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Biomedical subjects

D Y Graham

Publications and source records attributed to D Y Graham.

At least 127 records · Page 7Linked to original sources
PubMed2000

Helicobacter pylori infection is the primary cause of gastric cancer.

Helicobacter pylori causes gastric cancer in human and in experimental animals. The link between gastritis and H. pylori is causal. Differences in the incidence of gastric cancer in populations with similar high prevalence of H. pylori infection can be related to the differences in the age of acquisition of chronic atrophic gastritis, which in turn is related to an interaction between environmental factors, especially diet, and H. pylori infection. The low odds ratios reported in epidemiology studies evaluating the relation between gastric cancer and H. pylori infection reflect the high overall prevalence of H. pylori in the population and do not accurately reflect the strength of the association. It is time to stop doing serologic studies to confirm the association of gastric cancer with H. pylori and instead expend our efforts on eliminating the infection and investigating the mechanism(s) and interactions.

Cause of Death↗
PubMed1999

Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial.

CONTEXT: In vitro studies have shown that celecoxib inhibits cyclooxygenase 2 (COX-2) but not COX-1, suggesting that this drug may have anti-inflammatory and analgesic activity without adverse upper gastrointestinal (GI) tract effects that result from COX-1 inhibition. OBJECTIVE: To test whether celecoxib has efficacy as an anti-inflammatory and analgesic with reduced GI tract mucosal damage compared with conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial lasting 12 weeks, with follow-up at weeks 2, 6, and 12, from September 1996 thorugh February 1998. SETTING: Seventy-nine clinical sites in the United States and Canada. PATIENTS: A total of 1149 patients aged 18 years or older with symptomatic rheumatoid arthritis who met inclusion criteria were randomized; 688 (60%) of these completed the study. INTERVENTIONS: Patients were randomized to receive celecoxib, 100 mg, 200 mg, or 400 mg twice per day (n = 240, 235, and 218, respectively); naproxen, 500 mg twice per day (n = 225); or placebo (n = 231). MAIN OUTCOME MEASURES: Improvement in signs and symptoms of rheumatoid arthritis as assessed using standard measures of efficacy and GI tract safety as assessed by upper GI tract endoscopy before and after treatment, compared among treatment groups. RESULTS: All dosages of celecoxib and naproxen significantly improved the signs and symptoms of arthritis compared with placebo. Maximal anti-inflammatory and analgesic activity was evident within 2 weeks of initiating treatment and was sustained throughout the 12 weeks. The incidence of endoscopically determined gastroduodenal ulcers in placebo-treated patients was 4 (4%) of 99, and the incidences across all dosages of celecoxib were not significantly different (P>.40): 9 (6%) of 148 with 100 mg twice per day, 6 (4%) of 145 with 200 mg twice per day, and 8 (6%) of 130 with 400 mg twice per day. In contrast, the incidence with naproxen was 36 (26%) of 137, significantly greater than either placebo or celecoxib (P<.001). The overall incidences of GI tract adverse effects were 19% for placebo; 28%, 25%, and 26% for celecoxib 100 mg, 200 mg, and 400 mg twice per day, respectively; and 31 % for naproxen. CONCLUSION: In this study, all dosages of celecoxib were efficacious in the treatment of rheumatoid arthritis and did not affect COX-1 activity in the GI tract mucosa as evidenced by less frequent incidence of endoscopic ulcers compared with naproxen.

Adult↗
PubMed1999

Antibiotic treatment of gastric lymphoma of mucosa-associated lymphoid tissue. An uncontrolled trial.

BACKGROUND: Gastric lymphoma of mucosa-associated lymphoid tissue (MALT) is related to Helicobacter pylori infection and may depend on this infection for growth. OBJECTIVE: To determine the response of gastric MALT lymphoma to antibiotic treatment. DESIGN: Prospective, uncontrolled treatment trial. SETTING: University hospital referral center and three collaborating university and community hospitals. PATIENTS: 34 patients with stage I or stage II N1 gastric MALT lymphoma. INTERVENTION: Two of three oral antibiotic regimens--1) amoxicillin, 750 mg three times daily, and clarithromycin, 500 mg three times daily; 2)tetracycline, 500 mg four times daily, and clarithromycin, 500 mg three times daily; or 3) tetracycline, 500 mg four times daily, and metronidazole, 500 mg three times daily--were administered sequentially (usually in the order written) for 21 days at baseline and at 8 weeks, along with a proton-pump inhibitor (lansoprazole or omeprazole) and bismuth subsalicylate. MEASUREMENTS: Complete remission was defined as the absence of histopathologic evidence of lymphoma on endoscopic biopsy. Partial remission was defined as a reduction in endoscopic tumor stage or 50% reduction in the size of large tumors. RESULTS: 34 patients were followed for a mean (+/-SD) of 41 +/- 16 months (range, 18 to 70 months) after antibiotic treatment. Of 28 H. pylori-positive patients, 14 (50% [95% CI, 31% to 69%]) achieved complete remission, 8 (29%) achieved partial remission (treatment eventually failed in 4 of the 8), and 10 (36% [CI, 19% to 56%]) did not respond to treatment. Treatment failed in all 6 (100% [CI, 54% to 100%]) H. pylori-negative patients. Patients with endoscopic appearance of gastritis (stage I T1 disease) were most likely to achieve complete remission within 18 months. Tumors in the distal stomach were associated with more favorable response than tumors in the proximal stomach. CONCLUSIONS: A subset of H. pylori-positive gastric MALT lymphomas, including infiltrative tumors, may respond to antibiotics. The likelihood of early complete remission seems to be greatest for superficial and distal tumors.

Anti-Bacterial Agents↗
PubMed1999

Helicobacter pylori in sheep milk.

Helicobacter pylori was recovered from sheep milk, suggesting a role for animals in transmission. H. pylori may be a commensal in the sheep, which may be H. pylori's ancestral host.

Animals↗
PubMed1999

Characterization of Mycobacterium paratuberculosis p36 antigen and its seroreactivities in Crohn's disease.

Recent data using improved cultural, molecular, and serological techniques have strengthened the association of Mycobacterium paratuberculosis with Crohn's disease, an inflammatory bowel disease (IBD) with unknown etiology. To provide more evidence of an etiological association, antibody reactivities of Crohn's disease patients were tested by immunoblotting against M. paratuberculosis-recombinant antigens. A clone containing a 1,402-bp insert and expressing a 36K-antigen (p36) was analyzed. No homology was found between the deduced amino acid sequence of p36 and any protein sequences compiled in the GenBank indicating that p36 is a novel mycobacterial protein. The reactivity of 199 serum samples was tested against the p36 by immunoblotting technique. Sera from 77 of 89 (86.5%) Crohn's disease patients and 16 of 18 (89%) sera from patients with tuberculosis and leprosy reacted with p36 compared to 5 of 42 (12%) ulcerative colitis and non-IBD control sera (p < 0.0001). In addition, p36 reacted to all sera from 10 normal controls that were Bacillus Calmette-Guerin (BCG)-immunized and only to 10% of 40 normal controls that were not BCG-immunized. The fact that sera from Crohn's disease patients reacted to p36 with the same high frequency as the sera from patients that were exposed to mycobacterial antigens further supports the hypothesis of the mycobacterial etiology in Crohn's disease.

Antibodies, Bacterial↗
PubMed1999

Recombinant Norwalk virus-like particles given orally to volunteers: phase I study.

BACKGROUND & AIMS: Norwalk virus (NV) is a major cause of epidemic gastroenteritis. The NV capsid is composed of a single protein that forms recombinant (rNV) virus-like particles (VLPs). In mice, these VLPs are immunogenic when administered orally without adjuvant, and they elicit serum immunoglobulin (Ig) G and intestinal IgA responses. The aim of this study was to evaluate the safety and immunogenicity of rNV VLPs in healthy volunteers. METHODS: Twenty antibody-positive adults were orally administered rNV VLPs in sterile Milli-Q water on days 1 and 21. Vaccine safety and serum rNV-specific total and subclass IgG and IgA antibody responses were monitored. The immune response induced by the VLPs was compared with the response elicited by replicating virus. RESULTS: No side effects were observed or reported by the volunteers. Serum IgG responses to rNV VLPs were dose-dependent, and all vaccinees given 250 microgram of rNV VLPs responded with >/=4-fold increases in serum IgG titers. Most of the volunteers (83%; 15 of 18) responded after the first rNV VLP dose and showed no increase in serum IgG titer after the second dose. CONCLUSIONS: Orally administered rNV VLPs are safe and immunogenic in healthy adults when administered without adjuvant and are useful to test the mucosal delivery of immunogens.

Administration, Oral↗
PubMed1999

Evaluation of gastric mucosal biopsy site and number for identification of Helicobacter pylori or intestinal metaplasia: role of the Sydney System.

Pathologists are frequently asked to evaluate gastric mucosal biopsy specimens for the presence of Helicobacter pylori infection and for potentially important changes such as intestinal metaplasia. No agreed-on system is both available and prospectively shown to provide reliable estimates of the underlying pathological condition. The Sydney System combined topographical, morphological, and causative information for evaluation of gastric biopsy specimens and provided recommendations regarding biopsy site and number. Both the biopsy sites and number were changed in 1994. Gastric biopsy specimens from patients who had multiple biopsies performed on predetermined sites were examined to compare the original and the revised Sydney Systems for the detection of intestinal metaplasia and H pylori. The diagnosis based on both versions of the Sydney System was then compared with that obtained by evaluating all specimens. Forty-six patients were studied, 20 with H pylori infection and 36 with intestinal metaplasia. Using either version of the Sydney System correctly categorized H pylori infection status in 100%. Both the original and the revised Sydney recommendations seriously underestimated the prevalence of intestinal metaplasia. Intestinal metaplasia was missed in more than 50% of those with confirmed intestinal metaplasia. No set or site of biopsy specimens was found that could reliably exclude the presence of intestinal metaplasia. Current and future studies that use the Sydney System as basis for detecting intestinal metaplasia are not likely to be reliable. Likewise, using the Sydney System to test posttherapy or with time will not accurately reflect the true status of intestinal metaplasia.

Adult↗
PubMed1999

Metronidazole and clarithromycin resistance amongst Helicobacter pylori isolates from a large metropolitan hospital in the United States.

BACKGROUND: Metronidazole and clarithromycin-based therapies are among the most efficacious treatment regimens for H. pylori infection. Resistance to metronidazole or clarithromycin is associated with impaired therapy with these agents. We conducted a retrospective review of susceptibility data to determine the frequency of primary metronidazole and clarithromycin resistance among H. pylori isolates from a single metropolitan hospital in the United States. The database comprised 933 patients who presented at the Digestive Diseases Clinic at the Veterans Affairs Medical Center in Houston between September 1988 and January 1997 with complaints of dyspepsia, abdominal pain and peptic ulcer disease. One hundred and seventy-nine of these patients had both pharmaceutical records available for evaluation and culture and antimicrobial susceptibility data for analysis. The MICs were determined by both E-test and broth microdilution tests. The frequency of primary metronidazole resistance was 37.4% (67/179). The level of primary clarithromycin resistance was 6.1%. Dual metronidazole and clarithromycin resistance was present in approx. 3%. The high level of primary metronidazole and clarithromycin resistance in H. pylori isolates from this metropolitan hospital is such that antimicrobial susceptibility data should be available so that informed choice can be made for specific eradication therapies, especially in patients who fail treatment.

Anti-Bacterial Agents↗
PubMed1999

Diagnosis and management of Helicobacter pylori infection.

Helicobacter pylori infects more than half of the world's population, making it one of the most prevalent infections. H pylori is now accepted as the most common cause of histologic gastritis and is responsible for the majority of cases of peptic ulcer disease and gastric cancer. Approximately 1 in 6 (17%) persons with H pylori infection will develop peptic ulcer disease, and each year 1% to 2% of these will experience a major or life-threatening complication, such as bleeding, perforation, or gastric outlet obstruction. Peptic ulcer disease should no longer be regarded as a chronic, recurring, lifelong disease, but rather as a curable infectious disease. The diagnosis and therapy of this common infectious disorder have become increasingly straightforward. In this article, we discuss the possible outcomes of long-standing infection, the various diagnostic tests available, including whom and when to test, and the combination drug regimens approved for cure.

Anti-Bacterial Agents↗
PubMed1999

High prevalence of Helicobacter pylori infection in shepherds.

It has been suggested that Helicobacter pylori infection may, in some instances, be a zoonosis. The aim of this study was to evaluate the prevalence of H. pylori infection in Sardinian shepherds and their families in relation to exposure to sheep and sheep dogs. Sardinian shepherds and a control group of blood donors completed detailed questionnaires regarding demographics, childhood and current economic status, and the presence of symptoms related to the upper gastrointestinal tract. H. pylori status was determined by a sensitive ELISA for anti-H. pylori IgG and by western blot for anti-CagA IgG. A subgroup of shepherds had upper gastrointestinal endoscopy with biopsy to assess the severity of the gastritis. H. pylori infection in Sardinian shepherds approached 100% and was positively related to animal contact (98% of shepherds, 73% of family members without regular direct animal contact compared to 43% of blood donors) (P < 0.001). Importantly, the family members shared the same childhood with the shepherds but choose different careers (e.g., teachers, nurses, business) and did not have regular contact with sheep. In conclusion, the prevalence of H. pylori infection in Sardinian shepherds is among the highest in the world and is associated with direct contact with sheep and sheep dogs. These results suggest that the cycle of H. pylori infection might, in certain circumstances, include phases in the environment, animals (sheep or dogs) and human beings.

Adolescent↗
PubMed1999

Osmotic effect of honey on growth and viability of Helicobacter pylori.

Honey from New Zealand and Saudi Arabia at concentrations approximating 20% (v/v) inhibit the growth of H. pylori in vitro. The anti-H. pylori effect involves both hydrogen peroxide- and non-peroxide-mediated killing mechanisms. This study was designed to determine whether the anti-H. pylori activity of honey differed regionally (honey from Texas, Iowa, and New Zealand) and to determine whether this activity was due to the presence of hydrogen peroxide. Broth dilution susceptibility tests were performed using solutions of honey prepared in BHI broth ranging in concentration from 5 to 35% (v/v) in 5% increments. Control solutions containing glucose, fructose, and combined glucose/fructose solutions in ratios of 1:1.23 were also prepared. Paired catalase controls were included in all tests. Twenty-eight clinical isolates of H. pylori were tested. Growth was determined on the basis of a plus/minus grading score. All of the solutions containing either fructose, glucose, glucose and fructose combinations, or honey were equally effective in inhibiting the growth of H. pylori. All of the isolates were inhibited by solutions containing 15% (w/v) carbohydrate. Honey solutions, with or without catalase, inhibited 24/28 isolates at a concentration of 10%, and 28/28 isolates at a concentration of 15%. In conclusion, regional differences in honey activity against H. pylori were not detected, nor was the effect of killing related to the presence of hydrogen peroxide in the honey samples. Osmotic effects were shown to be the most important parameter for killing H. pylori as all carbohydrate solutions > or = 15% (v/v) inhibited 100% of the H. pylori.

Anti-Infective Agents, Local↗
PubMed1999

Novel therapies for Helicobacter pylori infection.

BACKGROUND: Increasing antibiotic resistance has begun to impair our ability to cure Helicobacter pylori infection. AIM: To evaluate orally administered novel therapies for the treatment of H. pylori infection. METHODS: Healthy H. pylori infected volunteers received: (a) hyperimmune bovine colostral immune globulins, (b) an oligosaccharide containing an H. pylori adhesion target, Neu5Aca2-3Galb1-4Glc-(3'-sialyllactose), or (c) recombinant human lactoferrin. Outcome was assessed by urea breath test or histological assessment of the number of H. pylori present. RESULTS: None of the novel therapies appeared effective and no adverse events occurred. CONCLUSION: Although in vitro data appeared promising, in vivo results were disappointing. Higher doses, longer duration of therapy, adjunctive acid suppression, or a combination could possibly yield better results.

Adjuvants, Immunologic↗
PubMed1999

Ranitidine bismuth citrate, tetracycline, clarithromycin twice-a-day triple therapy for clarithromycin susceptible Helicobacter pylori infection.

BACKGROUND: Although many combination therapies have been proposed, there is still interest in identifying simple, inexpensive, effective protocols that have high rates of success. AIM: To investigate the role of the new soluble form of bismuth, ranitidine bismuth citrate, in twice-a-day therapy for Helicobacter pylori infection. METHODS: Patients with histologically and culture proven H. pylori infection received ranitidine bismuth citrate 400 mg, tetracycline HCl 500 mg, and clarithromycin 500 mg, each b.d. for 14 days, followed by 300 mg ranitidine once a day for 4 additional weeks. Outcome was assessed 4 or more weeks after the end of antimicrobial therapy by repeat endoscopy with histology and culture (49 patients) or urea breath testing (14 patients). RESULTS: Sixty-three patients completed the therapy, 59 men and four women (average age 56.7 years; range 31-75 years). All patients had clarithromycin-susceptible strains prior to therapy. H. pylori infection was cured in 94% (95% CI: 85-98%). There was a therapy failure in one patient who took the medicine for only 1 day and stopped because of side-effects. Three of the isolates from treatment failures were available post-failure; two were clarithromycin-resistant and one was susceptible. Side-effects were severe in two patients (3%) and moderate in three (primarily diarrhoea). CONCLUSIONS: Twice-a-day ranitidine bismuth citrate, tetracycline, clarithromycin triple therapy was well tolerated and effective for the treatment of H. pylori infection in patients with clarithromycin-susceptible H. pylori.

Adult↗
PubMed1999

Alendronate gastric ulcers.

BACKGROUND: It appears likely that drugs other than NSAIDs may cause ulcers and ulcer complications (e.g. potassium chloride). Alendronate (Fosamax) is used in the treatment and prevention of metabolic bone disease and has also been associated with severe oesophageal damage and stricture. We have previously shown that the dose of alendronate used for Paget's disease (40 mg) causes gastric damage similar to NSAIDs. The usual dose for the treatment of postmenopausal osteoporosis is 10 mg per day. AIM: To investigate whether the 10 mg dose of alendronate causes gastric ulcers. METHODS: We performed an endoscopist-blind, crossover, randomized, single-centre comparison of 10 mg of alendronate/day and placebo in volunteers aged 40 years or more. Video-endoscopy was used to evaluate the presence and degree of mucosal damage to the oesophagus, stomach, or duodenal bulb after 7 and 14 days of treatment. RESULTS: Twenty-four healthy volunteers participated, including 15 women and nine men, ranging in age from 41 to 52 years. Visible gastric mucosal damage was present in nine (38%) who received alendronate compared to three (13%) in the placebo group. There was a marked difference in the severity of mucosal damage; there were no ulcers or large erosions in those receiving placebo. In contrast, potentially clinically significant gastric mucosal injury was seen in six subjects receiving alendronate (two developed antral ulcers and four had large (4-8 mm) superficial antral erosions) compared to none in the placebo group (P = 0.0219). One subject developed oesophageal damage in the form of multiple linear superficial erosions in the mid and distal oesophagus. Duodenal injury was not seen. CONCLUSION: Alendronate causes gastric ulceration, suggesting that alendronate use may be associated with ulcer complications such as acute upper gastrointestinal bleeding. The results of this study suggest the need for post-marketing surveillance to clarify the nature, frequency and magnitude of any potential gastrointestinal side-effects associated with the use of this drug.

Adult↗
PubMed1999

Pretreatment antibiotic resistance in Helicobacter pylori infection: results of three randomized controlled studies.

BACKGROUND: Although combinations of antibiotics and antisecretory drugs are useful for treatment of Helicobacter pylori infection, treatment failure is common. The aim of this study was to evaluate the relation between pretreatment antibiotic resistance and outcome by using six different treatment regimens for H. pylori infection. PATIENTS AND METHODS: Three hundred sixty-nine consecutive H. pylori-infected patients with dyspeptic symptoms were enrolled in three consecutive randomized, controlled, single-center clinical trials: trial A, 128 patients; trial B, 125 patients; trial C, 116 patients. Treatments consisted of (A) a 15-day course of dual therapy (omeprazole, 20 mg bid, and amoxicillin, 1 gm bid, or clarithromycin, 500 mg tid) (OA vs OC); (B) a 7-day triple therapy of omeprazole, 20 mg bid, plus metronidazole, 500 mg bid, and amoxicillin, 1,000 mg bid, or clarithromycin, 500 mg tid (OMA vs OMC); or (C) omeprazole, 20 mg bid, plus metronidazole, 500 mg bid, plus tetracycline, 500 mg qid, or doxycycline, 100 mg tid (OMT vs OMD). Diagnostic endoscopy was made in all patients before and 5 to 6 weeks after therapy. Six biopsies were taken from each patient for histology, rapid urease test, and H. pylori culture; antibiotic susceptibility testing was performed using the E-test method. RESULTS: Overall cure rates were poor for both dual therapies OA and OC (38% and 37%, respectively) and for triple therapies OMA, OMC, and OMD (57%, 55%, and 58%, respectively). The OMT combination was successful in 91% (95% confidence interval [CI], 80.4%-97%). Metronidazole resistance was present in 29.7% (95% CI, 24%-35%), amoxicillin resistance was present in 26% (95% CI, 21%-32%), clarithromycin resistance was present in 23.1% (95% CI, 18%-29%), tetracycline resistance was present in 14% (95% CI, 10%-20%), and doxycycline resistance was present in 33.3% (95% CI, 21%-47%). Antibiotic resistance markedly reduced the cure rates and accounted for most of the poor results with the triple therapies: 89% versus 23%; 77% versus 26%; 100% versus 60%; and 67% versus 23% for OMC, OMA, OMT, and OMD, respectively. OMT appeared to be the best because of the high success rate with metronidazole-resistant H. pylori (71%) and in low-level tetracycline resistance. CONCLUSIONS: Pretreatment antibiotic-resistant H. pylori can, in part, explain the low cure rate of the infection and the variability in outcome in reported trials.

Amoxicillin↗