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Biomedical subjects

P Loiseau

Publications and source records attributed to P Loiseau.

At least 91 records · Page 5Linked to original sources
PubMed1994

Indeterminate third-generation recombinant immunoblot assay in hepatitis C virus infection. Group d'Etudes Moléculaires des Hépatites (GEMHEP).

Third-generation recombinant immunoblot assay is widely used for the validation of the serological diagnosis of hepatitis C virus infection. To determine whether indeterminate recombinant immunoblot assay 3.0 patterns may be associated with viral replication and liver disease, 89 indeterminate patterns were studied (67 c22n 14 c33c, 5 c100p and 3 NS5); 35 (39%) had immunosuppression. Serum alanine aminotransferase activity was increased in 49 (55%); HCV RNA was evidenced through polymerase chain reaction in 52 (58%). The observation of indeterminate recombinant immunoblot assay 3.0 justifies investigation of liver disease and search for HCV RNA, since a large proportion of individuals with such patterns are hepatitis C virus-infected.

Adolescent↗
PubMed1993

Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial.

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.

Adolescent↗
PubMed1993

In vivo and in vitro correlation of microsomal epoxide hydrolase inhibition by progabide.

Progabide was investigated as a potential inhibitor of microsomal epoxide hydrolase as a result of reports of elevated levels of carbamazepine-10,11-epoxide after coadministration of progabide and carbamazepine to patients with epilepsy. The formation clearance of carbamazepine transdihydrodiol after administration of carbamazepine-10,11-epoxide to healthy volunteers was decreased 26% by progabide. Therapeutic concentrations of progabide inhibited S (+)-styrene oxide hydrolysis in human liver microsomes (inhibition constant [Ki] = 1.9 mumol/L) and purified human liver microsomal epoxide hydrolase (Ki = 4.4 mumol/L). A mixed competitive and noncompetitive mechanism of inhibition best described the effect of progabide on microsomal epoxide hydrolase; the most potent inhibition was competitive. A similar model described the inhibition by the acid metabolite of progabide, although inhibitory concentrations are higher than concentrations observed after progabide therapy. An excellent agreement between the in vivo and in vitro inhibitory potencies of progabide suggests that potential inhibitors of this important detoxification enzyme can be predicted in vitro.

Adult↗
PubMed1993

Measurement of in vivo microsomal epoxide hydrolase activity in white subjects.

An impairment or hereditary defect in microsomal epoxide hydrolase is considered a possible risk factor for drug and chemical toxicity. However, nothing is known about variability of in vivo epoxide hydrolase activity in humans. Our objectives were to develop and test a simple pharmacokinetic approach for measuring microsomal epoxide hydrolase activity in a population. After administration of carbamazepine-10,11-epoxide (100 mg), oral clearance showed a nearly linear relationship to the log (transdihydrodiol/epoxide) urine ratio in the 24- to 36-hour interval (log metabolic ratio). Intrasubject variability was assessed by administering the epoxide twice to 13 subjects (1- to 4-month interval); the log metabolic ratio did not change significantly (mean difference, 11%; paired t test, p = 0.79). In 110 healthy white adults, the log metabolic ratio ranged from 1.28 to 2.05 (mean +/- SD, 1.68 +/- 0.155). Outliers indicating enzyme-deficient phenotypes were not observed, and the frequency distribution was unimodal normal. The log metabolic ratio detected pronounced inhibition of epoxide hydrolase by valpromide (six subjects; median ratio, 0.91) and induction by phenobarbital/phenytoin (six subjects; median ratio, 2.42). We conclude that distribution of microsomal epoxide hydrolase activity in a study group can be measured pharmacokinetically by use of carbamazepine epoxide.

Adolescent↗
PubMed1993

HLA-DR and -DQB1 genotyping in a Chinese population.

Using molecular biological methods, 58 unrelated Chinese from Shanghai were typed for HLA-DR and DQ. The Shanghai population possesses the principal HLA-DR and DQ characteristics of the oriental populations but with an increase of the DRB1*12 allele. So HLA typing of populations appears to be important not only for anthropological studies but also for transplantations and HLA associations with diseases.

Alleles↗
PubMed1993

[Vascular hemi-parkinson disease].

A case of unilateral dopa-responsive parkinsonism of gradual onset in a 65 year-old woman suffering from severe ischemic lesions of the contralateral striatum is reported. This case appears to be an example of the rare entity of vascular parkinsonism.

Aged↗
PubMed1993

[Polysaccharide bodies: an unusual finding in a case of temporal epilepsy. Review of the literature].

Massive occurrence of polyglucosan bodies (PB) was found in the surgically removed temporal lobe of a 34 year-old woman presenting with complex partial seizures. The term of PB was proposed in order to group Lafora bodies (LB), corpora amylacea (CA) and Bielschowsky bodies (BB) on the basis of their biochemical similitude. A rigorous histochemical differentiation between these anomalies appears to be impossible at present. LB, BB and CA are mainly made up of glucose polymers i.e. polyglocusans. The pathway(s) leading from glycogen accumulation to PB formation is still unknown. PB are a hallmark of two diseases: Lafora disease and adult polyglucosan body disease. PB have occasionally been reported in rare cases of a variety of other neurological diseases. In all cases they were located within the neurons. This site characterizes Lafora bodies. BB are intraneuronal inclusions but restricted to neurons of the external pallidum. CA occur predominantly in the astroglia during the course of ageing. The significance of these structures depends on their regional distribution. The resemblance does not imply a common etiology for all conditions in which such bodies occur; it is probably due to the sharing of the final path in their causative pathway. Our case does not correspond to any of the classical diseases in which PB have been found. In our opinion, the patient exhibited a localized form of glycogen storage disease.

Adult↗
PubMed1993

Trypanocidal activity and platinum plasma kinetics of cis-Pt pentamidine iodide in Trypanosoma brucei sheep model.

The trypanocidal properties of cis-Pt pentamidine iodide have been studied on the T. b. brucei sheep model. The compound was evaluated on the lymphatic-plasma phase of the disease and appeared to be active on the circulating parasites. Cis-Pt pentamidine iodide was active at 5 mgl.kg-1 in one single dose both in mouse and sheep trypanosomiasis models. The chemotherapeutic index was about 200 in the mouse. As we observed previously with the chloride derivative, platinum plasma values for cis-Pt pentamidine iodide were rather constant between 24 and 48 hours. The nature of the salt associated to cis-Pt pentamidine had a direct effect on the compound kinetics. The iodide compound was distributed quickly and largely within deep compartments according to a monocompartmental model. The theoretical volume of distribution was 6.41.kg-1 for a 100% absorbed fraction. The two iodide ions of the complex probably played an important role in the compound kinetics mainly due to the extended release effect. The iodide salt of cis-Pt pentamidine could therefore be used in chemoprophylaxis of African trypanosomiasis.

Animals↗
PubMed1992

Unexpected consistent involvement of V beta gene segments in inappropriate T-cell receptor beta gene rearrangements occurring in B-lineage acute lymphoblastic leukemias.

T-cell receptor beta (TCR beta) gene rearrangements occur in a third of early B-cell acute lymphoblastic leukemias (ALLs). V, D, and J segments involved in these inappropriate rearrangements remain unknown and are of interest, both because partial D beta J beta and complete V beta D beta J beta recombinations occur at distinct stages of thymic maturation and because these rearrangements are regulated differently. We have therefore studied in detail seven cases of B-lineage ALL that show inappropriate clonal TCR beta gene rearrangements. Analysis of genomic DNA by Southern hybridization with C beta, J beta 1, V beta 8, and V beta 11 probes suggested the involvement of V beta segment in tumor cell rearrangements. A complete genomic library constructed from one case was screened with a C beta probe, and the TCR beta gene rearrangement was cloned and fully sequenced to show an out of frame V beta 2.2-J beta 2.6 recombination. TCR beta gene rearrangements occurring in other cases were further analyzed by polymerase chain reaction (PCR) using J beta and V beta primers and the resulting specific PCR products were sequenced. Evidence of clonal V beta rearrangements was obtained in all cases. These unexpected findings represent the first definitive demonstration that complete V beta(D beta)J beta rearrangements can occur in B-lineage cells and contrast with the previously reported lack of V beta(D beta)J beta rearrangement in B cells from V beta-J beta-C beta-E mu transgenic mice. In the context of increasing evidence that rearrangements are linked to transcription of unrearranged gene segments, these data prompt a search in B-lineage ALL cells for the presence of germline V beta transcripts whose deregulated expression may be linked to early transforming events.

Animals↗
PubMed1992

Human absence epilepsies.

A historical review of the concept of absence seizures. Their clinical features are very suggestive but a diagnosis made solely on clinical grounds is not always safe. Comparable pitfalls exist in the interpretation of EEG patterns. Absence seizures belong to several epileptic syndromes. They are briefly described.

Electroencephalography↗
PubMed1992

Occurrence of polyglucosan bodies in temporal lobe epilepsy.

Massive occurrence of polyglucosan bodies (PBs) was found within the surgically removed temporal lobe of a 34 year old woman with complex partial seizures. This peculiar feature is very unusual in neuropathological examinations of epileptogenic foci. This patient could not be included in any of the classic diseases in which PBs are found. She exhibited a localised form of glycogen storage disease.

Adult↗
PubMed1992

A longitudinal assessment of seizure outcome and overall benefit from 100 cortectomies for epilepsy.

Results of 100 cortical resections for 76 temporal, 23 frontal and one parietal lobe epilepsies were studied in terms of seizure relief and overall benefit. A non-homogenous Markov chain model was used to take into account both the intravariability of post-surgical outcome and the differences in duration of follow-up in a group of patients consecutively operated. The seizure free (SF) state was defined as no seizure in the previous five months at first follow up visit and none in the preceding 12 months at subsequent annual visits. For the whole of the population the SF probability was 82%, 66%, 61%, and 62% at six months, one year, two and five years respectively. A better outcome was found for temporal lobe epilepsy (SF probability: 68% at the fifth postoperative year) than for frontal lobe epilepsy (SF probability: 42% at the fifth postoperative year) with a statistically significant difference. Pre- and postoperative interictal signs and symptoms were classified according to their clinical significance: (a) mild handicap--symptoms recognisable but no interference with usual life, and (b) moderate or severe handicap--interference with some or all daily activities. The interictal state was considered more impaired after surgery than before in two situations: (a) either symptoms, absent before surgery, appeared in the postoperative period involving a moderate or severe handicap, or (b) symptoms present before surgery and answerable for a mild or moderate handicap that increased to involve a moderate or severe handicap respectively in the postoperative period. Surgery was considered a major benefit when two conditions were fulfilled-namely, a SF state and no deterioration of the interictal stage when compared with the preoperative period. The probability of obtaining such a benefit was 58%, 51%, 48% and 56% at six months, one year, two and five years respectively. The results suggest that surgery is an effective treatment for more than 50% of long lasting medically intractable epilepsies.

Adolescent↗
PubMed1992

The prognosis of benign localized epilepsy in early childhood.

Onset of seizures during early childhood is a not infrequent possibility in benign partial (localization-related) epilepsy (BPEC) when all these syndromes and not only benign partial epilepsy with centrotemporal spikes are considered. In patients followed up for long periods of time, temporal changes in the EEG often make impossible a distribution into discrete syndromes. The electroclinical patterns overlap and the determining factor is not the location but the morphology of the sharp waves. A complete remission is observed in all patients, with rolandic and/or extrarolandic foci. In rare patients, seizures occur during adolescence or later and an early onset is a possible risk factor for such an outcome. It is not a relapse of BPEC but another epileptic syndrome, usually a generalized idiopathic epilepsy. BPEC may be considered as a risk factor for late epilepsy. Patients with an early onset of BPEC tend to have a longer active period of epilepsy and a higher total number of seizures, whatever is the EEG pattern. But neither frequent seizures nor a long seizure period impair the children's abilities. Nonetheless, when BPEC begins in early childhood, the patient is prone to experience frequent seizures during several years. Drug therapy is advisable more often than in BPEC with a later onset.

Adolescent↗
PubMed1992

[Pilot study of Ginkgolide B, a PAF-acether specific inhibitor in the treatment of acute outbreaks of multiple sclerosis].

Ten patients with relapsing-remitting multiple sclerosis in acute relapse were treated with a five-day course of intravenous ginkgolide B, a specific inhibitor of PAF-acether. Eight patients had improvement of their neurological score, beginning 2 to 6 days after the initiation of therapy. This improvement was sustained in 5 patients and only transient in 3. Two out of these 3 patients with secondary failure and the other 2 who did not respond to ginkgolide therapy, received i.v. methylprednisolone. Three patients experienced mild side effects under ginkgolide therapy but none of the patients had any serious adverse effect. A controlled randomized study is underway, in order to confirm these results and test higher dosages and more prolonged administration.

Adult↗
PubMed1992

Synthesis of the orally macrofilaricidal and stable glycerolipidic prodrug of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)gl ycerol.

A new strategy is presented to develop macrofilaricidal compounds orally administered and able to concentrate in the lymphatic system. A diglyceride derivative of melphalan, 1,3-dipalmitoyl-2-(4'(bis(2''-chloroethyl)amino)phenylalaninoyl)gl y cerol, was synthesized. The esterification of melphalan by 1,3-dipalmitin allowed chemical stabilization of the alkylating agent in aqueous dispersion. No degradation of this prodrug was observed after a 3-month storage of an aqueous dispersion at 4 degrees C. The filaricidal activity of the prodrug was compared with those of melphalan in vitro against adults, infective larvae and microfilariae of Molinema dessetae, and evaluated in vivo on Molinema dessetae infected Proechimy oris. In vitro, melphalan and the glycerolipidic prodrug were inactive against microfilariae but active at 1 mmol/l against infective larvae and adults. In vivo studies were performed with rodents subcutaneously inoculated with infective larvae from Aedes aegypti. The number of macrofilariae was significantly reduced following treatment with a single oral dose of the alkylating agent prodrug (0.082 mmol/kg).

Aedes↗