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F Picard

Publications and source records attributed to F Picard.

At least 19 recordsLinked to original sources
PubMed2006

Computing power in case-control association studies through the use of quadratic approximations: application to meta-statistics.

In the framework of case-control studies many different test statistics are available to measure the association of a marker with a given disease. Nevertheless, choosing one particular statistic can lead to very different conclusions. In the absence of a consensus for this choice, a tempting option is to evaluate the power of these different statistics prior to make any decision. We review the available methods dedicated to power computation and assess their respective reliability in treating a wide range of tests on a wide range of alternative models. Considering Monte-Carlo, non-central chi-square and Delta-Method estimates, we evaluate empirical, asymptotic and numerical approaches. Additionally we introduce the use of the Delta-Method, extended to order 2, intended to provide better results than the traditional order-1 Delta-Method. Supplementary data can be found at: http://stat.genopole.cnrs.fr/software/dm2.

Alleles↗
PubMed2006

Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study.

Nicotinic acetylcholine receptors (nAChRs) are involved in a familial form of frontal lobe epilepsy, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In several ADNFLE families, mutations were identified in the nAChR alpha4 or beta2 subunit, which together compose the main cerebral nAChR. Electrophysiological assessment using in vitro expression systems indicated a gain of function of the mutant receptors. However the precise mechanisms by which they contribute to the pathogenesis of a focal epilepsy remain obscure, especially since alpha4beta2 nAChRs are known to be widely distributed within the entire brain. PET study using [18F]-F-A-85380, a high affinity agonist at the alpha4beta2 nAChRs, allows the determination of the regional distribution and density of the nAChRs in healthy volunteers and in ADNFLE patients, thus offering a unique opportunity to investigate some in vivo consequences of the molecular defect. We have assessed nAChR distribution in eight non-smoking ADNFLE patients (from five families) bearing an identified mutation in nAChRs and in seven age-matched non-smoking healthy volunteers using PET and [(18)F]-F-A-85380. Parametric images of volume of distribution (Vd) were generated as the ratio of tissue to plasma radioactivities. The images showed a clear difference in the pattern of the nAChR density in the brains of the patients compared to the healthy volunteers. Vd values revealed a significant increase (between 12 and 21%, P < 0.05) in the ADNFLE patients in the mesencephalon, the pons and the cerebellum when compared to control subjects. Statistical parametric mapping (SPM) was then used to better analyse subtle regional differences. This analysis confirmed clear regional differences between patients and controls: patients had increased nAChR density in the epithalamus, ventral mesencephalon and cerebellum, but decreased nAChR density in the right dorsolateral prefrontal region. In five patients who underwent an additional [(18)F]-fluorodeoxyglucose (FDG) PET experiment, hypometabolism was observed in the neighbouring area of the right orbitofrontal cortex. The demonstration of a regional nAChR density decrease in the prefrontal cortex, despite the known distribution of these receptors throughout the cerebral cortex, is consistent with a focal epilepsy involving the frontal lobe. We also propose that the nAChR density increase in mesencephalon is involved in the pathophysiology of ADNFLE through the role of brainstem ascending cholinergic systems in arousal.

Adult↗
PubMed2006

Increased cardiac mRNA expression of matrix metalloproteinase-1 (MMP-1) and its inhibitor (TIMP-1) in DCM patients.

Left ventricular dilation and myocardial remodeling are hallmarks of dilated cardiomyopathy (DCM). It is assumed that left ventricular dilation is caused by the disintegration of the collagenous network by increased collagenolytic activity of matrix metalloproteinases (MMPs) and their adequate tissue inhibitors (TIMPs). In this study the myocardial MMP-1 and TIMP-1 mRNA expressions were investigated by using real-time quantitative PCR analysis from right septal endomyocardial biopsies of patients with dilated cardiomyopathy (n = 46) and control subjects (n = 11). The volume density (Vv%) of collagen was measured morphometrically. Classification was done according to LV diameters [left ventricular enddiastolic diameter (LVEDD, cm) calculated to body surface area (BSA, m(2))] into three DCM groups: group I (LVEDD-BSA > 2.7-3.0 cm/m(2)), group II ( > 3.0-3.6 cm/m(2)), group III ( > 3.6 cm/m(2)), controls (< 2.7 cm/m(2)). Compared with controls, the MMP-1 expression in patients with DCM was significantly increased (119.2 +/- 45.2 vs. 1.3 +/- 0.4; p < 0.001) as was TIMP-1 expression (9.6 +/- 1.2 vs. 1.3 +/- 0.4; p < 0.01). Moreover the MMP-1 and TIMP-1 expression varied according to LV diameter: group I (MMP-1: 8.7 +/- 3.5; p = 0.33; TIMP- 1: 4.5 +/- 1.2; p < 0.01); group II (MMP-1: 211.4 +/- 86.0; p < 0.001; TIMP-1: 12.5 +/- 1.9 ; p < 0.001); group III (MMP-1: 38.8 +/- 22.6; p < 0.01; TIMP-1: 8.1 +/- 1.7; p < 0.001). Compared with controls, the collagen level in DCMPt. was significantly increased: 5.0 +/- 0.6 vol% vs 1.2 +/- 0.2 vol% p < 0.001 and correlates with LV diameter. This study reveals that the overexpression of MMP-1, which is associated with an increased ratio of MMP-1/TIMP-1 in DCM, indicates an activated collagenolytic system while replacement fibrosis is accumulating. The MMP-1 overexpression is mainly found in moderately dilated DCM hearts (group II) indicating the dynamic process of LV dilation and the importance of collagenases in the early phase of LV remodeling.

Biomarkers↗
PubMed2006

Favourable outcome of progressive multifocal leucoencephalopathy in two patients with dermatomyositis.

Progressive multifocal leucoencephalopathy (PML), a demyelinating disease caused by the JC virus (JCV), occurs in immunosuppressed patients and carries a poor prognosis. A favourable outcome is reported in two patients with PML and dermatomyositis. Immunosuppressive drugs were stopped in patient 1 but could only be partially tapered in patient 2. The JCV-specific CD8+ T cell response was strong in patient 1 and weak in patient 2. Both were treated with cytosine-arabinoside, and patient 2 was also treated with mirtazapine, a 5HT2A receptor antagonist. Combination of these drugs might be helpful to treat HIV-negative patients with PML.

Adrenergic alpha-Antagonists↗
PubMed2005

Mycophenolic acid metabolite profile in renal transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil.

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is an effective immunosuppressive treatment in renal transplant recipients but is known to have gastrointestinal side effects. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) is a new formulation for delivering MPA. This open-label, two-period, cross-over study was carried out to characterize the time course of MPA and its metabolites, mycophenolic acid glucuronide (MPAG) and acyl mycophenolic acid glucuronide (AcMPAG) in stable renal transplant patients (n = 40) after 28-day chronic dosing with EC-MPS (720 mg bid) or MMF (1000 mg bid). The relative abundance and exposure of all three compounds was also assessed. EC-MPS demonstrated the typical pharmacokinetic profile of an enteric-coated formulation with a delayed release of MPA compared with MMF (Tmax 2.5 versus 1.0 hours, respectively). Consistent with a similar disposition of MPA, both EC-MPS and MMF treatments resulted in the same ratio of MPAG to MPA exposure, 23:1. Furthermore, comparison of the AUC of MPAG and AcMPAG for both treatments indicated that steady state MPAG exposure was 75 to 90 times that of AcMPAG, confirming MPAG as the predominant metabolite of MPA. AcMPAG has been identified as a possible active metabolite of MPA; the present study indicates that AcMPAG may contribute around 14% of the exposure to active drug after administration of MPA. Both EC-MPS and MMF treatments were well tolerated over the 1-month period of chronic treatment. In summary, consistent with its enteric-coated design, EC-MPS delays delivery of MPA, but results in similar exposure to that provided by MMF.

Adolescent↗
PubMed2005

Molecular links between aging and adipose tissue.

White adipose tissue now emerges as a pivotal organ controlling lifespan. Calorie restriction, which so far extends lifespan in all organisms, primarily affects energy stores in adipose tissue. Genetic manipulations aiming at modifying fat mass also impact on the duration of life in several model organisms. We recently proposed that silent information regulator 2 (SIR2) ortholog, sirtuin 1 (SIRT1), the mammalian ortholog of the life-extending yeast gene SIR2, is involved in the molecular mechanisms linking lifespan to adipose tissue. SIRT1 represses peroxisome proliferator-activated receptors gamma transactivation and inhibits lipid accumulation in adipocytes. The effect of adipose tissue reduction on lifespan could be due to the production of adipokines acting on target tissues such as the brain, or due to the indirect prevention of age-related metabolic disorders like type 2 diabetes or atherosclerosis.

Adipose Tissue↗
PubMed2004

Elicited repetitive daily blindness: a new familial disorder related to migraine and epilepsy.

The authors report a family affected by multiple daily episodes of transient visual loss, elicited repetitive daily blindness (ERDB); the onset was early in life, and the disease followed a benign course. ERDB is associated with childhood epilepsy and familial hemiplegic migraine, apparently segregating as a monogenic, autosomal dominant condition with variable expression. Genetic linkage to CACNA1A was excluded.

Adolescent↗
PubMed2002

The effects of topiramate and sex hormones on energy balance of male and female rats.

OBJECTIVE: The effects of topiramate (TPM) on components of energy balance were tested in male and female rats that were (i) left intact, (ii) castrated or (iii) castrated with replacement therapies consisting of testosterone administration in orchidectomized (OCX) rats and of estradiol or progesterone treatments in ovariectomized (OVX) rats. METHODS: TPM was mixed into the diet and administered at a dose of 60 mg per kg of body weight. Male and female rats were treated for 28 and 35 days, respectively. At the end of the treatment period, variables of energy balance and determinants of lipid and glucose metabolism were assessed. RESULTS: TPM reduced energy and fat gains in both male and female rats either in the absence or in the presence of hormone replacement therapies. In male rats, it also decreased food intake, protein gain and energetic efficiency. In female animals, TPM reduced energetic efficiency while it stimulated lipoprotein lipase activity in brown adipose tissue. TPM also reduced plasma glucose and plasma leptin levels in female rats as well as plasma insulin and liver triglycerides in male animals. As expected, castration and sex hormones also strongly influenced energy balance. In male rats, OCX led to a decrease in energy and protein gains that was blocked by treatment with testosterone. In female rats, OVX caused increases in energy, fat and protein gains that were prevented by treatment with estradiol. CONCLUSION: In female rats, the effects of TPM on fat and energy gains were clearly not influenced by the sex hormone status of the rats. In male animals, there was also no interaction of TPM and the status of sex hormones on energy balance, suggesting that OCX and testosterone minimally interfere with the action of TPM on energy balance. The effects of TPM on energy balance were accounted for by a decrease in energetic efficiency, resulting from an effect exerted by the drug on both energy intake and thermogenesis. The present results also suggest that TPM can enhance insulin sensitivity.

Adipose Tissue↗
PubMed2002

Erythroleukemia: a need for a new definition.

The new WHO classification abolishes the frontier between RAEB-t with 20% of blasts and leukemia with 30% of blasts. We review the definitions of erythroleukemia and discuss the relationship between FAB AML6, RAEB-t and AML6 variant. We ask whether secondary erythroleukemias are the same entity as RAEB-t on survival, karyotype and cytologic characteristics. We suggest that 'AML6 variant' with pure erythroid lineage proliferation would be the real de novo erythroleukemia. Current FAB AML6 entity will probably be classified in either subgroup (1) multilineage dysplasia; (2) therapy-related leukemia; or (3) acute erythroid leukemia subdivided into erythroleukemia (erythroid/myeloid) and pure erythroid leukemia, in the WHO classification - a classification which highlights the importance of clinical and cytogenetic prognostic factors.

Adolescent↗
PubMed2002

How mutations in the nAChRs can cause ADNFLE epilepsy.

PURPOSE: The linkage between autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and neuronal nicotinic acetylcholine receptor has been strongly reinforced by the report of five distinct mutations in the two genes coding for the major brain alpha4beta2 nicotinic acetylcholine (ACh) receptors. As a first step toward understanding the basic mechanisms underlying this genetically transmissible neurologic disorder, we examined the similarities and differences of the functional properties displayed by naturally occurring mutant forms of this ligand-gated channel. METHODS: Functional studies of neuronal nicotinic ACh receptors reconstituted in Xenopus oocytes were designed to analyze the common traits displayed by the different mutations associated with ADNFLE. RESULTS: Coexpression of the control and mutated alleles harboring the alpha4S248F mutation obtained from patient DNAs yielded ACh-evoked currents of amplitude comparable to the control responses but with a higher sensitivity and desensitization to the natural agonist. Alternatively, the other mutants (alpha4L776ins3, alpha4S252L, and beta2V287M) displayed an increased ACh sensitivity without pronounced desensitization. In addition, whereas a reduction of calcium permeability was observed for the mutants (alpha4S248F and alpha4L776ins3), no significant modification of ionic selectivity could be detected in the alpha4S252L mutation. Hence increase in ACh sensitivity is the only common characteristic so far observed between the four naturally occurring mutant receptors investigated. CONCLUSIONS: Analyses of functional properties of four nAChR mutants associated with ADNFLE indicate that a gain of function of these mutant receptors may be at the origin of the neuronal network dysfunction that causes the epileptic seizures. These data are discussed in the context of our latest knowledge of the pyramidal cell function.

Acetylcholine↗
PubMed2001

Benign nocturnal alternating hemiplegia of childhood: six patients and long-term follow-up.

Benign familial nocturnal alternating hemiplegia of childhood refers to recurrent attacks of hemiplegia arising from sleep, described in young children without neurologic or mental impairment. It is probably migraine related. The authors report two unrelated patients with nocturnal attacks starting at 22 and 31 months, followed by daytime episodes in one. The authors confirm the benign course of this disorder. It is distinct from the classic malignant form of alternating hemiplegia of childhood.

Child↗
PubMed2001

[Computer-assisted knee arthroplasty: comparison with a conventional procedure. Results of 50 cases in a prospective randomized study].

PURPOSE OF THE STUDY: The aim of this work was to compare the radiographic findings after two techniques for total knee arthroplasty, one using a computer-assisted approach and the other a conventional approach. MATERIAL AND METHODS: Between January 1998 and April 1999, we conducted a prospective study randomizing 25 patients for conventional surgery (group A) and 25 for computer-assisted surgery (group B). All patients volunteered to participate in this study and gave their written informed consent. There were 35 women and 15 men, mean age 69.5 years (range 47-85). The two groups were comparable for age, gender, height, weight, orthopedic history, etiology and preoperative mobility. The preoperative hip-knee angle (HKA) was also comparable between the two groups. Mean HKA was 175 degrees, i.e. 5 degrees varus (range 162 degrees (18 degrees varus) to 210 degrees (30 degrees valgus)). Genu varum was found in 80 p. 100 of the patients in group A and in 76 p. 100 in group B, genu valgum in 16 p. 100 in group A and 24 p. 100 in group B. The same operator performed all the procedures) with the same type ok prosthesis for all patients. The goal of the operation was to position the prosthesis to produce an HKA of 180 +/- 3 degrees, a femoral angle of 90 degrees (from the mechanical axis), a tibial angle of 90 degrees and a posterior tibial slope of 0 degrees (tibial plateau at 90 degrees to the lateral tibial axis). Statview 5 PC was used for the statistical analysis. Comparisons between groups were made with the Student's t test to compare means when the validity conditions were met. RESULTS: The patients were reviewed by two surgeons, independently of the operator and the designers of the computer-assistance program. Mean duration of the procedure was longer in group B (102 mn versus 70 mn, p<0.001). There was no statistically significant difference in mean postoperative bleeding (group A=380 cc, group B=480 cc). The postoperative HKA was 181.2 +/- 2.72 degrees in group A and 179.04 +/- 2.53 degrees in group B (p > 0.05). The HKA was between 177 degrees and 183 degrees in 75 p. 100 of the patients in group A and in 84 p. 100 of those in group B. Implantation of the femoral component showed a mean angle of 91.12 +/- 2.07 degrees in group A and 89.56 +/- 1.61 degrees in group B (p=0.048). The mean tibial angle was 90.167 +/- 1.61 degrees in group A and 89.5 +/- 1.34 degrees in group B (p=0.11). On the lateral view, the femoral component was at 90 degrees to the mechanical axis in 16/21 patients in group B. These data were missing in group A. The posterior tibial slope was 90.76 +/- 2.19 degrees in group A and 89.44 +/- 2.14 in group B (p=0.18). CONCLUSION: Computer-assisted surgery for total knee arthroplasty was found to provide remarkably reliable results. Once the "growing pains" of this new material have been mastered, all surgeons should be able to expect an improvement in the positioning of prosthetic implantations.

Aged↗
PubMed2001

Evidence for digenic inheritance in a family with both febrile convulsions and temporal lobe epilepsy implicating chromosomes 18qter and 1q25-q31.

We report a clinical and genetic study of a French family among whom febrile convulsions (FC) are associated with subsequent temporal lobe epilepsy (TLE) in the same individual, without magnetic resonance imaging-identifiable hippocampal abnormalities. Linkage analyses excluded the loci FEB1 and FEB2, previously implicated in FC; the GEFS+1 locus responsible for generalized epilepsy with febrile seizures plus; and the locus implicated in lateral temporal lobe epilepsy. After scanning the entire genome, significant lod scores (>3) for markers on 18qter and suggestive lod scores (>2) for markers on 1q25-q31 were obtained. An analysis of the haplotypes at these two loci supported the hypothesis that two genes segregated with the phenotype. All patients shared common haplotypes for both 1q25-q31 and 18qter chromosomes. All but one unaffected at-risk individuals carried only one, or none, of the disease haplotypes. Under the assumption of digenic inheritance, haplotype reconstruction defined a 26 cM interval on chromosome 1 and a 10 cM interval on chromosome 18. This family suggests that the association between FC and TLE may be observed in the absence of hippocampal structural abnormalities and that they may have, in some cases, a common genetic basis.

Adolescent↗
PubMed2001

Accuracy in tunnel placement for ACL reconstruction. Comparison of traditional arthroscopic and computer-assisted navigation techniques.

The purpose of this randomized, prospective study was to compare accuracy in tunnel placement as performed with a traditional arthroscopic anterior cruciate ligament (ACL) reconstruction technique and with KneeNavTM ACL, a computer-assisted surgical navigation technique. Two surgeons experienced in ACL reconstruction, but inexperienced in computer-assisted surgical navigation technique, each randomly used traditional arthroscopic guides or KneeNavTM ACL to drill a tunnel in twenty identical foam knees. Placement of the resulting tibial and femoral tunnels was measured with a computer-assisted digitizing method and compared to traditional biplanar radiographs. Statistical analysis with Student's t-test was used to compare the distance from the ideal tunnel placement to the femoral and tibial tunnels. Accuracy of tunnel placement with KneeNavTM ACL was significantly better than that obtained with the traditional arthroscopic technique. Distances from the ideal tunnel placement to the femoral and tibial tunnels were 4.2 +/- 1.8 mm (mean +/- SD) and 4.9 +/- 2.3 mm, respectively, for the traditional arthroscopic technique, and 2.7 +/- 1.9 mm (femur) and 3.4 +/- 2.3 mm (tibia) for KneeNavTM ACL. These differences were statistically different. Tunnel placement for ACL reconstruction with KneeNavTM ACL, an image-based, computer-assisted surgical navigation device with a simple and intuitive interface, was more accurate than with the traditional arthroscopic technique.

Anterior Cruciate Ligament↗
PubMed2001

Ion channel variation causes epilepsies.

The discovery of genetically transmissible form of epilepsy associated with a mutation in a gene that codes for a subunit of a ligand-gated channel shined a new light in this field of neurological diseases. Because this gene (CHRNA4) codes for a neuronal nicotinic acetylcholine receptor subunit, functional studies could be designed to evaluate the alterations caused by this mutation. Since this initial observation, five mutations were identified and determination of their functional properties initiated. These experiments were extended to pairwise expression of the control and mutated allele to mimic the heterozygote human genotype. The first common functional trait identified so far, in four of these mutants, is an increased sensitivity to the acetylcholine, suggesting that these mutations may cause a gain of function. An alternative possibility that cannot be excluded is that conditions in the brain are such that these higher responding receptors may be more prone to desensitization. The importance of ionic channels as cause of epilepsies was further demonstrated with the identification of the association between the benign neonatal epilepsy and mutations in genes coding for potassium channel subunits (KCNQ2, KCNQ3). Additional evidences were brought by the identification of mutations in voltage-dependent sodium channels (SCN1A, SCN1B) in a form of generalized epilepsy with febrile seizures.

Acetylcholine↗
PubMed2001

Polymorphism analysis of JRK/JH8, the human homologue of mouse jerky, and description of a rare mutation in a case of CAE evolving to JME.

Disruption of the function of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy (IGE). A human homologue, JRK/JH8, has been cloned, which maps to 8q24, a chromosomal region associated with several forms of IGE. JRK/JH8 is, therefore, a candidate locus for at least some forms of IGE. We report corrected cDNA sequences and extended open reading frames for the mouse jerky and human JRK/JH8 genes, which add 48 amino acids to the N-terminus of the Jerky protein and which extends the region of homology with the N-terminal DNA-binding domain of the centromere-binding protein, CENP-B. Systematic sequencing of the coding region of the extended JRK/JH8 gene identified single nucleotide polymorphisms that define three haplotypes, which were used for association studies in patients with idiopathic generalized epilepsy. We report one subject with childhood absence epilepsy (CAE) that evolved to juvenile myoclonic epilepsy (JME) that has a unique de novo mutation that results in a non-conservative amino acid change at a potential protein glycosylation site. Familial analysis supports a causal role for this mutation in the disease.

Alleles↗