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Biomedical subjects

G Olive

Publications and source records attributed to G Olive.

At least 145 records · Page 8Linked to original sources

Influence of aspirin on the hemodynamic effects of sublingual nitroglycerin.

We studied the possible interaction between aspirin and nitroglycerin (NTG) in seven healthy volunteers. Effects of NTG (0.8 mg sublingual spray) were assessed by the decrease in diastolic arterial pressure, increase in heart rate, and decrease in M-mode echocardiographic end-diastolic and end-systolic diameters of the left ventricle. Measurements were performed before and during 30 min after NTG. Plasma levels of NTG were monitored during the experimental procedure. Each of the following trials was repeated three times, in random order, in each volunteer: NTG without aspirin pretreatment, NTG 1 h after 1 g of oral aspirin, and NTG after 8 days of aspirin, 500 mg every 48 h. Aspirin at the 1-g dose level significantly increased the effects of NTG on diastolic blood pressure (p less than 0.05) and left ventricular end-diastolic (p less than 0.001) and end-systolic (p less than 0.001) diameters. Aspirin (1 g) significantly increased (p less than 0.01) mean NTG plasma levels from 0.24 +/- 0.13 ng . ml-1 (control) to 0.37 +/- 0.26 ng . ml-1. We conclude that pretreatment with 1 g of aspirin increases NTG plasma levels and therefore significantly enhances the pharmacodynamic effects of NTG.

Adult↗

Phenytoin monitoring in status epilepticus in infants and children.

Two successive protocols of phenytoin (PHT) plasma concentration monitoring were tested in 60 children with status epilepticus (SE). In each protocol, a loading dose of 15 mg/kg was injected and followed by three injections during the first 24 h. Clinical evaluation was performed at the end of the study by grouping patients into three classes according to seizure frequency during treatment: complete effect, partial effect, and no effect. In protocol 1, a complementary dose at the fourth hour was adjusted from individual plasma concentrations. Plasma concentrations at the 40th hour were within the therapeutic range in the 19 patients with complete effect (CE, mean 19 mg/L) and in the 5 patients with no effect (NE, mean 23 mg/L) whereas in the 11 patients with partial effect (PE), plasma concentrations were higher (mean 31 mg/L). In protocol 2, we added monitoring of the doses injected at the 16th and 24th hours to prevent the increase in PHT concentration noted in protocol 1. All patients but 1 were classified as either CE (13 patients) or NE (4 patients). In NE patients, average plasma concentration at the 40th hour (mean 10.5 mg/L) was lower than in CE patients (mean 15.7 mg/L). In both protocols, the NE patients were the youngest. In SE, PHT doses should be adjusted according to plasma concentrations to avoid overdosage and paradoxical inefficacy. Younger children had lower concentrations and appeared to respond less well than older children, but the etiology of SE may also play an important role.

Adolescent↗

Magnesium and thermoregulation. I. Newborn and infant. Is sudden infant death syndrome a magnesium-dependent disease of the transition from chemical to physical thermoregulation?

The sudden infant death syndrome (SIDS) remains a leading cause of death during the first year. The common epidemiological and pathological data which characterize SIDS include the curve for age at death (with 3 months as modal age), the stigmata of early maternal intrauterine injury, the seasonal predominance in winter, and the absence of an adequate cause of death at autopsy. Some data characterize risk factor subgroups: for example low socioeconomic level, environmental pollution, stress, and mistakes in baby care. Symptoms before death may be lacking, they may be common and non-specific, or rarely they may be acute, corresponding to "apparent life-threatening events" (ALTE). SIDS may be a magnesium-dependent disease of the transition from chemical to physical thermoregulation. This theory originates from a synthesis of our present knowledge of SIDS, maternal magnesium status, and thermoregulation in the baby. It is consistent with all the epidemiological and pathological prerequisites characterizing SIDS. It eliminates the hiatus between relatively minor thermal stress and induced lethal thermal stroke. Logical scepticism about the role of an implausible lethal superacute magnesium deficiency is no longer justified with regard to well established chronic marginal magnesium deficiency. Further experimental and clinical research will be interesting, i.e. ex vivo studies on brown adipose tissue (BAT) and magnesium deficiency under various conditions of thermal exposure. But even now the theory leads to three therapeutic consequences: (1) the need to define the importance of magnesium deficiency in diagnosis and treatment of ALTE; (2) an assessment of the use of new techniques of rewarming (i.e. extracorporeal circulation) in hypothermia cases to distinguish cot death from "apparent death"; (3) investigation of the prevention of SIDS with magnesium through a blinded and randomized multicentre prospective cooperative study of magnesium supplementation in pregnant and lactating women, followed not only in the mother, fetus, and neonate at birth, but also through the first year of life.

Body Temperature Regulation↗

Effect of growth hormone on caffeine metabolism in hypophysectomized rats.

Two groups of six male Sprague-Dawley hypophysectomized rats (operated on day 0), 8 weeks old, treated by sc tetracosactid (ACTH, 10 micrograms every 24 hr), thyroxine (5 micrograms/100 g every 24 hr) and desmopressin (240 ng/kg/24 hr continuous infusion) received SC either saline (group I) or human growth hormone (hGH, 120 micrograms/24 hr) (group II) continuous infusion. ACTH and thyroxine were administered on days 7-19 and desmopressin and hGH on days 8-19, after surgery. They received po caffeine 4 mg/kg as citrate salt on day 15. The 0-12, 12-24 and 24-48 hr urine samples were collected after caffeine administration. Caffeine and metabolites concentrations in urines were determined using HPLC. Effect on hGH on caffeine metabolism was assessed comparing group I and group II. In 0-48-hr urine, 1-methylxanthine (154 +/- 169 pmol/g) and 3-7-dimethyluric acid (5.57 +/- 19.3 pmol/g) in group II were significantly lower than in group I (391 +/- 340 pmol/g and 262 +/- 338 nmol/g, respectively) (p less than 0.05). Other metabolites (6-amino-5-(N-methyl formylamino)-1,3-dimethyluracil included) excretion was not altered. Total, N3-, N7- and N1-demethylation ratios on 0-48 hr urine were not modified by hGH treatment. However, demethylation ratios on 12-24 and 24-48 hr (N3 + N7 + N1) and on 24-48 hr urine samples (N3 and N7) were significantly reduced in group II (p less than 0.05) suggesting an increase in the rate of appearance of demethylated metabolites during hGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Optimal dose of acetaminophen in children].

Acetaminophen is an antipyretic and analgesic drug frequently prescribed in children. Unlike aspirin, the recommended doses for acetaminophen are different in France (20-30 mg/kg/24 h) and in the USA (65 mg/kg/24 h). The authors reviewed literature data, looking for the scientific basis of these recommendations in children. The antipyretic effect of a 7-20 mg/kg single oral dose was demonstrated versus placebo. A dose-effect relationship was established: 20 mg/kg as a single oral dose was more effective than 10 mg/kg while 5 mg/kg had little antipyretic effect. More than 10 mg/kg were required to keep on average the temperature 1.5 degrees C below the starting point for 6 hours. There was no significant difference regarding the antipyretic effects of a single 10-15 mg/kg dose using suppositories or oral suspension, although there was a greater consistency of response with the oral suspension. There was no significant difference concerning the antipyretic effect between a 10-15 mg/kg acetaminophen oral dose and the same dose of aspirin. The analgesic effect of a single 10-15 mg/kg oral dose was also demonstrated versus placebo in children. Plasma concentrations between 4 and 18 mg/l seem appropriate to obtain an antipyretic effect. Half-life is 1-3.5 h. Based on these data different dose regimens including an initial loading dose have been proposed. The simplest one is as follows: 25 mg/kg loading dose and 12.5 mg/kg every 6 h as maintenance dose.

Acetaminophen↗

[Drug surveillance in children].

For the last decades, children have been the victims of severe and spectacular drug adverse reactions. Several risk factors explain the sensitivity and specificity of childhood to drug adverse effects. Newborn baby and infant are particularly affected. Three types of adverse effects which affect more specifically children, should be considered: a) Same effect as in adult but increase in intensity. b) Effects resulting from an interference with maturation and growth processes. c) Delayed reactions appearing a long time after drug exposition. Methods use to detect and collect drug adverse effects in children are not theoretically different from those used for adult patients except being more difficult to implement. A long term follow-up of adverse effects should be systematically organised for new drugs intend for children.

Child↗

Caffeine metabolism in liver slices during postnatal development in rats.

The metabolism of caffeine was investigated in liver slices from newborn, preweanling, postweanling, and adult rats. All metabolites were identified and quantified by HPLC without using radioactive compound. Caffeine metabolism underwent dramatic changes during maturation in rats. The specific activity of the enzyme system was extremely low when liver slices from 1-day and 7-day-old rats were used. This capacity increased gradually with increasing age and reached a peak following weaning at 21 days of age. In rat liver slices, N-1 demethylation to theobromine was the main pathway of in vitro caffeine metabolism at all ages. Theobromine represented 25% of total caffeine metabolites at day 1 and about 40% at all others ages. 1,3,7-6-amino-5-(N-formylmethylamino)-1,3-dimethyluracil is a minor metabolite in newborn (1-day-old), preweanling (7-day-old), and adult rats (120-day-old), but an important metabolite in postweanling rats. Conversely, 1,3,7-trimethyluric acid is a major metabolite in newborn and adult rats and a minor one in preweanling and postweanling rats. This liver slices model could be used as a simple and versatile model to study metabolism during maturation.

Animals↗