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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.

Resume Le but de cet article est de faire le point, par l'analyse de deux etudes, sur l'efficacite et la tolerance dans les asthmes persistants moderes a severes de la fluticasone a demi-dose par rapport a celles utilisees pour deux autres corticoides inhales (la beclometasone et le budesonide). La premiere etude a permis de comparer chez de tels patients 1 000 μg/jour de fluticasone a 2 000 μg/jour de beclometasone sur six semaines en deux groupes paralleles et en double aveugle. La deuxieme etude a compare selon la meme methodologie la fluticasone a 800 μg/jour administree pendant douze semaines comparee au budesonide a la dose de 1 600 μg/jour. Les deux etudes montrent que la fluticasone a 800 ou 1 000 μg/jour est au moins equivalente a 1 600 μg de budesonide ou 2 000 μg de beclometasone dans le controle de l'asthme persistant modere a severe de l'adulte. Ces etudes cliniques confirment dans l'asthme persistant modere a severe que la fluticasone a demi-dose est aussi efficace que les autres corticoides inhales. Dans ces deux etudes, les evaluations de la tolerance systemique portent essentiellement sur les effets sur l'axe hypothalamo-hypophyso-surrenalien. L'une et l'autre montrent des effets favorables de la fluticasone sur la surrenale par rapport au produit de comparaison. Cependant, la pertinence clinique de ces etudes de tolerance portant seulement sur l'axe hypothalamo-hypophyso-surrenalien est discutee. D'autres etudes portant sur la tolerance osseuse apparaissent plus interessantes au niveau clinique. Apres analyse des donnees efficacite et tolerance, le facteur ratio benefice/risque de la fluticasone apparait superieur par rapport aux autres corticoides inhales.

Resume Les aerosols-doseurs representent la pierre angulaire du traitement medicamenteux de l'asthme. Cependant, leurs limites ont conduit au developpement de solutions alternatives dont les systemes a base de poudre. Deux conceptions d'inhalateurs a poudre multidoses s'opposent dans leur principe: ceux comme Diskus ® qui font appel a des doses unitaires, scellees, conditionnees en usine et ceux bases sur un systeme a poudre avec reservoir. Les etudes in vitro montrent que le Diskus ® apparait comme un inhalateur fiable, delivrant des doses de medicaments homogenes et regulieres, peu influencees par le debit inspiratoire et le niveau de prise du medicament par rapport a la duree de vie de l'appareil. Une inspiration a faible debit influence peu les doses liberees et la fraction de particules fines respirables. Ces performances sont expliquees par le principe de conception du Diskus ® : doses unitaires scellees et faible resistance a l'ecoulement. Par ailleurs, le Diskus ® est facile a utiliser d'emblee. La sensation de prise grâce au lactose et le compteur precis de dose sont deux points importants pour une majorite de patients. La comparaison des deux types d'inhalateurs permet de se faire une idee plus precise de leurs differences et doit faciliter la prescription du systeme le plus adapte a chaque patient.

Resume Si les experts ont etabli des recommandations pour la prise en charge de l'asthme, peu d'etudes sont consacrees a la pratique de terrain. Pour mieux connaitre l'attitude des medecins francais vis-a-vis de l'asthme chronique, une enquete a ete conduite aupres des medecins generalistes. Cette enquete prospective voulait preciser specifiquement la place de la mesure du souffle (debit de pointe et EFR) et les traitements de fond utilises. Les 4 015 medecins ayant repondu, âges de 41,8 ± 6,7 ans, exercaient pour moitie seuls, pour moitie en groupe ; ils etaient plus souvent installes en milieu urbain (58,9 %) que rural (41,1 %). Ils suivaient entre 10 et 20 malades asthmatiques dans 38,3 p. cent des cas. Plus de la moitie des medecins utilisent regulierement le debitmetre de pointe a la phase diagnostique, seuls 17 p. cent ne l'utilisent jamais. Les epreuves fonctionnelles respiratoires sont demandees par 50,4 p. cent des medecins une fois par an. La decision de mise sous traitement de fond depend plus de l'utilisation frequente des β2-mimetiques (32,8 %) que de l'existence d'une obstruction bronchique chronique (29,4 %), de l'existence de plusieurs genes respiratoires par mois (18,5 %), de reveils nocturnes (13,8 %) ou d'un asthme d'effort (5,6 %). Le traitement de fond comprend le plus souvent des corticoides inhales chez l'adulte (50,5 %) et des anti-allergiques chez l'enfant (38,4 %). La pratique medicale des medecins generalistes devant l'asthme chronique tend a se rapprocher des recommandations des experts, en particulier chez les medecins generalistes de 45 ans ou moins ; cependant l'utilisation precoce et prolongee des corticoides inhales en premiere intention dans l'asthme modere doit encore progresser.

Resume Le diagnostic et les choix des traitements de l'asthme dependent avant tout de l'intensite de la gene respiratoire. Une enquete aupres d'un echantillon representatif de 5 622 patients asthmatiques vus en medecine generale a travers la France a etudie la relation entre la gravite de l'asthme, la perception du souffle par le malade et la mesure du debit de pointe. La population adulte etudiee etait majoritairement constituee de malades de plus de 40 ans (58 %), la consultation etait dans 56,2 p. cent des cas une consultation de suivi regulier, l'asthme etait dans 75 p. cent des cas un asthme ancien. Le pourcentage de fumeurs est moins eleve que dans la population generale quelle que soit la tranche d'âge. Sur l'echelle analogique de 0 a 100 mm, quantifiant la « gene respiratoire , les patients de moins de 20 ans situent leur gene a 35 mm et les plus de 40 ans a 65 mm. Parallelement, le debit de pointe baisse de 425 l/min chez les 20–40 ans a 360 l/min chez les plus de 40 ans. Globalement, la gene respiratoire s'aggrave parallelement a la severite de l'asthme qu'elle soit mesuree subjectivement par echelle analogique ou objectivement par le debit expiratoire de pointe. En cas de baisse du debit expiratoire de pointe en dessous de 80 p. cent de la normale, 69,3 p. cent des patients ressentent une gene respiratoire mais 30,7 p. cent des patients n'en ressentent pas. A l'inverse parmi les patients ayant un debit de pointe superieur a 80 p. cent de la normale, 54,2 p. cent ne ressentent pas de gene respiratoire mais 45,8 p. cent se disent genes. Ainsi l'evaluation subjective du souffle ne reflete pas la mesure objective chez pres d'un malade sur deux : une mesure du debit de pointe au cabinet et au domicile, pour les patients qui sous-estiment leur trouble, est necessaire.

L'efficacite de la prevention d'un risque medicamenteux depend de la precision avec laquelle ses facteurs declenchants ou favorisants sont connus et de la qualite de l'information donnee a son sujet aux prescripteurs et aux utilisateurs. L'identification d'un risque devrait mettre a profit l'ensemble des donnees precliniques et cliniques disponibles pour la specialite pharmaceutique consideree et les confronter aux donnees existantes pour des medicaments partageant un meme mode d'action ou une meme strategie therapeutique. L'information doit s'appuyer sur un plan de communication adapte au contexte de la pathologie traitee, des alternatives therapeutiques existantes et du benefice attendu.

Effective prevention of drug-induced risks depends on an accurate understanding of their triggering or predisposing factors, and the quality of information on these available to prescribing practitioners and users. All preclinical and clinical data available on the proprietary medicinal product concerned should facilitate identification of a risk, and these data should be compared with existing data on drugs sharing the same mode of action or therapeutic strategy. This information should be based on a communication plan adapted to the context of the disease under treatment, the therapeutic alternatives available and the benefits expected.

Maintenance treatment of duodenal ulcer (DU) with ranitidine 150 mg/day was compared with placebo in a two year prospective multicentre randomised study. Three hundred and ninety nine patients were included (mean age: 44.7 years, M/F ratio = 2.47/1; 37.6% of smokers) in placebo (n = 202) and ranitidine (n = 197) groups. Efficacy was assessed by the length of time to the first ulcer pain attack (with or without endoscopic confirmation) or DU complication. One hundred and fourteen patients of 399 (28.6%) had incomplete follow up. Actuarial survival curves of patients without ulcer pain (26 and 53% at two years in placebo and ranitidine groups, respectively) were significantly different (p < 0.0001). Endoscopies were performed depending on physicians' decision (mainly where there was severe pain or complication). Patients without relapses from endoscopy were more frequent in the ranitidine group (83%) than in the placebo group (47%, p < 0.0001). A greater incidence of complications, mainly bleeding, was also seen in the placebo group (13 complications v two in the ranitidine group, p < 0.002). No factor predicting DU relapse was identified. No important side effect was encountered. Ranitidine 150 mg/day is effective and well tolerated in preventing ulcer pain attacks and DU complications for up to two years.

The present study was designed to assess the role of the adrenergic tone in the regulation of carotid arterial compliance during aging. An experimental model of in situ isolated carotid arteries has been used to evaluate the elastic properties of the arterial wall in young (3-mo-old) and older (18-mo-old) Wistar rats. Binding experiments were performed in the same strain of rats to evaluate alpha 1- and beta-adrenoceptor affinity and density. In a third set of experiments, structural parameter of the carotid artery in younger and older rats was evaluated. Arterial distensibility (compliance per unit of volume) was significantly lower in older rats. This was associated with a significant thickness of the media (45.6 +/- 2.8 vs. 57.5 +/- 5.7 microns, P < 0.01) and increased collagen content in older rats (4,420 +/- 310 vs. 7,320 +/- 850 microns 2/mm, P < 0.001). However, carotid arterial compliance was not altered in older rats because of the significant increase in cross-sectional area with aging. Aging did not affect alpha 1-adrenoceptor affinity and density, whereas it decreased beta-density without changing their affinity. Pharmacological stimulation of alpha 1-adrenoceptor with phenylephrine (10(-5) M) decreased compliance in older but not in younger animals. Blockade of these receptors with prazosin or labetalol increased compliance in younger and had no effect on older rats. beta-receptor stimulation with isoproterenol or blockade with propranolol had no effect in any of the studied groups. We suggest that with aging there is an increased vasoconstricting effect of alpha-agonists and a decreased vasodilatative action of alpha-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Resume La ceftazidime est aujourd'hui largement utilisee dans les infections hospitalieres nosocomiales. Sa place dans le traitement des infections communautaires chez les patients a fort potentiel de complications est a mieux definir. Chez ce type de patients, la presence de criteres predictifs de la severite de l'infection, a l'arrivee en service hospitalier, influe sur le choix de l'antibiotherapie probabiliste. L'âge et la pathologie associee sont des elements essentiels. Les caracteristiques microbiologiques, pharmacocinetiques et cliniques de la ceftazidime permettent de preciser ses indications dans ces infections communautaires severes, la place de la monotherapie et les posologies a preconiser.

Resume Les resultats d'un protocole de traitement empirique de 223 episodes febriles chez le neutropenique montrent 1) que la frequence des septicemies inaugurales a germes a Gram positif atteint 50 %, 2) que l'indication de la vancomycine ne peut attendre la documentation bacteriologique, 3) qu'il est possible de donner une monoantibiotherapie par ceftazidime seule a la dose de 3g/j, mais 4) que les surinfections a germes a Gram negatif sont moins frequentes lorsqu'on l'associe a l'amikacine, et 5) que les surinfections a germe a Gram positif sont moins frequentes lorsqu'on associe la vancomycine a la ceftazidime.

The ketogenic diet has been successfully used in treatment of pediatric epilepsy for70 years. Few serious complications caused by the diet have been reported. We report complications that have been experienced by children receiving the ketogenic diet.In a 22-month period, we treated 52 children with the classic ketogenic diet and monitored them in a prospective manner.Five children (10%) experienced serious adverse events (AE) after initiation of the diet. Four patients (80%) were treated with valproate (VPA) in addition to the diet, as compared with 25 (53%) of the other 47 children. Two patients developed severe hypoproteinemia within 4 weeks of initiation of the diet, and 1 of them also developed lipemia and hemolytic anemia. A third child developed Fanconi's renal tubular acidosis within 1 month of diet initiation. Two other children manifested marked increases in liver function tests, 1 during the initiation phase and the other 13 months later.Clinicians who wish to use the ketogenic diet must be aware of the potential of serious AE and possible interactions of the diet with VPA.

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.

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.

Ondansetron and chemotherapy induced emesis.- Editorial.- Comparison of ondansetron and alizapride in the prophylaxis of lymphoma chemotherapy-indueed emesis.- Comparison of ondansetron with a combined regimen of alizapride and methylprednisolone in the prophylaxis of cisplatin-induced emesis in patients with lung cancer.- Ondansetron in paediatric patients.- A comparison of ondansetron and ondansetron plus dexamethasone in the prophylaxis of cisplatin-induced emesis.- Ondansetron: Dose schedules and duration of treatment.- Economic evaluation of the contribution of ondansetron in an anticancer centre.

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.

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.

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.

Infection is the first reason of mortality in children with bone marrow aplasia. It justifies the immediate treatment initiation before bacteriological cultures results. First line probabilistic treatment must have a bactericidal activity on the pathogens and must be atoxic. The empirical therapy consisted of ceftazidime 100 mg/k/d and vancomycine 40 mg/k/d three times a day. We treated 41 patients, ranged from 0.5 to 17 years (mean 9.5 years). 27 lymphoblastic leukaemias, 10 myeloblastic leukaemias, 4 lymphomas, presenting post therapeutic prolonged aplasia: PMN less than 500/mm3. 23 strains were isolated from 15 patients. 12 Gram+: 7 ceftazidime sensitive, 12 vancomycine sensitive and 11 Gram-: 10 ceftazidime sensitive. Only one is resistant to ceftazidime + vancomycine. Apyrexia was obtained in less than 48 hours in 36 patients. Mean treatment duration was 16 days. Hyperthermia relapsed 17 times and was susceptible to ampho B ten times, although no candida was isolated. When ceftazidime + vancomycine combination failed, other antibiotic treatment was ineffective. There were 4 superinfections (2 in blood, 1 enteric, 1 pharyngeal) and 2 germs were ceftazidime resistant.ceftazidime + vancomycine combination is a very effective treatment of infection in the neutropenic children: 88% success. 95% of the germs are sensitive to, at least, one of the 2 antibiotics. There are very few superinfections. Tolerance is excellent.

The aim of this multicenter, prospective randomized trial was to compare the efficacy and safety of cefuroxime-axetil and amoxycillin/clavulanic acid for the treatment of infectious bronchitis in the elderly patient. Between January and April 1989, 157 out patients aged 60 years or more and presenting with infectious bronchitis were treated with either cefuroxime-axetil (250 mg bid), or the association amoxycillin/clavulanic acid (500 mg/125 mg bid). The two treatment groups were comparable at the time of inclusion; the mean age was 70 years, 82% of the patients were febrile, 75% presented purulent expectoration, 24% had a history of chronic bronchitis and 19% received symptomatic treatment was NSAIDs. The mean duration of treatment was 9 days. Clinical efficacy was assessed by the investigators. While fever and cough resolved similarly in the two groups, statistically fewer patients presented persistent purulent expectoration in the cefuroxime-axetil treatment group than in the group receiving amoxycillin/clavulanic acid (2% and 13%, respectively, p = 0.03). The proportion of patients who reported at least one side-effect was 3.6% in the cefuroxime-axetil treatment group against 21.6% of those who received the association (p = 0.006).

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)

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)

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)

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.

Three hundred fifty-two patients from 20 intensive care units, suffering from pneumonia or nosocomial septicemia were treated at random with either ceftazidime + pefloxacin (CP) or ceftazidime + amikacin (CA). After exclusion of patients who did not comply with the protocol and of cases where no organism was isolated, 108 assessable patients received CP and 114 received CA. The cure rates achieved in infections due to a single organism were 82 per cent in the CA group and 62 per cent in the CP group. In infections due to multiple organisms, the cure rate was 67 per cent with both antibiotic regimens.

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.

The effects of labetalol on plasma lipoprotein metabolism were evaluated in a 3-month double-blind drug versus placebo study conducted on 30 consenting hypertensive patients, 15 of whom had normal plasma lipid levels and 15, minor type II hyperlipoproteinaemia; 20 patients received labetalol 400 mg/day and 10 the placebo. All patients remained in stable nutritional status throughout the study. Full clinical examination and blood sampling were carried out 30 days before, and on days 0, 30 and 90 of treatment. Whole blood was collected after 12 hours' fasting and immediately centrifuged prior to determination of plasma lipids (total cholesterol and triglycerides, by enzymatic assay), lipoprotein lipids (HDL, HDL2, HDL3, LDL, VLDL separated by ultracentrifugation in density gradient), apoproteins A1 and B (by laser immunonephelometry) and post-heparin lipoprotein lipase activity (PHLA). Significant changes in heart rate and systolic and diastolic blood pressures were noted in patients under labetalol but not in patients under placebo. Lipid and apolipoprotein levels were similar in both groups on day 0, and no significant variation in lipids, lipoprotein lipids and apolipoproteins were observed after 30 and 90 days of treatment with either labetalol or the placebo. At the end of treatment PHLA was unmodified in the group under placebo and raised in the group under labetalol (p = 0.05). The absence of changes in blood lipid values was found both in patients with normal lipidemia and in those with hyperlipidaemia. This study confirms that labetalol in doses of 400 mg/day has notable anti-hypertensive activity and, as previously reported and in contrast with other beta-blocking agents, is devoid of any adverse effect on lipid metabolism.

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.

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, whereas arterial compliance increased significantly. 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.

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.

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.

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)

The aim of this study was to evaluate, on a wide population of outpatients, the efficacy of ranitidine 300 mg given once a day at bedtime in duodenal and gastric ulcer. Healing rates observed on 1,208 patients were 85.2% (703/825) in duodenal ulcer, 79.5% (268/337) in gastric ulcer and 71.7% (33/46) in double localization, duodenal and gastric. Analysis of predictive factors of treatment failure showed no influence of smoking on the efficacy of ranitidine neither in duodenal nor gastric ulcer.

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)

The gastric pH of 8 healthy subjects was determined, in a continuous fashion, during three different 24 hour periods corresponding to the 3 following treatments: Placebo, ranitidine 150 mg twice per day, and ranitidine 300 mg in the evening. During each period, the feeding conditions were normal and standardized. The results are expressed in terms of the number of hours under a threshold pH value. In comparison with the placebo, ranitidine, regardless of its mode of administration, results in a significant decrease of the mean number of hours under pH 1.5, 2 and 3 during 24 hours; no significant difference was demonstrated between the two modes of administration in 24 hours. During the 12 night-hours, a single dose of 300 mg of ranitidine was more effective to ranitidine taken in 2 doses for pH thresholds of 2 and 3, while during the 12 day-hours, no difference was demonstrated for pH thresholds of 1.5, 2 and 3. The analysis of the mean pH graphs in relation to time, suggests that a single 300 mg dose is more effective than the same dose divided into 2 doses during the day. These results tally with the variations of ranitidine plasma levels in 24 hours. These results justify, from a pharmacological standpoint, the prescription of a single dose of ranitidine, in the evening.

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.

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.