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Biomedical subjects

David Y Graham

Publications and source records attributed to David Y Graham.

At least 73 records · Page 4Linked to original sources
PubMed2003

Seroepidemiology of Helicobacter pylori and hepatitis A virus and the mode of transmission of infection: a 9-year cohort study in rural Japan.

We compared the seroepidemiologic patterns of Helicobacter pylori and hepatitis A virus (HAV) infections among participants in 2 independent cross-sectional studies conducted in Japan in 1986 and 1994. Subgroups were monitored with successive blood sampling. H. pylori and HAV infection status was defined by results of enzyme-linked immunosorbent assay. In 1986, the prevalence of H. pylori infection and HAV infection, respectively, were 80% and 70% among adults and 31% and 5% among children. The prevalence of both infections increased with age. Concordant infections were found in 74.5% of adults (kappa=0.2) versus 2% of children (kappa=0.05). During the 9-year study period, the incidence of H. pylori infection was 1.1% among adults and 2% among children. The seroprevalence of HAV remained constant. The disparity between the increase in prevalence of H. pylori and HAV infection with age is likely associated with improvements in hygienic practices. The discordance between the presence of the infections among younger persons is evidence against a common source and/or vehicle for transmission.

Adolescent↗
PubMed2003

Traces of human migrations in Helicobacter pylori populations.

Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.

Africa↗
PubMed2003

Enterococcus gastritis.

Helicobacter pylori infection is the most common cause of gastritis with its associated sequelae. Gastritis secondary to other bacteria is rare. This report describes Enterococcus-associated gastritis in a 59-year-old diabetic man. Nine months after receiving treatment for H. pylori-associated gastritis, he underwent endoscopy to confirm H. pylori eradication and to evaluate the status of previously seen ulcers. Mucosal biopsy specimens revealed severe active but focal gastritis adjacent to gram-positive coccobacilli in short to long chains with no H. pylori. Culture grew an Enterococcus similar to E. hirae and E. durans. No treatment was given, and endoscopy done 2 months later showed complete resolution of the gastritis and absence of H. pylori or enterococci. Our patient's gastritis represents a previously undescribed manifestation of Enterococcus infection. It is possible that the presence of NSAID gastric mucosal injury and diabetes predisposed this individual to the development of transient Enterococcus gastritis.

Enterococcus↗
PubMed2003

Detection of Chlamydiae pneumoniae but not Helicobacter pylori DNA in atherosclerosis plaques.

Chronic infections have been associated with cardiovascular disease. We used bacterial culture, polymerase chain reaction (PCR), and immunohistochemical staining with anti-vacA and anticagA antibodies to search for Helicobacter pylori and Chlamydiae pneumoniae in atherosclerotic plaques obtained at endarterectomy. Serum IgG antibodies to H. pylori and C. pneumoniae were also determined. Thirty-two patients were enrolled. Anti-H. pylori and anti-C. pneumoniae IgG were present in 72% and 81%, respectively. Culture and PCR for H. pylori of vessel walls and plaques were negative. Atherosclerotic plaque and normal vessel sections from H. pylori-negative and- positive patients showed reactivity with anti-vacA and anti-cagA antibodies. C. pneumoniae DNA was amplified in three atherosclerotic lesions. These findings suggest that the association between H. pylori infection and atherosclerosis does not result from continuing direct effects of H. pylori antigens in the vessel walls. Antigens within vessel atherosclerotic plaques cross-react with H. pylori virulence factors and could act as cofactors in determining instability for the atherosclerotic plaques.

Aged↗
PubMed2003

Cyclooxygenase expression during Helicobacter pylori infection in Mongolian gerbils.

We investigated the expression of cyclooxygenase-2 (COX-2) and COX-1 mRNAs during longterm Helicobacter pylori infection of the Mongolian gerbil (18 months) as well as the effect of eradication therapy and the cag pathogenicity island on COX mRNA expression. COX mRNA levels were determined by reverse transcription-polymerase chain reaction. Pyloric channel ulcers were noted in one of 10 gerbils (10%) at 3 months, 33% at 6 months, 50% at 9 months, 17% at 10 months, 40% at 12 months and 25% at 18 months after inoculation of parental strains. Nineteen of 21 gerbils had successful H. pylori eradication and showed significant reduction of inflammation and no ulcerations. There were no significant differences in COX-1 mRNA expression between the groups. COX-2 mRNA expression was significantly increased 1 and 3 months after inoculation and then decreased to basal levels. In control animals, COX-2 mRNA expression was significantly higher at 12 and 18 months compared to younger animals. cagE knockout mutants did not induce gastric inflammation and induced significantly lower COX-2 mRNA expression compared to parental strains. COX-2 mRNA was induced early in H. pylori infection and then declined. COX-2 mRNA expression was also induced with aging.

Animals↗
PubMed2003

Interleukin-6 genetic polymorphisms are not related to Helicobacter pylori-associated gastroduodenal diseases.

BACKGROUND: Polymorphisms in the promoter region of the proinflammatory cytokine, interleukin (IL)-6 have been related to several chronic inflammatory diseases. Inter-individual variation in the severity of gastric inflammation may be important in determining the clinical outcome of an Helicobacter pylori infection and relate to polymorphisms in this region. MATERIALS AND METHODS: We studied H. pylori-infected patients with duodenal ulcer or gastric cancer. In addition six gastric cancer cell lines, AGS, SNU-668, MKN-1, MKN-7, MKN28 and KATOIII, were cocultured with both cag pathogenicity island-positive and -negative H. pylori. Single nucleotide polymorphisms at positions -174, -572, and -597 in the IL-6 promoter region were identified by PCR-RFLP. The IL-6 production from the cancer cells was determined by ELISA. RESULTS: Sixty patients with gastric cancer and 60 with duodenal ulcer were studied. The alleles at positions -174 and -597 were closely linked (-174G/-597G or -174C/-597A) regardless of the ethnic group or disease presentation. There was no difference in the allele frequency at any of the sites among patient groups. H. pylori-induced IL-6 production from the gastric cancer cell lines was also independent of the IL-6 polymorphisms or the presence of the cag pathogenicity island. CONCLUSIONS: The genetic polymorphisms in IL-6 can be attributable to ethnicity and appear to be independent of the clinical outcome of an H. pylori infection.

Adult↗
PubMed2003

Salvage therapy after two or more prior Helicobacter pylori treatment failures: the super salvage regimen.

BACKGROUND: Although effective therapies are available for curing Helicobacter pylori infection, the problem persists about what to do for patients who fail two or more treatment courses despite a good compliance. AIM: To test a twice a day midday quadruple therapy as salvage therapy. METHODS: Dyspeptic H. pylori-infected patients who failed two or more courses of anti-H. pylori therapy received omeprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate caplets 240 mg twice a day (with the midday and evening meals) for 14 days. H. pylori status was evaluated by 13C-urea breath test and histology 4-6 weeks after therapy. Eradication was defined as no positive test. RESULTS: Seventy-one patients were enrolled and 68 completed the full 14 days of therapy (mean age 46 years; 28 men). Thirty-three patients had failed prior treatment twice, 19 had failed three times, and 16 had failed four or more times. The cure rates were: intention to treat=93% (66/71); (95% CI=84% to 98%), per protocol=97% (66/68); (95% CI=89%- 100%). Success was excellent irrespective of diagnosis, age, prior treatment protocols, or smoking status. Moderate side-effects were experienced by only two patients. CONCLUSION: Midday bismuth subcitrate based twice a day quadruple therapy was an excellent salvage therapy. BID midday quadruple regimen should be considered as the therapy of choice.

Adult↗
PubMed2003

Eradication of Helicobacter pylori by 7-day triple-therapy regimens combining pantoprazole with clarithromycin, metronidazole, or amoxicillin in patients with peptic ulcer disease: results of two double-blind, randomized studies.

AIM: To compare the short-term (7-day) safety and efficacy of two triple-therapy regimens using pantoprazole with those of two dual-therapy regimens (one with pantoprazole and one without), for Helicobacter pylori eradication in patients with peptic ulcer disease. METHODS: H. pylori infection was identified by rapid urease (CLOtest), and confirmed by histology and culture. Patients were enrolled into one of two randomized, double-blind, multicenter, parallel-group studies. In study A, patients received oral pantoprazole 40 mg, clarithromycin 500 mg, and metronidazole 500 mg (PCM); pantoprazole, clarithromycin and amoxicillin 1000 mg (PCA); or pantoprazole and clarithromycin (PC). In study B, patients received PCM, PCA, PC, or clarithromycin and metronidazole without pantoprazole (CM). Treatments were given twice daily for 7 days. H. pylori status after therapy was assessed by histology and culture at 4 weeks after completing the course of study treatment. Modified intent-to-treat (MITT; each study: n = 424, n = 512) and per-protocol (PP; each study: n = 371, n = 454) populations were analyzed. The MITT population comprised all patients whose positive H. pylori status was confirmed by culture and histology; the PP population comprised patients who also complied with > or = 85% of study medication doses. RESULTS: A total of 1016 patients were enrolled. Cure rates among patients with clarithromycin-susceptible H. pylori strains were 82 and 86% for PCM, and 72 and 71% for PCA, in studies A and B, respectively. Cure rates among patients with metronidazole-susceptible H. pylori strains were 82 and 87% for PCM, and 71 and 69% for PCA, in studies A and B, respectively. The combined eradication rates observed with the PCM regimen were superior to those of all other regimens tested. Side-effects were infrequent and mild. CONCLUSIONS: PCM had the highest overall eradication rate in these two studies examining 7-day treatment regimens. All regimens were safe and well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Studies regarding the mechanism of false negative urea breath tests with proton pump inhibitors.

OBJECTIVE: The mechanism of false negative urea breath tests (UBTs) results among proton pump inhibitor (PPI) users is unknown. We studied the time course of PPI-associated negative UBT, the relation to Helicobacter pylori density, and whether gastric acidification would prevent false negative UBT results. METHOD: In the UBT experiment, H. pylori-infected volunteers received omeprazole 20 mg b.i.d. for 13.5 days. UBTs with citric acid were done before, after 6.5 days of PPI, and 1, 2, 4, 7, and 14 days after therapy. In the culture and histology experiment, after a wash-out of >5 months, nine of the original subjects were rechallenged with omeprazole for 6.5 days. Antral and corpus biopsies for histology and culture were done before and 1 day after PPI administration. RESULTS: Thirty subjects (mean age 42 yr) were enrolled. UBTs were significantly reduced on day 6.5 (p = 0.031); 10 subjects (33%) developed transient negative UBTs. The UBT recovered in all but one subject by the fourth day post-PPI and in all subjects by day 14. In the culture and histology experiment, upon PPI rechallenge, three of nine subjects (33%) had negative UBTs. H. pylori density, whether measured by culture or histology, decreased with PPI therapy; antral biopsies became histologically negative in five subjects and corpus biopsies in three subjects. CONCLUSION: PPI-induced negative UBT results were related to the anti-H. pylori effect of the PPI. Acidification of the stomach did not prevent false negative UBT results. Three days is likely the minimum delay from stopping PPI until one should perform a test for active infection. A delay of 14 days is preferred.

Adult↗
PubMed2003

Helicobacter pylori and hetertopic gastric mucosa in the upper esophagus (the inlet patch).

OBJECTIVES: Helicobacter pylori (H. pylori) may colonize gastric mucosa wherever it is found in the GI tract. Heterotopic gastric mucosa in the upper esophagus (inlet patch) is a potential site for H. pylori infection and may provide a reservoir for oral-oral transmission or a niche where antibiotics might have difficulty reaching. The aim of this study was to analyze the intensity and distribution of H. pylori in the inlet patch. METHODS: Whenever a cervical inlet patch was observed, mucosal biopsy samples were taken to confirm the endoscopic diagnosis and to search for H. pylori and active inflammation. In addition, mucosal biopsy samples were also taken from the gastric mucosa. Formalin-fixed biopsy specimens were cut and stained with a new dual stain developed in our laboratory. The stain is a combination of periodic acid-Schiff and a silver stain that allows simultaneous visualization of H. pylori and gastric type epithelium. The density of H. pylori was scored using a visual analog scale of 0 to 5. The type of mucosa in the inlet patch was also recorded. RESULTS: The study included 48 patients; 37 had H. pylori gastritis and 27 of these (73%) had H. pylori identified on their heterotopic gastric mucosa. A higher density of H. pylori in the stomach was associated with a higher prevalence in the inlets. Active inflammation correlated with active infection in the inlet patch and the presence of antral type mucosa. CONCLUSION: H. pylori colonization of heterotopic gastric mucosa in the upper esophagus is common and is closely related to the H. pylori density in the stomach. The fact that H. pylori was not found in all cases suggests that another event such as reflux may be required for H. pylori to colonize heterotopic mucosa.

Adolescent↗
PubMed2003

The changing epidemiology of GERD: geography and Helicobacter pylori.

BACKGROUND: Issues have arisen regarding H. pylori infection and GERD that have caused unnecessary confusion among practicing physicians. In the last century GERD became increasingly recognized in the West and it has become evident that the prevalence of GERD is now occurring in many previously underdeveloped countries. METHODS: This review article fosters understanding of the issues by focusing on the esophageal acid load and the factors that control it. In particular, we discuss the effects of the change in the patterns of gastritis that have occurred naturally as well as after H. pylori eradication and correlate those changes with their effects on the esophageal acid load. We show how it is possible to separate gastroesophageal reflux from gastroesophageal reflux disease based on differences in esophageal acid load. We also describe how the practice of assessing gastroesophageal reflux based on the time the intraesophageal pH is less than 4 resulted in investigators systematically discarding data critical to understanding of the effect of their interventions on esophageal acid load. Testable hypotheses are presented to explain the interactions between H. pylori and GERD and between H. pylori and the changing epidemiology of GERD. CONCLUSIONS: We propose that the confusion regarding H. pylori and the changing epidemiology of GERD is based on the failure to critically examine the historical evidence in relation to the other H. pylori-related diseases as well as reliance on techniques that are either unable to measure, or systematically discard data critical for understanding effects of various interventions on the esophageal acid load. This has resulted in propagation of erroneous concepts regarding H. pylori and adenocarcinoma of the esophagus and has resulted in some patients being denied appropriate therapy.

Acids↗
PubMed2003

Relation between seroreactivity to low-molecular-weight Helicobacter pylori-specific antigens and disease presentation.

The identification of Helicobacter pylori-strain specific factors that correlate with clinical outcome has remained elusive. We investigated possible relationships between a group of H. pylori antigens and clinical outcome and compared an immunoblot assay kit (HelicoBlot, version 2.1 [HB 2.1]; Genelabs Diagnostics) with an established serological test, the high-molecular-weight cell-associated protein test (HM-CAP). We used sera from 156 Thai patients with different disease presentations, including 43 patients with gastric cancer, 64 patients with gastric ulcer, and 49 patients with nonulcer dyspepsia (NUD). HB 2.1 was compared to HM-CAP as a diagnostic test for H. pylori infection. The seroprevalence of H. pylori was significantly higher among gastric cancer patients than among patients with NUD (93 and 67%, respectively; P < 0.01). Among the H. pylori-seropositive patients, the presence of the antibody to the 37,000-molecular-weight antigen (37K antigen) was inversely related to the presence of gastric cancer (e.g., for gastric cancer patients compared with NUD patients, odds ratio [OR] = 0.28 and 95% confidence interval [CI] = 0.1 to 0.8). The presence of antibody to the 35K antigen was higher in gastric ulcer patients than in NUD patients (OR = 11.5; 95% CI = 2.4 to 54.3). The disease associations of antibodies to the 35K and 37K antigens are consistent with the possibility that these antigens are either indirect markers for H. pylori-related diseases or have specific active or protective roles in H. pylori-related diseases.

Adult↗
PubMed2003

Evaluation of the effects of strain-specific antigen variation on the accuracy of serologic diagnosis of Helicobacter pylori infection.

It has been suggested that enzyme immunoassay (EIA) kits validated in one region may yield variable diagnostic performance results in different regions, possibly due to strain-specific differences in antibody responses in different populations. We tested (13)C-urea breath test-characterized serum samples from 109 U.S. patients and 288 Japanese patients using enzyme immunoassay with different preparations of high-molecular-weight cell-associated (HM-CAP) antigens that are conserved across Helicobacter pylori strains. Replicate antigens were prepared from five H. pylori clinical isolates. Eight antigen preparations were evaluated: two of U.S. origin and six of Japanese origin. The accuracies achieved with the eight antigen preparations ranged from 94.4 to 96.3% with the U.S. samples. With the Japanese samples the accuracies achieved ranged from 92.3 to 97.2%. Use of a pool of HM-CAP antigens prepared from isolates from Japan resulted in a higher median enzyme immunoassay value and slightly fewer samples with indeterminate results compared to the results obtained by use of the U.S. standard HM-CAP antigen for H. pylori-positive patients (accuracies, 97.2 and 92.3%, respectively), suggesting that variations in performance between both antigen source and patient population might be reduced by using antigens pooled from several strains.

Antibodies, Bacterial↗