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Notes: Abstract: The dihydrofolate reductase gene from Candida albicans has been cloned and partially characterized. A genomic bank from C. albicans strain 10127/5 was constructed in Escherichia coli and screened for trimethoprim resistance. A plasmid pMF1, carrying the resistance marker was isolated and characterized by restriction mapping and Southern blotting. Cells harbouring pMF1 were as sensitive as the parental cells to a wide spectrum of antibacterial agents, except for trimethoprim; the dihydrofolate reductase activity from these cells was trimethoprim resistant.

Notes: Background: No placebo-controlled clinical trials have yet been published on the efficacy of therapy in older subjects with oesophagitis.Aim: To evaluate the efficacy of pantoprazole in preventing the recurrence of oesophagitis in elderly subjects.Methods: One hundred and sixty-four patients aged 65 years and over with acute oesophagitis were treated openly with pantoprazole, 40 mg daily, for 8 weeks. Patients with documented healing of erosive oesophagitis were then treated with pantoprazole, 20 mg daily, for 6 months. Thereafter, cured patients were randomized to receive pantoprazole, 20 mg daily, or placebo for the following 6 months. Clinical evaluations were performed every 2 months, and endoscopy was repeated after 8 weeks and after 6 and 12 months and/or whenever symptoms suggested a relapse of oesophagitis.Results: After 8 weeks, the healing rates of oesophagitis were 81.1% (75.1–87.1%) and 93.7% (89.7–97.7%) by intention-to-treat and per protocol analyses, respectively. After 6 months, the corresponding values were 82% (75.4–88.5%) and 92.4% (87.6–97.2%), respectively. After 12 months, the per protocol and intention-to-treat healing rates of oesophagitis were 95.1% (88.5–100%) and 79.6% (68.3–90.9%), respectively, in the treatment group vs. 32.7% (19.9–45.4%) and 30.4% (18.3–42.4%), respectively, in the placebo group (P = 0.0001). Heartburn, acid regurgitation and chest pain were significantly associated with the relapse of oesophagitis (P = 0.0001), whereas hiatus hernia, Helicobacter pylori infection, concomitant diseases and treatments were not.Conclusion: In the elderly, pantoprazole was highly effective in healing and reducing the relapse of oesophagitis; discontinuing active treatment after 6 months was associated with a significant increase in the relapse rate.

Notes: Advancing age may influence clarithromycin’s pharmacokinetics. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor and amoxicillin in elderly patients.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To compare the efficacy and tolerability of clarithromycin 250 mg vs. clarithromycin 500 mg twice daily (b.d.) in combination with pantoprazole and amoxicillin in elderly patients.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:One hundred and fifty-four elderly patients with H. pylori-associated ulcer disease or chronic gastritis were consecutively randomized to receive pantoprazole 40 mg daily plus amoxicillin 1 g, and either clarithromycin 250 mg b.d. (PAC 250) or clarithromycin 500 mg b.d. (PAC 500). Two months after therapy, endoscopy and gastric biopsies were repeated.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The cure rates of H. pylori infection in the PAC 250 and PAC 500 groups were, respectively, 83% and 79% (ITT analysis) and 94% and 88% (PP analysis) (P=N.S.). Significant decreases in chronic gastritis activity both in the body (P 〈 0.00001) and the antrum (P 〈 0.0001) of the stomach were found in H. pylori-cured patients, independently of clarithromycin dosage. Four patients in PAC 250 (5%) and seven in PAC 500 (9%) reported adverse events (P=N.S.). One patient in PAC 250 (25%) and three in PAC 500 (43%) discontinued the study because of these drug-related side-effects (P=N.S.).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:In elderly patients, 1-week triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin is a highly effective and well tolerated anti-H. pylori treatment. With this combination, clarithromycin at the lower dose of 250 mg b.d. achieved excel- lent cure rates and minimized adverse events and costs.

Notes: Background: The aim of this study was to compare omeprazole 10 mg o.m. (daily) with omeprazole 20 mg o.m. on Friday to Sunday inclusive (weekend) in the prevention of duodenal ulcer relapse over a 6-month period.Methods: After an open healing phase (4 to 8 weeks) with omeprazole 20 mg o.m., 81 patients entered the follow-up phase. Forty-two were randomized in a double-blind double-dummy technique, to omeprazole 10 mg o.m., and 39 to omeprazole 20 mg at weekends, At 3 and 6 months or on symptomatic relapse the patients underwent endoscopy with gastric biopsies (quantitative assessment of argyrophilic and gastrin cells), symptom evaluation, and laboratory screening with fasting serum gastrin.Results: Five patients in the 10 mg group and four in the weekend group were lost to follow-up. The estimated relapse rates over six months in the two groups receiving 10 mg daily or 20 mg at weekends were 19% and 31%, respectively (95% CI of percentage difference: –33% to 8%; intention-to-treat analysis, P = N.S.). During the follow-up phase, symptoms tended to be milder in the omeprazole 10 mg daily group compared to the weekend group. Gastrin levels increased significantly during the healing phase but then stayed almost constant in the omeprazole 10 mg group, and significantly decreased with weekend treatment. The median number of argyrophilic cells showed a slight but statistically significant increase in the omeprazole 10 mg daily group, but did not change in the weekend group. Both the healing and long-term therapies were well tolerated.Conclusions: Our data do not show a clear difference between the two treatment regimens, but there was a tendency towards a lower recurrence rate with omeprazole 10 mg daily compared with 20 mg weekend therapy.

Notes: Background: Specific data on anti-H. pylori treatments in elderly people are very scarce. The aim of the study was to evaluate in the elderly the efficacy of different anti-H. pylori therapies and the behaviour of serum anti-H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio induced by the anti-H. pylori treatment. Methods: One hundred and twenty-one dyspeptic patients aged 〉60 years (mean age, 73 years; range, 61–89 years) with H. pylori-positive gastric ulcers (17 patients), duodenal ulcers (33 patients) or chronic gastritis (71 patients) were treated with one of the following anti-H. pylori treatments: (A) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days; (B) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 mg q.d.s. for 7 days; (C) omeprazole 40 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 q.d.s. for 7 days; (D) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days; (E) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days plus metronidazole 250 q.d.s. for 7 days; and (F) omeprazole 40 mg/day plus clarithromycin 250 mg b.d. for 7 days plus metronidazole 250 mg q.d.s. for 7 days. At the baseline and 2 months after therapy, endoscopy and serum anti-H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio were measured. Results: Ten patients (8.2%) dropped out of the study. Six patients (4.9%) reported side-effects. The eradication rates of the six regimens, expressed using intention-to-treat and per protocol analysis, were, respectively: (A) 39% and 44%; (B) 50% and 56%; (C) 65% and 77%; (D) 47% and 50%; (E) 85% and 90%; and (F) 83% and 87%. The triple therapy for regimens E and F was significantly more effective than dual therapies (regimens A and D; intention-to-treat=P〈0.007, per protocol=P〈0.001) or the triple therapy for regimens B and C (intention-to-treat=P〈0.009, per protocol=P〈0.03). Patients cured of H. pylori infection showed a significant decrease in the activity of gastritis (P〈0.0001), a significant drop in IgG anti-H. pylori (P=0.0004) and pepsinogen C (P〈0.0001), and an increase in PGA/PGC ratio (P〈0.001), while patients remaining H. pylori-positive showed no changes in the serum parameters. Conclusions: In the elderly, triple therapy with omeprazole +metronidazole+clarithromycin for 1 week is well tolerated and highly effective; anti-H. pylori antibody and PGC serum levels decrease soon after anti-H. pylori therapy only in patients cured of H. pylori infection.

Notes: The efficacy and safety of omeprazole, in 241 patients with active recurrent duodenal ulcer from 21 Italian centres, was studied in a multicentre double-blind randomized trial comparing 20 mg omeprazole o.m. or 40 mg famotidine nocte with endoscopic examination, symptom recording, laboratory screening and gastrin assay. In a per protocol analysis, the duodenal ulcer healing rates for omeprazole and famotidine, documented by endoscopy, were 62% (68/109) and 33% (39/117) after 2 weeks of treatment (P 〈 0.001), 92% (96/104) and 80% (86/108) cumulative after 4 weeks (P 〈 0.05), and 99% (102/103) and 92% (96/104) after 6 weeks (P 〈 0.05), respectively. The results of this trial demonstrate that 20 mg omeprazole o.m. is superior to 40 mg famotidine nocte in duodenal ulcer healing.

Notes: To compare the efficacy of pantoprazole vs. a one-week Helicobacter pylori eradication therapy for the prevention of NSAID-related gastroduodenal damage.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Patients over 60 years old with symptoms and/or a history of ulcer who needed NSAID treatment were evaluated by endoscopy. H. pylori positive subjects who had no severe gastroduodenal lesions were randomized to take, concomitantly with NSAID therapy, either: (i) pantoprazole 40 mg daily plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. for 1 week (35 subjects, Group PAC) or (ii) pantoprazole 40 mg daily for 1 month (34 subjects, Group P). Endoscopy was repeated after 1 month.〈section xml:id="abs1-3"〉〈title type="main"〉Results:A significantly higher incidence of severe gastroduodenal damage was found in Group PAC than in Group P (29% vs. 9%, P 〈 0.05). The percentages of patients worsened, unchanged and improved after 1 month were, respectively: Group PAC: 46%, 46%, and 9% and Group P: 7%, 65%, and 29% (P 〈 0.0008). The percentage of H. pylori-negative subjects was 89% in Group PAC and 52% in Group P (P=0.0009). The incidence of gastroduodenal damage was higher in Group PAC treatment failures than in cured patients (50% vs. 25.8%, P=ns).〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion:One month of pantoprazole was more effective than a proton pump inhibitor-based triple therapy in the prevention of gastroduodenal damage in elderly H. pylori-positive NSAID users.

Notes: Background:  The association between coxib or non-steroidal anti-inflammatory drug use with gastrointestinal symptoms and drug prescriptions in ambulatory elderly patients is not well defined.Aim:  To evaluate the association between non-steroidal anti-inflammatory drug NSAID and coxib use with gastrointestinal symptoms and therapies in elderly subjects managed by their general practitioner.Materials:  The study was carried out by 133 general practitioners in Italy. By using a structured interview, sex, age, physical function, current medications, new drug prescriptions and upper gastrointestinal symptoms were registered from all elderly subjects who were referred to their general practitioners during a 2-week period. The numbers of hospitalizations, gastrointestinal bleeding events and gastrointestinal diagnostic procedures occurring during the last 6-month period were recorded.Results:  Included in this study were 5515 elderly subjects. The overall prevalence of drug use was 92%. Musculo-skeletal drugs were taken by 15% of patients; NSAIDs were taken by 6%, and coxibs by 3% of patients. A significantly higher prevalence of upper gastrointestinal symptoms was observed in elderly NSAID users compared with coxib users and non-users of musculo-skeletal drugs (44% vs. 33% vs. 32% respectively, P = 0.001). The prescriptions of drugs for acid-related disorders were significantly higher in patients who were concomitantly taking NSAID rather than coxibs (13% vs. 6%, P 〈 0.01). The prescriptions of drugs for acid-related disorders were significantly associated with the presence of upper gastrointestinal symptoms (OR = 1.7, 95% CI = 1.6–1.9), previous gastrointestinal disorders (OR = 1.1, 95% CI = 1.0–1.3) and NSAID use (OR = 1.5, 95% CI = 1.0–2.2), but no coxib use.Conclusion:  In this elderly population, upper gastrointestinal symptoms and prescriptions for gastroenterological drugs were higher in non-steroidal anti-inflammatory drug users than coxib users and non-users of musculo-skeletal drugs.

Notes: Background : Although administration of gastroprotective drugs may reduce the risk of peptic ulcers associated with the chronic use of non-steroidal anti-inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy is effective for short-term prevention, particularly in old age.Aim : To evaluate the risk of peptic ulcer associated with acute and chronic non-steroidal anti-inflammatory drugs or aspirin therapy in elderly subjects, and the influence of antisecretory treatment on this risk.Methods : The study included 676 elderly non-steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who consecutively underwent upper gastrointestinal endoscopy. The use of non-steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview. Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylori infection were carried out by endoscopy and histological examination of the gastric mucosa.Results : About 47.3% of patients were acute and 52.7% chronic users of non-steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted for age, gender, H. pylori infection and antisecretory drug use was higher in acute (gastric ulcer: odds ratio, OR =4.47, 95% CI: 3.19–6.26 and duodenal ulcer: OR =2.39, 95% CI: 1.73–3.31) than chronic users (gastric ulcer: OR = 2.80, 95% CI: 1.97–3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22–2.33). Proton-pump inhibitor treatment was associated with a reduced risk of peptic ulcer in both acute (OR = 0.70, 95% CI: 0.24–2.04) and chronic (OR = 0.32, 95% CI: 0.15–0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely, concomitant treatment with H2-blockers was associated with a significantly higher risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87–30.9) and chronic (OR = 6.26, 95% CI: 2.56–15.3) non-steroidal anti-inflammatory drugs/aspirin users than non-users. Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users.Conclusions : These findings suggest that proton-pump inhibitor co-treatment is advisable in symptomatic elderly patients who need to be treated with non-steroidal anti-inflammatory drugs and/or aspirin for a short period of time.