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Biomedical subjects

P Loiseau

Publications and source records attributed to P Loiseau.

At least 73 records · Page 4Linked to original sources

GEMHEP multicenter quality control study of PCR detection of GB virus C/hepatitis G virus RNA in serum.

PCR is, to date, the only available tool for the detection of GB virus C (GBV-C) and hepatitis G virus (HGV) RNAs. Twenty-two French laboratories participated in a quality control study to assess the sensitivity and specificity of their procedures. The panel included 13 positive controls and 7 negative controls. The laboratories used either in-house PCR techniques adapted from the literature or partly standardized commercial tests. Three laboratories performed faultlessly with the entire panel. Most laboratories had excellent specificity (100% in 20 of 22 laboratories). Sensitivity was acceptable (85 to 100%) in 15 centers and insufficient (38 to 77%) in 7. As with nonstandardized in-house PCR, the commercial assays gave discrepant performances in different laboratories. These results suggest that laboratories willing to use PCR for detection of GBV-C/HGV RNA for research or diagnostic purposes should participate in multicenter quality control trials.

Flaviviridae↗

Callosotomy for intractable epilepsy: overall outcome.

The effectiveness of callosotomy to the control of medically intractable epilepsy is still discussed fifty years after the first reported cases. Nevertheless patient selection, type of seizures and epileptic syndromes are now better determined. Atonic and tonic astatic seizures characterized both by clinical and electroencephalographical specific patterns, are the most responsive. A favorable outcome, from > 50% reduction in seizure frequency to a complete cessation, is obtained from 60 to 80% of the patients. For tonic-clonic seizures, favorable outcome fluctuates from 40% to 80% principally according to the extension of the section. Other types of seizures are not indicated for callosotomy even though some improvement may be observed. Symptomatic secondary generalized epilepsy with predominent unilateral lesion and epileptic focus on bifrontal lobe epilepsy are the most suitable indication. True generalized epilepsies are associated with a less favorable outcome. Indeed, axial spasms, the most frequent type of drop attacks in the Lennox-Gastaut syndrome, probably do not have a cortical origin. Quality of life and social adjustment are assessed from a cohort of 20 cases of anterior two-third callosotomy. Actual benefits are in close connection with both seizure relief and age at operation. To obtain a gain in social independence not only seizure control has to be better but also surgery must be performed sooner.

Corpus Callosum↗

[New medical treatment of epilepsy].

Nearly three-fourths of all newly diagnosed cases of epilepsy are easily controlled with our current drug armamentarium. Further progress will undoubtedly come with use of three new drugs, gabapentin, lamotrigine, and vigabatrin now in diverse stages of clinical trials. Gabapentin is a gamma-aminobutyric acid (GABA) analog which passes the blood-brain barrier. Its mode of action is unknown. The anti-convultion effect of lamotrigine apparently results from its capacity to stabilize voltage-dependent sodium channels and thus limit release of the excitory neuromediator glutamate. Vigabatrin produces irreversible inhibition of GABA transaminase, increasing the concentration of this neurotransmittor inhibitor in the brain. The pharmacokinetic properties of these three anti-epileptics are more favorable than those of earlier drugs. Renal excretion is proportional to creatinine clearance allowing better dose adjustment and all three can be associated with oral contraception. They are as effective as the classical agents although indications may vary. There are fewer adverse effects and no teratogenic effect has been observed in animal studies. Clinical surveillance is usually sufficient without laboratory tests. One handicap is the increased cost although it has been demonstrated that the overall cost for the society for a patient with well controlled epilepsy is less. The prescription of a third-generation anti-epileptic drug is justified immediately whenever treatment with one of the classical drugs has been unsuccessful; however, in case of failure the new drug should not be continued.

Acetates↗

Progress report on new antiepileptic drugs: a summary of the Third Eilat Conference.

The Third Eilat Conference on New Antiepileptic Drugs was held at the Royal Beach Hotel from May 27 to May 30, 1996. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss critical issues in drug development, new antiepileptic drugs (AEDs) in development, progress reports and recent findings of newly marketed AEDs, the use of AEDs in special populations and their utilization in non-epileptic disorders. Over the last seven years, six new AEDs have been introduced worldwide and new information on their safety and efficacy has become available. These include felbamate, gabapentin, lamotrigine, oxcarbazepine, topiramate and vigabatrin. Drugs in development include those at an advanced stage, such as remacemide and tiagabine, as well as those just entering clinical trials, such as rufinamide (CGP 331010) and levetiracetam (ucb LO59). The following is a summary of the presentations for drugs in development and recent findings on newly marketed drugs.

Acetamides↗

Infection by hepatitis C virus through contaminated intravenous immune globulin: results of a prospective national inquiry in France.

BACKGROUND: A recent hepatitis C virus (HCV) outbreak has been suspected of being caused by an infusion of intravenous immune globulin. STUDY DESIGN AND METHODS: Three laboratories were mandated by the French regulatory agency to prospectively screen on a national scale those persons having received suspected batches: 233 exposed patients were recalled and tested for HCV antibody and for HCV RNA. RESULTS: Nineteen patients (8.1%) were found positive for HCV RNA; 7 of these 19 were positive for the HCV antibody. CONCLUSION: The link between HCV infection and intravenous immune globulin was reinforced by the overrepresentation of the 2b genotype (58%), which contrasts with the low prevalence of this genotype in France (1%).

Adult↗

Glucose transport and equilibrium across alveolar-airway barrier of rat.

The glucose concentration in the epithelial lining fluid (ELF) results from a balance between cellular uptake and paracellular leakage. The present study examines whether the ELF glucose concentration can be predicted from the kinetics of glucose transport obtained in fluid-filled lungs. Isolated rat lungs were filled via the trachea with instillate containing 0-10 mM glucose; the perfusate glucose concentration was 10 mM. The rate of glucose removal from airspaces depended on luminal glucose concentration and was saturable [maximum uptake rate = 101 +/- 8.6 mumol.h-1.g dry lung wt-1; apparent Michaelis constant K(m) = 1.5 +/- 0.43 mM; R2 = 0.79]. Glucose removal was inhibited by phloridzin but not by phloretin or by inhibiting glycolysis. The steady-state concentration in fluid-filled lungs was estimated to be 0.15 +/- 0.034 mM. It agreed with that (< 1/20 plasma) calculated using glucose transport kinetics and paracellular permeability. The ELF glucose concentration obtained by bronchoalveolar lavage was 0.39 +/- 0.012 plasma in vivo and 0.39 +/- 0.021 perfusate in air-filled isolated lungs. The equilibrium ELF/perfusate distribution ratio of alpha-methyl-glucose was similar to that of glucose. Thus there is a major difference between the alveolar steady-state glucose concentration in air- and fluid-filled lungs despite similar mechanisms of airspace glucose removal. This suggests that glucose kinetics or access to uptake sites differ in air- and fluid-filled lungs.

Air↗

Transmission of hepatitis C virus in allografted patients: use of viral genotyping as an epidemiological marker.

One hundred and ninety-two allografted patients were tested for hepatitis C virus (HCV) RNA from 1992 to 1995 in Saint-Louis Hospital (Paris). They received blood products and intravenous immunoglobulins (IVIG) and more particularly Gammagard IVIG suspected of transmitting HCV (batches distributed in France between January 1993 and February 1994). The presence of serum HCV RNA was tested by polymerase chain reaction (PCR) in 86 patients who received Gammagard IVIG during the critical period and in 106 patients treated with IVIG other than the suspected batches of Gammagard (negative controls). HCV RNA positive sera were HCV genotyped. Ten out of 86 patients who received Gammagard IVIG during the exposed period vs 0 out of 106 negative controls were HCV RNA positive showing a higher prevalence of HCV infection in the exposed patients that in the negative controls (P = 0.001). The link between HCV transmission and IVIG infusion was reinforced by the high frequency of genotype 2b (70%) in the exposed patients because genotype 2b is an underrepresented subtype in France (< 1%).

Biomarkers↗

HLA-Cw allele analysis by PCR-restriction fragment length polymorphism: study of known and additional alleles.

We describe a technique for HLA-Cw genotyping by digestion of PCR-amplified genes with restriction endonucleases. Locus-specific primers selectively amplified HLA-Cw sequences from exon 2 in a single PCR that avoided coamplification of other classical and nonclassical class I genes. Amplified DNAs were digested with selected enzymes. Sixty-three homozygous cell lines from International Histocompatibility Workshop X and 113 unrelated individual cells were genotypes for HLA-Cw and compared with serology. The present protocol can distinguish 23 alleles corresponding to the known HLA-Cw sequences. Genotyping of serologically undetectable alleles (HLA-Cw Blank) and of heterozygous cells was made possible by using this method. Six additional HLA-Cw alleles were identified by unusual restriction patterns and confirmed by sequencing; this observation suggests the presence of another family of allele-sharing clusters in the HLA-B locus. This PCR-restriction endonuclease method provides a simple and convenient approach for HLA-Cw DNA typing, allowing the definition of serologically undetectable alleles, and will contribute to the evaluation of the biological role of the HLA-C locus.

Alleles↗

TAP2 gene polymorphism contributes to genetic susceptibility to multiple sclerosis.

MS is an autoimmune demyelinating disease that has been known to be associated with the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype. TAP1 and TAP2, two genes encoded within the MHC class II region between HLA-DP and -DQ loci, display genetic variability and are involved in the transport of antigenic peptides from the cytoplasm to the endoplasmic reticulum. Comparison of 116 MS patients with Caucasoid controls did not reveal any significant correlation between the previously described alleles of the TAP1 and TAP2 genes and MS. We report here an additional TAP2 dimorphism at codon 386, called I and J, corresponding to a silent mutation. An increased frequency of the J variant was observed in the patient population. The J mutation was not found in linkage disequilibrium with the HLA-DRB1*1501 allele and can be considered an additional genetic susceptibility marker of the disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Progress report on new antiepileptic drugs. A summary of the Second Eilat Conference.

The Second Eilat Conference on New Antiepileptic Drugs was held at the King Solomon's Palace Hotel from October 31 to November 3, 1994. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss new trial designs, drug approval, early use of new antiepileptic drugs, and new drugs in development. Over the last six years, several novel antiepileptic drugs have been introduced worldwide, and new information on their safety and efficacy has become available. These include felbamate, gabapentin, lamotrigine, oxcarbazepine, and vigabatrin. Drugs in development include those at an advanced stage, such as topiramate and tiagabine, as well as those just entering clinical trials, such as remacemide and levetiracetam. The following is a summary of the presentations for drugs in development and newly marketed drugs. The meeting concluded with a presentation, 'Still Searching for the Magic Bullet'.

Anticonvulsants↗

Absence epilepsies.

Individuals fulfilling diagnostic criteria for childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) were selected from a large group of patients who were born between 1945 and 1973 and had presented with absence seizures (AS). Updated data allowed an analysis of 52 patients with CAE and of 62 patients with JAE age > or = 20 years. In CAE, complete control was achieved in 90% of patients (95%, AS only; 77%, AS + generalized tonic-clonic seizures, GTCS). Only 16% of patients with an onset < 9 years had developed GTCS. In JAE, complete control was achieved in 37% of patients (47%, AS; 37%, GTCS). These figures support the validity of the International Classification of Epilepsy (ICE). Stricter diagnostic criteria are discussed.

Adult↗

[Drug-resistant epilepsy in adults].

Various estimation of the proportion of difficult-to-treat epileptic patients is given in the literature. It varies from 5 percent to 25 percent, because of imprecise meaning of pharmacoresistancy and similar terms. There is no such thing as a unique pharmacoresistant epilepsy. Persisting seizures despite antiepileptic drug prescription does not necessarily mean refractory seizures. Seizures may be drug-resistant for a limited period only, or be intermittent, or be a long-lasting condition. Seizure frequency may remain unchanged, or decrease, more or less. Toxicity of AEDs must be considered. Unbearable side effects are a limiting factor for maintaining some active drugs. In practice, the term pharmacoresistancy may be used when seizures occur in spite of a convenient therapy, whatever their frequency, and whatever the resulting handicap. Predictive factors for intractibility may be considered under four headings, i.e. seizure types, patient, epileptic syndrome, and antiepileptic drugs. Most of the elements of the first three groups are available immediately after the first seizure and response to treatment may be estimated one or two years later. Outcome of an epilepsy may be evaluated, or guessed, rather early. This is crucial for management of epileptic patients.

Adult↗

[Social outcome of 20 anterior callosotomies for drug-resistant epilepsy].

Results of 20 anterior callosotomies with regard to quality of life and social outcome were analysed according to seizure control. Data arise from a retrospective study with the medico-social teams. Drop attacks with tonic or atonic seizures decreased in 11 cases. Nevertheless only 8 cases (40%) have experienced a reduction of more than 70% in seizure frequency. Neurocognitive status slightly worsened in 3 cases. Age at intervention and type of epileptic syndrome were not predictors of seizure outcome. A subjective improvement in quality of life was reported in 10 cases. A significant improvement in social adjustment was obtained in 7 cases (35%). There was a close correlation between life comfort improvement and reduction in drop attack frequency. Not only seizure control has to be better but also surgery must be performed sooner to obtain a gain in social independence. Finally, successful outcome should be considered as limited. Nevertheless results may be considered taking into account the high severity of the condition and the low morbidity of anterior callosotomy.

Adolescent↗