were given single antibiotic of either a penicillin or cephalosporin group. Serial 13 C-urea breath tests were performed within 24 hours of initiation of antibiotics, at one-week and at six-week post-therapy. H. pylori infection was diagnosed when one or more urea breath tests was positive. RESULTS: All 35 patients completed three serial urea breath tests and 26 (74 %) were H. pylori-positive. Ten (38 %) H. pylori-infected patients had at least one negative breath test results during the study period. The medium delta 13 C values were significantly lower at baseline (8.8) than at one-week (20.3) and six-week (24.5) post-treatment in H. pylori-positive individuals (P=0.022). Clearance of H. pylori at six-week was only seen in one patient who had received anti-helicobacter therapy from another source. CONCLUSION: Our results suggested that one-third of H. pylori-infected individuals had transient falsenegative urea breath test results during treatment with antibacterial agent. However, clearance of H. pylori infection by regular antibiotic consumption is rare. Leung WK, Hung LC-T, Kwok CK-L, Leong RW-L, Ng DK-K, Sung JJ-Y. Follow up of serial urea breath test results in patients after consumption of antibiotics for non-gastric infections.World J Gastroenterol 2002; 8(4):703-706

We report a case of gastric pseudoterranoviasis proven by gastrofiberscopy on Dec. 13, 1994. The 34-year-old male patient, residing in Chungju-shi, was admitted to Konkuk University Hospital complaining of prickling epigastric pain. The symptoms suddenly attacked him two days after eating raw marine fish at Chonan-shi. By the gastrofiberscopic examination, a long white-yellowish nematode was found from the fundus region of stomach. The worm was 34.50 x 0.84 mm in size, and was identified as a 3rd stage larva of Pseudoterranova decipiens judging from the position of the intestinal cecum. This is the 12th confirmed case of human pseudoterranoviasis in Korea.

Biopsy specimens were taken from intact areas of antral mucosa in 100 consecutive consenting patients presenting for gastroscopy. Spiral or curved bacilli were demonstrated in specimens from 58 patients. Bacilli cultured from 11 of these biopsies were gram-negative, flagellate, and microaerophilic and appeared to be a new species related to the genus Campylobacter. The bacteria were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer and thus may be an important factor in the aetiology of these diseases.

A breath-test has been developed for the detection of gastric infection with Campylobacter pylori. Urea that is labelled with carbon 14 is administered to a fasting patient and the patient's breath is sampled for radioactivity over the following 30 minutes. If C. pylori is present in the patient's stomach, urease activity causes hydrolysis of the urea and the 14C is absorbed as carbon dioxide. This carbon dioxide enters the patient's bicarbonate pool and eventually is excreted in the breath. The results are expressed as a percentage of the administered dose/mmol carbon dioxide x kg body weight. Sixty-three patients who were undergoing endoscopy were studied. The radioactivity in exhaled breath which was sampled within five minutes of 14C-urea administration was attributed to the presence of urease enzyme in mouth organisms and was discounted. The time-radioactivity curves for breath samples from five to 30 minutes after the administration of 14C-urea gave an excellent separation between subjects with negative results of the examination of gastric-biopsy samples and patients with microbiological and histological evidence of infection with C. pylori. The area under the time-radioactivity curve at between five and 30 minutes after the administration of 14C-urea in 24 patients with negative microbiological results was 6.9 +/- 4.4 area units; in 35 of 39 patients with positive microbiological results, this area was greater than 40 area units. Measured against the results of the microbiological examination of gastric-biopsy samples, the sensitivity of breath-testing was 90% and the specificity was 100%. Measured against the results of histological examination for the presence of C. pylori infection, breath-testing had a sensitivity of 94% and a specificity of 93%. A positive breath-test result also correlated well (P = 0.0001) with the serological antibody test-result. The role of non-invasive tests--enzyme-linked immunosorbent assays and 14C-urea breath-testing--in the management of gastritis and peptic ulcer disease is discussed. We consider that the 14C-urea breath-test has an important role in the noninvasive confirmation of gastric infection with C. pylori and in the follow-up of patients after treatment.

• A 44-year-old man with epigastric pain, fever, and atypical lymphocytosis was found to have severe antral gastritis with radiologic and endoscopic features suggestive of malignancy. Histopathologic and serologic findings were diagnostic of cytomegalovirus gastric infection. Clinical involvement of the stomach in the course of cytomegalovirus mononucleosis is unique, and this case expands further the spectrum of clinical disease in the otherwise healthy adult. (Arch Intern Med1987;147:787-788)

Campylobacter pylori organisms were found with similar frequency in the stomachs of patients with Barrett's esophagus and in age- and sex-matched controls (10 of 26 vs. 11 of 26). Campylobacter pylori was also observed in esophageal Barrett's mucosa in some patients with gastric C. pylori, but not when gastric infection was absent (4 of 10 vs. 0 of 16). Campylobacter pylori was not detected in esophageal squamous mucosa from patients with Barrett's esophagus or in 25 non-Barrett's patients with gastric C. pylori and histologic changes of esophageal reflux. Overall frequency of ulceration in Barrett's esophagus was 35% (9 of 26), and frequency of ulceration was similar whether or not C. pylori was noted in gastric or Barrett's mucosa.

Campylobacter pylori may not be the only organism that causes active chronic gastritis in man. We report two cases of gastric infection with a spiral organism distinct from C. pylori. The first patient is a 36-year-old female who presented with epigastric pain and abdominal colic present since childhood and who had 14 cats. Endoscopy was normal. The second patient kept two dogs. Histology of gastric mucosal biopsy specimens in both patients revealed active chronic gastritis, most severe in body mucosa. Giemsa stain revealed bacteria with four to eight spirals, 0.5 micron in diameter and 3-7 micron in length. The organisms had multiple sheathed flagella at the pole and smooth cell walls without axial filaments. The organisms resembled the gastric spirillum that has been seen in cats, dogs, and nonhuman primates. After antibacterial therapy with bismuth subsalicylate, amoxicillin, and metronidazole, the organisms disappeared in both patients and the gastritis healed. Unlike C. pylori, this new spirillum prefers to colonize gastric mucosa containing parietal cells. Whereas this type of organism is a common commensal in other mammals, it appears to be associated with and a possible cause of gastritis in humans.

A number of epidemiological studies have suggested associations between Helicobacter pylori seropositivity and coronary heart disease (2). High concentrations of immunoglobulin G antibody to H. pylori are fairly reliable indicators of chronic gastric infection, but the presence of antibodies in serum does not necessarily indicate persistent exposure of the coronary arteries to any type of insult. Although a number of pathological studies have reported the presence of Chlamydia pneumoniae DNA, antigens, or elementary bodies in diseased arterial specimens (3), there is little direct evidence available on the possible presence of H. pylori in the bloodstream or in vascular tissue. Hence, we investigated the presence of the H. pylori genome in buffy coat samples and in diseased arterial segments. We used a PCR that involved nested primers specific for the 16S rRNA gene of H. pylori, optimized to detect as little as 0.01 pg of genomic DNA (or about a dozen organisms) (6). DNA had been extracted from the buffy coat samples of 77 healthy individuals for a genetic study of myocardial infarction; 52 of these individuals were known to be strongly seropositive for immunoglobulin G antibodies to H. pylori, and 25 were chosen as seronegative controls. Samples of carotid atheroma were taken from another 39 individuals at carotid endarterectomy. DNA was extracted from the tissue by using a commercial kit (Puregene; Flowgen Ltd.) and analyzed by operators unaware of the tissue source. PCR products of samples appearing positive on gel electrophoresis were probed by Southern hybridization and autoradiographed for 1 week. Only 1 of the 77 buffy coat samples tested positive, and it belonged to a seropositive individual. Only 1 of the 39 atheromatous specimens collected at carotid surgery tested positive. A number of standard precautions were taken in the present study to protect against spurious results due to contamination, including the use of dedicated laboratory space, reagents, and instruments for pre- and post-PCR work and the testing of positive controls and negative controls in parallel with the test samples. Despite these precautions, the possibility of contamination in the two samples that tested positive for H. pylori DNA cannot be definitely excluded, nor can we exclude the possibility that a low-copy-number infection was actually present but undetected by our highly sensitive assay. Still, the present study adds to the sparse data that exists on H. pylori DNA in the bloodstream and in vascular tissue, being the first reported detection of H. pylori markers in human vascular tissue. It, however, does not support the likelihood of a high prevalence of the organism in buffy coat samples or in carotid atheroma. The only available report of H. pylori bacteremia involved positive blood cultures in a patient with gastric perforation due to malignancy (7), but in vitro studies suggest that any organisms penetrating beyond the gastric mucosa should be killed rapidly by complement proteins (5). Whereas a large number of studies have reported on the presence of markers of C. pneumoniae and cytomegalovirus in vascular lesions (2), there is only one previously reported study of H. pylori and atheroma (1). That study did not detect H. pylori DNA in any of the atherosclerotic plaques of 50 patients with abdominal aortic aneurysms, although about one-half of these samples tested positive for C. pneumoniae DNA (1). If H. pylori is relevant to the causation of vascular disease, it remains unclear how its effects are mediated. This suggests the need for further studies of coronary atheroma and comparisons of concentrations in plasma of vascular risk factors in seropositive and in seronegative individuals (4), as well as before and after H. pylori eradication treatment.

Infection of the human stomach by Helicobacter pylori remains a worldwide problem and greatly contributes to peptic ulcer disease and gastric cancer. Without active intervention approximately 50% of the world population will continue to be infected with this gastric pathogen. Current eradication, called triple therapy, entails a proton-pump inhibitor and two broadband antibiotics, however resistance to either clarithromycin or metronidazole is greater than 25% and rising. Therefore, there is an urgent need for a targeted, high-specificity eradication drug. Gastric infection by H. pylori depends on the expression of a nickel-dependent urease in the cytoplasm of the bacteria. Here, we report the 2.0 Å resolution structure of the 1.1 MDa urease in complex with an inhibitor by cryo-electron microscopy and compare it to a β-mercaptoethanol-inhibited structure at 2.5 Å resolution. The structural information is of sufficient detail to aid in the development of inhibitors with high specificity and affinity., Infection by Helicobacter pylori is associated with peptic ulcers and gastric cancer. H. pylori urease is required for colonization of the stomach and thus an attractive antimicrobial drug target. Cryo-EM analyses of the H. pylori urease with inhibitors bound reveal structural details useful in rational drug design.

Helicobacter (H.) heilmannii sensu stricto (s.s.) is a zoonotic bacterium that naturally colonizes the stomach of dogs and cats. In humans, this microorganism has been associated with gastritis, peptic ulcer disease and mucosa associated lymphoid tissue (MALT) lymphoma. Little information is available about the pathogenesis of H. heilmannii s.s. infections in humans and it is unknown whether differences in virulence exist within this species. Therefore, a Mongolian gerbil model was used to study bacterium-host interactions of 9 H. heilmannii s.s. strains. The colonization ability of the strains, the intensity of gastritis and gene expression of various inflammatory cytokines in the stomach were determined at 9 weeks after experimental infection. The induction of an antrum-dominant chronic active gastritis with formation of lymphocytic aggregates was shown for 7 strains. High-level antral colonization was seen for 4 strains, while colonization of 4 other strains was more restricted and one strain was not detected in the stomach at 9 weeks post infection. All strains inducing a chronic active gastritis caused an up-regulation of the pro-inflammatory cytokine IL-1 beta in the antrum. A reduced antral expression of H+/K+ ATPase was seen in the stomach after infection with 3 highly colonizing strains and 2 highly colonizing strains caused an increased gastrin expression in the fundus. In none of the H. heilmannii s.s.-infected groups, IFN-gamma expression was up-regulated. This study demonstrates diversity in bacterium-host interactions within the species H. heilmannii s.s. and that the pathogenesis of gastric infections with this microorganism is not identical to that of an H. pylori infection.