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Biomedical subjects

D Y Graham

Publications and source records attributed to D Y Graham.

At least 19 recordsLinked to original sources
PubMed1996

Prevalence of Helicobacter pylori infection in Korean children: inverse relation to socioeconomic status despite a uniformly high prevalence in adults.

The prevalence of Helicobacter pylori infection in US adults was shown to be inversely correlated with the socioeconomic status of the family during childhood, and it was suggested that this was additional evidence of transmission occurring in childhood. The present study of H. pylori infection was conducted in South Korea, which has emerged as a developed country in the last two decades. The authors attempted to determine whether there was a difference in prevalence of H. pylori infection in Korean children of different socioeconomic classes despite the high prevalence of infection in childbearing adults. The authors also attempted to identify the factors responsible for the different patterns of transmission by estimating the age-specific prevalence of H. pylori infection in 413 healthy 1- to 75-year-old asymptomatic volunteers who resided in Seoul. H. pylori status was evaluated using an enzyme-linked immunosorbent assay for anti-H. pylori immunoglobulin G. Demographic data were obtained from each individual, and socioeconomic class was assessed by the education level of the adults and of the children's parents as well as family income. H. pylori infection was present in 75% of adults and 22% of children, and its prevalence increased with age (p < 0.001). In adults, the rate of infection was high and independent of socioeconomic class. In children, it was inversely related to the socioeconomic class of the child's family: 12% among upper socioeconomic class, 25% among the middle class, and 41% among the lowest class (p = 0.016). No associations were found between prevalence of H. pylori infection and any factor tested including sex, smoking, and alcohol consumption. In addition, type of housing, whether owned or rented, number of family members living in the same household, water source, and type of community in which a child grew up were not found to be risk factors influencing H. pylori infection prevalence. The prevalence of H. pylori infection in Korea appears to be changing with markedly lower prevalence in children of families of higher socioeconomic status. The factor(s) responsible for the break in the pattern of transmission in children of the higher socioeconomic class was not discovered. Future studies will concentrate on possible differences, eating practices, hygiene, and sanitary practices.

Adolescent↗
PubMed1996

Interobserver variation in the histopathological assessment of Helicobacter pylori gastritis.

The histopathologic detection of Helicobacter pylori in gastric biopsy specimens is considered the gold standard for the diagnosis of H pylori infection. However, few studies have addressed the pathologists' reliability to detect the organism and to assess the degree of the related inflammatory changes. The objectives of this study were to determine the degree of agreement among the findings of four gastrointestinal pathologists in the semiquantitative evaluation of H pylori infection and gastritis. Three slides from specified areas of the stomach of 99 patients with and without H pylori infection were stained with the triple stain, coded, and examined independently by four pathologists. For each specimen, a visual analogue scale graded from 0 (absent/normal) to 5 (maximal intensity) was used to score (1) H pylori (2) neutrophils, and (3) atrophy. Data were analyzed using kappa-statistics. The kappa-coefficient for the detection of H pylori (present vs absent) was approximately .9 (excellent); for the intensity of infection, it was considerably lower on the 6-point scale (approximately .61) and improved slightly on an amalgamated 4-point scale (approximately .71). The agreement on presence or absence of neutrophils was excellent (kappa = .8) in antral biopsies and good (kappa = .67) in corpus biopsies. The kappa for the semiquantitative scoring of neutrophils was poor on the 6-point scale (approximately .43) and fair on the amalgamated scale (approximately .54). The interobserver agreement was the poorest in the evaluation of atrophy (presence, absence, categories, or group categories) with kappa coefficients varying from .08 and .29. This group of pathologists had a high level of concordance on the diagnosis of H pylori infection in any particular patient and a high index in the assessment of the intensity of infection. The agreement was less in the semiquantitative evaluation of active inflammation. When the evaluation concerned a loosely defined feature, such as atrophy, there was essentially no agreement among the pathologists. This study suggests the need for further assessments of pathologists' ability to provide reproducible diagnoses. These results also indicate that more stringent criteria for the diagnosis of "soft" histopathologic features (such as atrophy) are urgently needed.

Atrophy↗
PubMed1996

Extract of Helicobacter pylori induces neutrophils to injure endothelial cells and contains antielastase activity.

BACKGROUND & AIMS: Previous studies indicate that a water extract of Helicobacter pylori promotes leukocyte adhesion and emigration as well as endothelial barrier disruption (increased vascular protein leakage) in rat mesenteric venules. The aims of this study were to assess whether H. pylori extract-activated neutrophils disrupt endothelial cell monolayers and to identify the mechanisms involved in this process. METHODS: Human neutrophils were incubated with monolayers of human umbilical vein endothelial cells (HUVECs) in the presence or absence of H. pylori extract. RESULTS: H. pylori extract-activated human neutrophils produced endothelial cell detachment from HUVEC monolayers, the severity of which was dependent on the duration of exposure. Endothelial cell detachment was prevented by a monoclonal antibody directed against CD11/CD18 on neutrophils or a monoclonal antibody against intercellular adhesion molecule 1 on endothelial cells. HUVEC monolayer disruption was also prevented by superoxide dismutase, catalase, and a monoclonal antibody against elastase. Further studies indicated that H. pylori extract was capable of inhibiting human neutrophil elastase. The antielastase activity was not diminished by oxidants. CONCLUSIONS: These studies indicate that H. pylori extract-activated human neutrophils can disrupt HUVEC monolayers only when human neutrophils are allowed to adhere to HUVECs and may provide an explanation for the H. pylori extract-induced, neutrophil-dependent vascular protein leakage observed in vivo. The possibility that H. pylori releases antiproteases may explain, in part, why this bacterium is so virulent.

Antibodies, Monoclonal↗
PubMed1996

Helicobacter pylori in the drinking water in Peru.

BACKGROUND & AIMS: An association between water sources and the prevalence of Helicobacter pylori infection in Peruvian children was shown previously. The aim of this study was to confirm the presence of H. pylori in drinking water in the same community. METHODS: Forty-eight drinking water samples from different locations in pueblo jovenes (new towns) near Lima were collected. Samples were frozen until technology advanced to the point to the point at which H. pylori might be reliably detected. Immunomagnetic beads coated with anti-H. pylori immunoglobulin Gs were used to concentrate H. pylori, and two polymerase chain reaction assays based on different H. pylori genes were used. One was a polymerase chain reaction for the detection of the H. pylori adhesin subunit encoding gene, and the second was a previously validated H. pylori 16S ribosomal RNA reverse transcriptase-polymerase chain reaction. RESULTS: The expected 375-base pair fragment from the adhesin gene was amplified from 24 water samples. The expected 500-base pair fragment of the 16S ribosomal RNA and the 375-base pair fragment of the adhesin gene were amplified from 11 of the samples. CONCLUSIONS: These results confirm the presence of H. pylori in drinking water in Peru and are consistent with conclusions from a previous epidemiological study of the same population. This provides additional evidence for waterborne transmission of H. pylori in some environments.

Adhesins, Bacterial↗
PubMed1996

Ulcer site and complications: relation to Helicobacter pylori infection and NSAID use.

BACKGROUND AND STUDY AIM: The aim of this study was to investigate the relationship between the presence and location of ulcers, H. pylori infection, NSAID use, and major upper gastrointestinal tract bleeding. PATIENTS AND METHODS: We studied 100 consecutive patients with duodenal ulcers and 145 consecutive patients with benign gastric ulcers. RESULTS: Ninety-nine percent of the duodenal ulcer patients and 92% of the gastric ulcer patients had H. pylori infection; all gastric ulcer patients without H. pylori infection were using NSAIDs. Gastric ulcers in patients with H. pylori infection who were not using NSAIDs were more likely to be on the lesser curvature (85%) than ulcers in NSAID users who had no H. pylori infection (35%) (p < 0.01). Conversely, only 5% of gastric ulcers in H. pylori-positive patients who were not using NSAIDs were on the greater curvature, compared to 45% in H. pylori-negative NSAID users (p < 0.01), and 23% in patients with both possible etiologies. The frequency of NSAID use was very high in patients presenting with upper gastrointestinal tract bleeding: 21 of 25 with gastric ulcers (84%) and 13 of 21 with duodenal ulcers (62%; p < 0.01 for each, compared to bleeding without taking NSAIDs). Overall, 74% of patients with upper gastrointestinal hemorrhage from peptic ulcer were taking NSAIDs. The prevalence of H. pylori infection was similar among the ulcer patients presenting with and without upper gastrointestinal tract bleeding. CONCLUSIONS: The location of a gastric ulcer on the greater curvature, and presentation with upper gastrointestinal tract bleeding, are separate and valuable clues to the involvement of NSAIDs. NSAID use may now be responsible for most bleeding complications of ulcer disease, regardless of H. pylori status.

Adult↗
PubMed1996

Endoscopic retreatment after successful initial hemostasis prevents ulcer rebleeding: a prospective randomized trial.

BACKGROUND AND STUDY AIMS: Rebleeding after initial endoscopic hemostasis remains an important determinant of poor prognosis in patients with ulcer hemorrhage. Prospective identification of patients who are at high risk for rebleeding, and directing further therapeutic measures in these patients, would be expected to improve the prognosis. PATIENTS AND METHODS: We used our previously described scoring system (the Baylor Bleeding Score) to identify patients at increased risk for rebleeding after initially successful endoscopic hemostasis, and randomized them into retreatment and no-retreatment groups. Patients in the retreatment group received additional endoscopic heat probe therapy at 24 hours, the follow-up was otherwise similar. Forty men with major ulcer hemorrhage were randomized, 19 to the retreatment group and 21 to the no-retreatment group. Patients in the two groups had similar Baylor Bleeding Scores, blood transfusion needs (median three vs. two units), ulcer sites (duodenal 57% vs. 43%), stigmata of hemorrhage (actively bleeding 68% vs 67%), and received similar initial endoscopic therapy (heat probe 240 J vs. 300 J). Patients in the retreatment group received additional heat probe therapy (median 165 J) at 24 hours. RESULTS: Rebleeding, requiring significantly more blood transfusion, occurred in 24% of the no-retreatment group patients compared to none of the retreatment group patients (p < 0.05). CONCLUSIONS: Endoscopic retreatment after successful initial endoscopic hemostasis prevents rebleeding in highrisk patients with ulcer bleeding.

Adult↗
PubMed1996

Detection of Helicobacter pylori in paraffin-embedded gastric biopsy specimens by in situ hybridization.

Helicobacter pylori is the causative agent of chronic gastritis, peptic ulcers, and is also associated with gastric cancer. Eradication of H pylori infection has proven to be difficult to confirm. The authors developed a nonradioactive in situ hybridization method for detection of H pylori and compared it with conventional methods for diagnosis of the infection. Reverse transcription followed by polymerase chain reaction (PCR) with two 22-base primers was used to amplify a 520 base pair (bp) segment of 16S rRNA from H pylori. The PCR product was labeled with digoxigenin and used as a probe. Specificity of the probe was tested by dot blot hybridization against DNA from 30 different strains of related and unrelated bacteria. Specificity of in situ hybridization assay was proven by the lack of hybridization on sections with gram negative and positive bacteria other than H pylori, with an unrelated probe, without probe, and after RNase treatment. A random sample of 15 biopsy specimens was blindly studied by in situ hybridization method and the results were compared with those of culture and conventional histology. Comparison of in situ hybridization and conventional histology showed agreement in all 15 specimens (5 negative and 10 positive). Between culture and in situ hybridization there was agreement in 13 cases (8 positive, 5 negative). Two cases were negative by culture but positive by in situ hybridization and histology. Nonradioactive in situ hybridization provides a sensitive and specific method for detection of H pylori infection. It should be particularly useful for confirmation of infection in cases equivocal with other methods, and potentially useful in post-treatment evaluation.

Base Sequence↗
PubMed1996

Resolution of a metaplastic duodenal polyp after cure of Helicobacter pylori infection.

Although there have been several reports of hyperplastic gastric polyps associated with persistent Helicobacter pylori gastritis, the association of H. pylori infection with metaplastic polyps in the duodenum has not hitherto been described. After a 52-year-old man had a single episode of hematemesis, endoscopy showed a smooth polyp 1 cm in greatest dimension formed by a proliferation of gastric epithelial cells of fundic and antral type found in the duodenal bulb. The outer surface was entirely covered with a single layer of hyperplastic columnar epithelium with many H. pylori organisms. After administration of metronidazole 500 mg, omeprazole 20 mg for 4 weeks, and clarithromycin 250 mg twice a day for 2 weeks, endoscopy showed a decrease in size of the duodenal polyp. At 12 weeks there was complete regression of the polyp. This report documents a new and unusual finding: resolution of a gastric metaplastic polyp in the duodenum associated with cure of H. pylori.

Anti-Bacterial Agents↗
PubMed1996

How accurate is the determination of blood in gastric juice? Comparison of peroxidase and porphyrin methods.

BACKGROUND: Mucosal bleeding is frequently used as a measure of gastric mucosal integrity. We compared the orthotolidine method for quantifying haemoglobin in gastric juice with a method based on measurement of fluorescent porphyrins extracted from haem. We also investigated whether acid or pepsin had a deleterious effect on the results of either method. METHODS: We compared the effects of pH (2 or 7), time (up to 180 min), haemoglobin concentration and the addition of pepsin (2.5, 5 or 7.5 kU/mL hog pepsin) on the accuracy of the two methods. RESULTS: With the orthotolidine method there was a time-dependent decline in detectable haemoglobin concentration (P < 0.02) at pH 2 that was not seen at pH 7. The time- and pH-dependent decline in detectable haemoglobin was not seen using the porphyrin assay. CONCLUSION: The widely used orthotolidine method for determination of blood in gastric juice is less reliable than the porphyrin method as it is more likely to be influenced by acidic conditions in the stomach.

Benzidines↗
PubMed1996

Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori.

Twelve clarithromycin-resistant Helicobacter pylori isolates (100% of resistant isolates examined) from seven different patients each contained an A-->G transition mutation within a conserved loop of 23S rRNA. A-->G transition mutations at positions cognate with Escherichia coli 23S rRNA positions 2058 and 2059 were identified. Clarithromycin-susceptible H. pylori isolates from 14 different patients displayed no polymorphisms in a conserved loop within domain V of 23S rRNA. The study is the first to report mutations in H. pylori associated with resistance to an antimicrobial agent used in established peptic ulcer treatment regimens.

Anti-Bacterial Agents↗
PubMed1996

Population genetic analysis of Helicobacter pylori by multilocus enzyme electrophoresis: extensive allelic diversity and recombinational population structure.

Genetic diversity and relationships in 74 Helicobacter pylori isolates recovered from patients assigned to distinct clinical categories were estimated by examination of allelic variation in six genes encoding metabolic housekeeping enzymes by multilocus enzyme electrophoresis. Seventy-three distinct allele profiles, representing multilocus chromosomal genotypes, were identified. All six loci were highly polymorphic, with an average of 11.2 alleles per locus. The mean genetic diversity in the sample was 0.735, a value that exceeds the level of diversity recorded in virtually all bacterial species studied by multilocus enzyme electrophoresis. A high frequency of occurrence of null alleles (lack of enzyme activity) was identified and warrants further investigation at the molecular level. Lack of linkage disequilibrium (nonrandom association (of alleles over loci) indicates that horizontal transfer and recombination of metabolic enzyme genes have contributed to the generation of chromosomal diversity in H. pylori. In this sample of isolates, there was no statistically significant association of multilocus enzyme electrophoretic types or cluster of related chromosomal types and disease category.

Adult↗
PubMed1996

Evaluation of three commercial enzyme immunoassays compared with the 13C urea breath test for detection of Helicobacter pylori infection.

The diagnostic significance of the serological detection of antibodies to Helicobacter pylori has been established by numerous investigators. Reports of the clinical reliabilities of commercial enzyme immunoassay (EIA) kits available for this purpose vary as a result of the different H. pylori antigen sources and reference methods used. The 13C urea breath test (UBT) has been shown to be an extremely accurate and reliable method of detecting H. pylori infection. We used the 13C urea breath test as the confirmatory method for H. pylori status to evaluate three commercially available EIA kits designed to detect immunoglobulin G antibodies to H. pylori. These kits were the HM-CAP EIA kit (Enteric Products, Inc.), the PYLORI STAT EIA kit (BioWhittaker, Inc.), and the G.A.P. kit (Bio-Rad Laboratories/Biomerica, Inc.). The evaluations were performed in a double-blind manner with samples from 473 clinically characterized patients. This group included patients with symptomatic gastrointestinal disorders as well as nonsymptomatic volunteers. The sensitivities of the kits were as follows: HM-CAP, 98.4%; PYLORI STAT, 99.2%; and G.A.P., 100%. The specificities were as follows: HM-CAP, 96.4%; PYLORI STAT, 90.1%; and G.A.P., 26.0%. Although the HM-CAP and PYLORI STAT kits performed comparably, the G.A.P. test yielded significantly more false-positive results and an unacceptably high number of indeterminate results.

Antibodies, Bacterial↗
PubMed1996

Comparison of rapid serological tests (FlexSure HP and QuickVue) with conventional ELISA for detection of Helicobacter pylori infection.

BACKGROUND: There is a need for accurate and rapid tests for Helicobacter pylori infection especially since the recent National Institutes of Health Consensus Development Conference on H. pylori in peptic ulcer disease charged the medical community with treating H. pylori infection in all patients with H. pylori and ulcer disease. METHODS: We prospectively compared a simple, rapid serological test (FlexSure HP, SmithKline Diagnostics) for the detection of serum IgG antibodies against H. pylori with another rapid test (QuickVue, Quidel) and two enzyme immunoassays (HM-CAP, Enteric Products, and PyloriStat, BioWhittaker). Serum samples from 551 individuals including both symptomatic patients (196) and asymptomatic volunteers (355) were tested for the presence of IgG antibodies against H. pylori. The presence or absence of active H. pylori infections was determined using the [13C]-urea breath test. RESULTS: All of the serological tests performed well. FlexSure HP had calculated sensitivity, specificity, and accuracy of 94.4, 87.6, and 91.1%, respectively, relative to the urea breath test. In 49 of the 551 samples, the urea breath test and FlexSure HP did not agree. Those samples were tested with HM-CAP immunoassay to confirm presence or absence of IgG antibodies against H. pylori. After the resolution of the discordant results, the sensitivity, specificity, and accuracy of FlexSure HP were 96.0, 95.1, and 95.6%, respectively, and were comparable to HM-CAP and PyloriStat. FlexSure HP was compared with histology or culture in 75 cases, and the accuracy was 100%. FlexSure HP and QuickVue were compared using 200 serum samples. FlexSure HP was more specific (88.7 vs 79.4%) and accurate (91 vs 84%) than QuickVue (p < 0.05 for both), relative to the urea breath test with discordant samples unresolved. FlexSure HP was also simpler to use, easier to interpret, and faster than QuickVue. FlexSure HP required no sample dilution, one reagent, four steps, and 5 min to complete. CONCLUSION: FlexSure HP is an excellent option for in-office tests for the physician who desires immediate results or for small laboratories that do not have the volume of H. pylori testing to justify ELISA test formats.

Adolescent↗