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The neuropsychiatric complications of histamine H2 receptor antagonists are poorly described in children. In this case report, lethargy occurred in a neonate treated with ranitidine. We urge caution when a histamine H2 receptor antagonist needs to be prescribed in such cases.

"Almost half of...over-45s born in French overseas departments and living in mainland France had plans to return overseas by the year 2000. The desire to return is more clear-cut among the 50 to 54 year olds. The younger people have yet to think seriously about retirement, whilst a number of the oldest individuals have already made definite plans." Data are from a survey carried out in 1992. (SUMMARY IN ENG AND GER AND SPA), (excerpt)

Genetic-controlled drug oxidation and acetylation were studied using dextromethorphan and caffeine as test compounds respectively in white Briton subjects (41 Britons and 27 Bigoudens considered as an ethnic group). Phenotyping was performed using the metabolic ratio (MR) calculated as the urinary output dextromethorphan/dextrorphan ratio and the urinary output of 5-acetylamino-6-formylamino-3-methyluracil (AFMU)/1-methylxanthine (1-MX) ratio in subjects given 40 mg of dextromethorphan and 150 mg caffeine respectively. Frequence distribution of hydroxylator and acetylator status in Briton and Bigouden groups showed no significant difference relatively to the French population. However the frequence distribution of the intermediate acetylator group in the Bigouden population was significantly different from that observed in the Briton population (7.4% vs 31.7%). The signification of this latter result was discussed on the basis of genetic transmission.

25-hydroxyvitamin D (25 OH vit D) plasma levels were measured according to the method of Preece et al. in 2 groups of subjects. Group 1 consisted of 10 adult controls in whom 25 OH vit D levels were measured 11 times at 1 month intervals. Group 2 consisted of 93 mother-child pairs including 71 neonates with normal plasma calcium levels (group 2a) and 22 with hypocalcemia (group 2b). In mothers, 25 OH vit D levels (group 2a: 12 ng/ml +/- 6.4 SD, n = 71; group 2b: 9.5 ng/ml +/- 3.5 SD, n = 22) were lower than in controls (25.1 ng/ml +/- 7.9 SD). In neonates, 25 OH vit D levels were correlated with those of their mothers; however there was no significant difference in neonates with or without hypocalcemia (group 2a: means = 11.9 ng/ml +/- 6.1 SD, n = 71; group 2b: means = 10 ng/ml +/- 4.1 SD, n = 22). 25 OH vit D levels in adults of group 1 were significantly correlated with exposure to sunlight, while no significant correlation was found in the mothers-children pairs of group 2. These results confirm the relationship of 25 OH vit D plasma levels of neonates with their mothers' but do not support the concept of a relation between low plasma levels in mother and the occurrence of hypocalcemia in neonates.

Maximal and minimal tobramycin concentrations were studied in 16 preterm and 4 fullterm neonates on the last day of a four-day course of tobramycin (infusion of 2 mg/kg twice a day). Maximal concentrations were under 6 mg/l in all patients and minimal concentrations were above 2 mg/l in one-third of the preterm babies. Next, tobramycin pharmacokinetic parameters were studied in 4 fullterm and 4 preterm neonates following a first infusion of 2 mg/kg. Half-life was 4 hours in term babies and 7.75 hours in preterm babies. Mean clearance was 0.118 l/h/kg and 0.06 l/h/kg in fullterm and preterm babies respectively (significant difference). Our results show that the 2 mg/kg dosage is too low and that, in preterm neonates, the 12-hour interval between infusions is too short.

The optically active lignan (-)-steganol was prepared from natural (-)-steganacin by selective deacetylation and was transformed, via a three-step sequence, into the corresponding 4', 6'-O-ethylidene- and thenylidene-beta-D-glucopyranosides, 3b and 3c, respectively, which are the analogues, in the steganol series, of the podophyllotoxin derived, and clinically useful, anticancer drugs, VP16-213 and VM26. Formation of the dimeric compound distegyl ether as a minor by-product was established. Complete elucidation of all the asymmetric centres was performed with the help of high resolution 1H-nmr studies at 400 MHz, COSY experiment at 500 MHz and X-ray analysis. Contrary to the podophyllotoxin series, the glycosylation of (-)-steganol occurred with retention of configuration, and all the synthesized compounds, including distegyl ether, exhibited the starting natural R configuration at C-5.

The authors describe a micromethod for the determination of blood concentration of theophylline in premature newborn infants. The method includes the specificity of separation in gas phase chromatography on a glass capillary column, and the sensitivity of thermo-ionic detection. After addition of isobutyl-3-methyl-1-xanthine, which constitutes an internal standard, extraction is performed in acid pH, with the mixture dichloromethane-isopropanol. The derivation consists of an N-pentyl reaction. Analysis was carried out on a glass capillary column SE-30 measuring 75 m x 0.5 mm. The technic used is simple and rapid. Its application in pediatrics has been particularly studied; the limit of quantitative detection was 0.1 mg/l. The plasma sample may be 0.05 ml. The reproducibility is about 2% in usual therapeutic doses. The specificity of the method has been widely debated, in particular the stages of extraction, derivation, separation and detection. The authors are convinced that the analyses requiring systems of specific detection, more and more widely used, require a chromatographic apparatus with a high power of resolution; this is illustrated by an example.

Neonates with severe cerebral damage are usually given phenobarbital. The authors study the various means of administration and the influence of term and concomitant mannitol administration on the plasma levels of the drug. They recommend the intravenous administration of a load dose and show that phenobarbital blood levels are significantly less in prematures or in children who have been given mannitol.

The measurement of cardiac output by electrical impedance plethysmography (non-invasive technique) may be disturbed by a certain number of factors, including respiration. The authors sought to demonstrate that this factor could be eliminated during measurement calculations. By this method, in 18 adult subjects with coronary artery disease, 50 measurements during respiration and 50 measurements in apnoea (paired measurements) of stroke volume and of cardiac output were performed. Stroke volume was calculated using Kubicek's formula: SV = P(L2/Zo2) (dz/dt min)t Results were as follows: highly significant correlation between values for stroke volume obtained during respiration and in apnoea (r ;.9767; n=50; P < 0.001); highly significant correlation between values for cardiac output obtained under the same conditions (r = 0.9744; n=50; P < 0.001). The authors conclude that with the limits of certain technical conditions of measurement, respiration does not disturb measurements of stroke volume and of cardiac output by electrical impedance plethysmography.

The case of a female patient with longstanding epilepsy is reported. Many problems in achieving a satisfactory therapeutic regimen were encountered. They originated in storage of phenobarbital, which had been prescribed since childhood, interference between phenobarbital, dipropylacetic acid, and phenylhydantoins. Some pharmacokinetic principles are reviewed in the light of this clinical experience.

The authors describe a method of dosage of valproic acid by gas chromatography. The derivation consists of the synthesis of esters of the valproic acid using heavy alcohols. This method of derivation can be applied to other carboxylic acids.

Phenobarbital was used as first treatment in 198 subjects with different loading doses adjusted according to age, followed by a daily maintenance dose of 5 mg/kg. A loading dose was given per os to 136 infants in four groups and intravenously to 62 subjects in five groups (including 30 adults). We found that the intravenous route must be used for the rapid production of therapeutic plasma concentrations and accordingly we recommend it in intensive care. Posology of 20 mg/kg i.v. appears to be adequate in children up to 15 years old while a posology of 15 mg/kg seems to be too high in adults. The maximum probability of efficiency is delayed up to 12 h when phenobarbital is given per os. Various posologies were found to be adequate in infants except for premature newborns.

Blood levels of Maprotiline were analysed and their relationship to the clinical response was examined in 89 depressed inpatients, according DSM III criteria for Major Depressive Episode, given the drug treatment for 3 weeks. Maprotiline produced marked decreases in mean MADRS and COVI scale scores by the end of treatment. On day 21, no correlation between blood levels of Maprotiline and MADRS or COVI scores were found when all patients were considered. Nevertheless, significant correlations were observed on day 14 (r = .22; p less than .05 for MADRS and r = .23; p less than .05 for COVI scale). In addition, a significant correlation between MADRS or COVI scale scores and Maprotiline blood levels were observed on days 14 and 21 in subgroups of young patients, severe depression (high scores to clinical global investigations), during of at least 3 months, treated without other drug than Maprotiline and good responders.