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D Y Graham

Publications and source records attributed to D Y Graham.

At least 307 records · Page 17Linked to original sources
PubMed1995

Characterization of a Helicobacter pylori neutrophil-activating protein.

Helicobacter pylori-associated gastritis is mainly an inflammatory cell response. In earlier work we showed that activation of human neutrophils by a cell-free water extract of H. pylori is characterized by increased expression of neutrophil CD11b/CD18 and increased adhesiveness to endothelial cells. The work reported here indicates that the neutrophil-activating factor is a 150,000-molecular-weight protein (150K protein). Neutrophil proadhesive activity copurified with this protein, which is a polymer of identical 15K subunits. Specific antibody, prepared against the purified 15K subunit, neutralized the proadhesive activity of the pure protein and of water extracts obtained from different strains of H. pylori. The gene (napA) for this protein (termed HP-NAP, for H. pylori neutrophil-activating protein) was detected, by PCR amplification, in all of the H. pylori isolates tested; however, there was considerable strain variation in the level of expression of HP-NAP activity in vitro. HP-NAP could play an important role in the gastric inflammatory response to H. pylori infection.

Bacterial Adhesion↗
PubMed1995

Helicobacter pylori infection does not reduce the viscosity of human gastric mucus gel.

The mechanism by which Helicobacter pylori undermines host defence mechanisms is unclear. Several in vitro studies using soluble mucins have suggested that H pylori may compromise mucus function. Gastric mucus gel was obtained from 13 H pylori infected patients; six untreated subjects and seven after eradication of the infection. Gastric mucus is a non-Newtonian substance in that its viscosity changes with changing rates of shear, requiring mucus viscosity to be measured in a rotational cone-plate microviscometer. Viscosity was measured at shear rates varying from 1.15 s-1 to 46 s-1. The gastric mucus viscosity was significantly higher in patients infected with H pylori compared with mucus gel obtained after eradication of the infection. The results of our study suggest that the previous studies using in vitro methods involving soluble mucins or its components may have lead to erroneous conclusions about the in vivo interactions of H pylori and gastric mucus gel. The present findings argue against the hypothesis that degradation of gastric mucus by H pylori is important in the pathogenesis of peptic ulcer.

Female↗
PubMed1995

Comparison of agar based media for primary isolation of Helicobacter pylori.

AIMS: To determine the best medium for the primary isolation of Helicobacter pylori. METHODS: Sixty six gastric mucosal biopsy specimens frozen in 1 ml Cysteine Albimi media with 20% glycerol from 22 histologically proven H pylori infected patients were cultured on brain heart infusion agar (BHIA) with 7% fresh whole defibrinated horse blood, egg yolk agar (EYA), Columbia blood agar-cyclodextrin agar (CBA-Cd), and commercial trypticase soy agar (TSA) supplemented with 5% sheep blood. RESULTS: Successful primary isolation of H pylori was 96% with BHIA, 78% with TSA, 64% for EYA, and 32% with CBA-Cd. Colonies appeared earlier on BHIA (4.7 +/- 0.1 days, 5.3 +/- 0.4 days, 5.3 +/- 0.4 days, and 7.1 +/- 0.9 days for BHIA, TSA, EYA, and CBA-Cd) and there were more colonies on BHIA than on CBA-Cd, EYA or TSA (599 +/- 88, 104 +/- 66, 260 +/- 107, and 358 +/- 89, respectively). CONCLUSIONS: Success of a medium for passage of isolates apparently does not reliably predict usefulness for primary isolation. Freshly made BHIA with 7% horse blood medium is recommended for primary isolation. However, the easily obtainable TSA media would be the best alternative for routine clinical laboratories with no access to BHIA.

Agar↗
PubMed1995

Cluster analysis of Helicobacter pylori genomic DNA fingerprints suggests gastroduodenal disease-specific associations.

BACKGROUND: Helicobacter pylori infection is now accepted as the most common cause of chronic active gastritis and peptic ulcer disease. The etiologies of many infectious diseases have been attributed to specific or clonal strains of bacterial pathogens. Polymerase chain reaction (PCR) amplification of DNA between repetitive DNA sequences, REP elements (REP-PCR), has been utilized to generate DNA fingerprints to examine similarity among strains within a bacterial species. METHODS: Genomic DNA from H. pylori isolates obtained from 70 individuals (39 duodenal ulcers and 31 simple gastritis) was PCR-amplified using consensus probes to repetitive DNA elements. The H. pylori DNA fingerprints were analyzed for similarity and correlated with disease presentation using the NTSYS-pc computer program. RESULTS: Each H. pylori strain had a distinct DNA fingerprint except for two pairs. Single-colony DNA fingerprints of H. pylori from the same patient were identical, suggesting that each patient harbors a single strain. Computer-assisted cluster analysis of the REP-PCR DNA fingerprints showed two large clusters of isolates, one associated with simple gastritis and the other with duodenal ulcer disease. CONCLUSIONS: Cluster analysis of REP-PCR DNA fingerprints of H. pylori strains suggests that duodenal ulcer isolates, as a group, are more similar to one another and different from gastritis isolates. These results suggest that disease-specific strains may exist.

Adult↗
PubMed1995

Helicobacter pylori, duodenal ulcer, gastric cancer: tunnel vision or blinders?

The focus of this paper is on the relationship between Helicobacter pylori gastritis and gastric cancer, one of the most compelling issues after the recent decision of the IARC (International Agency for Research on Cancer) to categorize H. pylori as a carcinogen. Our aim is to identify areas where additional work is not needed and suggest new directions of inquiry. We review what has been accomplished with the advantage of hindsight. Our review of the data regarding current putative virulence factors found that disease and outcome specificity were lacking. The same can be said of the data regarding low gastric juice ascorbate or increased mucosal cell turnover in H. pylori gastritis. We conclude that, while it is certainly possible that some of the factors discovered to date may initiate or mediate certain pathogenetic aspects of H. pylori-related disease, none of them can be seriously proposed as the factor responsible for either gastric cancer or duodenal ulcer. Finally, we identified research areas that might lead to disease-specific associations as well as areas where helicobacters may be used as models for other diseases. We propose that it is time to pause, reflect on what has been done, and focus more sharply on the questions that remain unanswered.

Duodenal Ulcer↗
PubMed1995

Geographical pathology of Helicobacter pylori infection: is there more than one gastritis?

Helicobacter pylori is the aetiological agent of chronic gastritis and a major causative factor in duodenal and gastric peptic ulcer disease; a strong association also exists with gastric cancer and primary gastric lymphoma. The prevalence of infection in adults ranges from less than 15% in developed countries to virtually 100% in less developed areas. If H. pylori infection alone was responsible for the development of gastritis, peptic ulcer disease, gastric carcinoma and primary gastric lymphoma, one would expect the frequency of all these conditions to parallel closely the prevalence of H. pylori infection. This is clearly not the case: therefore, genetic, environmental and cultural factors must act in concert with H. pylori to induce different outcomes of the infection. This paper outlines the geographic approach to the study of disease and discusses the possible application of this methodology to the inquiry into the relationship between H. pylori, atrophic gastritis and gastric cancer. Preliminary results of a study showing great variation in the prevalence of intestinal metaplasia in duodenal ulcer patients from different geographic origin are presented and briefly discussed.

Adult↗
PubMed1995

Confirmation of successful therapy of Helicobacter pylori infection: number and site of biopsies or a rapid urease test.

BACKGROUND: Although a number of tests have been described to detect the presence of Helicobacter pylori in biopsy specimens, studies of positive and negative value have largely been performed on untreated patients; testing the reliability of posttherapy has not been done. METHODS: We examined the value of the number and site of biopsies performed and the method used for specimen evaluation posttherapy. For postantimicrobial therapy of 141 patients with previously confirmed H. pylori infection, three biopsies were taken, two from the antrum and one from the corpus. Individual slides were coded, randomized, and interpreted blindly by two pathologists. Furthermore, in 143 patients, a biopsy specimen was taken from the antrum and was immediately inserted into the gel of the rapid urease test, and the results were compared with those obtained from histopathology obtained at the same time. RESULTS: In 71 patients, H. pylori therapy was unsuccessful; in 61 (86%), all three sites were positive. The highest yield with a single large cup biopsy specimen was 94%; the lowest was 91%. Two antral biopsies were negative in 4% [95% confidence interval (CI) = 1-12%]. The combination of a biopsy from the angulus incisura and one from the greater curvature of the corpus correctly identified all treatment failures (95% CI = 95-100%). The rapid urease test was false-negative in 5% (95% CI = 1-13%); there were no false-positives. CONCLUSION: Use of either the rapid urease test or two antral biopsies for evaluation of success of antimicrobial therapy for H. pylori infection will result in a false declaration of cure in at least 5% of cases. Three large cup gastric mucosal biopsies for histology are recommended for evaluation of the success of anti-H. pylori therapy.

Bacteriological Techniques↗
PubMed1995

Restriction fragment length polymorphism in the adhesin gene hpaA of Helicobacter pylori.

OBJECTIVES: To assess the degree of restriction fragment length polymorphism (RFLP) in the Helicobacter pylori adhesin gene hpaA and to determine the molecular basis of RFLP in this gene. METHODS: A 375-bp, polymerase chain reaction-amplified internal sequence of hpaA, obtained from 50 different H. pylori isolates, was restricted with Sau3A and HinfI, individually. Polymerase chain reaction products representing different RFLP types were sequenced. RESULTS: Seven different polymorphic types were found in hpaA. Base substitutions at only four positions, two in Sau3A and two in HinfI sites, account for all of the RFLP types, including the size of the restriction fragments determined by gel electrophoresis. Most, 90%, of the base substitutions are very conservative, i.e., either do not change the encoded amino acid or substitute a homologous amino acid, and cause no detectable antigenic or functional effect on hpaA. The region of hpaA encoding the receptor-binding motif was particularly well conserved. CONCLUSIONS: RFLP typing of hpaA using Sau3A and HinfI provides an additional tool for comparing the genetic relatedness of H. pylori isolates collected during epidemiological and/or treatment studies.

Adhesins, Bacterial↗
PubMed1995

Treatment of Helicobacter pylori infection with omeprazole-amoxicillin combination therapy versus ranitidine/sodium bicarbonate-amoxicillin.

OBJECTIVES: Simpler, effective therapies to treat Helicobacter pylori infection are greatly needed. Omeprazole co-therapy apparently enhances effectiveness of some antimicrobials. Our objective in this study was to determine whether the apparent additional benefit provided by omeprazole to amoxicillin therapy could be equaled by a high dose of ranitidine plus sodium bicarbonate. METHODS: In a prospective randomized trial, we tested 1 g amoxicillin b.i.d. with either omeprazole 20 mg b.i.d., or high dose ranitidine (900 and 1800 mg) plus sodium bicarbonate tablets 650 t.i.d. (with meals) for 14 day. RESULTS: Fifty-two patients with documented H. pylori infection and peptic ulcer completed therapy. The cure rate with omeprazole and amoxicillin was poor (46%), with the 95% confidence interval (CI) = 25-67%. Ranitidine plus sodium bicarbonate was also poor (39% cure) with the 95% CI = 21.5-59% (p > 0.57). Average compliance was more than 92% for all three groups. Side effects were experienced in only two patients (stomatitis and mild diarrhea). CONCLUSION: Neither the omeprazole nor ranitidine plus bicarbonate plus amoxicillin therapies used here can be recommended for treatment of H. pylori infection.

Amoxicillin↗
PubMed1995

Variability with omeprazole-amoxicillin combinations for treatment of Helicobacter pylori infection.

OBJECTIVE: Although omeprazole co-therapy enhances the effectiveness of some antimicrobials for the treatment of Helicobacter pylori infection, results have not been uniform. A meta-analysis suggested that 20 mg of omeprazole b.i.d. and 2 g or more of amoxicillin would yield a > 80% success rate (Gastroenterology 1994; 106: 142A). Our objective in this study was to test that hypothesis. METHODS: Volunteers with H. pylori infection were studied. Anti-H. pylori therapy was administered with meals for 14 days (omeprazole 20 mg b.i.d. plus amoxicillin 1 g t.i.d., or omeprazole 20 mg b.i.d. plus amoxicillin 0.5 g t.i.d.). Endoscopy was performed 4-6 wk after antimicrobial therapy ended, and the presence or absence of H. pylori was determined with biopsy specimens by Genta stain. RESULTS: Fifty-nine volunteers completed the study; 30 were studied twice. The overall success for initial treatment with either combination of amoxicillin and omeprazole was 18 of 59 [30.5%; 95% confidence interval (CI) = 19-44%]. The success rate with 500 mg amoxicillin t.i.d. was 7 of 29 (24%; 95% CI = 10-43%). With 1 g t.i.d. amoxicillin, the cure rate was higher (36.6%) (11 of 30; 95% CI = 20-56%), or intention-to-treat result was 11 of 31 (35.4%), which includes the early dropout. Compliance was > 95% for both therapies. Side effects were experienced by eight patients, two receiving 1.5 g amoxicillin and six receiving 3 g amoxicillin (p > 0.2). German trials suggest that better results might be achieved when amoxicillin is given as suspension while fasting. Thirty treatment failures were re-treated with 1 g amoxicillin suspension t.i.d., given fasting, and omeprazole 20 mg b.i.d. The cure rate was 16.6% (95% CI = 6-35%). CONCLUSION: Amoxicillin/omeprazole combinations for treatment of H. pylori infection do not yield consistent results. The reason is unknown, but the reported high rate of success with 40 mg of omeprazole and 750 mg t.i.d. suggests that almost complete inhibition of acid secretion is necessary to obtain consistent results with this combination.

Adult↗
PubMed1995

Azithromycin triple therapy for Helicobacter pylori infection: azithromycin, tetracycline, and bismuth.

BACKGROUND: Azithromycin is new acid-stable macrolide that achieves 10- to 40-fold higher tissue levels than erythromycin after oral dosing. Important to note, the tissue half-life of azithromycin is measured in days instead of hours. METHOD: We evaluated two new triple therapies for Helicobacter pylori infection in which azithromycin was substituted for metronidazole either as 250 mg b.i.d. or t.i.d. along with tetracycline 500 mg q.i.d. and bismuth subsalicylate 2 tablets q.i.d. for 14 days. H. pylori status was determined by histology before and 6 wk or more after therapy. RESULTS: Thirty men with documented H. pylori peptic ulcers completed therapy. Twenty-one also received ranitidine (300 mg in the evening) along with the antimicrobial therapy. H. pylori infection was successfully treated in 15 (50%) (95% CI = 31-69%). The cure rate was significantly higher with the 250-mg-t.i.d.-azithromycin dosage regime (83%) (95% CI = 52-98%) compared to the 250-mg-b.i.d.-dosage regime (28%) (95% CI = 10-53%) (p < 0.01). Troublesome side effects were experienced by the majority of those receiving azithromycin t.i.d. CONCLUSION: We conclude that although 750 mg or more of azithromycin might eventually be able to replace metronidazole or clarithromycin in standard triple therapy, additional studies are required to identify a regime that is both effective and tolerable.

Azithromycin↗
PubMed1995

Clarithromycin for treatment of Helicobacter pylori infections.

BACKGROUND: A better appreciation of the causal relationship between Helicobacter pylori infection and peptic ulcer disease and the benefit conferred by curing this infection has led to the recommendation that all patients with duodenal ulcer disease receive anti-H. pylori treatment. Multi-drug regimens, including bismuth, metronidazole and tetracycline or amoxycillin with an antisecretory agent, are successful in > 90% of treated patients but the emergence of metronidazole-resistant H. pylori has begun to limit their effectiveness. DESIGN: The search for the optimal anti-H. pylori treatment has focused on simplifying the regimen (to decrease adverse drug-related events and increase patient compliance), while retaining the excellent clinical results of the traditional multi-drug regimens. This article reviews the data concerning clarithromycin for treatment of H. pylori infections. RESULTS: Numerous evaluations have shown that clarithromycin has desirable attributes for anti-H. pylori treatment: clarithromycin is resistant to gastric acid, penetrates in high concentrations into gastric tissue and mucus, shows excellent antimicrobial activity against H. pylori, results in a high cure rate when used in two- and three-drug combinations, is associated with a low incidence of acquired H. pylori resistance and is well tolerated. Successful clarithromycin therapies include clarithromycin+omeprazole, clarithromycin+amoxycillin, or clarithromycin+omeprazole+tinidazole or metronidazole, and clarithromycin triple therapy. CONCLUSION: Clarithromycin may become an integral component of anti-H. pylori therapy.

Anti-Bacterial Agents↗
PubMed1994

Helicobacter pylori infection: genetic and environmental influences. A study of twins.

OBJECTIVE: To investigate the importance of genetic effects for acquiring Helicobacter pylori infection. DESIGN: Cross-sectional study on monozygotic and dizygotic twins, reared apart and reared together. SETTING: Twins from a subregistry of the Swedish Twin Registry, which includes entries for about 25,000 twin pairs who were born in Sweden. MEASUREMENTS: Helicobacter pylori status was assessed as the presence of anti-H. pylori IgG in 269 pairs of twins, including 36 monozygotic twin pairs reared apart, 64 monozygotic twin pairs reared together, 88 dizygotic twin pairs reared apart, and 81 dizygotic twin pairs reared together. RESULTS: The probandwise concordance rate for H. pylori infection was higher in monozygotic twin pairs (81%) than in dizygotic twin pairs (63%) (P = 0.001). Probandwise concordance rates for H. pylori infection among 124 pairs of twins reared apart were 82% and 66% for monozygotic and dizygotic twins, respectively (P = 0.003). The correlation coefficient was 0.66 for monozygotic twins reared apart, and it provides the best single estimate of the relative importance of genetic effects (heritability) for variation in the acquisition of H. pylori infection. The heritability estimate from model-fitting analyses was 0.57, a similar result. The remaining variance was accounted for by shared rearing environmental (20%) and nonshared environmental factors (23%). The latter contribute to differences, not similarities, among family members. CONCLUSION: This twin study showed that genetic effects influence the acquisition of H. pylori infection because of greater similarities within the monozygotic twin pairs. Further, sharing the same rearing environment also contributes to the familial tendency for acquiring H. pylori infection.

Chi-Square Distribution↗
PubMed1994

Possible role of Helicobacter pylori infection in early gastric cancer development.

BACKGROUND: Gastric cancer is the most frequently diagnosed malignancy in Japan. The possible relationship between Helicobacter pylori infection and gastric cancer in Japan was evaluated. METHODS: H. pylori infection was identified by the presence of anti-H. pylori IgG. The frequency of H. pylori infection was compared in 213 patients with gastric cancer and the same number of asymptomatic control subjects matched for age and sex. RESULTS: The presence of IgG antibody to H. pylori was significantly more prevalent (P < 0.001) in those with gastric cancer compared with asymptomatic control subjects (88.2% versus 74.6%). H. pylori positive rates were significantly greater in patients with the intestinal type (90.4%, P < 0.001) and diffuse type (86.4%, P < 0.05) of gastric cancer than in control subjects. Ninety-three percent of the patients with early gastric cancer tested positive for H. pylori (P < 0.001 compared with control subjects), whereas no significant difference was observed between those with advanced gastric cancer and control subjects. The intestinal type of early gastric cancer showed only the significantly increased frequency of high titer (optical density > 1.50) of H. pylori IgG antibody (P < 0.001) compared with control subjects without cancer. CONCLUSIONS: These results suggest that H. pylori infection may be associated with the development of early gastric cancer in Japan.

Adult↗
PubMed1994

Benefits from elimination of Helicobacter pylori infection include major reduction in the incidence of peptic ulcer disease, gastric cancer, and primary gastric lymphoma.

BACKGROUND: It has recently been recognized that gastritis, gastric ulcer, duodenal ulcer, gastric carcinoma, and primary gastric B-cell lymphoma are all associated with gastroduodenal infection with the bacterium Helicobacter pylori. Ten percent of Americans develop a peptic ulcer: one in six of those is infected. Four to five million Americans have peptic ulcer disease and ulcer disease is responsible for $43 to $44 billion in annual health care costs. METHODS: We review the accumulated data showing that successful treatment of H. pylori infection results in healing of gastritis and cure of peptic ulcer disease. Current data suggest that by elimination of H. pylori infection it may be possible to prevent most gastric carcinomas and primary gastric lymphomas. CONCLUSIONS: H. pylori infection is currently considered primarily as a cause of peptic ulcer. H. pylori infection is a major public health problem and elimination or prevention of the H. pylori infection will result in a tremendous reduction in medical costs, morbidity, and mortality.

Gastritis↗