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Biomedical subjects

D Y Graham

Publications and source records attributed to D Y Graham.

At least 343 records · Page 19Linked to original sources
PubMed1994

Pancreatic secretion in man: effect of fasting, drugs, pancreatic enzymes, and somatostatin.

The inhibitory effect of different drugs on pancreatic secretions was assessed in a patient with a posttraumatic pancreatic-cutaneous fistula. The various drugs examined were: pancreatic enzymes, cimetidine, verapamil, propantheline, acetazolamide, and somatostatin analog octreotide. Only fasting and octreotide reduced pancreatic secretion. The optimum dose of octreotide was 50 micrograms bid given subcutaneously; increasing the dose up to 100 micrograms tid had no additional benefit. A stable pancreatic-cutaneous fistula is an excellent model to assess the effect of different therapeutic measures on pancreatic secretion.

Acetazolamide↗
PubMed1994

The epidemiology of Helicobacter pylori in Peruvian children between 6 and 30 months of age.

OBJECTIVES: Cross-sectional studies of children in developing countries show a high prevalence of Helicobacter pylori infection at 6 months of age, but a decrease in the prevalence of infection between 1 and 5 yr of age. The decrease suggests a loss or clearance of infection, an uncommon finding in adults. Our objective in this study was to determine the longitudinal persistence of H. pylori infection in young children. METHODS: We tested an initial cohort of 105 6-month-old infants at 6-month intervals with the 13C-urea breath test; 56 subjects were successfully studied for 2 yr or until 30 months of age. RESULTS: Overall prevalence decreased from 71.4% to 47.9% when children were between 6 and 18 months of age, and we found a significant gender difference (males 63.6-55.0%, females 80.0-38.7%, p = 0.03). Of the 56 subjects, six had negative breath tests at all 6-month intervals, 10 were consistently positive, and 36 subjects had one or more negative tests after a positive test. The overall probability of acquiring H. pylori in a given 6-month period ranged between 0.28 and 0.38; the probability of clearing the infection was between 0.22 and 0.45. During the first 18 months after birth, male infants were more likely to acquire H. pylori and less likely to clear the infection than female infants. CONCLUSION: We conclude that H. pylori colonization in infants may be a reversible process.

Breath Tests↗
PubMed1994

Diagnosis of intestinal tuberculosis by polymerase chain reaction on endoscopic biopsy specimens.

It is often difficult to establish the diagnosis of intestinal tuberculosis because of close similarities with other conditions, in particular, Crohn's disease. In the present study, we used the polymerase chain reaction (PCR) assay on endoscopic biopsy specimens obtained from a patient with chronic diarrhea. Positive hybridization was obtained with the Mycobacterium tuberculosis probe and the patient was treated with anti-tuberculous drugs with complete resolution of the endoscopic abnormalities. This study demonstrates that polymerase chain reaction assay can be used on endoscopic biopsy specimens to diagnose intestinal tuberculosis.

Adult↗
PubMed1994

Clarithromycin, tetracycline, and bismuth: a new non-metronidazole therapy for Helicobacter pylori infection.

OBJECTIVE: Metronidazole resistance has become an increasing problem that has limited the usefulness of the original triple therapy. Our objective was to evaluate clarithromycin, a new macrolide compound active against Helicobacter pylori. METHODS: We evaluated a new clarithromycin triple therapy for H. pylori infection consisting of the combination of clarithromycin (500 mg t.i.d.), tetracycline (500 mg q.i.d.), and bismuth subsalicylate tablets (2 q.i.d.) for 14 days. Patients with ulcer also received concomitant ranitidine, 300 mg after the evening meal, for 6 wk. RESULTS: Thirty men with documented H. pylori infection were studied; 29 had peptic ulcer disease. Seven had previously failed antimicrobial therapy, including three with metronidazole-based triple therapy. H. pylori status was determined by histology. H. pylori status and ulcer status were evaluated 4 wk after the end of antimicrobial therapy. The ulcer was healed in 90%. The H. pylori infection was cured in 93%, including all three patients who previously failed metronidazole-based triple therapy. CONCLUSION: We conclude that the combination of clarithromycin, tetracycline, and bismuth is an effective new therapy for treatment of H. pylori infection.

Adult↗
PubMed1994

All lactase preparations are not the same: results of a prospective, randomized, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of three commercially available oral lactase preparations in adults with lactose intolerance. METHODS: Design--Prospective, randomized, placebo-controlled trial. Setting--Outpatient study in a General Clinical Research Center. Subjects--Ten lactose-intolerant healthy volunteers were challenged with ice cream containing 18 g of lactose. Lactase or placebo was given immediately prior to challenge. Measurements--Symptoms and breath hydrogen excretion were recorded for 3 h following lactose challenge. RESULTS: The three products differed in their abilities to influence symptoms and breath hydrogen excretion. Only Lactaid reduced the breath hydrogen excretion with lactose (mean peak, area under the curve and cumulative breath hydrogen excretion) (p < 0.05). Lactrase and Dairy Ease influenced symptoms: Lactrase reduced pain, bloating and total symptomatic scores (p < 0.05), whereas Dairy Ease only reduced pain (p < 0.05). Lactaid administration did not reduce symptoms. CONCLUSION: In lactose-intolerant subjects, the available lactase preparations differ in their ability to improve both breath hydrogen excretion and symptoms. Lactrase may be the product of choice for achieving symptomatic improvement.

Adult↗
PubMed1994

Helicobacter pylori infection and development of gastric or duodenal ulcer in arthritic patients receiving chronic NSAID therapy. The Misoprostol Study Group.

OBJECTIVES: Helicobacter pylori infection and nonsteroidal anti-inflammatory drug use are both common causes of peptic ulcer. It remains unclear whether H. pylori/NSAID interactions occur, and if they do, with what result(s). METHODS: We prospectively evaluated development of gastric or duodenal ulcers in 181 arthritics followed for up to 3 months while receiving an NSAID chronically and with no active anti-ulcer medications. H. pylori status was determined with a sensitive, specific ELISA for anti-H. pylori IgG. RESULTS: H. pylori infection was present in 51%; peptic ulcers developed in 24. H. pylori infection was present in only 36% of those who developed a duodenal ulcer. Stepwise logistic regression analysis indicated none of the variable factors of age, gender, alcohol consumption, type of arthritis, or H. pylori status were significantly associated with development of peptic ulceration. CONCLUSIONS: These data suggest that H. pylori does not confer increased risk of ulceration in arthritics receiving NSAIDs chronically.

Adult↗
PubMed1993

Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.

OBJECTIVES: To determine the efficacy of misoprostol for the prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced duodenal and gastric ulcers in arthritis patients receiving NSAID therapy. DESIGN: A randomized, double-blind, multicenter, placebo-controlled trial. SETTING: Six hundred thirty-eight private, Veterans Affairs, health maintenance, and academic practices. PATIENTS: Six hundred thirty-eight patients with chronic inflammatory or noninflammatory arthritis who were taking an NSAID but who did not have a gastric or duodenal ulcer on screening endoscopy received treatment with ibuprofen, piroxicam, naproxen, sulindac, tolmetin, indomethacin, or diclofenac daily for 3 months. Four hundred fifty-five (71%) patients completed the trial. INTERVENTIONS: Patients meeting the entry criteria were randomized to receive either misoprostol, 200 micrograms, or placebo, four times a day for 12 weeks. MAIN OUTCOME MEASURES: The endoscopy was repeated at 4, 8, and 12 weeks. The development of a duodenal or gastric ulcer (defined as a circumscribed mucosal defect > or = 0.5 cm in diameter and with perceptible depth) was regarded as prophylactic failure. RESULTS: By 12 weeks, a duodenal ulcer developed in 2 of 320 (0.6%; 95% CI, 0.2% to 3.9%) patients randomized to receive misoprostol, compared with 15 of 323 (4.6%; CI, 2.8% to 8%) patients receiving placebo (P = 0.002). A gastric ulcer developed in 6 of 320 (1.9%; (CI, 0.8% to 4.4%) patients, compared with in 25 of 323 (7.7%; CI, 5.1% to 11.4%), respectively. CONCLUSION: Misoprostol significantly lowers the frequency of both duodenal and gastric ulcer development in patients who require long-term therapy with NSAIDS.

Adult↗
PubMed1993

DNA-DNA hybridization demonstrates apparent genetic differences between Helicobacter pylori from patients with duodenal ulcer and asymptomatic gastritis.

We asked whether different clinical outcomes of Helicobacter pylori infection might be a reflection of genetic differences in infecting organisms. Using DNA-DNA hybridization we examined whether hybridization levels grouped H. pylori isolates corresponding to the type of disease (gastric ulcer, duodenal ulcer, asymptomatic gastritis) from which they were recovered. Target DNAs were prepared from H. pylori strains cultured from gastric biopsy specimens of 25 patients; 5 with gastric ulcers, 9 with duodenal ulcers, and 11 from asymptomatic volunteers endoscopically proven not to have peptic ulcer disease. DNA-DNA hybridization was performed with whole genomic probes made from an isolate from each of the three disease categories. Using a DNA probe from an isolate from a duodenal ulcer patient, we found that isolates from patients with duodenal ulcer and nonulcer gastritis yielded significant differences in levels of hybridization. The levels of hybridization of DNA from H. pylori isolates from duodenal ulcer patients, gastric ulcer patients, and nonulcer gastritis controls were 85.5% +/- 7%, 83% +/- 3%, and 78.3% +/- 5%, respectively (mean +/- SD), and the difference between the hybridization levels obtained with duodenal ulcer and nonulcer control target DNAs was statistically significant (P = 0.025). These data suggest that the outcome of infection (eg, ulcer or no ulcer) may be due to virulence factors encoded by genomic DNA. If such differences exist, it should be possible to produce probes that would identify the ulcer virulence gene(s) and clearly distinguish between ulcerogenic and nonulcerogenic strains of H. pylori.

DNA Probes↗
PubMed1993

Phospholipase activity of Helicobacter pylori and its inhibition by bismuth salts. Biochemical and biophysical studies.

In this study we measured phospholipase A (PLA) and C (PLC) activity of media filtrates and French Press lysates of the gastritis-inducing bacteria Helicobacter pylori. We report here that both H. pylori lysates and filtrates contain PLA1, PLA2, and C enzymes, which readily hydrolyze a radiolabeled dipalmitoylphosphatidylcholine (DPPC) and phosphorylcholine substrates, respectively. The specific activity of both PLA and C enzymes were greatest in the 6.5-7.0 and 8.4-8.8 pH ranges, respectively. Colloidal bismuth subcitrate (CBS) induced a dose-dependent inhibition of PLA2 and C activity of both H. pylori lysates and filtrates. This inhibitory effect of CBS on PLA2 was antagonized in a dose-dependent fashion by the addition of CaCl2 to the incubation mixture, suggesting that calcium and bismuth may be competing for the same site on the enzyme. In contrast, the ability of bismuth salts to inhibit PLC activity of H. pylori lysates was not antagonized by CaCl2. Employing a biophysical assay system for surface wettability, it was determined that H. pylori lysates had the capacity to remove a synthetic phospholipid monolayer off a glass in a dose-dependent fashion. This ability of the bacterial lysates to catalyze the transformation of a hydrophobic surface to a wettable state was significantly attenuated in the presence of bismuth salts. Our experimental results are, therefore, consistent with the possibility that H. pylori colonization compromises the stomach's barrier to acid by eroding a phospholipid lining, possibly a monolayer, on the surface of the gastric mucus gel and that this process is blocked in response to bismuth therapy.

Anti-Bacterial Agents↗
PubMed1993

Mechanisms involved in Helicobacter pylori-induced inflammation.

BACKGROUND: Helicobacter pylori infection is associated with mucosal inflammation. The aims of the present study were to assess whether a water extract of H. pylori promotes neutrophil (polymorphonuclear leukocyte [PMN]) adherence to endothelial cells and define the molecular basis of this adhesive interaction. METHODS: Intravital microscopy was used to study leukocyte adhesive interactions in rat mesenteric venules in situ. PMN-endothelial cell adhesive interactions were studied in vitro using human PMNs and monolayers of human umbilical vein endothelial cells (HUVEC). RESULTS: In vivo, superfusion of rat mesentery with the H. pylori extract increased leukocyte adhesion and emigration in venules. In vitro, adhesion of human PMNs to HUVEC was increased by the H. pylori extract in a concentration-dependent manner. Pretreatment of HUVEC alone with H. pylori extract had no effect on PMN adherence, whereas pretreatment of PMN alone significantly increased their adherence to HUVEC. The extract-induced adhesion was significantly diminished by monoclonal antibodies (MAb) directed against either CD11a, CD11b, or CD18 on neutrophils, and by MAbs against intercellular adhesion molecule-1 (ICAM-1), but not E- or P-selectin, on endothelial cells. CONCLUSIONS: These studies suggest that products of H. pylori elicit gastrointestinal inflammation by promoting PMN adhesion to endothelial cells via CD11a/CD18- and CD11b/CD18-dependent interactions with ICAM-1.

Animals↗
PubMed1993

Antral G-cell and D-cell numbers in Helicobacter pylori infection: effect of H. pylori eradication.

BACKGROUND: It has recently been recognized that Helicobacter pylori infection is associated with abnormalities in the regulation of gastrin secretion. We investigated whether there was a relationship between H. pylori infection and G-cell and D-cell numbers. METHODS: The numbers of antral G cells and D cells were compared between 20 patients with duodenal ulcer and 24 volunteers, 12 with and 12 without H. pylori infection. The effect of eradication of H. pylori infection on G-cell number was also evaluated. Antral mucosal biopsy specimens were examined using immunohistochemical techniques specific for the presence of gastrin and somatostatin. RESULTS: The number of G cells was significantly (P < 0.02) less in patients with duodenal ulcer than in either infected or uninfected controls (3.7 +/- 0.3 vs. 6.2 +/- 0.6 and 5.3 +/- 0.5 G cells per gland for infected and uninfected controls, respectively). The ratio of G-cells to D-cells was similar in duodenal ulcer patients (2.2) and uninfected controls (2.0). It was found that, although eradication of the H. pylori infection results in a dramatic reduction in stimulated gastrin secretion, it is not associated with a change in the numbers of antral G cells or D cells in patients with duodenal ulcer. CONCLUSIONS: It is concluded that H. pylori infection-associated increase in gastrin secretion appear to be related to local factors regulating G-cell function.

Cell Count↗
PubMed1993

Gastric lymphoid follicles in Helicobacter pylori infection: frequency, distribution, and response to triple therapy.

To determine the prevalence and distribution of gastric lymphoid follicles in patients with Helicobacter pylori infection, to evaluate their relationship with gastroduodenal pathology, and to assess their evolution after eradication of H pylori, mapped gastric biopsy specimens were obtained from 20 H pylori-negative normal volunteers, 25 asymptomatic volunteers with H pylori infection and no ulcer disease, 21 duodenal ulcer patients, and 16 patients with gastric ulcer. Nine infected subjects were treated by triple therapy, and biopsy specimens were obtained at 1, 4, and 12 months posttreatment. Lymphoid follicles were counted and other histologic features were scored semiquantitatively. None of the noninfected subjects had lymphoid follicles. All subjects with H pylori had follicles, which were more numerous in the antrum than in the corpus (P < .001) and on the lesser rather than on the greater curvature (P = .003). Ulcer patients had greater numbers of follicles than asymptomatic infected volunteers (P < .05). There was no relationship between number or distribution of follicles and patients' age, sex, or other mucosal inflammatory responses (except for numbers of lymphocytes: r = .785, P < .001), intensity of H pylori infection, or intestinal metaplasia. Eradication of H pylori resulted in a slow decrease (but not in the disappearance) of lymphoid follicles in all patients. Our results indicate that the careful examination of multiple specimens will reveal lymphoid follicles in the gastric mucosa of all patients with H pylori infection. The normal stomach does not contain mucosa-associated lymphoid tissue, and this study supports the concept that H pylori may be a precursor in the development of primary gastric lymphomas.

Adult↗