Effects of acrivastine and terfenadine on skin reactivity to histamine.

The response to the histamine hydrochloride prick skin test was studied in 24 healthy volunteers who received, in random order and at least four days apart, acrivastine (8 mg), terfenadine (120 mg), and placebo. The tests were performed on either side of the back before and at the time of administration (single dose), then every 30 minutes for two hours, and every hour for the following four hours. Evaluation was based on the mean of two measurements of the surface area of the wheal-and-flare reaction accompanied by assessment of topical pruritus. The response to histamine was decreased markedly in the two active treatment groups. Although within one hour of injection, the activity of both antihistamines was consistently greater than that of placebo, the kinetics of action of the two products nevertheless differed; indeed acrivastine was active against flare and wheal earlier (within 30 minutes); terfenadine proved to be more active than acrivastine only on flare and only at the later times (four, five, and six hours). The safety study primarily demonstrated drowsiness in one-fourth of the patients receiving placebo and active treatment.

Efficacy and safety of low-dose aztreonam in the treatment of moderate to severe infections due to gram-negative bacilli.

One hundred fifty-three patients with moderate to severe infections due to gram-negative bacilli, including septicemia (60 cases), lower respiratory tract infection (32 cases), intraabdominal infection (40 cases), and urinary tract infection (21 cases), were treated with aztreonam (1 g every 12 h). This dosage is lower than usual. Criteria for inclusion in the study included documented infection due to gram-negative bacilli and a measurement of severity of disease of less than 12 (as defined by a Simplified Acute Physiology Score for the 115 cases of community-acquired infection). Other than aztreonam, no antibiotic active against gram-negative bacilli was allowed to be used for treatment. Seventy-one patients in whom gram-positive or anaerobic organisms were detected or suspected were given additional agents effective against the organisms. One hundred forty-one patients (92.2%) were cured; the mean duration of treatment was 10.9 +/- 4.0 days. None of the gram-negative bacilli initially isolated became resistant to aztreonam. Colonization, generally by a gram-positive organism, was observed in 27 patients and superinfection was observed in five. Aztreonam was well tolerated. This study suggests that a dosage of 2 g daily of aztreonam should be appropriate in the treatment of moderate to severe infections due to susceptible gram-negative bacilli.

Efficacy and safety of low dose aztreonam in the treatment of moderate to severe gram-negative bacterial infections.

One hundred and fifty-three patients with moderate to severe infections due to Gram-negative bacteria, including septicaemia (60 cases), lower respiratory tract infection (32 cases), intra-abdominal infection (40 cases) and urinary tract infection (21 cases), were treated with aztreonam 1 g every 12 h. This dosage is lower than usual. Criteria for inclusion included documented Gram-negative bacterial infections, and assessment of the severity of the disease by a scoring system for both community and hospital acquired infections. No other antibiotic active against Gram-negative bacteria was allowed. In 71 patients, in whom Gram-positive or anaerobic organisms were detected or suspected, additional agents effective against these organisms were administered. One hundred and forty-one patients (92.2%) were cured with a mean duration of treatment of 10.9 +/- 4.0 days. None of the Gram-negative bacteria initially isolated became resistant to aztreonam. Colonization, generally by a Gram-positive organism, was observed in 27 patients and superinfection in five. Aztreonam was well tolerated. This study suggests that a daily dosage of 2 g of aztreonam should be sufficient in the treatment of moderate to severe Gram-negative bacillary infections due to sensitive organisms.

[Double-blind study of the efficacy of an antiserotoninergic drug, pizotifen, in Duchenne's muscular dystrophy]. / Etude en double aveugle de l'efficacité d'un antisérotoninergique, le pizotifène, dans la myopathie de Duchenne de Boulogne.

In 40 patients presenting with Duchenne muscular dystrophy, a double blind therapeutic trial of 18 months was undertaken in order to appreciate the efficacy of pizotifen, an anti-serotoninergic drug. Quarterly evaluations were performed. Each of them included muscular testing on 31 pairs of muscles, timed tests, dynamometric study of the thumb-forefinger grip, functional testing, respiratory function tests, muscular enzyme determinations, parents' subjective estimation and search for side-effects. With respect to the evolution of Duchenne muscular dystrophy, this study did not show significant differences between pizotifen at a dose of 1.5 mg/day and placebo, except for a parents' preference for the drug.

Effects of long-term maintenance therapy with a new glucocorticoid, deflazacort, on mineral metabolism and statural growth.

Deflazacort was substituted for Prednisone (based on the equivalence 1 mg Prednisone equals 1.2 mg Deflazacort), during maintenance glucocorticoid therapy in 9 children, 5 with renal diseases and 4 with connective tissue or immunoproliferative disorders. Six patients received 0.26-0.35 mg/kg body weight (B.W.)/day and 3 0.48-1.2 mg/kg B.W. on alternate days, for 10-16 months. Except for a child with chronic juvenile arthritis, who was also unresponsive to Prednisone, the therapeutic effects of Deflazacort were excellent. Steroid side effects present in 8 patients decreased or disappeared. Plasma Ca, P, Mg, creatinine, alkaline phosphatase, iPTH(1-34), urinary excretion of Ca, cAMP, and TRP remained normal. Plasma iPTH(1-84) remained normal in 5 children; in the other 4 patients it increased from normal to slightly elevated values. On Deflazacort, plasma calcidiol concentrations were within the normal range in 6/8 patients prescribed daily doses of vitamin D2 (1,600-2,400 IU) or calcidiol (20 micrograms). Plasma 1,25(OH)2D levels monitored in 5 children were also normal. The osteoporosis, evaluated on the tibial cortico-diaphyseal ratio and the trabecular aspect of bone radiograms, present in 5 patients, persisted in 1 and improved in the others. On Deflazacort, statural growth proceeded normally in all subjects, with a modest acceleration of growth velocity in 3 children. These results seem encouraging for extending clinical trials with Deflazacort to the active phase of pediatric diseases requiring glucocorticoid.

Determination of the optimal dosage regimen of captopril + hydrochlorothiazide in the treatment of moderate arterial hypertension.

A multicentre controlled trial was carried out to determine the optimal dosage of a 2/1 combination of captopril plus hydrochlorothiazide (HCTZ) in mild hypertension at three doses against placebo in a 6 week double-blind trial. The number of patients was 111:27 received placebo; 26 were treated with captopril 25 mg plus HCTZ 12.5 mg (25/12.5); 25 with captopril 50 mg plus HCTZ 25 mg (50/25); and 33 with captopril 100 mg plus HCTZ 50 mg (100/50). A significant fall in blood pressure was seen in all four groups, but was greater with the active treatments. The percentage of patients who were normalized [diastolic blood pressure (DBP) less than or equal to 90 mm Hg] or good responders (10% fall in DBP) increased as a function of the dose. At Day 21, the antihypertensive effect of 50/25 was similar to that of 100/50, but greater than that of captopril 25-HCTZ 12.5. At Day 42, the antihypertensive effects of the three doses were similar. Tolerance data showed a higher incidence of side-effects with 100/50 than with the other dosages. Thus, 50/25 appeared to be the optimal dosage for the control of mild hypertension.

Sodium valproate monotherapy in childhood epilepsy.

154 patients with a mean age of 6 years 1 month were followed on valproate monotherapy for a period ranging from 5 to 27 months (mean 22 months). Absence epilepsies, benign myoclonic epilepsies and epilepsies with tonic-clonic seizures on awakening were the best controlled, followed by benign partial epilepsies and infantile spasms. Reduction to monotherapy resulted in improvement in 13 of 14 patients with primary generalized epilepsy. Sixteen per cent of the 154 patients suffered mild to moderate adverse effects. After cessation of treatment in 28 seizure-free patients, no recurrence was observed in absence epilepsy, benign myoclonic epilepsy, infantile spasms or benign partial epilepsy, whereas two thirds of the patients with generalized tonic-clonic seizures on awakening relapsed in the year following the cessation of the treatment.

[Ceftazidime absorption into bronchial secretions in mucoviscidosis patients]. / Etude de la pénétration de la ceftazidime chez les patients atteints de mucoviscidose.

Penetration of ceftazidime into bronchial secretions was studied in 23 patients, of which 18 had cystic fibrosis. Ceftazidime was used as the single drug for treating exacerbations caused by Pseudomonas aeruginosa. Dosage was 6 g/1.73 m2/day divided into three intravenous injections for 14 to 21 days. Bronchial secretion samples were obtained by fiber-optic bronchoscopy or physical therapy. Serum and bronchial secretion ceftazidime concentrations were assayed using a microbiological method. Ceftazidime concentrations in both media were lower in children than in adults : elimination half-life is shorter (1.7 h against 2.45 h in adults), extravascular distribution is faster, with earlier (1 h against 2 h in adults) achievement of the peak bronchial secretion concentration (2 micrograms/ml). The ratio of bronchial secretion concentration to concomitant serum concentration did not exceed 5% at the time of peak bronchial concentration. These results suggest that in cystic fibrosis patients, the faster and lower bronchial penetration of ceftazidime may be due to faster elimination as compared to adults. Although transient elimination of Pseudomonas aeruginosa was achieved in 12 study patients, our findings support the use of higher dosages or alternative administration modalities designed to increase in situ ceftazidime concentrations.

[Hypophosphatemic rickets in premature infants independent of vitamin D]. / Rachitisme hypophosphatémique du prématuré indépendant de la vitamine D.

The etiology and prevention of rickets in prematures infants are still controversial: insufficient storage or intake in minerals and/or vitamin D, immature vitamin D metabolism, necessitating early vitamin supplementation, for some associated with calcium and phosphate supplementation. The authors report a case of rickets which could be related to an immaturity of the tubular mechanisms of phosphate reabsorption, with a favourable outcome following an increase in calcium and phosphate intake.

Cardiac involvement in cystic fibrosis revealed by a ventricular arrhythmia.

Cardiac involvement in cystic fibrosis (CF) is characterized by acute cardiac failure in the infant with myocardial fibrosis found on pathological examination. In the older child with chronic pulmonary disease, cor pulmonale tends to predominate the clinical picture. We report the case of an adolescent with CF presenting with ventricular arrhythmia. Cardiac scan, repeated echocardiograms and Holter monitoring were suggestive of an infiltrative process. We propose this case to be similar to those of CF in infants with cardiac involvement.

[Sodium valproate (Na VPa) monotherapy in childhood epilepsy ]. / Monothérapie par le valproate de sodium dans les épilepsies de l'enfant.

80 epileptic children were treated with sodium valproate as a monotherapy for a mean duration of 15 months. The fits stopped in 50% and diminished in 27.5% of cases. The treatment was particularly efficient in primary generalized epilepsies (cessation in 77%, reduction in 18% of cases), in the photosensitive epilepsies, and in children with a normal mental development. Reducing a multiple treatment to valproate monotherapy resulted in behavioral improvement in 10 of 11 cases and in a reduction or even a discontinuation of the fits. Drowsiness, insomnia, hair loss, gastrointestinal disturbances and weight gaining were the most important side effects. Evaluations of the plasmatic levels in relation to daily doses allow to advise a mean daily dose of 20-30 mg/kg depending on the child's age.