Influence of the timing of administration of 300 mg ranitidine on 24-hour gastric pH in patients acute duodenal ulcer.

The 24-hour intragastric pH of 12 patients with an acute duodenal ulcer was recorded with the aim of comparing the effects of two different times of administration of 300 mg ranitidine: post evening meal, or bedtime. This double-blind crossover trial involved 3 centres. Twenty-four-hour gastric pH was measured under standard conditions (meals, time schedule) at the middle of each 14-day treatment period. The analysis was performed on the percentage of times spent at pH levels below 1.5, 2, 3 and 4 for different periods and for the total 24 hours. During the whole day and night combined, as well as during the afternoon (12.00 hours-19.00 hours), there was no difference between the 2 regimens regardless of the pH profile studied. During the morning (07.30 hours-12.00 hours), the time spent below pH 1.5 and 2 was less when the drug was taken at bedtime (P less than 0.05). In contrast, during the whole night (19.00 hours-07.30 hours) the percentage of time spent below pH 1.5, 2 and 3 was significantly less when the drug was taken at post evening meal (P less than 0.05). These results show that in patients with acute duodenal ulcer, 300 mg ranitidine administered at the end of the evening meal provides better control of nocturnal acidity than administration at bedtime and hence is suggested for optimization of therapeutic efficacy.

[Ondansetron: a specific 5-HT3 serotonin receptor inhibitor, a new antiemetic in oncology]. / Ondansétron: un nouvel antiémétique en oncologie, inhibiteur spécifique des récepteurs à la sérotonine du type 5-HT3.

Serotonin (5-Hydroxytryptamine) seems to play a dominant role in triggering vomiting induced by cytotoxic agents through the stimulation of 5-HT3 receptors. They have been observed in the GI tract as well as in the brain (area postrema). Ondansetron is a specific antagonist of 5-HT3 serotonin receptors. Its anti-emetic activity is very powerful in the ferret. The availability of an injectable or oral form of this product allows the overall treatment of acute and delayed emesis and its administration is in accordance with different schedules: single IV injection or a continuous 24 hour infusion or repeated IV injection followed by oral treatment. The pharmacokinetics of the drug are as follows: absorption begins about 30 minutes after the administration per os, its biodisponibility is about 60%, its clearance: 20 ml/minute and its elimination half life about 3 hours. Different double blind studies, carried out in parallel groups or in cross over, demonstrated the superiority of ondansetron over metoclopramide in the control of nausea and vomiting, whether or not the chemotherapy contained cisplatin; a more recent study shows also that ondansetron was superior to alizapride and methylprednisolone in combination. Side effects of ondansetron do not include extrapyramidal symptoms but only headaches and constipation. The use of ondansetron improves the well-being of patients receiving chemotherapy and increases protocol compliance.

[Essential arterial hypertension and quality of life. Comparative crossed double-blind study of labetalol and captopril]. / Hypertension artérielle essentielle et qualité de vie. Essai comparatif en double-insu croisé du labétatol et du captopril.

The purpose of this multicenter randomised, double-blind and cross-over study was to compare the antihypertensive effects of labetalol (L) and captopril (C) in 42 moderate hypertensive patients (mean age: 52 years). The drugs were given during two 4-weeks periods at the end of which the systolic (SBP) and diastolic blood pressures (DBP) were measured at rest in supine and standing positions. The assessment of the quality of life was realized with 4 scales completed by the practitioner [anxiety, depression, well-being, visual analog scale (VAS)] and 4 scales of auto-assessment completed by the patient [2 VAS, well-being, sub-scale of pleasure]. At the end of the first treatment's period (D28), both drugs had decreased significantly supine SBP and DBP (p less than 0.001), standing DBP (L = p less than 0.01; C = p less than 0.05), while only L lowered supine SBP (p less than 0.01). The cross-over analysis was unable to conclude, due to the number of patients and a significant interaction which reduced its power. Thus the effect of the first treatment's period seemed to influence the efficacy of the second one. The percentages of patients with a controlled BP were respectively: after 4 weeks of treatment, L = 61 p. 100 vs C = 42 p. 100 and at the end of study (D56), L = 67 p. 100 vs C = 64 p. 100.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparative effectiveness of ranitidine (150 mg X 2) and cimetidine (400 mg x 2) in the treatment of acute duodenal ulcer. A French multicenter controlled clinical trial]. / Efficacité comparée de la ranitidine (150 mg X 2) et de la cimétidine (400 mg X 2) dans le traitement de l'ulcère duodénal en poussée. Essai thérapeutique contrôlé multicentrique français.

In a single-blind multicenter trial, 444 patients with duodenal ulcer (DU) proven by endoscopy were randomly assigned to treatment with either ranitidine, 150 mg, or cimetidine, 400 mg, morning and evening. Clinical assessments were carried out at 2 and 4 weeks and endoscopy at 4 weeks. The patients in the 2 groups were comparable. Cumulative healing rates at 4 weeks were 78.3 p. 100 in the ranitidine group (n = 226) and 65.6 p. 100 in the cimetidine group (n = 218) (p less than 0.003). Pain at the start was of similar severity in both groups, and disappeared at the same rate under ranitidine or cimetidine: 64 p. 100 patients were painless at 1 week, 80 p. 100 at 2 weeks and 88 p. 100 at 4 weeks. Thirty-eight patients complained of mild side effects: 22 on ranitidine (2 trial withdrawals) and 16 on cimetidine (1 trial withdrawal). Multifactorial analysis (logistic model) revealed that linear ulcers had a lower healing probability than round ulcers (p less than 0.002) whatever the treatment group (cimetidine: 47 p. 100 vs 68 p. 100, ranitidine 57 p. 100 vs 80 p. 100 respectively). Smoking habits (p less than 0.057) and age less than 40 years (p = 0.056) did not significantly influence healing rates, although smokers and younger patients under cimetidine had the lowest healing rate. Thus, at the dosage used in our trial, ranitidine is more efficient for healing DU at 4 weeks than cimetidine but not for pain relief.(ABSTRACT TRUNCATED AT 250 WORDS)

[Semiology of gastroduodenal ulcer proved by endoscopy: epidemiological analysis of 1,800 cases]. / Séméiologie de l'ulcère gastro-duodénal prouvé par endoscopie: analyse épidémiologique de 1,800 cas.

The aim of this study was to describe the clinical and endoscopic signs, the nutritional status, the consumption of alcohol and tobacco, and other associated factors in a population of 1,800 patients with endoscopically proven gastric (n = 501) or duodenal ulcer (n = 1235) and then to identify the risk factors in comparison to the French population. Patients with gastric ulcer were older, more often widowed if male, otherwise more often female, were more frequently treated by non-steroid drugs, and had a lipid-rich nutrition more often in comparison to patients with duodenal ulcers. Patients with duodenal ulcer were more often native from the Magreb and their nutrition was more often rich in spices in comparison to patients with gastric ulcer. The associations between use of non-steroidal drugs and consumption of spices disappeared after adjustment by multidimensional analysis. Patients with duodenal ulcer lived more frequently in the Ile de France area in comparison to patients with gastric ulcer. Patients with gastric ulcer worked more often as farmers in comparison to patients with duodenal ulcer and in comparison to the total French population. These differences remained after adjustment. The consumption of tobacco was higher in patients with gastric or duodenal ulcer in comparison to the mean consumption of the total French population.

[Intermittent treatment or preventive treatment of recurrence in duodenal ulcer disease? A controlled, double-blind study with 150 mg ranitidine daily for one year]. / Traitement des poussées ou traitement préventif des récidives dans la maladie ulcéreuse duodénale? Etude contrôlée en double aveugle d'une prise quotidienne de ranitidine 150 mg pendant un an.

This 1-year study compared two pragmatic strategies in long-term management of duodenal ulcer: continuous treatment with ranitidine 150 mg after dinner and treatment of duodenal ulcer attacks with ranitidine 300 mg and placebo in the interval. A multicentric, randomized double-blind study was conducted in 399 patients, 197 in the ranitidine group and 202 in the placebo group. Efficacy was judged by the prevalence of ulcer-pain recurrences; secondary criteria were the prevalence of endoscopic recurrences, complications and the number of facultative visits, hospitalizations and days off work related to duodenal ulcer disease. Both groups were similar with regard to main epidemiologic features and number of drop-outs (10.5 percent). Fifty-two patients were withdrawn for symptomatic or endoscopic relapses: 6 in the ranitidine group, 46 in the placebo group (p less than 0.05). Sixty-six percent of the patients remained asymptomatic at one year in the ranitidine group versus 33 percent in the placebo group (p less than 0.001). Seventeen patients with ranitidine (8.6 percent) and 59 with placebo (29.2 percent) experienced at least one endoscopic recurrence (p less than 0.05). In the placebo group, 8 complications were observed (bleeding = 5, duodenal stenosis = 3), and none in the ranitidine group (p less than 0.005). Patients with ranitidine had significantly less facultative visits and endoscopies, number of days off work, and hospitalizations (p less than 0.05). Tolerance was good (5 percent side-effects, all minor) and identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of the time of ingestion of 300 mg of ranitidine on cicatrization of duodenal ulcer in crisis (ingestion after dinner versus ingestion at bedtime]. / Effet de l'horaire de prise de 300 mg de ranitidine sur la cicatrisation de l'ulcère duodénal en poussée (prise en fin de repas du soir versus prise au coucher).

Recent studies have shown that a single dose of ranitidine given for 2 weeks at 6 p.m. resulted in a higher healing rate of duodenal ulcer than the same dose given at 10 p.m. Our study was designed to confirm these results in a large population in France. Three hundred and fifty patients with endoscopically proven duodenal ulcer were randomly assigned to open treatment with ranitidine 300 mg, immediately after dinner (dinner group), or at bedtime (bedtime group). Endoscopy was performed after 2 and 4 weeks. Forty six patients were excluded from analysis (default: 3, date of endoscopies not respected: 43). Of the 304 patients analysed (mean age: 45.5 years, sex ration M/F: 3.2), 146 received ranitidine after dinner, 158 at bedtime. Age, sex, ethnic groups, smoking habits and alcohol consumption were comparable in the two groups. At endoscopy, before treatment, the mean diameter of ulcers was greater in the bedtime group than in the dinner group (bedtime: 9.6 mm, dinner: 7.9 mm). Healing rates after 2 weeks were 58 p. 100 in the dinner group and 40 p. 100 in the bedtime group (p = 0.002). After 4 weeks treatment, cumulative healing rates were 87.5 p. 100 and 83.5 p. 100, respectively. Smoking had an influence on healing after 2 weeks but not after 4 weeks of treatment. In conclusion, a single dose of 300 mg of ranitidine resulted in a higher healing rate of duodenal ulcer when given immediately after dinner than when given at bedtime.

[Blood pressure control and quality of life: a comparative multicenter double-blind and cross-over trial of labetalol and captopril]. / Contrôle tensionnel et qualité de vie: essai multicentrique comparatif en double-aveugle et croisé du labétalol et du captopril.

The purpose of this multicenter randomised, double-blind and cross-over study was to compare the antihypertensive effects of labetalol (L) and captopril (C) in 42 moderate hypertensive patients (mean age: 52 years). The drugs were given during two 4-weeks periods at the end of which the systolic (SBP) and diastolic blood pressures (DBP) were measured at rest in supine and standing positions. The assessment of the quality of life was realized with 4 scales completed by the practitioner [anxiety, depression, well-being, visual analog scale (VAS)] and 4 scales of auto-assessment completed by the patient [2 VAS, well-being, sub-scale of pleasure]. At the end of the first treatment's period (D28), both drugs had decreased significantly supine SBP and DBP (p less than 0.001), standing DBP (L = p less than 0.01; C = p less than 0.05), while only L lowered supine SBP (p less than 0.01). The cross-over analysis was unable to conclude, due to the number of patients and a significant interaction which reduced its power. Thus the effect of the first treatment's period seemed to influence the efficacy of the second one. The percentages of patients with a controlled BP were respectively: after 4 weeks of treatment, L = 61 p. 100 vs C = 42 p. 100 and at the end of study (D56), L = 67 p. 100 vs C = 64 p. 100. The cross-over analysis didn't show any difference between the effects of L and C on the quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypertension in the elderly. Comparison of the efficacy and tolerability of labetalol and nifedipine. A multicenter, randomized, single-blind study]. / HTA du sujet âgé. Comparaison de l'efficacité et de la tolérance du labétalol et de la nifédipine. Etude multicentrique, randomisée, en simple insu.

This randomized multicentre study in elderly hypertensives with two unbalanced groups (2 patients under labetalol for 1 patient under nifedipine) compared the efficacy and safety of labetalol, whose dosage could be adjusted (1, 2, then 3 tablets/day) according to blood pressure level (BP greater than or equal to 160/95 mmHg), to that of nifedipine given at its recommended dosage (2 tablets/day). The treatment period lasted 6 weeks (D42). The main judgment criteria was the rate of patients with normalized BP under treatment (SBP less than 160 and DBP less than 95 mmHg). The analysis was carried out on 170 patients, 112 labetalol and 58 nifedipine. Both groups were homogeneous when entering into the study. The only difference was a higher rate of smokers in the nifedipine group compared with labetalol's (29% vs 13%). The rate of patients with normalized BP (SBP less than 160 and DBP less than 95 mmHg) were 66% in the labetalol group and 48% in the nifedipine's (p less than 0.05). Treatment withdrawals for all causes during the study were more frequent in the nifedipine group (19%) than in the labetalol's (6%). Treatment withdrawals for adverse events occurred in 3.5% of patients in the labetalol group and in 12% of the nifedipine's. The overall adverse events rate was 9% with labetalol and 29% with nifedipine (p less than 0.001). In this comparative study in elderly hypertensives, labetalol given in a dose titration schedule proved significantly superior to nifedipine, given at recommended maximal dosage, in terms of both BP control and side effects profile.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemodynamic effects of labetalol on the humeral artery of the hypertensive patient. A double-blind study versus placebo]. / Effets hémodynamiques du labétalol sur l'artère humérale du sujet hypertendu. Etude en double-aveugle contre placebo.

Forearm arterial hemodynamics, including measurements of brachial artery diameter and compliance with pulsed Doppler velocimetry were determined before and after acute administration of labetalol in patients with sustained essential hypertension. Labetalol caused a significant and rapid drop in blood pressure with a decrease in forearm vascular resistance and an increase in brachial blood flow. Brachial artery diameter did not change while arterial compliance significantly increased. The study provided evidence that labetalol caused a shift of the pressure-brachial artery diameter curve toward lower values of blood pressure, indicating a pharmacological effect of alpha and beta blockade on the hypertensive arterial wall.

[Arterial hypertension in the elderly. Double-blind study versus placebo of the efficacy and tolerability of an alpha-beta blocker: labetalol]. / Hypertension artérielle du sujet âgé. Etude en double-insu contre placebo de l'efficacité et de la tolérance d'un alpha-bêtabloquant: le labétalol.

The purpose of this study was to investigate the efficacy and safety of labetalol, an alpha and beta-adrenergic receptor blocking agent in 32 patients aged from 72 to 97 years (mean = 85 years) with blood pressure (B.P.) greater than or equal to 160/95 mmHg. This study was carried out in a double-blind, randomized, placebo-controlled design. After 6 weeks of treatment with labetalol (mean dose = 235 +/- 47.5 mg/day), the systolic pressure was lowered from 187 +/- 24 to 145 +/- 28 mmHg (p less than 0.001) and the diastolic pressure from 98 +/- 10 to 82 +/- 9 mmHg (p less than 0.001). Likewise, in the placebo group, both systolic and diastolic pressures were significantly reduced but the changes were significantly greater in the labetalol group, -33 +/- 26 versus -13 +/- 20 mmHg and -14 +/- 10 versus -8 +/- 14 mmHg respectively. Labetalol achieved B.P. control (160/95 mmHg) in 64% of the treated patients, compared to 40% in the placebo group. Two patients on labetalol discontinued their treatment due to side-effects (one bradycardia and one cutaneous reaction) compared with one patient on placebo (cardiac failure). Two other cases in the labetalol group had side-effects (one fatigue and one dizziness) which prevented increasing the treatment as necessary.

[Salmeterol and prolonged treatment of asthma: international clinical data]. / Salmétérol et traitement prolongé de l'asthme: données cliniques internationales.

Salmeterol is an original molecule with a selective-beta-2-sympathomimetic effect which is intended to a prolonged treatment of asthma. This inhaled preparation has a long duration of action which points to its use on a BID regimen. Results of the phase III development has been assessed in 2,277 subjects. Salmeterol administered at a dose of 50 micrograms morning and evening results in a marked increase in FEV1, which remains superior to 15% by comparison with baseline 12 hours after the last dose in the majority of subjects. In the specific case of more severe asthma (FEV1 less than 50% of predicted), the use of 100 micrograms morning and evening allows for an extra-improvement in FEV1. In the majority of studies, salmeterol has resulted in an almost complete remission of the clinical symptomatology: disappearance or major diminution in the use of inhaled salbutamol administered as a rescue medication on a PRN basis (during the day and at night) and of nocturnal awakenings, global improvement of clinical scores. Daily peak expiratory flow rates (morning and night values) are considerably improved (greater than or equal to 50 l/min) with a significant reduction of daily swings. Lung function tests are also very significantly improved. Salmeterol has proved to be largely superior to the comparison medications, salbutamol taken at a dose of 200 micrograms four times a day, and optimal therapy with theophylline. Clinical acceptability of salmeterol is good and is not different from salbutamol.

[First-line treatment of febrile episodes in leukemia in adults. Randomized, multicenter study of ceftazidime in single antibiotic therapy versus a cefotaxime-amikacin combination]. / Traitement de première intention des épisodes fébriles des leucémies de l'adulte. Etude randomisée, multicentrique de la ceftazidime en monoantibiothérapie versus l'association céfotaxime-amikacine.

A prospective study was conducted in 10 haematology departments of university hospitals on 174 leukaemic patients with prolonged bone marrow aplasia and presenting with a febrile episode. The patients were allocated at random to either ceftazidime or the cefotaxime-amikacin combination. The two treatment group were similar as regards age, sex, underlying blood disease, duration of neutropenia, presence of a venous catheter, type of digestive tract contamination, clinical and bacteriological findings. Results were assessed mainly on the course of the fever at 48 hours and on the clinical and bacteriological changes observed until the patients came out of aplasia. Documented infections were specifically analyzed. There was no significant difference in terms of success or failure between the two treatment groups. Ceftazidime administered as monotherapy proved as effective as the cefotaxime-amikacin combination in the empirical first-line treatment of febrile episodes in leukaemic patients with neutropenia.

[Use of inhaled beclomethasone dipropionate in adult asthma]. / Utilisation du dipropionate de béclométasone inhalé dans l'asthme de l'adulte.

Beclomethasone dipropionate has now been used for more than 10 years during which our knowledge of how to use inhaled corticosteroids has gradually improved: high dose initial treatment followed by progressive reduction down to the minimum effective dosage; administration in 2 daily doses when the asthma is stable and 4 daily doses in case of instability; mild and transient undesirable effects, often minimized by a correct use of the inhaler; effectiveness assessed from bronchial hyper-reactivity and respiratory function tests, reduction or avoidance of oral corticosteroid therapy, or results of association with other treatments, and in particular bronchodilators. When exactly should inhaled corticosteroid therapy should be started and how long should it be pursued are controversial points, but an early and prolonged treatment must probably be recommended.

[Controlled randomized prospective study of a ceftazidime-pefloxacin combination versus a ceftazidime-amikacin combination in the empirical treatment of nosocomial pneumonias and septicemias of resuscitation. Preliminary results]. / Etude prospective randomisée contrôlée de l'association ceftazidime-péfloxacine versus ceftazidime-amikacine dans le traitement empirique des pneumonies et septicémies nosocomiales de réanimation. Résultats préliminaires.

The preliminary results obtained in 212 patients from 20 intensive care units, suffering from pneumonia or nosocomial septicemia and treated at random with either ceftazidime + pefloxacin (CP) or ceftazidime + amikacin (CA) were analyzed. After exclusion of patients who did not comply with the protocol and of cases where no organism was isolated, 57 assessable patients received CP and 72 received CA. The cure rates achieved in infections due to a single organism were 85 per cent in the CA group and 63 per cent in the CP group. In infections due to multiple organisms, the cure rate was 74 +/- 2 per cent with both antibiotic regimens.

[Bronchial tolerance to inhalation of beclomethasone. Histologic and microbiologic study in asthmatic patients]. / Tolérance bronchique à l'inhalation de béclométasone. Etude histologique et microbiologique chez l'asthmatique.

The aim of the present study was to investigate the effects of a three months' treatment with beclomethasone dipropionate on the bronchial mucosa of asthmatic patients. Eleven patients suffering from a mild chronic asthma treated with inhaled salbutamol and theophylline were randomly assigned to receive either 1000 mu g of beclomethasone dipropionate (6 patients) or an aerosolized placebo (5 patients) in a double-blind manner. Bronchial biopsies and bronchial secretions were obtained through a fiberoptic procedure at the beginning and the end of the study. Repeated clinical and spirometric investigations were performed each month. Inter- and intra-group mean changes of clinical symptoms and of spirometric values were not significantly different. Pathogens were rarely found in bronchial aspirates and their occurrence did not seem to be influenced by the beclomethasone therapy. Sixty percent of the bronchial biopsies displayed pathological changes of the mucosa that observed at the beginning and at the end of the study; however, no sign of mucosal atrophy was noted.

[Efficacy and tolerability of cefuroxime-axetil in infections of the upper respiratory tract. Comparative study with cefadroxil]. / Efficacité et tolérance du céfuroxime-axetil dans les infections des voies aériennes supérieures et de leurs cavités annexes. Etude comparative au céfadroxil.

Cefuroxime-axetil is the first oral broad spectrum cephalosporin to be naturally stable in the presence of bêta-lactamases. The aim of this randomized trial was to evaluate the efficacy and safety of cefuroxime-axetil (250 mg twice daily after meal) with cefadroxil (1 g twice daily during meal) for the treatment of upper respiratory tract infection. In this study 150 patients were enrolled. Before treatment, the two groups were comparable. Clinical success was achieved for 94.3% of the patients treated with cefuroxime-axetil versus 90.4% for cefadroxil. Statistical significance was reached (p less than 0.05) concerning the number of days with facial pain for sinusitis (3 days for the cefuroxime-axetil treated group versus 4 days), the rate of normal tympanum at the second examination (58.3% vs 20% respectively) for otitis, and the number of day with painful dysphagia for tonsillitis (2.6 vs 3.8 days respectively). Cefuroxime-axetil was safe (a few advers events occurred, almost all gastro-intestinal). Cefuroxime-axetil is a safe and effective treatment of upper respiratory tract infections.

[Slow-release salbutamol in the treatment of nocturnal asthma. Result of a comparative study vs. long-acting theophylline]. / Salbutamol à libération prolongée dans le traitement de l'asthme nocturne. Résultat d'une étude comparative versus théophylline L.A..

In a multicentre, randomized, cross-over double-blind, double placebo trial the effectiveness and tolerability of slow-release oral salbutamol (SRS) were compared with those of long-acting (LA) theophylline (T) in the treatment of nocturnal asthma of adults. Forty-nine patients (mean age 37 years) entered the study after a pre-trial period during which a placebo and inhaled salbutamol were used as reference and to test the criteria of inclusion. The number of awakenings due to asthma symptoms was the same with SRS, and T, falling from 1.27 in the pre-trial period to 0.44 under SRS and 0.42 under T. The scores of nocturnal asthma symptoms were improved with both types of treatment. The number of puffs of inhaled salbutamol necessary during the night decreased from 1.94 in the pre-trial period to 1.15 under SRS and 0.92 under T. The number of patients improved was exactly the same in both groups. The ventilatory parameters measured by respiratory function tests at different visits and daily by the patients themselves were also improved. The principal minor side-effects were tremor (5 cases) and irritability (3 cases) with SRS, and nausea (6 cases), headache (3 cases) and asthenia (2 cases) with T; an overdose of T resulted in malaise in one patients. It is concluded that slow-release oral salbutamol administered in doses of 8 mg b.d. is effective in controlling nocturnal asthma, easy to take and very well tolerated.