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David Y Graham

Publications and source records attributed to David Y Graham.

At least 19 recordsLinked to original sources
PubMed2005

Iron deficiency and Helicobacter pylori infection in the United States.

Using data from the current National Health and Nutrition Examination Survey (1999-2000), the authors assessed whether Helicobacter pylori infection is associated with iron deficiency and iron-deficiency anemia (IDA) in the United States. Iron deficiency was defined as at least two abnormal results out of three biomarkers of iron stores. IDA was defined as a low hemoglobin level in the presence of iron deficiency. H. pylori infection was measured by serology. Complex survey estimators were used in the analysis. For 7,462 survey participants aged >or=3 years, H. pylori infection was associated with decreased serum ferritin levels (percent change = -13.9%, 95% confidence interval (CI): -19.5, -8.0) but not with levels of free erythrocyte protoporphyrin, transferrin saturation, or hemoglobin (percent change = 1.5%, -2.8%, and -1.1%, respectively). Multinomial logistic regression analyses indicated that H. pylori infection was associated with the prevalence of IDA (prevalence odds ratio (POR) = 2.6, 95% CI: 1.5, 4.6) and, to a lesser degree, other types of anemia (POR = 1.3, 95% CI: 1.0, 1.7). H. pylori infection was associated with a 40% increase in the prevalence of iron deficiency (POR = 1.4, 95% CI: 0.9, 2.0) after controlling for relevant covariates. In the United States, H. pylori infection was associated with iron deficiency/IDA regardless of the presence or absence of peptic ulcer disease.

Adolescent↗
PubMed2005

Regulation of interleukin-6 promoter activation in gastric epithelial cells infected with Helicobacter pylori.

The regulation of Helicobacter pylori induced interleukin (IL)-6 in the gastric epithelium remains unclear. Primary gastric epithelial cells and MKN28 cells were cocultured with H. pylori and its isogenic cag pathogenicity island (PAI) mutant and/or oipA mutants. H. pylori infection-induced IL-6 mRNA expression and IL-6 protein production, which was further enhanced by the cag PAI and OipA. Luciferase reporter gene assays and electrophoretic mobility shift assays showed that full IL-6 transcription required binding sites for nuclear factor-kappaB (NF-kappaB), cAMP response element (CRE), CCAAT/enhancer binding protein (C/EBP), and activator protein (AP)-1. The cag PAI and OipA were involved in binding to NF-kappaB, AP-1, CRE, and C/EBP sites. The cag PAI activated the extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) pathways; OipA activated the p38 pathway. Transfection of dominant negative G-protein confirmed roles for Raf, Rac1, and RhoA in IL-6 induction. Overall, the cag PAI-related IL-6 signal transduction pathway involved the Ras/Raf/MEK1/2/ERK/AP-1/CRE pathway and the JNK/AP-1/CRE pathway; the OipA-related pathway is p38/AP-1/CRE and both the cag PAI and OipA appear to be involved in the RhoA/Rac1/NF-kappaB pathway. Combination of different pathways by the cag PAI and OipA will lead to the maximum IL-6 induction.

CCAAT-Enhancer-Binding Proteins↗
PubMed2005

Histologic and serum risk markers for noncardia early gastric cancer.

Corpus dominant gastritis and intestinal metaplasia (IM) are considered markers of increased risk of gastric carcinoma. The aim of our study was to determine serum and histologic risk markers of gastric cancer. Antral and corpus histology, pepsinogen and gastrin 17 levels were compared among patients with history of endoscopic mucosal resection (EMR) for early gastric cancer and controls. Serum pepsinogen (PG) and gastrin 17 levels were measured by RIA. There were 53 gastric cancer patients and 75 controls. The scores for IM in each region and atrophy at the lesser curvature of the corpus were significantly higher in the cancer group than in the H. pylori-positive control group. IM at the greater curvature of the corpus and atrophy at the lesser curvature of the corpus were associated with multiple malignant lesions. Although corpus gastritis was associated with an increased risk of gastric cancer (odds ratio [OR] = 3.4; 95% confidence interval [CI] 1.6-7.0) (p = 0.001), the most important marker was the presence of IM at the lesser curvature of the corpus (OR = 15.1; 95% CI 4.3-52.6) (p < 0.001)). The best cut-off points of serum markers for gastric cancer were a PG I concentration of 45 ng/mL or less and a gastrin 17 >60 pg/mL (sensitivity = 83%; specificity = 68%). IM at the lesser curvature of the corpus and the combination of serum gastrin 17 and PG I identified a group at high risk for development of gastric cancer. Annual endoscopic follow-up is warranted for patients with IM found at the greater curvature of the corpus.

Aged↗
PubMed2005

A pilot study of Helicobacter pylori infection and risk of laryngopharyngeal cancer.

BACKGROUND: Squamous cell carcinoma of the laryngopharynx has been linked to laryngopharyngeal reflux disease. Helicobacter pylori corpus gastritis decreases gastric acid secretion and provides some protection against complications of gastroesophageal reflux, including adenocarcinoma of the distal esophagus. The aim of this study was to investigate whether H. pylori infection also protects against laryngopharyngeal carcinoma. METHODS: This was a case-control study comparing patients with histologically confirmed, previously untreated laryngeal or pharyngeal squamous cell carcinomas with cancer-free controls selected from a pool of hospital-based cancer-free controls identified during a similar time period. Each subject completed a self-administered questionnaire that elicited information on age, sex, ethnicity, and tobacco and alcohol consumption. The 120 case subjects were frequency matched to 120 control subjects on age (+/- 5 years), sex, tobacco use, and alcohol use; all subjects were non-Hispanic whites. H. pylori and human papillomavirus type 16 (HPV-16) seropositivity was determined by use of an enzyme-linked immunosorbent assay. RESULTS: The serologic assay was unsuccessful in one case subject and nine control subjects; therefore, 119 case subjects and 111 control subjects were included in the analysis. The proportion of subjects with anti-H. pylori immunoglobulin G was similar between the two groups (32.8% among cases vs 27.0% among controls; p = .342). Although seropositivity was more common in the patients with laryngeal cancer (39.1%) than in the patients with pharyngeal cancer (28.8%), this difference was neither significant (p = .241) nor associated with a significant risk of laryngeal cancer (adjusted odds ratio, 1.53; 95% confidence interval, 0.69-3.41). H. pylori seropositivity was more common among patients who were HPV-16 seronegative (38.2% vs 22.9%, p = .081), and this was particularly true among patients with laryngeal cancer (47.1% vs 18.2%; p = .089). CONCLUSIONS: These results do not show that H. pylori infection either protects against or promotes laryngopharyngeal carcinoma. However, segregation analyses suggested that H. pylori may play a role in laryngeal cancers not associated with HPV-16 infection, and further study in this group is warranted.

Aged↗
PubMed2005

Appropriate use of intravenous proton pump inhibitors in the management of bleeding peptic ulcer.

Rebleeding from peptic ulcers is a major unsolved problem in the management of acute upper gastrointestinal bleeding. Our goal was to review what is known and what remains to be learned about the effectiveness of antisecretory therapy for acute upper gastrointestinal bleeding. We reviewed the data regarding the effectiveness of endoscopic therapy, the prediction of those at increased risk for rebleeding, and the effectiveness of antisecretory drug therapy in preventing rebleeding with or without endoscopic hemostasis. Proton pump inhibitor therapy without endoscopic hemostasis is ineffective clinically for stopping bleeding or preventing rebleeding. Endoscopic hemostasis remains the cornerstone of therapy. The data are consistent with the notion that reliable maintenance of the intragastric pH at > or = 6 after endoscopic hemostasis is associated with the lowest rebleeding rates. H2-receptor antagonists are ineffective for achieving this goal. Intermittent bolus and oral administration of proton pump inhibitors are equivalent and fail to achieve this goal, which can only be accomplished by bolus administration of a proton pump inhibitor (e.g., 80 mg) followed by a constant infusion (e.g., 8 mg/hr). Whether the combination of endoscopic hemostasis and pH control is equal or superior to selected second-look endoscopy is unknown. A treatment algorithm is suggested.

Administration, Oral↗
PubMed2005

Improved infrared spectrophotometer for point-of-care patient 13C-urea breath testing in the primary care setting.

UNLABELLED: The 13C-urea breath test provides non-invasive testing for Helicobacter pylori infection with the possibility of analysis at the point of care. Point of care tests require accurate and efficient desktop instrumentation. OBJECTIVE: To compare results obtained from a new infrared spectrophotometer (10 kg, 2 min sample measurement) to the previously approved UBiT-IR300 (22.5 kg, 5-6 min sample measurement). DESIGN AND METHODS: Adults underwent urea breath testing; breath samples were analyzed using the new and the predicate instruments. RESULTS: There were 220 adults enrolled (age range 18-74 years; M/F = 35:65); with 86 UBT positive and 134 negative cases. The overall agreement between instruments was 99.6% (95% C.I. = 97.6 to 99.9); the positive agreement was 100%. CONCLUSION: Technical performance of the new instrument was excellent.

Adolescent↗
PubMed2005

Molecular markers in Helicobacter pylori-associated gastric carcinogenesis.

Helicobacter pylori infection is a known risk factor of gastric carcino-genesis. This article presents early molecular alterations associated with H. pylori chronic gastritis and advances in the molecular characterization of preneoplastic intestinal metaplasia (IM) and premalignant gastric mucosal lesions. H. pylori infection induces changes in gene expression, genomic instability and accumulation of gene mutations in the stomach epithelium. Mutations, including LOH and microsatellite instability, and gene hypermethylation are seen not only in gastric cancer, but are already detectable in IM and gastric dysplasia/adenoma. Recent reports using microarray expression analysis identified several gastric epithelial genes that are regulated by H. pylori. Among the many genes showing altered epithelial expression in response to H. pylori, some might be useful as markers to assess gastric cancer risk. Profiles of mutagenesis and gene expression in IM and dysplasia/adenoma have been characterized and represent potential markers of preneoplastic and premalignant lesions during gastric carcinogenesis.

Adenocarcinoma↗
PubMed2005

Polyomavirus SV40 infections in Kazakhstan.

OBJECTIVES: To examine the prevalence of polyomavirus SV40 infections in Kazakhstan, a central Asian country known to have used potentially contaminated SV40 poliovaccines before 1962. METHODS: Cross-sectional study of 307 healthy volunteers from two ethnic groups (Kazakhs and Russians) in Almaty, Kazakhstan, from May through August 1999 using a specific SV40 plaque-reduction neutralization assay. RESULTS: Of the 307 volunteers enrolled in the study, 154 were Kazakhs and 153 were Russians. The overall prevalence of SV40 antibodies was 4.9%, and there was no significant difference between the ethnic groups (p = 0.7) or between males and females. The median SV40 neutralizing antibody titers in Kazakhs and Russians were 1:40 (range 1:10-1:500) and 1:20 (range 1:10-1:500), respectively. The median ages of SV40-infected Kazakhs and Russians were not different (42 vs. 24 years; p = 0.1), although there was a trend for increased seropositivity among older Kazakhs. There was no difference in SV40 positivity between those whose childhoods were spent in rural or in urban areas (p = 0.4). Importantly, 60% (9/15) of the subjects seropositive for SV40 were born from 1969 to 1980s, when poliovaccines were free from SV40. CONCLUSIONS: This study showed evidence of polyomavirus SV40 infections in Kazakhstan, not only among individuals potentially exposed to contaminated poliovaccines, but in younger people not exposed to such vaccines. As increasing evidence indicates an association of SV40 with selected types of human malignancies, prospective studies are needed to examine the risk of SV40 infection with the development of neoplasias.

Adolescent↗
PubMed2005

Visible small-intestinal mucosal injury in chronic NSAID users.

BACKGROUND & AIMS: Patients who regularly take nonsteroidal anti-inflammatory drugs (NSAIDs) have an increased risk for small-intestinal mucosal ulceration and bleeding, which may present as anemia of undetermined gastrointestinal origin or protein loss. The prevalence and severity of small-intestinal lesions remains unclear. Our aim was to assess the frequency of NSAID-induced small-bowel injury among chronic NSAID users. METHODS: Ambulatory patients with various types of arthritides who took NSAIDs daily (>3 mo duration) or took either acetaminophen alone or nothing were enrolled in the study. All patients fasted overnight and underwent wireless video capsule endoscopy. Two investigators, blind to therapy, reviewed each video beginning after the pylorus. Lesions were scored as normal, red spots, small erosions, large erosions, or ulcers. An ulcer was defined as a larger lesion with apparent depth and a definite rim. RESULTS: Forty-one patients, 36 men and 5 women, ages ranging from 22 to 66 years (mean age, 49.8 y) were analyzed including 21 chronic NSAID users and 20 control patients. Small-bowel injury was seen in 71% of NSAID users compared with 10% of controls (P < .001). Injury was mild (few or no erosions, absence of large erosions/ulcers) in 10 NSAID users compared with 2 controls. Five NSAID users had major (>4 erosions or large ulcers/ulcers) damage compared with none in the control group. There were no complications or problems with the capsule endoscopy procedure. CONCLUSIONS: Endoscopically evident small-intestinal mucosal injury is very common among chronic NSAID users. The role of endoscopically evident injury in unexplained iron-deficiency anemia and hypoalbuminemia among chronic NSAID users remains undetermined.

Adult↗
PubMed2005

Duodenal ulcer promoting gene of Helicobacter pylori.

BACKGROUND & AIMS: Identification of a disease-specific H pylori virulence factors predictive of the outcome of infection remains unachieved. METHODS: We used the polymerase chain reaction and Southern blot to compare the presence of 14 vir homologue genes with clinical presentation of H pylori infection, mucosal histology, and mucosal interleukin (IL)-8 levels. RESULTS: We examined 500 H pylori strains from East Asia and South America, including 120 with gastritis, 140 with duodenal ulcer (DU), 110 with gastric ulcer (GU), and 130 with gastric cancer. Only 1 gene that encompassed both jhp0917 and jhp0918 called dupA (duodenal ulcer promoting gene) was associated with a specific clinical outcome. dupA was present in 42% of DU vs. 21% of gastritis (adjusted odds ratio [OR] = 3.1, 95% confidence interval [CI]: 1.7-5.7). Its presence was also associated with more intense antral neutrophil infiltration and IL-8 levels and was a marker for protection against gastric atrophy, intestinal metaplasia, and gastric cancer (OR for gastric cancer = 0.42, 95% CI: 0.2-0.9 compared with gastritis). In vitro studies in gastric epithelial cells using dupA -deleted and -complemented mutants showed that the dupA plays roles in IL-8 production, in activation of transcription factors responsible for IL-8 promoter activity, and in increased survivability at low pH. CONCLUSIONS: dupA is a novel marker associated with an increased risk for DU and reduced risk for gastric atrophy and cancer. Its association with DU-promoting and -protective effects against atrophy/cancer was evident in both Asian and Western countries.

Acids↗
PubMed2005

Evidence-based examination of the African enigma in relation to Helicobacter pylori infection.

OBJECTIVE: The African enigma describes the dissociation between the prevalence of Helicobacter pylori infection and H. pylori-related diseases. The aim of this study was to use an evidence-based review of endoscopic data from African countries to test whether there are data to support the concept of an African enigma. MATERIAL AND METHODS: A Medline search was carried out to identify prospective endoscopic studies in African populations. Data collected included: the number of endoscopies, age range (or mean age if available), indications for endoscopy, country, years during which data were collected, male to female ratio, and specific outcome of duodenal ulcer, gastric ulcer, or gastric cancer. RESULTS: Forty prospective endoscopic studies from 17 African countries were identified (20,531 patients) and evaluated between 1972 and 2001. Mean ages ranged from 31 to 53.1 years and male to female ratios from 0.67:1 to 4.64:1. H. pylori-related clinical outcomes were common; duodenal ulcers in 4326 patients (21.1%), gastric ulcers in 691 patients (3.4%), and gastric cancers in 503 patients (2.4%). CONCLUSIONS: Prospective upper endoscopic trials suggest that the clinical outcomes associated with H. pylori infection in Africa are similar to those seen in industrialized countries. No dissociation between the prevalence of H. pylori infection and H. pylori-related diseases existed; the African enigma as such does not exist and the continued study of the mechanism of a non-existent phenomenon is a misuse of resources. The myth resulted from reliance on anecdotal data and selection bias in populations with extremely limited access to health care and a relatively short life expectancy.

Adult↗
PubMed2005

Gastric mucosal cytokine levels in relation to host interleukin-1 polymorphisms and Helicobacter pyloricagA genotype.

OBJECTIVE: The outcome of a Helicobacter pylori infection is related in part to interrelationships among H. pylori virulence factors and the H. pylori-induced mucosal response. The host inflammatory response is partly governed by polymorphisms in pro-inflammatory genes. MATERIAL AND METHODS: Cytokine levels (interleukin (IL)-1beta, IL-6 and IL-8) were examined in H. pylori-infected and uninfected normal-appearing mucosa from patients with non-ulcer dyspepsia (NUD), margins of gastric ulcers and cancer tissues. Cytokine levels were compared with cagA genotypes and host interleukin (IL)-1 polymorphisms. RESULTS: The study comprised 168 Thai patients. All infected patients possessed anti-CagA antibody. Gastric mucosal IL-8 levels were significantly higher in H.pylori-positive cases than in -negative cases in all three tissue types (e.g. 1115 versus 217 pg/mg protein for NUD) (p<0.001). Normal-appearing but H. pylori-infected antral mucosa of patients with cagA type 1a strains had higher IL-8 levels than those with type 2a strains (2632 versus 1036 pg/mg protein) (p<0.005). IL-1B-511T/T carriers had higher antral mucosal IL-1ss levels versus non-carriers (pg/mg protein) (T/T=221, T/C=178, C/C=70) (p=0.005). IL-1B-511T/T carriers also had higher IL-1beta levels versus non-carriers in H. pylori-negative patients. CONCLUSIONS: It was found that both the host factors (IL-1 polymorphisms) and bacterial factors (cagA type 1a versus type 2a) influenced gastric mucosal cytokine levels. Future studies should concentrate on interactions among host factors (e.g. genetics and tissue responses) and bacterial and environmental factors.

Antigens, Bacterial↗
PubMed2005

Smoking and Helicobacter pylori infection in a sample of U.S. adults.

BACKGROUND: Although the prevalence of Helicobacter pylori infection has been assessed in the National Health and Nutritional Examination Survey (NHANES), its possible relation with smoking has not been fully explored. METHODS: We used the 1999-2000 NHANES data to examine whether smoking affects the prevalence of H. pylori infection in adults (n = 3689). The prevalence of H. pylori infection, as assessed by anti-H. pylori IgG enzyme-linked immunoassay, was computed according to smoking history and levels of serum cotinine. RESULTS: Current smoking was associated with an increased prevalence of H. pylori infection (prevalence odds ratio =1.9; 95% confidence interval = 1.4-2.5) after controlling for possible confounders. Current smoking, as measured by increased serum cotinine, was also associated with an increased prevalence of H. pylori infection (1.6; 1.3-2.0). There was no evidence of a dose-response relation. CONCLUSIONS: Smoking may contribute to the persistence of H. pylori infection.

Adult↗
PubMed2005

Helicobacter pylori virulence factors: facts and fantasies.

PURPOSE OF REVIEW: Virulence factors are related to the ability of a microbe to induce disease. True virulence factors must therefore have a disease association, an in-vivo correlate with disease such as increased mucosal inflammation, or both. RECENT FINDINGS: The cytotoxin-associated gene pathogenicity island; the outer membrane inflammatory protein; the duodenal ulcer-promoting gene, and possibly the blood group antigen-binding adhesion, are the only factors that to date qualify as virulence factors. Numerous recent studies have investigated the interaction of vacuolating cytotoxin A or cytotoxin-associated gene A with cells and cell lines in vitro. It remains unclear, however, whether any of the findings, for example, in-vitro experiments showing that vacuolating cytotoxin A affect the regulation of T or B lymphocytes, have an in-vivo counterpart, or play any role in disease pathogenesis. SUMMARY: The criteria for a virulence factor include evidence of an association with a disease or a disease surrogate such as the severity of mucosal inflammation, epidemiologic consistency, and biologic plausibility. Confirmation of the proposed mechanism requires elimination of the effect by gene deletion and restoration by complementation. Cytotoxin-associated gene A has been the subject of elegant biochemistry despite lack of evidence that it is involved in pathogenesis. The current focus of research on Helicobacter pylori relates to exploring the biology of Helicobacter pylori, often using systems that only vaguely relate to the in-vivo conditions or to disease pathogenesis.

Animals↗
PubMed2005

Practical rapid, minimally invasive, reliable nonendoscopic method to obtain Helicobacter pylori for culture.

BACKGROUND: Helicobacter pylori culture typically requires endoscopy. AIM: To develop a minimally invasive rapid and reliable method to obtain H. pylori cultures. METHODS: An extendable oro-gastric brush, contained within a plastic over-tube, was constructed (Baylor Brush, US Endoscopy). After topical oral anesthesia, the 5-mm diameter brush assembly was swallowed. The brush was extended in the stomach and the mucosa was brushed three or four times. The brush was then retracted into the protective sleeve and withdrawn from the patient. The brush was either cultured directly or placed in cysteine transport medium with 20% glycerol which was then sampled immediately or after freezing at -70 degrees C. RESULTS: Twenty-five adult H. pylori-infected subjects (13 male, 12 female) were studied. Helicobacter pylori recovery rate was 100% (11 of 11) when cultured immediately or after storage in transport medium at -70 degrees C for 1 or 2 weeks or after storage at 4 degrees C for 24 hours (four of four) or 72 hours (four of four) before being cultured. Freezing on dry ice and air shipment did not reduce recovery. CONCLUSION: Rapid, reliable, nonendoscopic culture of gastric mucus is a practical method to obtain culture of H. pylori for clinical or research purposes. The method is amenable to being performed in a doctor's office or in the field.

Adult↗
PubMed2005

Effect of the carbonic anhydrase inhibitor, acetazolamide, on Helicobacter pylori infection in vivo: a pilot study.

BACKGROUND: Carbonic anhydrase inhibitors have been successfully used to treat peptic ulcers. Although carbonic anhydrase restriction does not inhibit Helicobacter pylori in vitro, recent studies suggest that carbonic anhydrase inhibition reduces the ability of H. pylori to survive in an acid environment as present in the stomach. METHODS: In a pilot study, we examined the effect of acetazolamide 500 mg as twice a day for 4 days in volunteers with active H. pylori infection. Effectiveness was judged by changes in the results of the urea breath test. RESULTS: Eight H. pylori infected volunteers completed the test. No urea breath test reverted to negative and there was a trend for the urea breath test value to increase [e.g. delta over baseline (DOB) mean +/- SE increased from 50.9 +/- 13 at baseline to 64.9 +/- 13 at day 5] during treatment with acetazolamide. CONCLUSION: The potential effect of carbonic anhydrase inhibitors on acid secretion may prevent effect on H. pylori in vivo and/or the sites of infection at the surface of the stomach may have a pH higher for any postulated acid-dependent effect to have an effect clinically.

Acetazolamide↗