PubMed Health⌕ Search

Biomedical subjects

F Lenfant

Publications and source records attributed to F Lenfant.

At least 19 recordsLinked to original sources
PubMed2006

Understanding the oestrogen action in experimental and clinical atherosclerosis.

Whereas hormone replacement/menopause therapy (HRT) in postmenopausal women increases the coronary artery risk, epidemiological studies (protection in premenopaused women) suggest and experimental studies (prevention of the development of fatty streaks in animals) demonstrate a major atheroprotective action of oestradiol (E2). The understanding of the deleterious and beneficial effects of oestrogens is thus required. The immuno-inflammatory system plays a key role in the development of fatty streak deposit as well as in the rupture of the atherosclerotic plaque. Whereas E2 favours an anti-inflammatory effect in vitro (cultured cells), it rather elicits in vivo a proinflammation at the level of several subpopulations of the immuno-inflammatory system, which could contribute to plaque destabilization. Endothelium is another important target for E2, as it potentiates endothelial NO and prostacyclin production, thus promoting the beneficial effects as vasorelaxation and inhibition of platelet aggregation. Prostacyclin, but not NO, appears to be involved in the atheroprotective effect of E2. E2 also accelerates endothelial regrowth, thus favouring vascular healing. Finally, most of these effects of E2 are mediated by oestrogen receptor alpha, and are independent of oestrogen receptor beta. In summary, a better understanding of the mechanisms of oestrogen action not only on the normal and atheromatous arteries, but also on innate and adaptive immune responses is required and should help to optimize the prevention of cardiovascular disease after menopause. These mouse models should help to screen existing and future selective oestrogen receptor modulators.

Animals↗
PubMed2005

[Risk assessment before non-cardiac surgery: what do anesthesiologists expect from cardiologists?].

Patients with a cardiac pathology are at high risk of perioperative cardiac complications. Therefore, an evaluation of the cardiac risk before a non-cardiac surgery has to be performed. The importance of the risk depends on the type of surgery, the patient's clinical symptoms and his adaptation to a physical effort. Exams are chosen according to the pathology, the information searched for and should be non invasive. After the evaluation, a specific preparation of the patient and the institution or an adaptation of cardioprotective medications should be discussed. The cardiologic consultation also allows a better management of antithrombotic or antiplatelet therapy. Preoperative evaluation of the cardiac risk is based on the collaboration between cardiologist and anesthesiologist to select the patients to evaluate, optimize their management, and decrease the risk of complications.

Anesthesia, General↗
PubMed2005

Optimization of a model of red blood cells for the study of anti-oxidant drugs, in terms of concentration of oxidant and phosphate buffer.

The aggression of erythrocytes by an oxidative stress induces hemolysis. This paper aims to valid a model of erythrocytes in terms of composition of the phosphate buffer solution and of concentration of a well-known oxidant, AAPH. Three compositions of phosphate buffer solution are mixed with three concentrations of oxidant. The influence of these two parameters on hemolysis is independently studied by a variance analysis and a Kruskal-Wallis test when ANOVA is not available. The hemolysis rate increases with time at fixed oxidant concentration, but is not influenced by the composition of the buffer solution. The highest hemolysis rate, 90%, was only measured within 2 h with the highest oxidant concentration. If we retain this concentration of oxidant, the lower concentration of the buffer can by eliminated by a significant less hemolysis and the highest concentration of the buffer can by chosen in regard of the better precision for a similar hemolysis compared to the mean buffer. We hope to study the effect of anti-oxidant agent with such a model of erythrocytes.

Antioxidants↗
PubMed2003

In vivo and in vitro antioxidant properties of furosemide.

The aim of this study was to investigate in vivo and in vitro antioxidant properties of furosemide. In vitro, human red blood cells were submitted to oxidative stress (AAPH), in absence or in presence of different concentrations of furosemide. Potassium efflux was measured in order to quantify the oxidative stress after the action of AAPH on red blood cells. Allophycocyanin assay was also used to investigate antioxidant capacities of furosemide. For the in vivo experiment, male Wistar rats were used. A control group (n = 5) was treated by a daily intraperitoneal injection of saline solution (0.2 ml); 2 other groups (J0 and J+) were treated for 7 days by one daily intraperitoneal injection of furosemide (0.10 mg/kg/day). In the J+group, the injection of furosemide was done one hour before the experiment, while in the J0 group the last injection of furosemide was done on the 6th day and an injection of saline was performed one hour before the experiment. On the day of experiment, a laparotomy was performed under general anesthesia and blood was collected from abdominal aorta. Oxidative stress and antioxidant capacities were evaluated on Wistar rat red blood cells and plasma. In vitro results (oxidative challenge with AAPH) showed that oxidative stress was decreased in presence of furosemide. This was due to a potent free radical scavenging effect of furosemide. In vivo studies confirmed that furosemide had antioxidant properties. These data may be of great relevance in clinical practice, considering the use of large doses of furosemide in patients presenting pathology involving the production of free radicals.

Amidines↗
PubMed2002

[Value of cervical plain radiography in unconscious trauma patient].

INTRODUCTION: The aim of this study was to evaluate the diagnostic value of cervical spine standard radiographs, performed in emergency, and compared with entire cervical helical CT with multiplanar reconstructions as reference. STUDY DESIGN: Open prospective study. PATIENTS AND METHODS: We conducted a six months prospective study including all patients over 15 years of age and unconscious (Glasgow Coma Scale < or = 12). Each patient underwent standard radiographs as well as helical CT of the entire cervical spine. Three senior surgeons and one senior radiologist evaluated the standard radiographs quality. The interpretation was performed by 7 different groups of judges. Two radiologists interpreted the helical CT. For each group, the sensibility, the specificity and the count of correct diagnosis for the standard radiographs were evaluated. The results of the correct diagnosis of each group were then compared to determine the most performant group. RESULTS: Fifty-one patients were included. Helical CT diagnosed spine injuries in 11 patients. The quality of standard radiographs was poor with less than 10% judged correct and 90% of the C7-D1 junction not visible. In the best group (radiologist), the sensibility was 50%, the specificity was 85% and the count of correct diagnosis was 78%. For the correct diagnosis, senior radiologist was significantly better than anaesthetist students, radiologist students and emergency physicians. CONCLUSION: The diagnostic value of standard radiographs was weak whatever the physician. Therefore, helical CT of the entire cervical spine is absolutely necessary and must be performed during the initial evaluation, if the haemodynamic conditions are required.

Adult↗
PubMed2002

[Evaluation of the learning curve of a new intubation technique: intubating laryngeal mask].

OBJECTIVE: Assessment of the learning curve of a new device for blind orotracheal intubation: Intubating laryngeal mask. STUDY DESIGN: Prospective clinical study. METHODS: Ten persons practicing anaesthesia (specialist, fellow, nurse) underwent videotape learning and manikin training required with the device. Each person had to carry out a tracheal intubation in ten consecutive patients undergoing scheduled surgery. No patient presented history or clinical sign of difficult airway management. Results were expressed as mean +/- SD. Main percentages were provided with their 95% confidence interval; the percentage comparison were performed using Chi 2 test. The significance level for overall analysis was p < 0.05. RESULTS: One hundred patients were included. The overall success rate of tracheal intubation with the intubating laryngeal mask was 88%. An easy learning curve was obtained according to the low failure rate that was observed. No failure was noticed after eight procedures. Significant diminution of the delay for tube insertion was observed during the practice (3 +/- 1.30 min for the first procedure and 1.16 +/- 0.60 min for the tenth procedure). Circumstances of the oral intubation were improved with muscle relaxation. Finally, all failure with the intubating laryngeal mask were followed by successful intubation using direct laryngoscopy. CONCLUSION: The intubating laryngeal mask is a new device for blind orotracheal intubation with an easy learning curve in patients without difficulty in airway management, even for non-selected operators.

Aged↗
PubMed2001

HLA-G unique promoter region: functional implications.

In contrast to the highly polymorphic HLA class Ia genes that exhibit a broad somatic tissue distribution, the restricted constitutive expression of HLA-G to trophoblast and a subset of thymic epithelial cells suggests tight transcriptional control of this MHC class Ib gene. Transactivation of MHC class I genes is mediated by three major regulatory modules present in their promoter region namely enhancer A, ISRE, and SXY. The 220-bp promoter sequence of HLA-G comprises modified enhancer A and SXY modules and lacks the ISRE which renders this gene unresponsive to NK-kappaB, IRF1, and class II transactivator DNA-binding factors. A number of other HLA-G upstream regulatory elements have recently been described. Using different transgenic HLA-G mouse models under the control of the HLA-G promoter, several groups have shown by in situ hybridization and/or qualitative or quantitative RT-PCR that constitutive HLA-G transcriptional expression in placental tissue decreased with gestational time. This suggests that once the placenta is fully formed, the functions of HLA-G might not be so crucial.

Animals↗
PubMed2001

[Recurrent fatal pseudomembranous colitis].

BACKGROUND: Clostridium difficile pseudomembranous colitis may trace a fulminent course and require surgery. CASE REPORTS: Outcome was fatal despite subtotal colectomy in the reported case of recurrent Clostridium difficile pseudomembranous colitis. Infrequent localization, low serum albumin and an unfavorable clinical course were observed. DISCUSSION: Rapid surgical treatment with large resection is mandatory in such cases, particularly in patients of rectal and sigmoid remnant involvement.

Adult↗
PubMed2001

Maturation of antigen-presenting cells is compromised in HLA-G transgenic mice.

The human MHC class Ib antigen HLA-G is thought to regulate maternal immune responses during pregnancy. Here we show that expression of HLA-G in transgenic mice diminished cellular immunity by inhibiting maturation of myelomonocytic cells into functional antigen-presenting cells (APC). Skin allografts applied to HLA-G transgenic mice survived longer and resultant T cell responses were less potent compared to control mice. T cells from HLA-G mice responded normally to allogeneic APC and immunohistological analyses of spleen revealed no marked abnormalities. However, spontaneous outgrowths of myeloid cells were observed when bone marrow or splenocytes from HLA-G mice were cultured in vitro, but functionally competent APC did not develop spontaneously in bone marrow cultures supplemented with granulocyte macrophage colony stimulating factor (GM-CSF). Addition of lipopolysaccharide (LPS) to GM-CSF-derived bone marrow cultures rescued APC maturation. Studies using HLA-G tetrameric reagents revealed that HLA-G-specific binding activity was associated with CD11c(+) myelomonocytic cells, while binding to lymphoid and NK cell subsets was undetectable. These data show that spontaneous maturation of functionally competent dendritic cells (DC) is compromised in HLA-G mice. We hypothesize that HLA-G inhibits maturation of DC via receptor-mediated interactions with myelomonocytic precursors, which render immature DC precursors unable to receive signals from activated T cells.

Animals↗
PubMed2001

Could heart rate variability predict outcome in patients with severe head injury? A pilot study.

Despite major improvements in the resuscitation of patients with head injury, the outcome of patients with head trauma often remains poor and difficult to establish. Heart rate variability (HRV) analysis is a noninvasive tool used to measure autonomic nervous system (ANS) activity. The aim of this prospective study was to investigate whether HRV analysis might be a useful adjunct for predicting outcome in patients with severe head injury. Twenty patients with severe head trauma (Glasgow Coma Scale [GCS] or= 10) to HRV in patients characterized by a worsened neurologic state (GCS < 10). Statistical analysis used the Kruskal-Wallis test, P < .05. To assess whether HRV could predict evolution to brain death, receiver operating characteristic (ROC) curves were generated the day after trauma for Total Power, natural logarithm of high-frequency component of spectral analysis (LnHF), natural logarithm of low-frequency component of spectral analysis (LnLF), and root mean square for successive interval differences (rMSSD). Seven patients died between Day 1 and Day 5 after trauma. Six of those had progressed to brain death. In these six patients, at Day 1, Global HRV and parasympathetic tone were significantly higher. Referring to the area under the rMSSD ROC curve, HRV might provide useful information in predicting early evolution of patients with severe head trauma. During the awakening period, global HRV and the parasympathetic tone were significantly lower in the worsened neurologic state group. In conclusion, HRV could be helpful as a predictor of imminent brain death and a useful adjunct for predicting the outcome of patients with severe head injury.

Accidental Falls↗
PubMed2000

Cutting edge: soluble HLA-G1 triggers CD95/CD95 ligand-mediated apoptosis in activated CD8+ cells by interacting with CD8.

The nonpolymorphic soluble HLA-G1 (sHLA-G1) isoform has been reported to be secreted by trophoblast cells at the materno-fetal interface, suggesting that it may act as immunomodulator during pregnancy. In this paper, we report that affinity-purified beta2-microglobulin-associated sHLA-G1 triggered apoptosis in activated, but not resting CD8+ peripheral blood cells. We demonstrate by Western blotting that sHLA-G1 enhanced CD95 ligand expression in activated CD8+ cells. Cytotoxicity was inhibited by preincubation of the cells with a CD95 antagonist mAb (ZB4) or a soluble recombinant CD95-Fc, indicating that apoptosis is mediated through the CD95/CD95 ligand pathway. Finally, we show that such sHLA-G1-induced apoptosis depends on the interaction with CD8 molecules, with cell death being blocked by various CD8 mAbs.

Adjuvants, Immunologic↗
PubMed2000

The full length HLA-G1 and no other alternative form of HLA-G is expressed at the cell surface of transfected cells.

In contrast to HLA class Ia, the HLA-G class Ib transcripts can be alternativeley spliced to yield several isoforms including four potentially membrane-bound variants, namely HLA-G1, -G2, -G3 and G4. It is so far unclear whether each of these splice variants lacking one or two external domains is properly translated and expressed at the cell surface. We used targeted Enhanced Green Fluorescence Protein (EGFP)-HLA-G fusion cDNA to track HLA-G isoform expression in living murine (L-human beta2m) and human (JAR) transiently transfected cells. It was demonstrated that the four HLA-G1, -G2, -G3, and -G4 isoforms were translated in these transfectants by the means of (i) Western blotting analysis, using an anti-EGFP mAb; (ii) intracellular double labeling flow cytometry analysis, using the EGFP natural fluorescence and phycoerythrin-labeled HCA2 anti-HLA-G mAb; and (iii) immunocytochemistry on isolated acetone fixed transfectants with the use of different anti-HLA-G mAbs. Cell surface flow cytometry analysis using the HCA2 mAb revealed that only the HLA-G1 isoform was expressed as a membrane-bound protein. Two color confocal microscopy performed on fixed, permeabilized cells further showed that the EGFP green fluorescence co-localized with anti-calnexin rhodamine fluorescence in the four HLA-G isoform transfectants but only in HLA-G1 transfectant was the green EGFP fluorescence also detectable at the outer part of the cells, suggesting that the HLA-G2, -G3, and G4 were retained in the endoplasmic reticulum. Such intracellular retention of the three shorter forms of HLA-G suggest that they may play a role in regulating cell surface expression either of the full length HLA-G1 form or of HLA-E.

Animals↗
PubMed2000

Lidocaine inhibits potassium efflux and hemolysis in erythrocytes during oxidative stress in vitro.

Lidocaine is a widely used local anesthetic agent. The aim of this work was to study the action of lidocaine on human red blood cells exposed to an oxidative stress in vitro. Blood was obtained from healthy volunteers. After separation from plasma, the erythrocytes were suspended in phosphate buffer. Oxidative stress was induced by incubation with a free radical generator, the 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Erythrocytes were incubated with or without lidocaine at two concentrations (36.93 and 73.85 microM) and with or without AAPH (20 mM). Electron paramagnetic resonance (EPR) spectroscopy was performed to identify the free radical species generated by AAPH using the spin trap 5-5'-dimethyl-L-pyroline-N-oxide (DMPO). Different sets of experiments were run. Potassium efflux was measured by flame photometry in each group at time 0 min and every 30 min of the experiment for 2 h. Hemolysis was studied by the Drabkin method at increasing concentrations of AAPH (20, 50, and 100 mM) and with or without lidocaine (36.93 microM). The oxygen radical absorbance capacity (ORAC) was measured by using allophycocyanin (APC) as a fluorescent indicator protein, and the antioxidant capacity of lidocaine (36.93 microM) was studied by the analysis of fluorescence of the APC. AAPH was shown to produce alkoxyl free radicals. Oxidative stress induced a marked increase in the potassium efflux and the hemolysis that was AAPH dose-dependent. Lidocaine inhibited the potassium efflux and delayed the occurrence of hemolysis. Lidocaine did not show any antioxidant properties for the free radical species generated by AAPH. In this model, lidocaine protects erythrocytes against oxidative stress. This effect is not explained by a free radical scavenging property. The results may be of great interest in clinical practice such as intravenous regional anesthesia or the prevention of ischemia-reperfusion injury.

Amidines↗
PubMed2000

Comparative reactivity of different HLA-G monoclonal antibodies to soluble HLA-G molecules.

Different HLA-G monoclonal antibodies (mAbs) were first evaluated for their capability to identify soluble HLA-G (sHLA-G) in ELISA. Three of them, namely 87G, BFL.1 and MEM-G/9, when used as coating mAbs together with W6/32 capture mAb, identified beta2-microglobulin (beta2m)-associated-sHLA-G but not soluble HLA-B7 (sHLA-B7) in cell culture supernatants from transfected cells. By comparison, the anti-HLA class I mAb 90 did recognize both sHLA-G and sHLA-B7. By using these HLA-G mAbs, sHLA-G was identified in amniotic fluids as well as in culture supernatants of first trimester and term placental explants but not in cord blood. Intron 4-retaining sHLA-G isoforms were identified in some amniotic fluids by the use of an intron 4-specific mAb (16G1). Reactivity of these different HLA-G mAbs was then compared to determine their respective binding sites on soluble and membrane-bound HLA-G. Using both ELISA and flow cytometry analysis, we showed that they did not compete with each other, which suggested that they did not recognize the same determinants. Finally, we report that two mAbs directed against the alpha1 domain of HLA class I heavy chain (mAb 90 and YTH 862) did compete with 87G, therefore demonstrating that this latter mAb recognized an epitope localized on this external domain of HLA-G.

Antibodies, Monoclonal↗