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Biomedical subjects

F Picard

Publications and source records attributed to F Picard.

At least 19 recordsLinked to original sources
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↗
PubMed2001

A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity.

FMOC-L-Leucine (F-L-Leu) is a chemically distinct PPARgamma ligand. Two molecules of F-L-Leu bind to the ligand binding domain of a single PPARgamma molecule, making its mode of receptor interaction distinct from that of other nuclear receptor ligands. F-L-Leu induces a particular allosteric configuration of PPARgamma, resulting in differential cofactor recruitment and translating in distinct pharmacological properties. F-L-Leu activates PPARgamma with a lower potency, but a similar maximal efficacy, than rosiglitazone. The particular PPARgamma configuration induced by F-L-Leu leads to a modified pattern of target gene activation. F-L-Leu improves insulin sensitivity in normal, diet-induced glucose-intolerant, and in diabetic db/db mice, yet it has a lower adipogenic activity. These biological effects suggest that F-L-Leu is a selective PPARgamma modulator that activates some (insulin sensitization), but not all (adipogenesis), PPARgamma-signaling pathways.

Adipocytes↗
PubMed2001

Symptomatic postictal cardiac asystole in a young patient with partial seizures.

This report describes a patient with complex partial seizures arising from the right temporal lobe who developed symptomatic sinus arrest following the end of his seizure activity. A ventricular pacemaker was implanted and was documented to function appropriately, preventing development of bradycardia associated symptoms during subsequent seizures. Possibly relevant cerebral structures are briefly discussed.

Adult↗
PubMed2001

Lipid deposition in rats centrally infused with leptin in the presence or absence of corticosterone.

The aim of the present study was to assess whether the glucocorticoid corticosterone (Cort) modulates the effects of leptin on food intake and lipid deposition. Rats were subjected to a 6-day intracerebroventricular infusion of leptin and were either sham-adrenalectomized (Sham-ADX) or ADX and supplemented with 0 (C0), 40 (C40), or 80 mg (C80) of Cort. Investigation of potential peripheral sites of interaction of leptin and Cort included liver and plasma triglyceride (TG) content and lipoprotein lipase (LPL) activity in adipose and muscle tissues. The study confirmed the respective anorectic and orexigenic effects of leptin and Cort and revealed that the leptin-induced reduction in food intake was dampened by the high dose of Cort replacement. Such an interaction did not, however, extend to body and adipose tissue weights, which were lowered by leptin infusion independently of the Cort status. Leptin and ADX significantly reduced liver TG content and triglyceridemia, whereas Cort replacement significantly increased these variables. Central infusion of leptin also lowered plasma insulin levels, accompanied by a reduction in LPL activity of storage tissues (inguinal and epididymal white adipose tissue, 2- and 3-fold, respectively). In contrast, leptin infusion increased LPL activity in oxidative tissues (soleus and vastus lateralis muscles, 3- and 4-fold, respectively). Cort replacement prevented the ADX-induced fall in epididymal LPL activity but failed to do so in leptin-infused rats. The study demonstrates that, whereas the anorectic effect of leptin is dampened by high but physiological plasma levels of corticosterone, leptin can produce its effects on body weight, lipid transport and accumulation, and adipose and muscle LPL activity in the absence or presence of an intact hypothalamic-pituitary-adrenal axis.

Adipose Tissue↗
PubMed2001

Bodyweight gain and anticonvulsants: a comparative review.

Bodyweight gain is a common and frequent undesirable effect associated with the use of anticonvulsant drugs. This has been observed for many years with valproic acid (sodium valproate) and carbamazepine, and also, more recently, with some of the newer anticonvulsants such as vigabatrin and gabapentin. Very often bodyweight gain in children, adolescents and adults with epilepsy taking such anticonvulsants results in cosmetic adverse effects. On the other hand, bodyweight gain is disturbing to general health, with a possible increase in the risk of diabetes mellitus or heart disease. Other potential adverse effects, such as the association of obesity with polycystic ovaries, have been reported with the use of valproic acid. Potential mechanisms of anticonvulsant-associated bodyweight gain are not yet clear and differ between drugs used. The involvement of lowered blood glucose level, which may stimulate eating through an effect on the hypothalamus, constitutes one of the possible mechanisms. Lowered blood glucose levels may result from a competition between the binding of the drug and long chain fatty acids. An increased availability of the latter stimulates insulin production and lowers the serum glucose levels. Another possible explanation for lowered blood glucose may be a deficiency in carnitine directly caused by the drug, that would result in a reduction of fatty acid metabolism and an increase in glucose consumption. An enhancing effect of gamma-aminobutyric acid-mediated neurotransmission may increase appetite for carbohydrates and reduce energy expenditure. An antidiuretic hormone-like effect or effects on norepinephrine (noradrenaline) or serotonin-mediated neurotransmission are more rarely considered. Many studies on anticonvulsant-associated bodyweight gain illustrate how we could better define the risk factors for the development of anticonvulsant-induced bodyweight gain and uncover the mechanisms behind it.

Anticonvulsants↗
PubMed2001

[Acute anterior instability of the shoulder: short- and mid-term outcome after conservative treatment].

PURPOSE OF THE STUDY: We assessed short and mid-term outcome after emergency care for acute anterior instability of the shoulder. MATERIALS AND METHOD: Between October 1990 and May 1996, 233 shoulders (206 anteromedial dislocations, 21 dislocations with spontaneous reduction, and 6 painful shoulders with unknown instability) were treated, mainly orthopedically. The series included 165 men and 68 women, mean age 42 years (range 13-95 years). One hundred fifty-eight practiced sports more or less regularly (73% of the 216 patients) and a sports accident was involved in 121 cases (52.8%). Besides the usual lesions secondary to bone displacement, there were 51 fracture-avulsions of the greater tuberosity, 7 major fractures of the anteroinferior border of the glenoid cavity, 2 fractures of the coracoid process, 10 nerve lesions (6 axillary nerve palsies and 4 partial palsies of the brachial plexus) and 10 rotator cuff tears. Orthopedic reduction was performed in the emergency room in all patients with a dislocated shoulder (82%). Immobilization, elbow to body, was prescribed for 8 to 15 days. Sixteen patients (6.8%) underwent surgery during the days following reduction, 8 for displaced fracture of the greater tuberosity, 7 for important fracture of the glenoid cavity and 1 for avulsion of the rotator cuff. RESULTS: Patient files (n=210) or phone interviews (n=185) were used to assess outcome. Mean follow-up was 38 months (12 - 72 months). All nerve lesions regressed within a few weeks without sequelae. We had 6 cases of retractile capsulitis and 4 cases of reflex dystrophy that regressed totally in 3 to 6 months. Recurrent dislocation was observed in 52 cases (24.7% recurrence rate) with 29 occurring within one year (55.8%). Among the 145 other shoulders, 84 recovered completely (58%), 52 were occasionally bothersome (36%), 8 exhibited repeated subdislocation (5.5%) and one remained pseudoparalytic. Among the factors favoring recurrence, we found patient age (higher risk in younger subjects) and lack of rehabilitation (p<0.05). DISCUSSION: Acute anterior dislocation of the shoulder is frequent, but emergency surgical repair is rarely needed (15 cases in our series, 6.9%). Mid-term recurrence is not as frequent as is often thought, warranting the choice of first intention orthopedic care. Our findings demonstrated that emergency surgery is not indicated in most cases of anterior shoulder instability, even with the arthroscopic approach, especially since the results of this method remain unclear.

Accidents↗
PubMed2001

Flow cytometry detection of platelet procoagulation activity and microparticles in patients with unstable angina treated by percutaneous coronary angioplasty and stent implantation.

Platelet activation is known to participate to the pathogenesis of acute coronary syndromes. Aminophospholipid exposure and microparticles shedding are hallmarks of full platelet activation and may account for the dissemination of prothrombotic seats. Using flow cytometry analysis of annexin V binding to externalized aminophospholipids, we followed platelet procoagulant activity (PPA) and platelet microparticles (PMP) shedding in venous and coronary whole blood samples from 30 patients with unstable angina before and after percutaneous coronary angioplasty (PTCA) and stent implantation. Baseline values of PPA and PMP were significantly more elevated in patients than in control subjects (p < 0.005). PMP percentage was significantly higher in coronary than in venous blood, and in coronary blood of patients with proximal instead of mid/distal lesions of coronary arteries. No enhancement of platelet reactivity to TRAP and collagen was induced by procedure. Whereas activated GpIIb-IIIa and P-selectin expression decreased 24 h and 48 h after procedure, PPA and PMP remained as elevated as before. Thus, flow cytometry is a reliable method for detection of fully activated platelets in whole blood samples. Annexin V binding analysis demonstrates the persistance of in vivo platelet activation, despite the use of antiaggregating agents.

Aged↗
PubMed2000

Genome search for susceptibility loci of common idiopathic generalised epilepsies.

Genetic factors play a major role in the aetiology of idiopathic generalised epilepsies (IGEs). The present genome scan was designed to identify susceptibility loci that predispose to a spectrum of common IGE syndromes. Our collaborative study included 130 IGE-multiplex families ascertained through a proband with either an idiopathic absence epilepsy or juvenile myoclonic epilepsy, and one or more siblings affected by an IGE trait. In total, 413 microsatellite polymorphisms were genotyped in 617 family members. Non-parametric multipoint linkage analysis, using the GeneHunter program, provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkage findings provide suggestive evidence that at least three genetic factors confer susceptibility to generalised seizures in a broad spectrum of IGE syndromes. The chromosomal segments identified harbour several genes involved in the regulation of neuronal ion influx which are plausible candidates for mutation screening.

Chromosomes, Human, Pair 14↗