Pantoprazole versus lansoprazole in French patients with reflux esophagitis.

OBJECTIVES: The aim of this study was to compare the efficacy of pantoprazole 40 mg and lansoprazole 30 mg given for 4 to 8 weeks on endoscopic healing and symptom relief in grade II-III reflux esophagitis patients (according to Savary-Miller classification). METHODS: Four hundred and sixty one patients were included (pantoprazole n=226, lansoprazole n=235) in this prospective, randomized, multicenter double-blind study. Endoscopic control was performed at 4 weeks and at 8 weeks if esophagitis was not healed. RESULTS: In the intention-to-treat analysis, the healing rates at 4 weeks were 81 and 80% in the pantoprazole and lansoprazole groups, respectively (NS), 90 and 86% at 8 weeks (NS). In the per-protocol analysis, the healing rates at 4 weeks were 86% in the 2 groups and at 8 weeks 97% in the pantoprazole group and 93% in the lansoprazole group (NS). The heartburn relief rates at day 14 were 88% and 86% in the pantoprazole and lansoprazole groups, respectively. Only esophagitis grade at entry was shown to be a predictive factor for healing at 4 weeks (P<0.0001). CONCLUSION: This study showed that pantoprazole 40 mg once daily is as effective and well tolerated as lansoprazole 30 mg once daily in the treatment of grade II-III acute reflux esophagitis.

cagA Status and eradication treatment outcome of anti-Helicobacter pylori triple therapies in patients with nonulcer dyspepsia.

The differences in eradication rates reported in clinical trials aiming to cure Helicobacter pylori infection cannot be entirely explained by the type of regimen, bacterial resistance, or lack of compliance. Using data from a clinical trial, a logistic regression model was constructed to determine whether cagA status, assessed by PCR, affects the outcome of eradication. Resistance to clarithromycin (10% of the strains) predicted failure perfectly. In the model (n = 156), a cagA-lacking strain (odds ratio [OR] = 2.2; 95% confidence interval [CI], (1.1 to 4.7), tobacco smoking OR = 3.1; 95% CI, 1.3 to 7.0), and a double dose of proton pump inhibitor in the treatment regimen (OR = 0.3; 95% CI, 0.2 to 0.7) were associated with the treatment outcome. The exact role of cagA in the outcome of H. pylori eradication therapy has not been explored. However, the type of histological lesions which it causes in the gastric mucosa may be implicated. Regardless of the mechanism involved, cagA status is a good predictive marker of eradication outcome.

Double vs. single dose of pantoprazole in combination with clarithromycin and amoxycillin for 7 days, in eradication of Helicobacter pylori in patients with non-ulcer dyspepsia.

BACKGROUND: The necessity of increasing intragastric pH during eradication treatment in Helicobacter pylori infected patients is well established. However, the optimal dose of the proton pump inhibitors used in eradication regimen is still a subject of debate. AIMS: To compare the efficacy and tolerability of a double vs. a single daily dose of pantoprazole in a 7-day triple therapy in eradicating H. pylori. METHODS: In this regional, multicentre, comparative, randomized and double-blind study, H. pylori-positive patients with non-ulcer dyspepsia were treated for 7 days with clarithromycin 500 mg b.d. and amoxycillin 1000 mg b.d. and either a double (2 x 40 mg, Group 2PCA) or a single (40 mg, Group 1PCA) daily dose of pantoprazole. H. pylori infection was assessed at entry and at the end (day 38) of the study by histology and culture, or in some cases by 13C-urea breath test. RESULTS: From 203 patients recruited, 192 patients (96 in Group 2PCA and 96 in Group 1PCA) formed the intention-to-treat population. Twenty-six of them judged as major protocol violators were excluded from the per protocol analysis. H. pylori eradication rate was 75% in Group 2PCA and 56% in Group 1PCA in intention-to-treat analysis, and 80% in Group 2PCA and 59% in Group 1PCA in per protocol analysis (P < 0.05). The primary resistance to clarithromycin was 10.5%. The eradication rates for the clarithromycin susceptible strains were 86% for Group 2PCA and 71% for Group 1PCA in per protocol analysis (P < 0.05). Both regimens led to similar improvement of clinical symptoms and were equally well tolerated. CONCLUSION: A double (2 x 40 mg) daily dose of pantoprazole in a 7-day triple therapy is more effective than a single (40 mg) dose of this drug in eradication of H. pylori.

Effect of slow-release theophylline on nasal antigen challenge in subjects with allergic rhinitis.

It has been recognized recently that theophylline possesses anti-inflammatory effects that could be of clinical interest in patients with airway inflammatory diseases such as asthma and allergic rhinitis (AR). The aim of the present study was to explore the effect of theophylline on the nasal eosinophilic inflammatory response following allergen challenge in patients with AR. Fourteen subjects suffering from seasonal rhinitis with an early reaction after nasal allergen provocation were challenged outside the pollen season after pretreatment for 3 weeks with placebo or slow-release theophylline (Euphylong in a randomized double-blind, cross-over study. Nasal blocking index (NBI), nasal airway resistance and symptoms were recorded before, and 1 and 5 h after challenge; additionally, nasal lavage fluid was collected before, as well as 1 and 5 h after challenge. Eosinophil cationic protein (ECP) was measured in the lavage as well as the number of eosinophils before, and 1 h and 5 h after allergen challenge. After 3 weeks of treatment, baseline concentrations of ECP in nasal lavage amounted to 826+/-329 ng x L(-1) (placebo) and 936+/-351 ng x L(-1) (theophylline). The ECP levels did not increase during the early phase response. Five hours after challenge, ECP in the placebo group increased markedly (p<0.01), whereas no significant increase was observed during theophylline treatment. In parallel, the number of eosinophils in the nasal lavage fluid was lower during theophylline treatment. Additionally, theophylline therapy also significantly reduced the nasal symptoms and had some protective effect against nasal obstruction following allergen challenge. These results confirm the anti-inflammatory effects of theophylline and suggest that these effects may be of clinical benefit in patients with allergic rhinitis.

Treatment of pulmonary hypertension in patients with chronic obstructive pulmonary disease: position of vasodilators with special focus on urapidil.

Pulmonary hypertension, generally defined by a resting pulmonary artery mean pressure higher than 20 mmHg, is a common complication of advanced chronic obstructive pulmonary disease (COPD). Pulmonary hypertension in COPD is of the "precapillary type" and is almost exclusively accounted for by the increased pulmonary vascular resistance (PVR). Among the factors leading to an increased PVR, acute as well as chronic alveolar hypoxia is by far the most important. Pulmonary hypertension is usually mild (between 20 and 35 mmHg) in COPD patients, but pulmonary artery pressure (PAP) may increase markedly and suddenly during exercise, sleep and episodes of acute respiratory failure. These acute increases of afterload can favour the development of right heart failure. Furthermore, even if the progression of pulmonary hypertension is rather slow (PAP increases by + 0.5 mmHg/year as a mean), the level of PAP is a good indicator of prognosis in COPD patients. Consequently the treatment of pulmonary hypertension is justified in COPD. There are two treatments available so far, which are not mutually exclusive: vasodilators and long-term oxygen therapy (LTOT). LTOT may partly reverse hypoxic pulmonary vasoconstriction but is not always effective in reducing PAP in COPD. Patients with severe and persistent pulmonary hypertension despite oxygen and bronchodilator may be candidates for vasodilator therapy. Numerous vasodilators have been tested, but none has proved entirely satisfactory. Ideally the predominant vasodilator effect would occur in the pulmonary rather than in the systemic vascular bed, and systemic blood pressure should be maintained. The drug should not cause tachycardia and should be well tolerated. At the present time, inhaled nitric oxide (NO) is the only selective pulmonary vasodilator currently available, but NO inhalation is limited by toxicological consideration. Urapidil is known to be an alpha 1-adrenoceptor antagonist and an agonist of central 5HT1A-receptors, and should be considered as a vasodilator. Several studies have already demonstrated that this antihypertensive agent exerts favourable effects on pulmonary and cardiac haemodynamics when administered intravenously or orally to COPD patients with secondary pulmonary hypertension or cor pulmonale. Furthermore in patients with COPD or bronchial hyperreactivity no adverse effect is observed on ventilatory function, bronchial reactivity and gas exchange. Nevertheless, the potential benefit of this vasodilator needs to be confirmed in combination with LTOT by a pragmatic evaluation of its clinical efficacy and safety in COPD patients with secondary pulmonary hypertension.

[Treatment of acute phase of myocardial infarction with injectable bisoprolol with oral versus]. / Traitement de la phase aiguë de l'infarctus du myocarde par le bisoprolol injectable avec relais oral.

The early treatment of acute myocardial infarction with beta-blockers represents a major advance in the management of this condition which was proved in a large serie of international studies including a total of about 30,000 patients, and in recent overviews. As a whole such treatment reduces total mortality by 13 to 14% during the first week (p less than .02) in the treated group compared with the controls. The mortality reduction appears most marked in the first two days, about 25%, after early intravenous infusion. Data on non fatal reinfarction in hospital suggest that early treatment reduces this risk by about 19% (p less than .01). Furthermore data on all patients suffering deaths, non fatal arrest and non fatal reinfarction indicate a 16% reduction in the risk of suffering one of these major events (p less than .001) and provide strong evidence of the beneficial effect of this class. Bisoprolol (Detensiel) is a high beta 1-selective beta-adrenoceptor blocking agent without intrinsic sympathomimetric activity and local anaesthetic activity. Its pharmacokinetic profile appears extremely favourable with a plasma elimination half-life of about 10 h and a balanced clearance: bisoprolol is inactivated by liver metabolism (about 50%) and excreted unchanged in the urine (about 50%). Two pilot open studies were performed up to now with IV bisoprolol in acute myocardial infarction (MI). The first trial (n = 37) confirms the clinical and ECG safety of the administered dose regimen: repeated IV infusion of 1 mg up to a cumulative maximum dose of 5 mg and subsequent oral treatment with 10 mg once daily (o.d.).(ABSTRACT TRUNCATED AT 250 WORDS)

Study of the electrophysiological properties of intravenous bisoprolol in patients with and without coronary artery disease by programmed stimulation.

The objective of this study was to assess the electrophysiological properties of intravenous bisoprolol in patients with and without coronary artery disease (CAD) by programmed stimulation. Sixteen inpatients subjected to an electrophysiological investigation because of dizziness or palpitations were given 10 mg of intravenous bisoprolol after basal measurement and were checked again 15 and 45 min after infusion. Eight patients with CAD (seven males and one female; mean age of 60+/-4 years) and eight patients without CAD (five males and three females; mean age of 59+/-4 years) were investigated after washout of prior antiarrhythmic drugs. For coronary patients, the CAD was documented by a history of myocardial infarction or by a confirmatory coronary arteriography. Main outcome measures were parameters of invasive electrophysiological exploration, with measurement of conduction intervals at rest and during pacing and of refractory periods by means of extrastimulus technique. No significant difference was noted at baseline between the two groups except for CSNRT. After infusion of 10 mg of bisoprolol, with the exception of CSNRT (increased in the group without CAD), no significant differences were noted on comparison between coronary and noncoronary patients. Bisoprolol significantly increased the sinus cycle length, SACT, and FRP of the atria. Regarding atrioventricular nodal conduction, bisoprolol significantly increased the AH 100, ERP, and FRP and significantly decreased the Wenckebach point. In the right ventricle, bisoprolol moderately, but significantly, decreased the corrected QT and induced a small, temporary, significant increase in ERP. Bisoprolol appears to be a very potent beta-blocker that is well tolerated at an intravenous dose of 10 mg. Its depressant effects concern mainly the atrial function and the nodal conduction, without significant differences between the two groups of patients. The decrease in QTc may be a favorable aspect regarding its electrophysiologic tolerance especially in the acute phase of myocardial infarction.