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D Y Graham

Publications and source records attributed to D Y Graham.

At least 361 records · Page 20Linked to original sources
PubMed1993

Clarithromycin for the eradication of Helicobacter pylori.

Helicobacter pylori infection has proven to be extraordinarily difficult to eradicate. Antimicrobial monotherapies have been particularly disappointing, with most eradication rates in the range of 0-15%. Clarithromycin has potential advantages over other macrolides to which H. pylori is susceptible because of its acid stability and solubility at low pH. We evaluated clarithromycin therapy (250 mg four times daily for 14 days) in 12 H. pylori-infected patients. The 13C-urea breath test was used to evaluate the effectiveness of therapy. Eradication was defined as a negative urea breath test 4-6 weeks after the end of treatment. Suppression of H. pylori was demonstrated in 11 of 12 patients (92%) by a negative urea breath test 2 days after start of treatment. H. pylori was eradicated in five (42%) of 12 patients. Adverse events were intermittent and mild. Clarithromycin is the first antimicrobial agent that appears to offer promise as monotherapy for the eradication of H. pylori.

Adolescent↗
PubMed1993

Short report: a non-metronidazole triple therapy for eradication of Helicobacter pylori infection--tetracycline, amoxicillin, bismuth.

Triple therapies using bismuth, metronidazole and tetracycline or amoxicillin were the first truly successful anti-H. pylori therapies. Metronidazole resistance has become an increasing problem that has severely limited the usefulness of the original triple therapy. Resistance to tetracycline or amoxicillin has not been reported and both are effective against H. pylori. We therefore tested a new triple therapy consisting of 500 mg tetracycline, 500 mg amoxicillin, and 2 tablets of bismuth subsalicylate each administered four times daily (with meals and at bedtime) for 14 days during treatment with ranitidine 300 mg daily. H. pylori eradication was defined as no evidence of H. pylori one or more months after stopping therapy. H. pylori status was evaluated by a combination of urea breath test and histology. Sixteen patients with H. pylori infection and active peptic ulcers were enrolled. The new triple therapy was successful in only 7 individuals (43%). Metronidazole appears to be critical for the effectiveness of the original triple therapy. An alternative to metronidazole will be required for a new successful triple therapy.

Adult↗
PubMed1993

Cloning, nucleotide sequence, and expression of a gene encoding an adhesin subunit protein of Helicobacter pylori.

Gene hpaA, which codes for the receptor-binding subunit of the N-acetylneuraminyllactose-binding fibrillar hemagglutinin (NLBH) of Helicobacter pylori, was cloned and sequenced. The protein expressed by hpaA, designated HpaA, was identified as the adhesin subunit on the basis of its fetuin-binding activity and its reactivity with a polyclonal, monospecific rabbit serum prepared against NLBH purified from H. pylori. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and Western blots (immunoblots) showed that the cloned adhesin has the same molecular weight (20,000) as that found on H. pylori. Also, HpaA contains a short sequence of amino acids (KRTIQK) which are all either identical or functionally similar to those which compose the sialic acid-binding motif of Escherichia coli SfaS, K99, and CFA/I. Affinity-purified antibody specific for a 12-residue synthetic peptide that included this sequence blocked the hemagglutinating activity of H. pylori and was shown by immuno-gold electron microscopy to react with almost transparent material on unstained H. pylori cells, which is consistent with previous observations concerning the location and morphology of the NLBH.

Adhesins, Bacterial↗
PubMed1993

Detection of Helicobacter pylori in dental plaque by reverse transcription-polymerase chain reaction.

To investigate whether the oral cavity is a potential reservoir and possible sanctuary for Helicobacter pylori, supragingival and subgingival plaques were analyzed by a Helicobacter genus-specific reverse transcriptase-polymerase chain reaction based on the sequence data of H. pylori 16S rRNA. The amplified 500-bp DNA fragment was identified by ethidium bromide staining after agarose gel electrophoresis and by Southern hybridization. Twenty-five dyspeptic patients were studied. Histologic examination of gastric biopsy specimens revealed that 18 had H. pylori gastritis and 7 did not. For seven of the 18 (38.8%) patients with proven H. pylori gastritis, H. pylori was also identified in their dental plaque. None of the patients without H. pylori gastritis had H. pylori in their dental plaque. The detection of H. pylori in dental plaque suggests that this H. pylori colonization is not restricted to the gastric mucosa and that this ecological niche may serve as a possible sanctuary which may be responsible for reinoculation of the stomach after topical anti-H. pylori therapies such as bismuth.

Adult↗
PubMed1993

Helicobacter pylori infection and exaggerated gastrin release. Effects of inflammation and progastrin processing.

Helicobacter pylori infection is associated with exaggerated gastrin release. We investigated whether this abnormality was due to the bacteria or the immune response. Fasting and meal-stimulated 'total' and amidated gastrin were measured in 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after completion of therapy. The exaggerated meal-stimulated gastrin concentration remained unchanged after 2 days of therapy, although the polymorphonuclear cell infiltrate and H. pylori bacteria were no longer evident. The expected fall in gastrin concentration after 14 days of therapy was associated with a reduction in the density of mucosal mononuclear cells, suggesting exaggerated gastrin release was related to chronic inflammation or to H. pylori or its products. The effect of H. pylori on normal progastrin processing was also assessed; 2 control groups were included: 10 H. pylori-uninfected volunteers and 13 patients with H. pylori peptic ulcers. There was a significant difference in the proportion of circulating gastrins that were biologically active amidated gastrins between ulcer patients and uninfected controls (56.7 +/- 4% versus 33.8 +/- 4%, p < 0.001). The proportion of amidated to total gastrins did not increase after successful eradication.

Adult↗
PubMed1993

Treatment of Helicobacter pylori reduces the rate of rebleeding in peptic ulcer disease.

BACKGROUND: We evaluated whether therapy designed to eradicate Helicobacter pylori infection resulted in a reduction in rebleeding in patients with peptic ulcer disease. Patients presenting because of major upper gastrointestinal hemorrhage from peptic ulcer and whose ulcers healed in a study in which they were randomized to receive ranitidine alone or triple therapy plus ranitidine were followed up regularly with endoscopy. No maintenance anti-ulcer therapy was given after ulcer healing. METHODS: Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet), and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. Development of ulcer recurrence with or without recurrent upper gastrointestinal bleeding was evaluated. RESULTS: Thirty-one patients with major upper gastrointestinal bleeding from peptic ulcer were studied; 17 received triple therapy and 14 ranitidine alone. Major rebleeding occurred significantly (p = 0.031) more often in those in the ranitidine group (28.6%), compared with none (0%) in the triple therapy group. CONCLUSION: Eradication of H. pylori infection reduces the rate of ulcer recurrence and rebleeding in complicated ulcer disease.

Adult↗
PubMed1993

Intestinal metaplasia, not atrophy or achlorhydria, creates a hostile environment for Helicobacter pylori.

A 54-year-old man with dyspepsia, Helicobacter pylori-associated chronic active atrophic gastritis without intestinal metaplasia, and hyperplastic gastric polyps was followed up for 1 year after H. pylori eradication with sequential endoscopic gastric mucosal mapping and gastric function tests. Eradication of H. pylori by triple therapy resulted in the histologic resolution of gastritis. However, the patient's condition, gastric function, and morphology of the polyps were not affected. This case illustrates that: a) in the absence of intestinal metaplasia, H. pylori can infect the stomach with gastric atrophy; b) the absence of acid does not preclude H. pylori infection; c) advanced atrophic gastritis may be an irreversible condition; and (d) the neutrophilic infiltrate in hyperplastic polyps is independent of the presence of H. pylori.

Achlorhydria↗
PubMed1993

A scoring system to predict rebleeding after endoscopic therapy of nonvariceal upper gastrointestinal hemorrhage, with a comparison of heat probe and ethanol injection.

We prospectively and randomly compared heat probe and ethanol injection in 80 patients with major nonvariceal upper gastrointestinal hemorrhage who were bleeding actively or had endoscopic stigmata associated with a high risk for rebleeding. We also attempted to predict which patients would rebleed within 72 h after successful endoscopic therapy, using a three-component scoring system. Heat probe and ethanol injection proved to be similar in efficacy and safety. Active bleeding was controlled with equal success with heat probe and ethanol injection (92% vs. 82%), and there was no difference in the rebleeding rate (11% vs. 13%). The scoring system was useful in predicting which patients would rebleed. Significant differences were seen in the mean values of all three scores, and specific cut-offs in the pre-endoscopy and post-endoscopy scores predicted patients who rebled. High likelihood ratios and post-test probabilities for rebleeding were found for the number and severity of concurrent illnesses, but not for endoscopic stigmata, implying that the excess risk associated with stigmata is eliminated after effective endoscopic therapy, and clinical factors become the primary determinants of rebleeding.

Electrocoagulation↗
PubMed1993

Clarithromycin as monotherapy for eradication of Helicobacter pylori: a randomized, double-blind trial.

UNLABELLED: Current regimens to eradicate Helicobacter pylori usually consist of metronidazole plus a bismuth compound, as well as a third agent such as tetracycline. Such regimens are not ideal because organisms may be metronidazole-resistant, side-effects occur, and compliance is often poor. This randomized, double-blind study was designed to assess the ability of clarithromycin, a new macrolide antimicrobial, as monotherapy to eradicate H. pylori. Thirty-seven healthy volunteers who were H. pylori positive by 13C-urea breath test plus histology and/or culture completed 14 days of oral therapy with clarithromycin in one of three dosages. Eradication, defined as all three tests negative at 4-6 wk after the end of therapy, was achieved in 2/13 (15%) with clarithromycin 500 mg bid, 4/11 (36%) with 1000 mg bid, and 7/13 (54%) with 500 mg qid. Isolates of H. pylori were resistant to clarithromycin prior to therapy in 12% of subjects, and became resistant during therapy in 21% of subjects. Taste perversion, the most common side effect, resulted in one subject terminating therapy. CONCLUSIONS: Whereas clarithromycin is a promising antimicrobial in the eradication of H. pylori, it is not sufficient to be used as monotherapy.

Adult↗
PubMed1993

Minimum analysis requirements for the detection of Helicobacter pylori infection by the 13C-urea breath test.

BACKGROUND: In an attempt to identify the minimum criteria for scoring the 13C-urea breath test, we examined test results from 96 healthy subjects, 270 duodenal ulcer patients undergoing treatment to eradicate Helicobacter pylori, and 1000 consecutive breath tests analyzed in our laboratory. METHODS: The 13CO2/12CO2 isotope ratio in a baseline sample was compared with that of samples collected at 20, 30, 40, and 50 min post-dosing. A positive test was defined as an average increase in the ratio of 6/1000 over baseline. Values for a two-sample analysis (baseline and one other) and for a single-sample analysis were extracted from the data and compared with the original analysis outcome. RESULTS: Test results were negative for 186 patients and positive for 84. The two-sample method had high specificity (94-99/1000), sensitivity (95-99/1000), and positive predictive value (88-97/1000). False-positive results occurred most often with samples collected at 20 min and least often with the sample at 40 min (11 and 1, respectively). Analyses based on a single sample collected beyond 20 min, in which samples with an isotope ratio > or = -15/1000 versus the standard were defined as positive, gave comparable specificity (98-99/1000), slightly reduced sensitivity (92-94%), and positive predictive value (96-99%). The analyses of 1000 consecutive breath tests yielded approximately 1% false-positive and false-negative results by the two-sample method; the single-sample method yielded a 2% false-positive and false-negative result. CONCLUSION: The 13C-urea breath test can determine H. pylori infective status from a single breath sample collected at least 30 min post-dose in which the absolute 13C abundance is > or = -15/1000 versus the standard.

Breath Tests↗
PubMed1993

Acid secretion and serum gastrin in normal subjects and patients with duodenal ulcer: the role of Helicobacter pylori.

OBJECTIVES: To compare gastric secretory function in patients with duodenal ulcer and in healthy volunteers with and without Helicobacter pylori infection. METHODS: Basal acid output, peak acid output, meal-stimulated acid output, fasting and meal-stimulated serum gastrin concentrations were measured in 136 healthy volunteers (63 H. pylori positive, 73 H. pylori negative) and 52 duodenal ulcer patients, all but one of whom were H. pylori positive. RESULTS: By multivariate linear regression analysis, H. pylori infection was a significant negative predictor of basal acid output and a positive predictor of fasting and meal-stimulated gastrin concentrations. When compared to truly normal (i.e., H. pylori-negative) control subjects, duodenal ulcer patients had elevated basal acid output, peak acid output, fasting and meal-stimulated gastrin concentrations. CONCLUSIONS: Our results show that in patients with duodenal ulcer disease, hypergastrinemia is largely related to gastric H. pylori infection, whereas acid hypersecretion is due to factors other than H. pylori.

Adult↗
PubMed1993

Changes in the gastric mucosa following eradication of Helicobacter pylori.

Although most studies reporting on the examination of Helicobacter pylori infection have focused on the clearance of the bacteria and the rapid disappearance of the neutrophil infiltrates, the evolution of inflammatory and architectural changes in the antral and corporal mucosa following the eradication of H. pylori has not been addressed systematically. This study examines in detail the histopathologic appearance of the antral and corporal mucosa in a group of patients infected with H. pylori and follows the spectrum of morphologic changes in each of them after the eradication of the infection. At least 11 biopsies ("gastric mapping") were obtained from the antrum and body of each of 15 patients with H. pylori. Complete mapping was then repeated 1, 4, and 10 to 12 mo after the eradication of H. pylori by a course of "triple therapy." Each biopsy was assessed in a semi-quantitative fashion for presence of H. pylori, neutrophils, eosinophils, lymphocytes, lymphoid follicles, and intestinal metaplasia. Other features (integrity of surface epithelium, architecture, fibrosis) were evaluated descriptively. Results were compared with those obtained from a control group of 16 uninfected, healthy adult volunteers. H. pylori infection was eradicated in 11 subjects. The disappearance of neutrophils and the normalization of the surface epithelium closely paralleled that of H. pylori. Persistence of even small numbers of neutrophils was a predictor of relapse. Eosinophils and lymphocytes decreased slowly and did not return to normal levels within 1 yr. Lymphoid follicles decreased very slowly in all patients but were still present in all gastric locations at one year after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Gastric mucosal hydrophobicity and Helicobacter pylori: response to antimicrobial therapy.

The hydrophobic properties of the gastric mucosa are reduced by NSAIDs and by Helicobacter pylori infection. Our investigation was to determine whether this abnormality was due to the bacteria or to the inflammatory response. Contact angle measurements were made on gastric antral and corpus biopsies taken from 10 H. pylori-infected volunteers before eradication therapy, after 2 and 14 days of therapy, and 4 weeks after therapy. The contact angle improved steadily and statistically throughout the 2 weeks of therapy (for day 0, 3, 14, respectively) antral mucosa 54.2 +/- 2, 59.3 +/- 2, and 63.2 +/- 2; corpus mucosa 55 +/- 1, 57.8 +/- 3, and 66.6 +/- 1. After 2 days of therapy, H. pylori bacteria were no longer evident, and yet the contact angle continued to improve, suggesting that bacteria and bacterial products (e.g., lipases) may not be critical factors. H. pylori was eradicated in five and failed in five. One month after ending therapy, the contact angles of those with recrudescence of infection and those with eradication were similar and higher (p < 0.05) than before therapy (antrum: 69.8 +/- 1 vs. 71.1 +/- 2, corpus: 66.4 +/- 4 vs. 70.8 +/- 2) (p > 0.25 for both). We conclude that gastric surface hydrophobicity abnormalities do not appear to be directly related to the presence of H. pylori organisms or the histologic features of acute inflammation, but are responsive to antimicrobial therapy.

Adult↗
PubMed1993

A study of the frequency of recovery of unexpected Giardia lamblia and Cryptosporidium from duodenal aspirates taken during routine upper endoscopy.

UNLABELLED: In this study, our objective was to determine whether the microscopic examination of duodenal aspirates recovered during routine upper endoscopy in unselected, immunocompetent patients, would disclose unsuspected Giardia lamblia or Cryptosporidium. DESIGN: Prospective, cross-sectional study to determine the prevalence of duodenal parasitosis. SETTING: Endoscopy unit in a university hospital. PATIENTS: One hundred and thirty-one unselected, immunocompetent patients undergoing upper endoscopy. MEASUREMENTS: Microscopic examination of duodenal aspirates, obtained during upper endoscopy. No pathogenic or commensal parasite was identified in any patient. CONCLUSIONS: No case of unsuspected parasitosis was found in the present study. On the basis of our findings, we do not recommend routine collection of duodenal aspirates during upper endoscopy.

Adult↗
PubMed1992

Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study.

OBJECTIVE: To determine the effect of treating Helicobacter pylori infection on the recurrence of gastric and duodenal ulcer disease. DESIGN: Follow-up of up to 2 years in patients with healed ulcers who had participated in randomized, controlled trials. SETTING: A Veterans Affairs hospital. PARTICIPANTS: A total of 109 patients infected with H. pylori who had a recently healed duodenal (83 patients) or gastric ulcer (26 patients) as confirmed by endoscopy. INTERVENTION: Patients received ranitidine, 300 mg, or ranitidine plus triple therapy. Triple therapy consisted of tetracycline, 2 g; metronidazole, 750 mg; and bismuth subsalicylate, 5 or 8 tablets (151 mg bismuth per tablet) and was administered for the first 2 weeks of treatment; ranitidine therapy was continued until the ulcer had healed or 16 weeks had elapsed. After ulcer healing, no maintenance antiulcer therapy was given. MEASUREMENTS: Endoscopy to assess ulcer recurrence was done at 3-month intervals or when a patient developed symptoms, for a maximum of 2 years. RESULTS: The probability of recurrence for patients who received triple therapy plus ranitidine was significantly lower than that for patients who received ranitidine alone: for patients with duodenal ulcer, 12% (95% CI, 1% to 24%) compared with 95% (CI, 84% to 100%); for patients with gastric ulcer, 13% (CI, 4% to 31%) compared with 74% (44% to 100%). Fifty percent of patients who received ranitidine alone for healing of duodenal or gastric ulcer had a relapse within 12 weeks of healing. Ulcer recurrence in the triple therapy group was related to the failure to eradicate H. pylori and to the use of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Eradication of H. pylori infection markedly changes the natural history of peptic ulcer in patients with duodenal or gastric ulcer. Most peptic ulcers associated with H. pylori infection are curable.

Adult↗
PubMed1992

Treatment of nonsteroidal antiinflammatory drug-induced gastric ulcers with misoprostol. A double-blind multicenter study.

One hundred sixty-two patients chronically ingesting ibuprofen, piroxicam, or naproxen for osteoarthritis, who had abdominal pain and an endoscopically proven gastric ulcer were evaluated for eight weeks in a randomized, double-blind trial comparing misoprostol (200 micrograms four times daily with meals and at bedtime) (N = 77) with placebo (N = 85). Patients discontinued their usual daily dose of antiarthritic medication throughout the study period, and an endoscopy was performed at four weeks and eight weeks (if necessary) to assess ulcer healing. Gastric ulcers were defined as circumscribed breaks in the gastric mucosa of 0.3 cm in diameter or greater. Misoprostol therapy significantly accelerated the rate of gastric ulcer healing compared to placebo (P = 0.033). The cumulative percent healed after four and eight weeks of therapy for misoprostol versus placebo were: 83% vs 61% at four weeks and 96% vs 90% at eight weeks (P = 0.0028 and P = 0.0977, respectively by lifetable analysis). Relief of abdominal pain did not differ significantly between the treatment groups. Misoprostol significantly accelerates the healing of ibuprofen-, piroxicam-, or naproxen-induced gastric ulcers.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

Helicobacter pylori in Hispanics: comparison with blacks and whites of similar age and socioeconomic class.

Helicobacter pylori infection is twice as frequent in blacks as in whites. It has been postulated that the apparent increase in susceptibility to H. pylori infection in blacks might have a genetic basis. A case-control seroepidemiologic study of H. pylori prevalence was performed in 108 healthy Hispanic volunteers. Eighty-nine Hispanics were matched (1:1:1) with blacks and whites for age and socioeconomic status. There was an inverse correlation between H. pylori infection and educational level that remained after logistic regression analysis adjusting for age and sex. The adjusted prevalence of H. pylori infection was almost identical in Hispanics and blacks and significantly higher than in whites. Because Hispanics do not constitute a race, the increased prevalence of H. pylori in Hispanics and blacks is unlikely to be genetic. It is speculated that the unrecognized bias is a reflection of a generation cohort phenomenon related to the generational distance from very low socioeconomic status, i.e., the prevalence of H. pylori in Hispanics and blacks is currently lower than that of their parents but higher than that of the white population, which has experienced higher socioeconomic status for several generations.

Adult↗