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Biomedical subjects

Y Furet

Publications and source records attributed to Y Furet.

At least 37 records · Page 2Linked to original sources
PubMed1988

[Onset of convulsive crises with theophylline therapy at therapeutic doses].

Six patients treated with theophylline, including five with advanced chronic obstructive pulmonary disease, developed generalized seizures with serum theophylline concentrations ranging from 7 to 21 mg/l. Cerebral computed tomographic scans showed a small sylvian infarction in one patient. In the other five patients nothing, except theophylline, could account for the seizures. There were no clinical signs of theophylline toxicity prior to the failures, all of which had a favourable outcome. Patients with acute exacerbations of chronic obstructive pulmonary disease seem to be prone to develop generalized seizures when treated with theophylline.

Aged↗
PubMed1988

[Comparison of plasma levels of amoxicillin administered by oral and intravenous routes in neonatal bacterial colonization].

Twenty-one full-term neonates who had a diagnosis of bacterial colonization were randomly assigned to receive amoxicillin 40 mg.kg-1 every 12 hours by either IV or oral route. Plasma levels of amoxicillin were assayed by HPLC at 0.5 (H0.5), 2 (H2), 6 (H6), 9 (H9) hours after the amoxicillin dose for both administration routes and also at the end of the infusion for the IV route. Average levels of plasma amoxicillin with IV and oral routes were not different except at H0.5 where they were higher with the IV route. With oral route Cmax was measured at H2 (6 times) or H6 (4 times). At the end of the infusion, plasma levels were between 55 and 154 mg.l-1 (81 +/- 32 mg.l-1). They decreased quickly so half life of amoxicillin by IV route was between 1.79 and 8.9 hs (4.28 +/- 2.4 hs). They were always above MIC for germs encountered in neonates except at H9 twice with IV and once with oral route. Pharmacokinetic data of this study allow to use oral route for amoxicillin for bacterial colonization in neonates: this administration route could also be proposed in infections following IV route as soon as hemodynamic and gastrointestinal conditions permit. The efficacy of such an attitude could be evaluated by a clinical trial.

Administration, Oral↗
PubMed1987

[A new molecule in antiparasitic therapy: alpha-difluoromethylornithine].

Alpha-difluoromethylornithine (DFMO) is a specific irreversible inhibitor of ornithine-decarboxylase (ODC), key enzyme in the biosynthesis of polyamines, physiological compounds involved in cell multiplication. Pharmacokinetic studies of the drug revealed good oral absorption, low metabolisation and mainly urinary excretion. Short half-life (3 hrs to 3 hrs 30) implicates daily repeated administrations. DFMO is well tolerated, side effects being reversible on discontinuing drug therapy. They chiefly include diarrheas, hematological perturbations (thrombocytopenia) and hear losses (high dosages). Experimental studies show best results on trypanosomes: curative action in mice infected with Trypanosoma brucei brucei. DFMO is effective too against infection with sporozoïtes of Plasmodium berghei. Early clinical observations in African patients with Trypanosoma brucei gambiense sleeping sickness show favorable results: efficacy in both stages of the disease, without significant toxicity. Further trials are required to define optimal therapeutic applications. By the way, DFMO already seems to be a promising alternative to conventional therapy of African trypanosomiasis, expecting other indications in the field of antiparasitic chemotherapy.

Animals↗
PubMed1987

[Hepatitis due to nonsteroidal anti-inflammatory agents].

The extended prescription of non-steroidal anti-inflammatory drugs in medical practice involve numerous adverse effects. Among them, hepatic injuries, rather uncommon, are very diverse with regard to clinical type and evolution scheme, according to the derivatives used. Salicylates, when taken at high doses, increase serum transaminases, mostly without overt clinical symptoms. Phenylbutazone is obviously hepatotoxic: it induces cytolytic hepatitis, in some cases with fatal issue. Among the indole derivatives, indometacine was involved, especially in children; mixed hepatitis have been noted during sulindac therapy, mostly with favourable outcome. In the group of propionic acid derivatives, ibuprofen, pirprofen and naproxen have been implicated in hepatitis of various types; ibufenac and benoxaprofen were quickly retired after occasioning several deaths. Concerning others non-steroidal anti-inflammatory drugs, some cases have been reported with piroxicam and diclofenac. Hepatotoxicity mechanisms are often unknown; they appear different according to each drug. Besides, the rheumatic disease under treatment and pharmacokinetic particularities (sulindac, diclofenac) might be important in this view. Monitoring of serum hepatic-enzyme concentrations seems recommended for patients receiving non-steroidal anti-inflammatory for long time therapy.

Adult↗
PubMedDate not supplied

[Issues in therapeutic drug monitoring evaluation].

A reassessment of the interest of therapeutic drug monitoring (TDM) is needed for a better definition of its applications. It rests on the hypothesis of the existence of an interindividual variability of the dose-effect relationship, this variability being influenced by pharmacokinetic variability. Different types of endpoints were used in validation studies (pharmacokinetic, indirect, economic) and few studies have used clinical endpoints. The question should be: does TDM allow for a better dose adjustment than one based only on criteria other than drug concentration? Retrospective studies have a 'diagnostic test' approach and only prospective clinical trials will provide a real validation. Factors which limit the setting up of such studies are: the number of subjects to include, the often imprecise measurement of drug exposure and poor knowledge of the pharmacokinetic-pharmacodynamic relationship and its variability.

Dose-Response Relationship, Drug↗
PubMedDate not supplied

[Clinical relevance of N-acetyltransferase type 2 (NAT2) genetic polymorphism].

Polymorphic N-acetyltransferase (NAT2) is involved in the metabolism of several compounds relevant in pharmacology or toxicology, with diverse clinical consequences. Inter-ethnic variations in distribution of the acetylation phenotype are significant. The caffeine test is most often used to assess the acetylation phenotype and to identify rapid and slow acetylators. The NAT2 phenotype could account for the increased risk of certain side effects in slow acetylators treated with isoniazid (particularly peripheral neuropathies and lupus erythematosus), although therapeutic efficacy seems to be independent of the acetylation status. Hypersensibility reactions with sulfonamides (including Lyell and Stevens-Johnson syndromes) are more frequent in slow acetylators, who also show poor tolerance to sulfasalazine and dapsone. In contrast, myelotoxicity induced by amonafide is more frequent in rapid acetylators, probably because of increased production of a toxic metabolite of the drug. In carcinogenesis, NAT2 may play a protective role against bladder cancer, although studies have shown contradictory results. Slow acetylators may have a risk of developing primitive liver cancer. For lung cancer, data are not conclusive, but slow acetylation status may predispose to mesothelioma in subjects exposed to asbestos. No relation has been found between acetylation phenotype and breast cancer. Contradictory results were reported on its role in colorectal cancer. Non-smoking type 1 diabetics may be at increased risk of nephropathy if they are rapid acetylators. Parkinson's disease may be more frequent among slow acetylators, but again, data have shown contradictory results. Finally, a poor acetylator phenotype may predispose to atopic diseases.

Acetylation↗
PubMedDate not supplied

[Study of residual levels of delayed-action neuroleptics].

Pharmacokinetics of the depot antipsychotics are unclear and mainly depend on releasing from the depot site (according to a "flip-flop" model). Few data are available on residual plasma concentrations of those drugs. We have practiced 38 blood determinations among 15 patients treated by long-acting neuroleptics (10 by fluphenazine decanoate, 4 by flupentixol decanoate and 1 by pipotiazine palmitate). Radio Receptor Assay method was used (based on competition for dopamine receptors binding), with results expressed as chlorpromazine equivalents. They showed; a wide interindividual variability; considering each subject, intraindividual variability is attenuated; blood measurements are mainly higher than therapeutic ranges (especially for patients on fluphenazine decanoate). Those results might involve that some patients are overdosed, but other studies are needed in this way.

Adult↗
PubMedDate not supplied

[Epidemiology of pediatric paracetamol poisoning (retrospective analysis of calls received by the Poison Control Center of Tours)].

The authors analysed 101 phone calls received in 3 years and 8 months at the Poison Control Center of Tours for paracetamol poisoning in children under 15 years of age. 70% of children were between 1 and 5 years old, 15% under 1 year and 15% over 5 years old. The kind of poisoning differ according to age: iatrogenic in 93% of cases under 1 year old (medication given by parents; error in dosage); accidental in 85% of cases between 1 and 5 years old and "willful" poisoning (43%) or accidental (36%) over 5 years old. The average quantity of ingested paracetamol was low (58mg/kg). The delay before phone call from an individual or a doctor was usually quite short. The neurologic or digestive signs were present in 12% of the children. The outcome was uneventful in all cases indicating that this form of poisoning is being in childrens.

Acetaminophen↗