Search PubMed⌕ Search

Biomedical subjects

F Giraud

Publications and source records attributed to F Giraud.

At least 19 recordsLinked to original sources
PubMed2006

[Computer-assisted positioning of the acetabular cup for total hip arthroplasty based on joint kinematics without prior imaging: preliminary results with computed tomographic assessment].

PURPOSE OF THE STUDY: Most navigation systems for computer-assisted total hip arthroplasty (THA) require prior computed tomography (CT) or acquisition of multiple bone landmarks on the pelvis. In order to avoid these problems, we developed a computer-assisted navigation system without CT based on a kinematic approach to the hip joint. The principle is to orient the cup in relation to the cone describing the hip joint range of motion. The purpose of this work was to analyze preliminary results. MATERIAL AND METHODS: Eighteen primary THA were implanted with the system (16 women, two men, mean age 68 +/- 7.8 years, age range 54-83 years, 18 degenerative hip disease). Two optoelectronic captors were fixed percutaneously on the pelvis and the distal femur. The acetabulum was prepared first followed by the femur using reamers and broaches of increasing size. The last broach placed in the femur was equipped with a large head adapted to the newly prepared acetabulum. The range of hip motion was recorded to determine the maximal range of motion cone. The acetabular cup was thus positioned in order the prosthesis range of motion included entirely the maximal range of motion of the hip joint. RESULTS: One patient fell three weeks after implantation causing posterior dislocation; there was no recurrence. The Postel-Merle-d'Aubligné score improved from 8 +/- 2.9 (range 3-12) preoperatively to 17 +/- 0.8 (range 16-18) at last follow-up. None of the patients complained about the captor insertion and there were no cases of hematoma or fracture. Operative time was 35-40 minutes longer for the first four cases and was progressively reduced 15-20 minutes for the last four cases. Mean leg length discrepancy was 5.6 +/- 7.5 mm (range 0-25) before implantation and 0.6 +/- 3 mm (range -5 to 10 mm) at last follow-up. CT-scan measurements revealed a mean anteversion of the femoral implant of 18.2 +/- 8.5 degrees (range 0-31). Anatomic anteversion of the cup (measured from the pelvis landmark and thus independently of the position of the pelvis) was 24.7 +/- 8.8 degrees (range 12-40). The sum of the femoral and anatomic acetabular anteversions was 43 +/- 13.1 degrees (range 22-71). Anteversions were 16 degrees for the cup and 16 degrees for the stem for the one case of dislocation. CONCLUSION: This method can be used in routine without lengthening operative time significantly. It safely controls leg length and helps position the cup. This study demonstrated that there is no ideal position for the cup which can be used for all patients. Because of the wide range of inclination and anteversion figures, half of the cases were outside the safety zone recommended by Lewinnek.

Acetabulum↗
PubMed2006

A 3D-QSAR CoMSIA study on 3-azolylmethylindoles as anti-leishmanial agents.

A three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Similarity Indices Analysis (CoMSIA) was conducted on a series of 3-azolylmethylindoles as anti-leishmanial agents. Evaluation of 24 compounds synthesized in our laboratory served to establish the model. A random search was performed on the library of compounds, and molecules of the training set were aligned on common elements of template molecule 13, one of the most active compounds. The best predictions were obtained from multifit procedure with a CoMSIA model combining steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (q2 = 0.594, r2 = 0.897). The model was validated using an external test set of 7 compounds giving a satisfactory predictive r2 value of 0.649. Information obtained from CoMSIA contour maps could be used for further design of more promising inhibitors.

Animals↗
PubMed2005

ATP-induced apoptosis of thymocytes is mediated by activation of P2 X 7 receptor and involves de novo ceramide synthesis and mitochondria.

Thymocytes were reported to undergo apoptosis in the presence of extracellular ATP through the activation of the purinergic receptors P2 X 1R, P2 X 7R or both. We investigated the identity of the P2 X R and the signaling pathways involved in ATP-mediated apoptosis. Apoptosis elicited by ATP was prevented by inhibition of P2 X 7R, or in thymocytes bearing a mutated P2 X 7R, and reproduced with a P2 X 7R agonist, but not with a P2 X 1R agonist. Stimulation of thymocytes with either ATP or a P2 X 7R agonist was found to stimulate a late de novo ceramide synthesis and mitochondrial alterations. Inhibition of either processes attenuated apoptosis. Interestingly, stimulation with either ATP or a P2 X 1R agonist induced an early ceramide accumulation and a weak caspases-3/7 activation that did not lead to apoptosis. In conclusion, de novo ceramide generation and mitochondrial alterations, both resulting from P2 X 7R activation, were implicated in ATP-induced thymocyte apoptosis.

Adenosine Triphosphate↗
PubMed2003

Regulation of K-Cl cotransport by Syk and Src protein tyrosine kinases in deoxygenated sickle cells.

Protein tyrosine kinases (PTK) of the Src family are thought to suppress K-Cl cotransport (KCC) activity via negative regulation of protein phosphatases. However, some PTK inhibitors reduce KCC activity, suggesting opposite regulation by different PTK families. We have reported previously that deoxygenation of sickle cells stimulates KCC and activates Syk (a Syk family PTK), but not Lyn (an Src family PTK). In this study the same results were obtained when PTK activities were measured under the conditions used to measure KCC activity and which prevent any change in intracellular [Mg(2+)]. Methyl-2,5-dihydroxycinnamate (DHC), a PTK inhibitor, was more selective for Syk than Lyn, while staurosporine (ST), a broad-specificity protein kinase inhibitor, inhibited Lyn more than Syk. Deoxygenation or 4-amino-5-(4-chlorophenyl)-7-( t-butyl)pyrazolo[3,4- d] pyrimidine (pp2, a specific Src inhibitor) stimulated KCC independently. These effects were not additive and were inhibited by DHC. In contrast, ST-induced KCC activation was resistant to DHC, suggesting a different pathway of activation. Overall, these data indicate that Syk activity is required for KCC activation, either induced by deoxygenation of sickle cells, or mediated by Src inhibition in oxygenated cells, and that Syk and Src PTKs exert opposing and interconnected regulatory effects on the activity of the transporter.

Dose-Response Relationship, Drug↗
PubMed2003

Flavonoid inhibition of platelet procoagulant activity and phosphoinositide synthesis.

Dietary flavonoids are known for their antiplatelet activity resulting in cardiovascular protection. Phosphatidylinositol 4,5-bisphosphate (PIP2) was previously reported to play a direct role in phosphatidylserine (PS) exposure, as a Ca2+ target. Thrombin formation and platelet procoagulant activity are dependent on PS exposure. As flavonoids can inhibit phosphoinositide (PPI) kinases, we examined whether changes in PPI metabolism in flavonoid-treated platelets could be involved in their antiplatelet effects. Treatment with the flavonoids quercetin or catechin reduced PS exposure, thrombin formation, PIP2 level and resynthesis after platelet activation with collagen, thrombin or calcium ionophore. Flavonoids also prevented [Ca2+]i increase induced by collagen, but not by the ionophore. The ability of flavonoids to decrease PS exposure induced by ionophore treatment could result from the diminution of PIP2 levels, whereas PS exposure induced by collagen could also be diminished by flavonoids' effects on calcium signaling dependent on PIP2 hydrolysis. These data favor a role for PIP2 in the antiplatelet effects of flavonoids.

Blood Platelets↗
PubMed2001

Involvement of phosphatidylinositol 4,5-bisphosphate in phosphatidylserine exposure in platelets: use of a permeant phosphoinositide-binding peptide.

During platelet activation, phosphatidylserine (PS) exposure on the extracellular face of the plasma membrane is associated with increased procoagulant activity. PS externalization is generally attributed to an increase in intracellular Ca(2+). Various phospholipid transporters, such as specific scramblases or proteins from the family of multidrug resistance proteins, and cofactors such as phosphatidylinositol 4,5-bisphosphate (PIP2) have been proposed to participate in this process. In this study, we used a membrane-permeant polycationic peptide (RhB-QRLFQVKGRR), derived from the PIP2-binding site of gelsolin (GS 160-169) and linked to rhodamine B, to investigate the role of PIP2 in PS externalization in whole platelets. The peptide penetrated rapidly into the platelets, specifically bound to PIP2, and induced PS exposure to a similar extent as thrombin or collagen, but independently of changes in intracellular Ca(2+) or phosphoinositide 3-kinase activity. A pretreatment of platelets with quercetin, an inhibitor of phosphoinositide metabolism, drastically decreased PS exposure induced by agonists or peptide. In large unilamellar vesicles (LUVs), the presence of PIP2 was strictly required for the induction of scrambling of NBD-labeled phospholipids (PC and PS) by the peptide. In inside-out vesicles from erythrocytes (IOVs), the peptide also induced redistribution of PC and PS. Our data suggest that, in intact platelets, PIP2 acts as a target of polycationic effectors, including Ca(2+), to promote PS exposure. The use of a membrane-permeant and fluorescent peptide which binds to PIP2 is a promising tool to investigate the role of PIP2 in various cellular processes.

4-Chloro-7-nitrobenzofurazan↗
PubMed2001

Deoxygenation of sickle cells stimulates Syk tyrosine kinase and inhibits a membrane tyrosine phosphatase.

Polymerization of hemoglobin S in sickle red cells, in deoxygenated conditions, is associated with K+ loss and cellular dehydration. It was previously reported that deoxygenation of sickle cells increases protein tyrosine kinase (PTK) activity and band 3 tyrosine phosphorylation and that PTK inhibitors reduce cell dehydration. Here, the study investigates which PTKs are involved and the mechanism of their activation. Deoxygenation of sickle cells induced a 2-fold increase in Syk activity, measured by autophosphorylation in immune complex assays, but had no effect on Lyn. Syk was not stimulated by deoxygenation of normal red cells, and stimulation was partly reversible on reoxygenation of sickle cells. Syk activation was independent of the increase in intracellular Ca++ and Mg2+ associated with deoxygenation. Lectins that promote glycophorin or band 3 aggregation did not activate Syk. In parallel to Syk stimulation, deoxygenation of sickle cells, but not of normal red cells, decreased the activity of both membrane-associated protein tyrosine phosphatase (PTPs) and membrane protein thiol content. In vitro pretreatment of Syk immune complexes with membrane PTP inhibited Syk autophosphorylation. It is suggested that Syk activation in vivo could be mediated by PTP inhibition, itself resulting from thiol oxidation, as PTPs are known to be inhibited by oxidants. Altogether these data indicate that Syk could be involved in the mechanisms leading to sickle cell dehydration.

Anemia, Sickle Cell↗
PubMed2001

Biodegradation of anthracene and fluoranthene by fungi isolated from an experimental constructed wetland for wastewater treatment.

Pilot-scale constructed wetlands were used to treat water contaminated by polycyclic aromatic hydrocarbons (PAHs), particularly fluoranthene, and the possible role of fungi present in these ecosystems was investigated. A total of 40 fungal species (24 genera) were isolated and identified from samples (gravel and sediments) from a contaminated wetland and a control wetland. All of them were assayed for their ability to remove anthracene (AC) and fluoranthene (FA) from liquid medium. FA was degraded efficiently by 33 species while only 2 species were able to remove AC over 70%. A selection of 10 strains of micromycetes belonging to various taxonomic groups was further investigated for FA and AC degradation, toxicity assays and phenoloxidases (POx) detection. Interesting and not previously reported species were revealed (Absidia cylindrospora, Cladosporium sphaerospermum, and Ulocladium chartarum). They were all able to highly degrade the PAH-model compounds chosen. An interesting inducibility was noted for Ulocladium chartarum. Degradative ability of fungi was not related to their extracellular POx activity. This study may contribute to the improvement of constructed wetlands for water treatment, which may be enriched in efficient fungi.

Anthracenes↗
PubMed2001

Sciatica caused by epidural gas. Four case reports.

We report four cases of sciatica caused by gas in the epidural space with no other abnormality. Only 21 similar cases have been reported. Clinical features are identical to those of common sciatica, and plain radiographs are often uninformative. Computed tomography shows a low-density epidural collection displacing the nerve root.

Adult↗
PubMed2001

Influence of remnant accumulation markers on plasma concentrations of two lipoprotein(a) subspecies (containing or free of apoE).

Lipoprotein(a) [Lp(a)], an atherosclerosis marker, has 2 subspecies differing in structure and composition that can easily be distinguished by the presence or absence of apolipoprotein E (apoE). The subspecies containing apo E [Lp(a):B:E] is found mainly in the very-low-density lipoprotein (VLDL) size range, while that free of apoE [Lp(a):B] is found mainly in the LDL size range. As little is known about the physiologic function of these subspecies, this study investigated Lp(a):B and Lp(a):B:E concentrations in a population of normotriglyceridemic and moderately hypertriglyceridemic subjects in fasting state and attempted to determine the parameters influencing their plasma concentrations. The subjects studied (n = 98) had a mean total Lp(a) concentration of 108 mg/dL (28 to 252, minimum to maximum), a mean Lp(a):B concentration of 92.6 mg/dL (5 to 254), and a mean Lp(a):B:E concentration of 15.6 mg/dL (0 to 137). These results indicate that Lp(a):B:E, even in normolipidemic subjects, constitutes a detectable part of total Lp(a), ie, a mean percentage of 16.2% (0% to 96%). Multiple stepwise regression analyses showed that triacylglycerol has no independent effect on the concentration of Lp(a) subspecies, and that remnant accumulation markers, such as the E/LpB:E molar ratio (number of apoE per particle containing both apoB and apoE) and apoE-LpB (mass of apoE bound to particles containing both apoB and apoE), have a strong independent effect on this concentration. A strong positive influence of E/LpB:E on Lp(a):B:E subspecies was noted, as well as a negative influence of apo E-LpB on Lp(a):B subspecies. Taken together, these results suggest that the apoE bound to LpB:E particles plays a dominant role in the concentration of Lp(a) subspecies and that a redistribution of Lp(a) subspecies occurs under the influence of the apoE content of triacylglycerol-rich lipoprotein particles.

Adult↗
PubMed2001

Plasma levels of free and total TFPI, relationship with cardiovascular risk factors and endothelial cell markers.

Free-TFPI (f-TFPI) presents high anticoagulant activity and its plasma level correlates with unfavorable outcomes in unstable angina. Total TFPI (t-TFPI) represents mainly the lipid-bound form which seems to have a poor anticoagulant activity. Until now, it is not known whether the variations of f-TFPI plasma levels are determined by environmental factors. The aim of our study was to evaluate the influence of cardiovascular risk factors on plasma levels of f-TFPI and relations with other endothelial derived molecules in a population of 626 patients (277 men and 349 women) attending a metabolic ward for primary prevention of coronary disease. Free and total TFPI plasma levels were poorly correlated. f-TFPI levels increased with age in both sexes, t-TFPI in women only. Age-adjusted correlations of TFPI levels with conventional cardiovascular risk factors and endothelial cell markers showed different patterns for f-TFPI and t-TFPI. f-TFPI correlated with parameters associated with insulin resistance, particularly in females. f-TFPI was also positively associated in both genders with fibrinogen and endothelial cell markers: t-PA, thrombomodulin (TM) and von Willebrand factor (vWF). t-TFPI correlated strongly with LDL-C in both sexes. It also correlated negatively with parameters of the insulin resistance syndrome. t-TFPI also correlated with TM but not with other endothelial cell markers. The results of the multivariate step by step analysis showed that cardiovascular risk factors poorly explained the f-TFPI variability (7% and 4% in men and women, respectively), whereas they explained 16 and 20% of t-TFPI variability in men and women respectively (mostly related to LDL-C). In conclusion, this study showed that free- and total-TFPI are regulated differently. f-TFPI strongly correlates with endothelial cell markers and t-TFPI is more related to conventional cardiovascular risk factors. The strong gender effect on f-TFPI levels remains to be explained.

Age Factors↗
PubMed2001

[Anterior iliopsoas impingement after total hip arthroplasty: diagnosis and conservative treatment in 9 cases].

PURPOSE OF THE STUDY: Impingement of the iliopsoas muscle due to a protruding acetabular component is an uncommon cause of pain after total hip arthroplasty. Diagnostic signs may be misleading and therapeutic management has varied, leading to divergent findings reported in the literature. The purpose of this prospective work was to determine the frequency of groin pain due to iliopsoas impingement (with or without an identified causal mechanism) in patients with painful total hip arthroplasties and to identify diagnostic criteria that can be used to determine the appropriate therapeutic strategy. MATERIAL AND METHODS: This prospective study was conducted between 1998 and 2000 and included 206 painful total hip arthroplasties. From this series, we excluded cases where pain was related to loosening (139 cases, 67%), infection (45 cases, 21.7%), bursitis on trochanteric sutures (2 cases, 1%), and aortic aneurysm with gluteal claudication and resulting from a lumbosacral disorder (10 cases, 4.8%). This left 9 cases (4.3%) with a clinical picture suggestive of iliopsoas impingement. These 9 patients (mean age 50 years, age range 38 - 65) had 8 uncemented press-fix cups and 1 cemented cup with an acetabular mesh. Mean delay to the development of pain after the arthroplasty procedure was 7.3 months (1 - 48 months). The most suggestive clinical sign was groin pain triggered by active flexion of the hip and flexion of the hip against force with a painful arc measuring 30 degrees to 70 degrees. None of these 9 patients had any sign of material loosening and puncture aspiration ruled out infection. The final diagnosis was confirmed by sedation of pain after extra-articular infiltration at the anterior border of the cup (overhanging cup in 6/9 cases) under computed tomographic guidance. RESULTS: Infiltrations with xylocaine and long-release corticosteroids led to complete sedation of pain in 4 out of 9 patients and partial sedation in 1 other. Recurrent pain led to terminal tenotomy of the iliopsoas in 4 patients, that provided total sedation in 3 and partial sedation in 1. In all, successful pain relief was achieved in 7 out of 9 cases: 4 after infiltration (repeated in 1 cases) and 3 after tenotomy. At last follow-up physical examination has not identified any loss of flexion force. DISCUSSION AND CONCLUSION: Irritation of the iliopsoas muscle can be the cause of pain in 4.3% of patients experiencing pain after total hip arthroplasty. The delay to symptom onset is variable but there appears to be a pain-free period after implantation. An anatomic element (anterior cup overhang) is not necessary for diagnosis since the infiltration test was positive in 1 out of 3 cases without any identified acetabular factor. The infiltration test is an important element for positive diagnosis and should be the first therapeutic measure taken. We achieved success in 4 out of 9 cases. Tenotomy is indicated in case of recurrence, providing complete cure in 3 out of 4 cases in our series. Cure may be achieved without changing the cup by simple infiltration or tenotomy of the iliopsoas that led to complete cure in 7 out of 9 cases in our series, even in patients with an overhanging cup (6 out of 9 cases). An elective procedure might be indicated if a specific anomaly is identified (overly long screw, cement leakage) or for a screwed cup. The infiltration test should however be performed beforehand to confirm the diagnosis.

Adrenal Cortex Hormones↗
PubMed2001

[Quality of life study in chronic psychotic patients using a day hospital].

This survey concerned 24 adult patients, who are chronic psychotics, living in town and followed by a day hospital team. Their life quality was evaluated with the help of a validated questionnaire, "Subjective Life Quality Profile" ("PQVS"). The same version of this questionnaire was filled in by the patients and their referent nurse, two times, at six month interval. In the mean-time, the service psychiatrist also filled in questionnaires, assessing the psychiatric symptomatology. The main results confirm the reliability of the tool used and the feasibility of this type of survey with a population of chronic psychotics. The results are coherent at six month interval, and the points of view correspond between the patient and this referent. Finally the life quality is less good when the symptomatology quotation is bad. The aim of this work was to give an account of the patient's life, as seen by himself and by the caretakers.

Attitude of Health Personnel↗
PubMed2000

Phosphatidylinositol 4,5-bisphosphate domain inducers promote phospholipid transverse redistribution in biological membranes.

Transmembrane phospholipid redistribution (scrambling), leading to exposure of phosphatidylserine on the cell surface, plays a physiological role to induce platelet procoagulant activity and clearance of injured or apoptotic cells. Scrambling is generally attributed to an increase in intracellular Ca(2+) and would be mediated by a protein (scramblase), whose activity could be modulated by cofactors. We reported previously that phosphatidylinositol 4,5-bisphosphate (PIP(2)) is a positive regulator of Ca(2+)-induced scrambling. We show here, using inside-out vesicles from erythrocyte membranes, that a pleckstrin homology (PH) domain, which interacts with high affinity with PIP(2), inhibited Ca(2+)-induced scrambling, confirming the role of PIP(2). As Ca(2+) is known to interact with PIP(2) and to promote the formation of lateral domains of acidic phospholipids in membranes, we investigated whether PIP(2) domain formation could be involved in scrambling. Spermine, polylysine, and MARCKS (151-175) peptide caused scrambling in parallel to their reported ability to form domains of acidic phospholipids, including PIP(2). Similarly, neomycine, another PIP(2)-interacting polycation, induced scrambling. A PIP(2) antibody was also found to induce scrambling, presumably by a similar mechanism, since phospholipid antibodies are known to promote phospholipid capping. In conclusion, Ca(2+) is not the sole inducer of scrambling, and formation of PIP(2) domains could play a critical role in this process.

Antibodies, Monoclonal↗
PubMed2000

Insulin stimulates NHE1 activity by sequential activation of phosphatidylinositol 3-kinase and protein kinase C zeta in human erythrocytes.

The signaling cascade linking insulin receptor stimulation to the activation of Na/H exchanger (NHE) was investigated in human erythrocytes, a simple cell model expressing the NHE1 isoform and protein kinase C (PKC) alpha and zeta isoforms only. Our results demonstrate the presence of phosphatidylinositol (PtdIns) 3-kinase in these cells and its activation by insulin. With a similar time-course, insulin also promoted both the translocation and activation of PKC zeta, but had no effect on PKC alpha. Inhibition of PtdIns 3-kinase with wortmannin prevented the activation of PKC zeta by insulin. Stimulation of NHE1 was observed after 10 min of insulin treatment and persisted for at least 60 min. This effect was totally abolished by wortmannin or GF 109203X, an inhibitor of all PKC isoforms, but not by Gö 6976, a specific inhibitor of conventional and novel PKCs (e.g. PKC alpha). These data indicate that PKC zeta activation is mediated by a PtdIns 3-kinase-dependent mechanism and that NHE1 stimulation involves the sequential activation of PtdIns 3-kinase and PKC zeta. In addition, insulin stimulation of NHE1 occurred without altering the phosphorylation state of the exchanger, suggesting that the phosphorylation of an ancillary protein by PKC zeta would be responsible for activation of the transporter.

Androstadienes↗
PubMed1998

Calcium induces phospholipid redistribution and microvesicle release in human erythrocyte membranes by independent pathways.

The increase in intracellular Ca2+ concentration in erythrocytes and platelets results in simultaneous phospholipid scrambling and microvesicle shedding. Microvesicle formation involves membrane fusion events which were proposed either to be tightly linked to phospholipid transversal redistribution or to occur by a separate mechanism. We report here that in erythrocytes incubated in high K+ medium, or in resealed ghosts, phospholipid scrambling can be fully induced by intracellular Ca2+ without microvesicle formation. Furthermore, in ghosts resealed in the presence of spermine, intracellular Ca2+, at low concentration, was able to induce microvesicles, whereas scrambling was drastically inhibited. Surprisingly, in spermine-containing ghosts prepared from erythrocytes of a patient with a bleeding disorder, due to a lack of Ca2+-induced phospholipid scrambling and vesicle shedding (characterized as a Scott syndrome), Ca2+ also promoted microvesicle release. Data show that phospholipid scrambling and microvesicle production, although closely regulated, proceed by independent pathways.

Aged↗