Helicobacter pylori eradication and ulcer healing with daily lansoprazole, plus 1 or 2 weeks co-therapy with amoxycillin and clarithromycin

BACKGROUND: Proton pump inhibitor based combination therapy is one standard strategy for Helicobacter pylori eradication. AIM: To compare the eradication and duodenal ulcer healing efficacy of two 2-week, single dose, lansoprazole based combination therapies. METHODS: Healthy adult patients with endoscopically confirmed, H. pylori associated duodenal ulcer disease (3 mm > ulcer < 20 mm) were eligible for the study. All patients received a 14 day course of lansoprazole 30 mg o.m., and were randomized to receive either 7 or 14 days of amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. Patients were endoscoped at entry and 14-17 days later. Symptomatic, unhealed patients received a further 14 days of therapy with lansoprazole 30 mg o.m. Eradication was confirmed a minimum of 28 days after cessation of all therapy by urease reaction and histological assessment of gastric body and antral biopsies (three biopsies each site). RESULTS: Sixty-two patients were randomized to a treatment arm, of which 58 could be included in an intention-to-treat and key-point-available analysis. H. pylori eradication rates were identical, at 93% (95% CI: 73-98% (1 week), 78-99% (2 week)). In the combined group, all but 13 ulcers were healed at 2 weeks; six required further therapy because of symptoms, while six of the seven asymptomatic patients went on to heal. CONCLUSION: An eradication regimen, based on a 2-week course of single dose lansoprazole with 1 week of antibiotic co-therapy, is effective in eradicating H. pylori, while the 2 weeks of acid suppression is usually effective in duodenal ulcer healing.     

Age-dependent eradication of Helicobacter pylori with dual therapy

BACKGROUND: Combined treatment using an acid-inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. METHODS: In a single-blind study, 60 H. pylori-positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. RESULTS: The overall eradication rates were 45% (intention-to-treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 +/- 1.7; 51 +/- 25%) than for omeprazole (5.4 +/- 1.1: 77 +/- 25%; P < 0.05) or lansoprazole (4.4 +/- 1.6: 68 +/- 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post-treatment H. pylori status was not dependent on those levels, or the drug-induced extent or duration of increased intragastric pH. However, H. pylori-eradicated patients were significantly (P < 0.05) older (56 +/- 13 years) than patients still H. pylori-positive (47 +/- 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75-83%) in subgroups of patients (> 50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. CONCLUSION: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.     

Enhanced levels of C-X-C chemokine, human GROalpha, in Helicobacter pylori-associated gastric disease

C-X-C Chemokines play an important role for neutrophil extravasation through microvessels. Although the level of interleukin (IL)-8 is known to increase in the Helicobacter pylori-infected gastric mucosa, another C-X-C chemokine, GROalpha, has not been evaluated in the H. pylori-associated gastric mucosal injury. The present study was designed to investigate gastric contents of GROalpha in relation to those of IL-8 in the gastric mucosa of H. pylori-infected peptic ulcer patients. Thirty-eight patients with gastric ulcer and 41 with gastritis underwent endoscopy with informed consent and 49 were found to be H. pylori positive and 30 H. pylori negative. Biopsies from the gastric corpus were performed in each patient to examine the H. pylori colonization by bacterial culture, the rapid urease test and histological specimens as well as measurement of the contents of human GROalpha and IL-8. Helicobacter pylori infection was eradicated in 21 patients by triple therapy (lansoprazole 30 mg, amoxycillin 2.0 g, clarithromycin 600 mg; 2 weeks). The samples for GROalpha and IL-8 assay were homogenized in 0.02% aprotinin containing phosphate-buffered solution and the mucosal contents of GROalpha and IL-8 in the supernatants were quantified by sandwich enzyme immunoassay methods. The levels of GROalpha and IL-8 in H. pylori-positive gastric mucosa were significantly higher than those in the H. pylori-negative mucosa. There was a significant linear correlation between the levels of GROalpha and IL-8 (r = 0.798, P < 0.01). After the eradication of H. pylori by the triple therapy, the levels of GROalpha and IL-8 were significantly decreased. The GROalpha showed an increase in the H. pylori-positive gastric mucosa in a similar fashion as IL-8 contents, suggesting a pathogenetic role for GROalpha in H. pylori-associated gastric mucosal injury.     

Comparative effect of lansoprazole/amoxicillin with omeprazole/amoxicillin for the eradication of Helicobacter pylori in patients with duodenal ulcer

Lansoprazole, a potent antisecretory drug, possesses on an equimolar basis a 4-fold higher in vitro anti-Helicobacter pylori activity than omeprazole. In a prospective randomized study we compared lansoprazole 30 mg b.i.d. and amoxicillin 1 g b.i.d. with omeprazole 40 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days followed by lansoprazole 30 mg q.d. or omeprazole 20 mg q.d. for 14 additional days in 50 H. pylori positive duodenal ulcer patients (14f, 36m, age 27-83 [mean 43] years). H. pylori infection was diagnosed by histology (3 antral biopsies and 2 from gastric body, H & E- and Giemsa stain), rapid urease test (CLO) and culture in 39 patients, or by histology and rapid urease test in 11 patients. Control endoscopy was performed 4-6 weeks after the end of treatment. For eradication, a negative result in all 3 diagnostic modalities was required. The eradication rate was 43% (9/21 patients) in both treatment groups. 8 patients were lost to follow-up. The ulcer healing rate was 100% in both groups. Nonsmokers had a significantly higher (p = 0.026) eradication rate than smokers. No relevant adverse effects of the therapy occurred. 24 patients with persistent H. pylori infection were subsequently treated with lansoprazole 60 mg b.i.d. and amoxicillin 1 g b.i.d. for 14 days. Eradication was achieved in 5/22 (23%) patients (3/14 smokers, 2/8 nonsmokers), while 2 patients were lost to follow-up. 17 patients with persistent H. pylori infection after the second treatment received quadruple therapy consisting of metronidazole 500 mg t.i.d., tetracycline 500 mg q.i.d. bismuth-subcitrate 120 mg q.i.d. and lansoprazole 30 mg for 10 days. H. pylori eradication was achieved in 12/15 patients (80%). In conclusion, lansoprazole plus amoxicillin was equal to omeprazole plus amoxicillin in the treatment of H. pylori infected duodenal ulcer patients. Patients with eradication failure after dual therapy were successfully treated by quadruple therapy. In contrast, high dose lansoprazole and amoxicillin therapy was effective in only 23% of patients with persistent infection after standard dual therapy.     

Midazolam improves postoperative epidural analgesia with continuous infusion of local anaesthetics

BACKGROUND: A number of triple drug regimens using proton pump inhibitors and two antibiotics have been evaluated in the West and reported to achieve Helicobacter pylori eradication rates of over 90%. In developing countries however, these combinations have neither been well evaluated, nor the optimum treatment for H. pylori infection well defined. AIM: To compare the combination of a proton pump inhibitor with a nitroimidazole and another antibiotic in eradicating H. pylori infection and healing duodenal ulcer. METHODS: Sixty consecutive patients with active duodenal ulcer who were positive for H. pylori (by rapid urease test and 14C-urea breath test) were randomized into three treatments groups: (1) LAS (n=21): lansoprazole 30 mg o.m., amoxycillin 500 mg q.d.s. and secnidazole 2 g on alternate days for 2 weeks; (2) LCS (n=18): lansoprazole 30 mg o.m., clarithromycin 500 mg b.d. and secnidazole 2 g on alternate days for 1 week; (3) LPS (n=21): lansoprazole 30 mg o.m., pefloxacin 400 mg o.m. and secnidazole 2 g on alternate days for 2 weeks. Urease and breath tests were performed at 0, 6 and 12 weeks to check for H. pylori eradication. RESULTS: Intention-to-treat eradication rates were as follows: LAS 86%, LCS 83%, LPS 71%; the overall ulcer healing rate was 90% at 6 weeks. CONCLUSIONS: High H. pylori eradication rates were achieved using the amoxycillin- and clarithromycin-based therapies. Fewer side-effects, better compliance and low cost favoured the amoxycillin-based therapy.     

High-dose proton pump inhibitor plus amoxycillin for the treatment or retreatment of Helicobacter pylori infection

BACKGROUND: The combination of 120 mg of omeprazole (40 mg t.d.s.) and amoxycillin has been reported to be effective for treating H. pylori infections. METHODS: Normal volunteers with H. pylori infection received high-dose omeprazole (40 mg t.d.s.) or lansoprazole (60 mg t.d.s.) plus amoxycillin 750 mg t.d.s. for 14 days. The studies were open label and not randomized as those receiving omeprazole plus amoxycillin had previously failed lower dose omeprazole (20 mg b.d.) plus amoxycillin therapy more than 6 months previously. Those receiving lansoprazole plus amoxycillin had not been previously treated. Four to 6 weeks after ending antimicrobial therapy, H. pylori status was determined by Genta stain of gastric mucosal biopsies. RESULTS: Forty-three volunteers entered the study and 41 completed it. The overall success with high-dose proton pump inhibitor plus amoxycillin was 34.9%. For the individual regimens the per-protocol results were 48% (95% CI = 28-69%) with lansoprazole and 12.5% (95% CI = 2-38%) with omeprazole. Compliance was > 95% for both regimens. Side-effects were experienced by four lansoprazole and three omeprazole subjects, and caused two omeprazole subjects to withdraw. Cure rates were similar among different races and ethnic groups, between men and women, and between smokers and non-smokers. The level of the pre-treatment urea breath test also did not predict outcome. CONCLUSION: High-dose proton pump inhibitor plus amoxycillin combinations for treatment of H. pylori infection yielded unacceptable results, as the 95% confidence intervals did not include an 80% cure rate. These combinations do not yield consistent results worldwide and cannot be recommended as primary therapy.     

Erosive duodenitis: prevalence of Helicobacter pylori infection and response to eradication therapy with omeprazole plus two antibiotics

OBJECTIVES: To study the prevalence of Helicobacter pylori infection in patients with erosive duodenitis (ED), the associated gastric histological lesions and their response to eradication therapy with omeprazole plus two antibiotics. METHODS: A prospective study was made of 57 patients with ED (mean age 46 +/- 16 years, 72% males). At endoscopy, biopsies from gastric antrum and body were obtained for histological study (haematoxylin and eosin). A 13C-urea breath test was also performed. Omeprazole 20 mg twice daily plus two antibiotics (amoxycillin 1 g twice daily, clarithromycin 500 mg twice daily, metronidazole 500 mg twice daily) were administered for 1 week. Endoscopy and breath test were repeated 1 month after completing therapy, and the breath test was performed again at 6 months. RESULTS: All patients were H. pylori positive. Overall eradication was achieved in 86% (95% CI 75-93%). Duodenal erosion healing was obtained in 45 patients (79%). Healing was achieved in 86% (CI 73-93%) of cases with successful eradication therapy, but only in 3/8 (37%; CI 8.5-75%) patients with therapy failure (P < 0.01). In the multivariate analysis, H. pylori eradication was the only variable which correlated with erosion healing (odds ratio 10; CI 2-51; P < 0.01). Histological improvement, in both the gastric antrum and body, was demonstrated when eradication was achieved (P < 0.001). Six months after diagnosis H. pylori absence was confirmed in all patients with initial therapy success (all of them asymptomatic), and infection was confirmed in the eight patients who were H. pylori positive after therapy (six of them symptomatic). At 6-month follow-up, endoscopy was normal in 6/7 H. pylori-negative patients with previously persistent ED, while erosions were still present in 4/5 H. pylori-positive patients with previously persistent ED. CONCLUSION: A high prevalence (100%) of H. pylori infection in patients with ED was observed. A 1-week twice daily therapy with omeprazole plus two antibiotics (clarithromycin plus amoxycillin or metronidazole) was very effective in H. pylori eradication, duodenal erosion healing, symptomatic improvement, and in disappearance of associated histological gastritis. These observations suggest that ED should be considered a variant form of duodenal ulcer disease and treated accordingly; that is, with H. pylori eradication therapy.     

Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers

BACKGROUND: Helicobacter pylori infection is common in patients with peptic ulcers caused by the use of non-steroidal anti-inflammatory drugs (NSAIDs). But the pathogenic role of H pylori in this disease is controversial. We studied the efficacy of eradication of H pylori in the prevention of NSAID-induced peptic ulcers. METHODS: We recruited patients with musculoskeletal pain who required NSAID treatment. None of the patients had previous exposure to NSAID therapy. Patients who had H pylori infection but no pre-existing ulcers on endoscopy were randomly allocated naproxen alone (750 mg daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, each given orally four times daily) before administration of naproxen (750 mg daily). Endoscopy was repeated after 8 weeks of naproxen treatment or when naproxen treatment was stopped early because of bleeding or intractable dyspepsia. All endoscopic examinations were done by one endoscopist who was unaware of treatment assignment. The primary endpoint was the cumulative rate of gastric and duodenal ulcers. FINDINGS: 202 patients underwent endoscopic screening for enrolment in the trial, and 100 eligible patients were randomly assigned treatment. 92 patients completed the trial (47 in the naproxen group, 45 in the triple-therapy group). At 8 weeks, H pylori had been eradicated from no patients in the naproxen group and 40 (89%) in the triple-therapy group (p < 0.001). 12 (26%) naproxen-group patients developed ulcers: five had ulcer pain and one developed ulcer bleeding. Only three (7%) patients on triple therapy had ulcers, and two of these patients had failure of H pylori eradication (p = 0.01). Thus, 12 (26%) patients with persistent H pylori infection but only one (3%) with successful H pylori eradication developed ulcers with naproxen (p = 0.002). INTERPRETATION: Eradication of H pylori before NSAID therapy reduces the occurrence of NSAID-induced peptic ulcers.     

Improving management of duodenal ulcer disease

Audit of treatment of duodenal ulcer disease has allowed management to improve and keep abreast of rapid advances in care. Eradication of Helicobacter pylori was assessed by 14C urea breath test one to two months after anti-Helicobacter therapy. The old triple therapy regime of bismuth, tetracycline and metronidazole for two weeks was found to be toxic and of low effectiveness (82%). Regimes with lansoprazole for one month and antibiotics for one week gave 90-98% success rates. The best success has been with regimes containing both clarithromycin and a nitro-imidazole. There was complete success in 98% of 109 patients given quadruple therapy with lansoprazole 30 mg daily for one month plus tetracycline 500 mg twice daily, clarithromycin 250 mg twice daily and metronidazole 400 mg twice daily for one week.     

One week triple therapy for Helicobacter pylori: a multicentre comparative study. Lansoprazole Helicobacter Study Group

BACKGROUND: Eradication of Helicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis. AIM: To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori. PATIENTS: Men or women with H pylori positive duodenal ulceration or gastritis, or both. METHODS: A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pylori status. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment. RESULTS: H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. CONCLUSIONS: All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.     

A comparison of 10 and 14 days of lansoprazole triple therapy for eradication of Helicobacter pylori

BACKGROUND: Data from large, multicenter, US studies determining the efficacy of triple therapy for the eradication of Helicobacter pylori are lacking, especially for a treatment duration of less than 14 days. METHODS: Patients with H pylori infection and active duodenal ulcer disease or a history of duodenal ulcer disease within the past year were randomized to receive 30 mg of lansoprazole, 1 g of amoxicillin, and 500 mg of clarithromycin twice daily for 10 or 14 days. The primary efficacy end point was the eradication of H pylori as confirmed by negative histological and culture results at 4 to 6 weeks after the completion of treatment. RESULTS: Of 284 patients enrolled in the study from 46 US sites, 236 met the entry criteria. At 4 to 6 weeks after the end of therapy, H pylori was eradicated in 85% (96/ 113) of the patients receiving 14-day triple therapy and in 84% (103/123) of those receiving 10-day triple therapy by per-protocol analysis (95% confidence interval for treatment group differences, -10.5 to 8.1; P>.05). There was also no significant difference between the 14- and 10-day treatment groups when analyzed by an intent-to-treat analysis of H pylori eradication. A similar proportion of patients in each treatment group reported an adverse event related to therapy (34% [46/136] vs 38% [56/148], respectively). CONCLUSIONS: In patients with an active or a recent history of duodenal ulcer, lansoprazole-based triple therapy for 10 or 14 days is highly effective in the eradication of H pylori. The duration of therapy may be reduced from 14 to 10 days without a significant effect on regimen efficacy.     

One-week low-dose triple therapy vs. two-week medium-dose double therapy for H.pylori infection

BACKGROUND/AIMS: Our study is to compare a short-term low-dose triple therapy with a long-term medium-dose double therapy for H.pylori eradication. MATERIALS AND METHODS: One hundred and ten consecutive patients, suffering from dyspeptic symptoms, with H.pylori infection, were randomly allocated to one of the following 2 groups with different therapeutic regimens: A) omeprazole 20 mg/day for 7 days, tinidazole 500 mg bid for 7 days, clarithromycin 250 mg bid for 7 days (55 pts, 20 with peptic ulcer); B) omeprazole 20 mg bid for 14 days, amoxycillin 1000 mg bid for 14 days (55 pts, 28 with peptic ulcer). The "H.pylori status" was evaluated by means of histology, culture and urease test, at entry and 8 weeks after treatment. RESULTS: Two group A and one group B pts didn't complete the treatment. The H.pylori eradication was obtained in 38 pts of group A (71.69%) (C.I.95%: 55.19176-80.86293), in 31 of group B (58.49%) (C.I.95%: 42.32777-69.7017); on Intention-to-Treat analysis, the rate of eradication gave similar results. Side effects occurred in 9 pts of group A (16.98%), in 8 of group B (14.81%). CONCLUSIONS: Short-term low-dose triple therapy with omeprazole/tinidazole/clarithromycin has a better cost/benefit ratio than long-term dual therapy with omeprazole/amoxycillin in the H.pylori eradication, but it causes more side-effects.     

Combination amoxycillin and metronidazole with famotidine in the eradication of Helicobacter pylori--a randomized, double-blind comparison of a three times daily and twice daily regimen

OBJECTIVES: To determine the efficacy of a three times daily (t.i.d.) versus a twice daily (b.i.d.) regimen of combination amoxycillin and metronidazole and famotidine in the eradication of Helicobacter pylori and the influence of metronidazole resistance on the outcome of treatment. PATIENTS: Patients selected had unequivocal evidence of H. pylori infection based on the urease test, culture and histology and had either peptic ulcer disease or non-ulcer dyspepsia. DESIGN: The study was a comparative and double-blind study and patients were randomized to receive either amoxycillin 750 mg t.i.d. and metronidazole 500 mg t.i.d. for 12 days or amoxycillin 1000 mg b.i.d. and metronidazole 500 mg b.i.d. for 12 days. Both groups also received famotidine 40 mg for 6 weeks. MAIN OUTCOME MEASURE: Patients were assessed for successful eradication, defined as absence of bacteria in all tests, at least 4 weeks after completion of antibiotic therapy by repeat gastroscopy. RESULTS: One hundred and twenty-nine patients were recruited for the study. Two patients defaulted follow-up, two patients were withdrawn from the study and six patients were found to be non-compliant with medications. The eradication rates of the t.i.d. regimen was higher than the b.i.d. regimen (per protocol (PP) analysis: 83.3% (50/60) vs. 76.3% (45/59), P=0.337; intention-to-treat (ITT) analysis: 78.5% (51/65) vs. 75.0% (48/64), P=0.642). Seventy-five patients had pre-treatment cultures checked for metronidazole resistance, 33 (44.0%) were found to be resistant. Acquired resistance occurred in 3/40 (7.5%) patients. Eradication rates of metronidazole-sensitive and metronidazole-resistant patients: t.i.d. regimen - 100% (17/17) and 88.2% (15/17), b.i.d. regimen - 19/21 (90.5%) and 11/15 (73.3%). Side effects were reported in up to 70% of patients but were mild and tolerable in the majority. Two patients were withdrawn from the study because of a fixed drug eruption in one and generalized macular rash in the other. CONCLUSION: Combination amoxycillin and metronidazole is effective in eradicating H. pylori. There was a tendency for the t.i.d. regimen to be better than the b.i.d. regimen and for metronidazole-resistant infections to be associated with a lower eradication rate but these differences did not reach statistical significance.     

A comparison of the effect of ski sidecut on three-dimensional knee joint kinematics during a ski run

BACKGROUND: Knowledge of Helicobacter pylori infection has grown rapidly during the last decade and management of its associated pathology has changed concordantly. METHODS: We surveyed the management of H. pylori infection among members of the Dutch Society of Gastroenterology in 1995 via a postal questionnaire. RESULTS: Almost all 226 respondents (response rate 54%) treated patients for H. pylori infection and the responses suggested that at least 0.1% of Dutch citizens were treated for H. pylori infection in 1995 by this group of specialists. 98% of the respondents treated the H. pylori infection in patients with duodenal ulcer, 91% in cases of gastric ulcer, 56% in cases of gastric lymphoma, 33% in cases of premalignant changes in gastric mucosal histology, 32% in cases of non-ulcer dyspepsia, and 30% in cases of chronic use of proton pump inhibitors. The main diagnostic methods used were histology (93%), urease test (60%), and culture (46%). Triple therapy was most commonly used (54%), followed by quadruple therapy (26%) and double therapy (13%). Follow-up detection of H. pylori was routinely done by 42% of the respondents, while 48% did so only when confirmation of eradication was considered clinically relevant. Most specialists did follow-up detection after 8-12 weeks. CONCLUSIONS: In 1995 most Dutch specialists treated H. pylori in patients with associated ulcer disease. There was no consensus on its role in other diseases. Diagnostic methods and treatment regimens for eradication differed widely.     

Effect of ring size on conformations of aromatic amine-DNA adducts: the aniline-C8 guanine adduct resides in the B-DNA major groove

We isolated strains of Helicobacter pylori from gastric mucosa of patients with peptic ulcer before and after eradication therapy, and studied their sensitivity to amoxicillin (AMPC) and clarythromycin (CAM). Of 85 strains of H. pylori isolated before therapy, MIC90 was 0.025 microgram/ml and no strains were resistant to AMPC. On the other hand, MIC90 of CAM was 0.05 microgram/ml and seven (8.2%) were already resistant to CAM. The H. pylori strains from eight cases of failed eradication therapy with lansoprazole + AMPC remained AMPC sensitive. However H. pylori strains from nineteen cases (82.6%) out of 23 of failed eradication therapy with lansoprazole + CAM became CAM resistant. The situation was similar for the cases of failed eradication therapy with lansoprazole + AMPC + CAM. Drug sensitivity tests prior to eradication therapy are to be recommended. A disc method may be used as a simple alternative to MIC measurement.     

Eradication of Helicobacter pylori with lansoprazole, roxithromycin and metronidazole--an open pilot study

BACKGROUND: The most extensively studied Helicobacter pylori eradication regimen comprises omeprazole, clarithromycin and metronidazole. Macrolide antibiotics other than clarithromycin should achieve similar efficacy, but they have not yet been thoroughly tested. AIM: To determine the efficacy and safety of a triple therapy regimen using lansoprazole, roxithromycin, and metronidazole on the basis of multicentre outpatient care in an open pilot study. METHODS: 163 patients with duodenal ulcer and proven H. pylori infection received lansoprazole 30 mg b.d., roxithromycin 300 mg b.d. and metronidazole 500 mg b.d. for 7 days followed by another 7 days of lansoprazole 30 mg once daily. H. pylori status was determined by urease quick test, histology, microbiology and 13C-urea breath test before starting and at least 4 weeks after completing treatment. RESULTS: 150 patients were available for evaluation; H. pylori was successfully eradicated in 84.7% (127/ 150) as determined by urease quick test, 78.0% (117/150) by histology, 81.3% (109/134) by 13C-urea breath test; and in 75.3% (113/150), at least two tests were negative. Side-effects were reported in 34 patients (most commonly diarrhoea and changes in liver function tests), in two cases the study medication was interrupted. Prior to treatment, 23% of the H. pylori isolates were resistant against metronidazole and 3.4% against roxithromycin. After unsuccessful treatment, 84% of the isolates were resistant against metronidazole and 21% against roxithromycin. Primary resistance to metronidazole increased the chance of treatment failure approximately sevenfold (7% vs. 53%). CONCLUSIONS: For H. pylori eradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole-resistant H. pylori is not rare in Germany and, in the present study, has strongly influenced treatment success.     

Eradication of Helicobacter pylori in patients with end-stage renal disease undergoing dialysis treatment

The aim of the present study was to examine the efficacy and safety of combination therapy with amoxicillin (AMPC), lansoprazole, and plaunotol for the eradication of H. pylori in dialysis patients. The subjects consisted of 15 dialysis patients (10 men and 5 women, mean age of 56 +/- 2.4 years) in whom H. pylori was found in the stomach. H. pylori status was evaluated by histology, culture and rapid urease test with biopsy specimens of the gastric mucosa. The patients were treated with AMPC 500 mg once a day for 3 weeks, lansoprazole 30 mg once a day for 8 weeks and plaunotol 80 mg three times a day for 24 weeks. In addition, the concentrations of serum gastrin and gastric juice ammonia were measured. Fourteen patients completed the treatment schedule, while one discontinued treatment because of nausea and diarrhea. Among the 14 patients, H. pylori was eradicated in 11 without any side effects (eradication rate 78.6%). Concentrations of gastric juice ammonia and serum gastrin were reduced significantly in patients who became H. pylori-negative. The present study indicates that combination therapy with AMPC, lansoprazole and plaunotol is safe and efficient for the eradication of H. pylori in dialysis patients. The results also suggested that elevated concentrations of gastric juice ammonia and serum gastrin in dialysis patients can be attributed, at least in part, to H. pylori infection.     

Improvement of glucose/insulin metabolism reduces hypertension in insulin-dependent diabetes mellitus recipients of kidney-pancreas transplantation

OBJECTIVE: The current guidelines recommend 1-wk triple therapy regimens for eradicating H. pylori infection. Until now, shorter regimens have scarcely been investigated. Azithromycin is a new generation macrolide antibiotic with unusual and favorable pharmacokinetics, and seems to be a very promising agent for innovative anti-H. pylori regimens. We assessed the efficacy and tolerability of a new 4-day low dose triple therapy in comparison with a well established 1-wk triple therapy in the treatment of Helicobacter pylori infection. METHODS: One hundred-sixty consecutive patients with biopsy-proven H. pylori infection were randomized to receive lansoprazole 30 mg b.i.d. on days 1-4, azithromycin 500 mg u.i.d. on days 2-4, and tinidazole 2000 mg u.i.d. on day 3 (LAT group), or 7 days of triple therapy of omeprazole 20 mg u.i.d., clarithromycin 250 mg b.i.d., and tinidazole 500 mg b.i.d. (OCT group). Patients with gastric or duodenal active ulcer received proton pump inhibitors for an additional 4 wk. H. pylori eradication was defined as negative of both rapid urease test and histology on biopsies taken from the gastric body and antrum at least 1 month after the end of treatment. RESULTS: Seven patients in the LAT group and four in the OCT group were lost to follow-up. No significant difference in either efficacy or tolerability was observed between the two regimens. Active ulcers healed in 97.8% of cases with LAT and in 100% of cases with OCT. The eradication rate was 80.8% in the LAT group and 85.5% in the OCT group, considering the per-protocol results, and 73.3% and 81.2%, respectively, considering the intention-to-treat results. Side effects occurred in one LAzT patient and in two OCT patients; they were mild and did not interfere with compliance. CONCLUSION: The new proposed ultrashort triple therapy, including lansoprazole, low dose azithromycin for 3 days, and a single dose of tinidazole, appears to be a very effective anti-H. pylori regimen, a simpler, cheaper, well-tolerated, and equally effective alternative to 1-wk triple therapy.     

Image cytometric nuclear DNA quantitation of paragangliomas in tissue sections. Prognostic significance

BACKGROUND: It has been reported that dual therapy with high doses of omeprazole and amoxycillin proves efficient for Helicobacter pylori eradication. AIM: To compare the efficacy, safety and tolerability of eradicating regimens with omeprazole/amoxycillin. METHODS: In this randomized multicentre study, 267 duodenal ulcer patients were treated for 2 weeks with omeprazole 40 bid (Group A) or 20 mg bid (Group B), respectively, and with amoxycillin 0.5 g. qid followed by 4 weeks of 20 mg omeprazole om. Helicobacter pylori status was assessed by both histology and urease test in the antrum and the corpus. The patients were then followed-up for 9 months. RESULTS: Helicobacter pylori infection was cured in 62.9% of group A (95% CI: 53.8-71.4) and in 44.8% of group B (95% CI: 35.6-54.3; p = 0.007). Healing was achieved in 91.9% of patients in group A (95% CI:85.7-96.1), and in 87.9% of patients in group B (95% CI:80.6-93.2). The estimated probability of being in ulcer remission for cured patients was 0.95 (95% CI: 0.90-0.99) and for the not cured was 0.41 (95% CI: 0.24-0.59; p = 0.0001). However, between the two treatment groups no significant differences in symptom relief or ulcer recurrence were observed. Both regimens were well tolerated with minor side-effects occurring likewise within the two groups. At two months in cured patients antral histology revealed a total (group A + B) prevalence of 13.7% of active chronic gastritis. CONCLUSIONS: This long-term, large-size study clearly indicates that dual therapy does not represent a truly effective eradication therapy and this regime cannot be recommended.     

Significant improvement of atrophy after eradication therapy in atrophic body gastritis

Chronic atrophic body gastritis may be induced by H. pylori. Results on the effect of H. pylori eradication therapy have been conflicting. Here, we report on the effect of eradication therapy on both body atrophy and inflammation in 7 patients. They presented with severe or moderate atrophy of the oxyntic mucosa and positive H. pylori histology (Warthin-Starry) and/or serology. Eradication was performed with a standard double or triple therapy regimen. At least 6 weeks after successful eradication therapy, patients underwent rebiopsy and histopathological evaluation of the gastric body. In all 7 patients, the grade of body gastritis improved significantly. Among the patients with severe atrophy before H. pylori eradication, 2 had normal mucosa, 3 low-grade atrophy, and one moderate atrophy after treatment. The one case with moderate atrophy before treatment had normal mucosa after H. pylori eradication. In addition, inflammatory infiltration of the mucosa cleared up in 6 cases and improved from severe to mild in one case after treatment. From these results, we conclude that in patients with histologically demonstrated H. pylori and/or positive H. pylori serology atrophic body mucosa can recover after successful eradication therapy.