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D Y Graham

Publications and source records attributed to D Y Graham.

At least 199 records · Page 11Linked to original sources
PubMed1998

Managing dyspepsia: what do we know and what do we need to know?

OBJECTIVE: The conceptual revolution concerning the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease has raised the larger question of how to integrate this new information into the management of patients with dyspepsia. The aim of this research was to critically evaluate current knowledge about dyspepsia and its management. METHODS: Relevant articles on dyspepsia were identified from MEDLINE searches and from the bibliographies of identified articles. Studies that contained information on the prevalence of dyspepsia, endoscopic findings, and evaluations of alternative management strategies were reviewed. RESULTS: By coupling H. pylori serological testing with clinical factors such as age and nonsteroidal antiinflammatory drug use, strategies have been developed that identify patients with organic disease. Although the use of these strategies can reduce the volume of endoscopies, their effects on dyspepsia symptoms are unknown. Computerized decision analysis models have been used to evaluate the cost-effectiveness of alternative strategies. The indirect evidence obtained from these models suggests that empiric therapy, guided by H. pylori testing, may be the preferred approach. However, the models have been hampered by the lack of information concerning dyspepsia symptoms, the primary health outcome of the majority of patients seen in primary practice settings. CONCLUSIONS: Currently, the knowledge needed to integrate H. pylori tests and antimicrobial therapies into the management of patients with dyspepsia in primary practice settings has not been developed. A pressing need exists for a randomized controlled trial to evaluate alternative management strategies. In conducting such a trial, valid, reliable instruments for measuring dyspepsia will be needed.

Computer Simulation↗
PubMed1998

Comparison of four serological tests to determine the CagA or VacA status of Helicobacter pylori strains.

We compared four tests for antibodies to CagA or VacA, HelicoBlot 2. 0, RIDA Blot Helicobacter, CHIRON RIBA H. pylori SIA, and an enzyme-linked immunosorbent assay using recombinant CagA. Immunoblot assays were accurate for determining Helicobacter pylori status but poor for determining CagA or VacA status (accuracy, 66 to 80% for CagA status and 34 to 67% for VacA status). None can be recommended for determining CagA or VacA status.

Antigens, Bacterial↗
PubMed1998

Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases.

The CagA protein of Helicobacter pylori is an immunogenic antigen of variable size and unknown function that has been associated with increased virulence as well as two mutually exclusive diseases, duodenal ulcer and gastric carcinoma. The 3' region of the cagA gene contains repeated sequences. To determine whether there are structural changes in the 3' region of cagA that predict outcome of H. pylori infection, we examined 155 cagA gene-positive H. pylori isolates from Japanese patients including 50 patients with simple gastritis, 40 with gastric ulcer, 35 with duodenal ulcer, and 30 with gastric cancer. The 3' region of the cagA gene was amplified by PCR followed by sequencing. CagA proteins were detected by immunoblotting using a polyclonal antibody against recombinant CagA. One hundred forty-five strains yielded PCR products of 642 to 651 bp; 10 strains had products of 756 to 813 bp. The sequence of the 3' region of the cagA gene in Japan differs markedly from the primary sequence of cagA genes from Western isolates. Sequence analysis of the PCR products showed four types of primary gene structure (designated types A, B, C, and D) depending on the type and number of repeats. Six of the seven type C strains were found in patients with gastric cancer (P < 0.01 in comparison to noncancer patients). Comparison of type A and type C strains from patients with gastric cancer showed that type C was associated with higher levels of CagA antibody and more severe degrees of atrophy. Differences in cagA genotype may be useful for molecular epidemiology and may provide a marker for differences in virulence among cagA-positive H. pylori strains.

Adult↗
PubMed1998

Frequency of vacA genotypes and cytotoxin activity in Helicobacter pylori associated with low-grade gastric mucosa-associated lymphoid tissue lymphoma.

The vacA genotypes s1,m1 and s1,m2 were detected in 44 and 30% of Helicobacter pylori isolates, respectively, from patients with gastric mucosa-associated lymphoid tissue lymphoma, compared to 26 and 56% of isolates, respectively, from individuals with gastritis. The vacA s1 genotype was significantly associated with, but not predictive of, the presence of vacuolating cytotoxin activity.

Bacterial Proteins↗
PubMed1998

Houseflies are an unlikely reservoir or vector for Helicobacter pylori.

The route of transmission of Helicobacter pylori from individual to individual remains undefined. It has recently been reported that the domestic housefly, Musca domestica, when fed pure cultures of H. pylori, was able to harbor the organism in its midgut for up to 30 h (P. Grubel, S. Hoffman, F. K. Chong, N. A. Barstein, C. Mepani, and D. R. Cave, J. Clin. Microbiol. 35:1300-1303, 1997). Our investigation examined whether houseflies could acquire H. pylori from fresh human feces. Domestic houseflies (40 flies/group) were exposed for 24 h to feces from an H. pylori-positive volunteer, feces from an H. pylori-negative volunteer, or feces from an H. pylori-negative volunteer to which a known amount of viable H. pylori had been added. At various intervals, flies were sacrificed and the midguts were excised, homogenized, and plated in duplicate onto selective horse blood agar plates. All plates were incubated under microaerobic conditions at 37 degreesC for 14 days. Emergent colonies presumptive of H. pylori were picked and tested biochemically to confirm the identity as H. pylori. H. pylori was not recovered from houseflies fed human feces either naturally infected or artificially infected with H. pylori. These results suggest that the domestic housefly is not a vector for transmission or a reservoir for H. pylori infection.

Animals↗
PubMed1998

Histologic assessment of Helicobacter pylori status after therapy: comparison of Giemsa, Diff-Quik, and Genta stains.

To compare the Giemsa, Diff-Quik, and Genta stains for detection of Helicobacter pylori in gastric biopsy specimens, we stained, coded, and randomized slides, which were then independently reviewed by two pathologists and one trainee. H. pylori was graded from 0 (absent) to 5 (maximal intensity). Negative cases were from recently cured patients to ensure that a background of chronic inflammation was present. The time required to complete the evaluation was tabulated. The pathologists interpreted 72 H. pylori-negative slides, of which 1 (1.3%), 2 (3%), and 3 (4%) were scored positive (each with the score of 1) with Diff-Quik, Genta, and Giemsa stains, respectively (P = ns). Of the 128 H. pylori-positive slides, 5 (4%) had false-negative results with Diff-Quik, 8 with Genta (6%), and 14 with Giemsa stains( 11%). No Grade 2 slides were missed by Genta or Diff-Quik stains, but 3 of 20 were missed by Giemsa stain. The combination of hematoxylin and eosin and Diff-Quik provides accuracy similar to that of the Genta stain but requires more processing time. No stain was excellent after therapy for detecting one or two bacteria per slide; this finding emphasizes the need for obtaining multiple biopsy specimen to exclude failure of H. pylori therapy.

Azure Stains↗
PubMed1998

A new triple stain for Helicobacter pylori suitable for the autostainer: carbol fuchsin/Alcian blue/hematoxylin-eosin.

OBJECTIVE: To develop an inexpensive stain to simultaneously visualize gastric morphology and Helicobacter pylori. METHODS: Gastric biopsies were stained with Genta stain using manual methods, and with carbol fuchsin/Alcian blue/hematoxylin-eosin using an automatic slide stainer (Sakura DRS-601). Slides were then coded and interpreted by 2 pathologists. Helicobacter pylori was scored using a visual scale (0 [none] to 5 [maximum]). RESULTS: One hundred slides were scored; H pylori was present in 64%. Carbol fuchsin/Alcian blue/hematoxylin-eosin stain gave excellent demonstration of gastric morphology. All positive cases (score > or =2) were correctly interpreted. Thirty-six slides had a score of 1 (< or =2 bacteria per entire slide). Of these, 10 were scored negative by Genta stain and 12 were scored negative by the carbol fuchsin/Alcian blue/hematoxylin-eosin stain (P = not significant). Hematoxylin-eosin was significantly less accurate than either of the other 2 stains (P < .02). CONCLUSION: The carbol fuchsin/Alcian blue/hematoxylin-eosin (El-Zimaity) stain is an economical stain suitable for simultaneous visualization of H pylori infection and gastric morphology.

Alcian Blue↗
PubMed1998

Serologic detection of Helicobacter pylori infection with cagA-positive strains in duodenal ulcer, gastric cancer, and asymptomatic gastritis.

CagA has been suggested as a marker for more virulent strains of Helicobacter pylori. Studies using purified proteins and an enzyme-linked immunosorbent assay (ELISA) method for serological detection of antibodies against CagA reported considerable discordance between the results of the ELISA and molecular detection of the cagA gene, with a tendency for estimation of the prevalence of cagA-positive H. Pylori to be higher by ELISA than by colony hybridization. It is not clear whether the discordance was either due to simultaneous infections with both cagA-positive and -negative strains or because of false-positive ELISA results. We correlated the presence of cagA-positive H. pylori by Polymerase chain reaction (PCR) with the presence of serum antibodies against the CagA protein from denatured H. pylori lysates. Gastric biopsies and sera were obtained from 75 patients from Korea; 25 each with gastric carcinoma, duodenal ulcer, and simple gastritis. Seventy-four of 75 isolates (98.6%) were cagA-positive by PCR and 70 sera were CagA antibody-positive by Western blotting. The cagA gene is common in H. pylori isolates from Korea regardless of the underlying disease. The presence of cagA is almost always associated with antibody to the CagA protein as determined by Western blotting. Western blotting may be the preferred method for serological detection of infection with cagA-positive H. pylori.

Adult↗
PubMed1997

Virus-like particle vaccines for mucosal immunization.

Viruses which infect the gastrointestinal tract are well suited for examining the immune response(s) to oral delivery of antigen and exploring the advantages and pitfalls of oral vaccines. We have used recombinant DNA techniques to produce nonreplicating self-assembled virus-like particles (VLPs) from two gastrointestinal viruses, rotavirus and Norwalk virus. Both of these viruses normally cause acute gastroenteritis in man or animals. The VLPs are morphologically and antigenically similar to the native virus and quite stable, features which are advantageous for their use as subunit vaccines. In addition, these VLPs could be useful as carriers of foreign epitopes from heterologous pathogens or of drugs which need to be delivered to the gastrointestinal track. This paper briefly reviews the properties of these VLPs made in insect cells and data showing their potential as subunit vaccines for parenteral or oral delivery.

Administration, Oral↗
PubMed1997

Determination of the duration of a primary immune response and the ID50 of ALA rabbit rotavirus in rabbits.

The rabbit model of rotavirus infection has been used to examine the immune response to rotavirus infection and to evaluate strategies for rotavirus vaccine development. To determine the 50% infectious does (ID50) of tissue culture adapted ALA virus, rabbit were orally inoculated with 10(1)-10(3) PFU of ALA rotavirus. The ID50 of ALA virus was determined to be 1.7 x 10(2) PFU. The immune response induced in rabbits infected at low virus doses (10(2)-10(3) PFU) was of similar magnitude to the immune responses induced with a high dose (10(6) PFU) inoculum, indicating that the immune response to ALA rotavirus in rabbits is not dose dependent. To determine if a single rotavirus inoculation would induce a long lasting immune response, four rabbits were inoculated once with ALA virus (3.5 x 10(5) PFU) and their serologic and mucosal antirotavirus titers were monitored at intervals for 1.5-2 years. The infected rabbits maintained serologic and mucosal rotavirus antibody titers until the final time point more than 700 days post inoculation. These data are important because they indicate that the antigenic load achieved following a single oral inoculation is sufficient to achieve long lasting immunity, the goal of any potential vaccine.

Animals↗
PubMed1997

Mast cell involvement in gastritis with or without Helicobacter pylori infection.

BACKGROUND & AIMS: Mast cells are initiators and regulators of inflammation, but their role in the human stomach remains unclear. Therefore, the extent and distribution of mast cell involvement in gastritis with or without Helicobacter pylori infection was investigated. METHODS: Mapped biopsy specimens from 17 H. pylori-positive and 20 H. pylori-negative subjects were examined. Sections were assessed for infection and inflammation and stained with anti-human mast cell tryptase to count mucosal and epithelial mast cells. Density of mast cells in different gastric compartments, their response to infection treatment, and their relationship with other inflammatory cells were evaluated. Mast cell degranulation was evaluated by electron microscopy. RESULTS: Mast cell density was significantly greater in the mucosa with gastritis, with or without H. pylori infection, than in the mucosa of noninfected normal subjects. In the antrum, density was much greater in H. pylori-infected peptic ulcer subjects than in the other gastritis groups. It also correlated significantly with the intensity of inflammation. Mast cell degranulation was demonstrated by electron microscopy in H. pylori-infected mucosa. Mast cell density in ulcer patients decreased significantly after cure of H. pylori infection. CONCLUSIONS: Mast cells may be important effector cells in the pathogenesis of gastritis, especially in H. pylori-associated peptic ulcer.

Adult↗
PubMed1997

Can therapy even be denied for Helicobacter pylori infection?

Helicobacter pylori infection is a transmissible bacterial infection of the gastric mucosal surface that causes progressive damage with eventual destruction of the stomach. In the United States, the presence of H. pylori infection in patients carries a lifetime risk of developing peptic ulcer of at least 16% and a 1%-3% risk of developing gastric cancer. An infected individual is also a risk to the community because the infection can be transmitted. A review of the data shows that H. pylori is the only treatable infectious disease with such a high rate of morbidity and mortality that is not the subject of an all-out program to eradicate it from the population. The risk of a serious outcome of untreated asymptomatic H. pylori infection is great, or greater, than with asymptomatic syphilis or tuberculosis. H. pylori infection is a serious public health problem, and thus the presence of H. pylori infection justifies treatment. The question is not whom to treat, but whom to test. The gastroenterology community appears to have been unduly influenced by the fact that H. pylori infection is widespread and often asymptomatic, as well as by the costs and complications of current treatment. H. pylori infection is a serious, worldwide infectious disease with tremendous and unacceptable morbidity and mortality. Although there are no emotional reasons to treat H. pylori infection, there are logical and persuasive scientific reasons to treat. If the tools are available, screening the population for the presence of H. pylori infection with the goal of preventing all H. pylori-related diseases is recommended. Our goal should be to totally eliminate H. pylori from the face of the earth, just as we eliminated smallpox.

Helicobacter Infections↗
PubMed1997

An objective end point for dilation improves outcome of peptic esophageal strictures: a prospective randomized trial.

BACKGROUND: The usual end point for defining success of dilation is subjective (relief of dysphagia). In most patents thus managed strictures recur. We asked whether an objective end point would improve outcome. METHODS: After dilation to 15 mm, patients were randomized into subjective and objective groups. In subjective group patients, end point for dilation was alleviation of dysphagia; in objective group patients, passing the 12 mm barium pill test. Objective group patients who failed underwent redilation until they passed the pill or failed three times. During Part 1 of the study, patients received ranitidine, during Part 2 they received omeprazole. RESULTS: In part 1, dysphagia was alleviated in 7 of 8 subjective group patients. Only 2 of 10 objective group patients passed the pill test and no additional patients passed after 3 sessions, although most had no dysphagia. In Part 2, 19 subjective groups and 15 objective group patients were studied. End point was not achieved in 3 objective group patients. Over long-term follow-up, objective group patients had less recurrent dysphagia (p = 0.02) and required fewer redilation sessions (p < 0.05). Overall, the pill test correlated with the presence or absence of dysphagia (P < 0.001). Predictive value of passing the pill 1 week after dilation for the absence of dysphagia was 100%, but of failing the pill test and the presence of dysphagia was only 18%. CONCLUSIONS: Achieving an objective end point reduces stricture recurrence and the need for subsequent dilation. Initial subjective improvement does not predict long-term success.

Adult↗