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Biomedical subjects

E Perrier

Publications and source records attributed to E Perrier.

At least 19 recordsLinked to original sources

Mechanistic model of fuel selection in the muscle.

Fuel selection in human muscle is key to explaining insulin resistance. In obesity and type 2 diabetes mellitus, there is an increased content of lipid within and around muscle fibers. Changes in muscle fuel partitioning of lipid, between oxidation and storage of fat, contribute to the accumulation of intramuscular triglycerides and to the pathogenesis of both obesity and type 2 diabetes mellitus. A mathematical model of the aggregated metabolism in skeletal muscle was developed and the effects of fuel selection for lean and obese individuals under fasting conditions, insulin-stimulated conditions, and oscillating insulin conditions were examined. Model results were complementary to prior observations that elevated lipid oxidation during insulin-stimulated conditions is correlated with insulin resistance. The model also adequately simulated metabolic inflexibility between fat and glucose oxidation in the obese individual. A novel sensitivity analysis indicated the strong interaction effects of parameters of glucose and lipid oxidation pathways on the variables of each pathway.

Blood Glucose↗

[Vasoplegic shock and myocardial infarction during administration of iloprost].

INTRODUCTION: The association of vasoplegic shock and myocardial infarction in a patient under iloprost treatment for critical ischemia of the lower limbs has not previously been reported. OBSERVATION: A 56 year-old man suffering from type 2 diabetes, hypertension and dyslipidemia developed critical ischemia of the right leg and was treated with iloprost. On the 19th day of infusion, he developed a vasoplegic shock with myocardial infarction. The shock resolved and he recovered from the infarction. DISCUSSION: This case report indicates the need for reinforced blood pressure and electrocardiographic monitoring in diabetes patients treated with iloprost.

Diabetes Mellitus, Type 2↗

[3D cellular models: a powerful access to cutaneous physiology and to innovative developments of cosmetic active compounds].

Two different anti-ageing cosmetic actives based respectively, on dermal compartment regeneration and on dermoepidermal reinforcement, have been developed using tissular engineering models. Conjointly use of different innovative three-dimensional models such as reconstructed dermis and skin built with human cells coming from variable aged donors allowed first, a better understanding of matrix modifications due to ageing and second, the screening of active ingredients highly targeted to reverse observed damages. The validity of such three-dimensional models has been then confirmed by in vivo studies on healthy volunteers.

Adult↗

[Multislice computed tomography to detect coronary stenosis among asymptomatic patients with cardiovascular risk factors and equivocal prior stress test: preliminary study].

UNLABELLED: Multislice computed tomography (MSCT) is a non-invasive and validated technique to detect coronary stenoses. Some questions remain about its accuracy to detect coronary stenoses (CS), especially for asymptomatic patients (P) when a prior stress test isn't conclusive. METHODS: MSCT was performed among 45 asymptomatic men (mean age: 58,3 +/- 16), with a high ten year risk of fatal cardiovascular disease (SCORE 2003 data for low-risk regions of Europe), without any previous coronary history and with previous non conclusive exercise testing. When significant (> 50%) CS was suspected at MSCT, an angiocoronarography (AC) was done. RESULTS: Eighteen MSCT were normal, unsignificant CS (< 50%) were detected on 14 MSCT and significant coronary stenoses (SCS) for 13 P. Among this 13 P, 19 SCS were identified: 2 SCS of left main coronary artery (CA), 9 of the left descending CA, 6 of the right CA and 2 of the left circumflex CA. 13 CS were confirmed at AC. Finally, because of critical angiographic lesions +/- ischemia at nuclear tomoscintigraphy (NT), 9 P had coronary revascularization (7 catheter based, 2 surgical bypass), 4 P had medical treatment. DISCUSSION: Benefits of this preliminary study are obvious: 9 coronary revascularization/45 P. However, the place of MSCT for the screening of CS is uncertain, but may be usefull as a complement for the screening of coronary arterial disease.

Aged↗

[The heart and aerobatics].

Aerobatics is an aerial sport which has many physiological constraints, principally cardiovascular, with a risk if not adapted of sudden mid-air incapacity which could jeopardise aviation safety, and thus justifies the selection and surveillance of pilots. The aeronautical constraints during flight are multiple, related to the environment traversed, how the aircraft functions and its movements. Those which cause accelerations (+G in particular) pose the problem of haemodynamic tolerance because they can induce loss of consciousness due to cerebral hypoxia. Tolerance of acceleration varies among individuals; it can be improved with training, certain protective manoeuvres, and is reduced by hypoxia, certain medications, dehydration and heat. Moreover, in aerobatics certain tricks require manoeuvres which reduce this tolerance to +G accelerations. This is the "push-pull" effect (_G acceleration immediately followed by +G acceleration). This leads to a risk of sudden loss of consciousness with a load factor much lower than that which the pilot knows he is capable of tolerating. Besides the haemodynamic effects, the existence of an actual acceleration cardiomyopathy has been suggested but has not been proven in man. Finally, while changes in cardiac rhythm during accelerations are usual and relate to changes in vaso-sympathetic balance, ventricular and supra-ventricular rhythm disturbances are rare and are related to the intensity and duration of the acceleration.

Aerospace Medicine↗

[Automobile driving and implantable defibrillators].

The consequences of implanting an automatic cardioverter defibrillator (ICD) on vehicle driving in France are poorly known. This retrospective study examined the behaviour at the wheel of ICD recipients who were recommended to abstain from driving for 3 to 6 months after device implantation. The study population included 98 patients (mean age = 59.5 +/- 14.8 years) followed for a mean of 24. +/- 23.9 months, who underwent ICD implant for ventricular tachycardia (65% of patients ventricular fibrillation (15%), syncope (8%), as part of a research protocol of myocardial cell transplantation 6%, or for primary prevention (5%). The underlying heart disease was ischemic in 59% of patients dilated cardiomyopathy in 11%,hypertrophic cardiomyopathy in 8%, valvular in 6%. Brugada syndrome in 4%, right ventricular arrhythmogenic cardiomyopathy in 2%, and miscellaneous disorders in 9% of patients. Five patients died without post mortem interrogation of the ICD. Only 28% of drivers remembered, and 13% observed, the recommended driving limitations. However, 45% (the oldest) claimed to drive prudently. During follow-up, 47% of patients received an ICD shock. Their mean it ventricular ejection fraction was 34 +/- 14%, versus 43 +/- 18% in patients who received no ICD therapy (p = 0.015). Syncope occurred in 16% who received ICD shocks. Shocks were delivered during driving in 6 patients, without consequent accident. Despite their non-observance of recommended driving limitations. ICD recipients suffered few traffic accidents. Legislation in France should reproduce the guidelines issued by European professional societies and enacted by the British laws.

Accidents, Traffic↗

[Right bundle branch block: electrocardiographic and prognostic features].

The electrocardiographic appearances and the significance of right bundle branch block were described at the beginning of the 20th century. Typical appearances include prolongation > 0.12 s of the QRS complex, RR' or rR' or Rr' appearances in V1 and widened S waves in the leads exploring the left ventricle (SI, aVL, V5 and V6). A delay in the appearance of the intrinsic deflection > 0.08 s may also be observed in the right precordial leads and negative T waves with ST depression may be seen in V1 and sometimes in V2. Left axis deviation of the QRS complex greater than - 45 degrees suggests associated left anterior hemiblock. Right axis deviation beyond + 120 degrees is equivocal. The principal differential ECG diagnosis is the Brugada syndrome, a familial arrhythmogenic autosomal dominant cardiomyopathy of variable penetration. This diagnosis is suggested when ECG abnormalities are observed in patients with a personal or family history of sudden death. Right bundle branch block only seems to have haemodynamic consequences in cardiac failure with associated asynchrony of the left ventricle or in certain cases of right ventricular dilatation encountered in congenital heart disease. The prognosis of right bundle branch block in the absence of underlying cardiac disease is good but it may be poor in other cases, particularly coronary artery disease. Moreover, the prognosis of right bundle branch block to complete atrioventricular block is rare in the absence of associated cardiac disease.

Bundle-Branch Block↗

Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation.

Nano-emulsions consist of fine oil-in-water dispersions, having droplets covering the size range of 100-600 nm. In the present work, nano-emulsions were prepared using the spontaneous emulsification mechanism which occurs when an organic phase and an aqueous phase are mixed. The organic phase is an homogeneous solution of oil, lipophilic surfactant and water-miscible solvent, the aqueous phase consists on hydrophilic surfactant and water. An experimental study of nano-emulsion process optimisation based on the required size distribution was performed in relation with the type of oil, surfactant and the water-miscible solvent. The results showed that the composition of the initial organic phase was of great importance for the spontaneous emulsification process, and so, for the physico-chemical properties of the obtained emulsions. First, oil viscosity and HLB surfactants were changed, alpha-tocopherol, the most viscous oil, gave the smallest droplets size (171 +/- 2 nm), HLB required for the resulting oil-in-water emulsion was superior to 8. Second, the effect of water-solvent miscibility on the emulsification process was studied by decreasing acetone proportion in the organic phase. The solvent-acetone proportion leading to a fine nano-emulsion was fixed at 15/85% (v/v) with EtAc-acetone and 30/70% (v/v) with MEK-acetone mixture. To strength the choice of solvents, physical characteristics were compared, in particular, the auto-inflammation temperature and the flash point. This phase of emulsion optimisation represents an important step in the process of polymeric nanocapsules preparation using nanoprecipitation or interfacial polycondensation combined with spontaneous emulsification technique.

Chemistry, Pharmaceutical↗

Synthesis and characterization of polyurethane and poly(ether urethane) nanocapsules using a new technique of interfacial polycondensation combined to spontaneous emulsification.

Polyurethane polymers and poly(ether urethane) copolymers were chosen as drug carriers for alpha-tocopherol. This active ingredient is widely used as a strong antioxidant in many medical and cosmetic applications, but is rapidly degraded, because of its light, heat and oxygen sensitivity. Polyurethane and poly(ether urethane)-based nanocapsules were synthesized by interfacial reaction between two monomers. Interfacial polycondensation combined with spontaneous emulsification is a new technique for nanoparticles formation. Nanocapsules were characterized by studying particle size (150-500 nm), pH, yield of encapsulation and morphologies. Polyurethanes (PUR) were obtained from the condensation of diisocyanate (isophorone diisocyanate: IPDI) and polyol: 1,2-ethanediol (EG), 1,4-butanediol (BD), 1,6-hexanediol (HD). Poly(ether urethane) copolymers were obtained by replacing diols by polyethylene glycol oligomers (PEG) M(w) 200, 300, 400 and 600. Molecular weights of di- and polyols have a considerable influence on nanocapsules characteristics cited above. The increase of molecular weight of polyols tends to increase the mean size of nanocapsules from (232+/-3)nm using EG to (615+/-39)nm using PEG 600, and led to the apparition of a population of agglomerate particles. We also noted that the yield of encapsulation increases with the increase of polyol length (from 85.6 to 92.2% w/w). Microscopic observations confirmed particle size analysis, but cannot predict the membrane structure owing the small size of the particles.

Administration, Topical↗

[Anaesthesia and amiodarone-associated hyperthyroidism].

Amiodarone can induce severe hyperthyroidism that justifies its withdrawal and initiation of antithyroid drugs. Impossibility to stop amiodarone, failure to control hyperthyroidism and unfavourable evolution can lead to thyroidectomy. Cardiac manifestations, persistence of hyperthyroidism and interactions between amiodarone and anaesthetic or haemodynamic drugs may contraindicate anaesthesia. We report nine consecutive cases of amiodarone-associated hyperthyroidism that prompted us to perform thyroidectomy under general anaesthesia. The features and anaesthetic data of patients were noted. The antithyroid medical treatment failed in all patients. After thyroidectomy, evolution was favourable in all nine cases, without any intra or postoperative complication, in spite of the extent of hyperthyroidism and the severity of the associated cardiac problems. Despite potential high risks, thyroidectomy for amiodarone-induced hyperthyroidism does not seem to increase morbidity or mortality and allows a quick return to euthyroidism and reintroduction of amiodarone.

Adult↗

Calcium triggers beta-defensin (hBD-2 and hBD-3) and chemokine macrophage inflammatory protein-3 alpha (MIP-3alpha/CCL20) expression in monolayers of activated human keratinocytes.

The inducible epidermal beta-defensins and the chemokine macrophage inflammatory protein-3alpha (MIP-3alpha/CCL20) are important mediators involved in innate and adaptive immunity and in the recruitment of immune cells. The aim of our study was to determine whether calcium could trigger the induction of beta-defensins (hBD-2 and hBD-3) mRNA and the release of MIP-3alpha by normal human keratinocyte monolayers. Epidermal cells derived from foreskin were cultured in defined medium supplemented with different calcium levels (0.09, 0.8 and 1.7 mM) and were stimulated or not with the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha 1-500 ng/ml) or interferon-gamma (INF-gamma 1-100 ng/ml). A high calcium concentration (1.7 mM) alone applied in culture medium for 4 days was sufficient to induce hBD-2 and hBD-3 mRNA expression. Whatever interindividual variability in the expression of hBD-2 and hBD-3 mRNA and MIP-3alpha secretion, the addition of TNF-alpha for a short duration (26h), initiated a dose-dependent and coordinated up-regulation of hBD-2 and hBD-3 mRNA and MIP-3alpha release in keratinocyte cultures. Unlike hBD-2 and hBD-3 mRNA was preferentially stimulated by IFN-gamma rather than TNF-alpha. In our experimental conditions, L-isoleucine, described to stimulate beta-defensin in bovine epithelial cells, did not exert any effect either on hBD-2 and hBD-3 transcripts or MIP-3alpha protein. Taken together, these results confirm the major role of the maturation/differentiation process of normal human keratinocytes in the induction of inducible beta-defensins and MIP-3alpha chemokine, which contribute in vivo to the immunosurveillance of the skin barrier function.

Calcium↗

Voltage-gated Ca2+ currents in the human pathophysiologic heart: a review.

The L-type Ca2+ current (I(Ca-L)) plays a key role in the cardiac excitation-contraction (E-C) coupling. Thus, it is a major target for many transmitters and hormones modulating cardiac function and, therefore, for pharmacological drugs to regulate inotropy. Ca2+ (and other) ion currents are commonly studied in animal tissues for practical reasons. Investigations in human cardiomyocytes started extensively only ten years ago with the development of patch-clamp techniques, enzymatic cell dissociation procedures, and surgical techniques. These studies have already provided valuable information concerning the nature, biophysics, pharmacology and regulation of human cardiac ionic currents in normal and diseased tissues. Interesting advances have been made to understand the role of I(Ca-L) in the development of chronic atrial fibrillation (AF). Alterations of single channel activity and regulation of macroscopic I(Ca-L) have also been found in heart failure (HF), ugh some of the data are divergent and puzzling. The T-type Ca2+ current (I(Ca-T)) has never been recorded in human cardiomyocytes. After a rapid overview of the basic properties of human cardiac Ca2+ currents, we focus on selected aspects of pathophysiology that are still unsolved.

Atrial Fibrillation↗

Effects of aldosterone on transient outward K+ current density in rat ventricular myocytes.

1. Aldosterone, a major ionic homeostasis regulator, might also regulate cardiac ion currents. Using the whole-cell patch-clamp technique, we investigated whether aldosterone affects the 4-aminopyridine-sensitive transient outward K+ current (I(to1)). 2. Exposure to 100 nM aldosterone for 48 h at 37 degrees C produced a 1.6-fold decrease in the I(to1) density compared to control myocytes incubated without aldosterone. Neither the time- nor voltage-dependent properties of the current were significantly altered after aldosterone treatment. RU28318 (1 microM), a specific mineralocorticoid receptor antagonist, prevented the aldosterone-induced decrease in I(to1) density. 3. When myocytes were incubated for 24 h with aldosterone, concentrations up to 1 microM did not change I(to1) density, whereas L-type Ca(2+) current (I(Ca,L)) density increased. After 48 h, aldosterone caused a further increase in I(Ca,L). The delay in the I(to1) response to aldosterone might indicate that it occurs secondary to an increase in I(Ca,L). 4. After 24 h of aldosterone pretreatment, further co-incubation for 24 h either with an I(Ca,L) antagonist (100 nM nifedipine) or with a permeant Ca(2+) chelator (10 microM BAPTA-AM) prevented a decrease in I(to1) density. 5. After 48 h of aldosterone treatment, we observed a 2.5-fold increase in the occurrence of spontaneous Ca(2+) sparks, which was blunted by co-treatment with nifedipine. 6. We conclude that aldosterone decreases I(to1) density. We suggest that this decrease is secondary to the modulation of intracellular Ca(2+) signalling, which probably arises from the aldosterone-induced increase in I(Ca,L). These results provide new insights into how cardiac ionic currents are modulated by hormones.

Aldosterone↗

[Cardiovascular effects linked to the use of chloroquine].

The chloroquine is the mainly and most frequently drug used as antimalaric in the world, in spite of the extension of resistance phenomena. Besides, the chloroquine is also commonly indicated in rheumatology and dermatology as a chronic treatment of some connective tissue disease. The chloroquine has three main cardiovascular effect: membrane stabilizer, direct negative inotropic effect and direct arterial vasodilator. Thus, these cardiovascular iatrogenic effects of the chloroquine are important both through their potential frequency and seriousness. Personal clinical cases and medical review enables to identify the main effects, observed either with prophylactic, or curative, or even toxic dosages. The more often, there are some rhythm and conductance disorders, myocardiopathy, even sometimes vasoplegic shocks. A list of the commercial patent medicine including chloroquine enables to be aware, to prevent and to take into account the cardiovascular risks of a treatment newly set or carried on for long years.

Antimalarials↗

[Value of total thyroidectomy in amiodarone-induced hyperthyroidism].

The potential severity of amiodarone-induced hyperthyroidism, particularly in severe cardiopathy cases, necessitates a regular clinic and biologic thyroid control. The break in amiodarone and a medical treatment (synthetic antithyroid drugs, steroids, perchlorate of potassium) can be ineffective. The authors report the case of a patient with an right ventricle arythmogenic dysplasia, without thyroid history, who came back 3 years after the introducing of amiodarone with major hyperthyroidism. After failure of medical treatment, a total thyroidectomy permitted to quickly stop hyperthyroidism and to early reintroduce amiodarone. Surgery seems to be the radical treatment when hyperthyroidism doesn't respond to the medical treatment and when the cardiopathy requires amiodarone.

Adult↗

[Comparison of magnetic resonance angiography with injection of gadolinium and conventional arteriography of the ilio-femoral arteries].

Twenty-three patients underwent conventional arteriography and 3D contrast enhanced magnetic resonance angiography explorations. The study was limited to the iliofemoral arteries (13 segments for each patient). Each segment was classified as having 0-49%, 50-99% or 100% stenosis. Overall results were excellent with K = 0.822, sensitivity 92% and specificity 93%. Segment by segment analysis corroborated the overall results except for the internal iliac arteries and the deep femoral arteries, demonstrating the limitations of this technique in this series.

Aged↗