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Biomedical subjects

Olivier Morel

Publications and source records attributed to Olivier Morel.

15 recordsLinked to original sources

Procoagulant microparticles: disrupting the vascular homeostasis equation?

Apoptosis and vascular cell activation are main contributors to the release of procoagulant microparticles (MPs), deleterious partners in atherothrombosis. Elevated levels of circulating platelet, monocyte, or endothelial-derived MPs are associated with most of the cardiovascular risk factors and appear indicative of poor clinical outcome. In addition to being a valuable hallmark of vascular cell damage, MPs are at the crossroad of atherothrombosis processes by exerting direct effects on vascular or blood cells. Under pathological circumstances, circulating MPs would support cellular cross-talk leading to vascular inflammation and tissue remodeling, endothelial dysfunction, leukocyte adhesion, and stimulation. Exposed membrane phosphatidylserine and functional tissue factor (TF) are 2 procoagulant entities conveyed by circulating MPs. At sites of vascular injury, P-selectin exposure by activated endothelial cells or platelets leads to the rapid recruitment of MPs bearing the P-selectin glycoprotein ligand-1 and blood-borne TF, thereby triggering coagulation. Within the atherosclerotic plaque, sequestered MPs constitute the main reservoir of TF activity, promoting coagulation after plaque erosion or rupture. Lesion-bound MPs, eventually harboring proteolytic and angiogenic effectors are additional actors in plaque vulnerability. Pharmacological strategies aimed at modulating the release of procoagulant MPs appear a promising therapeutic approach of both thrombotic processes and bleeding disorders.

Animals↗

Active lighting applied to three-dimensional reconstruction of specular metallic surfaces by polarization imaging.

In the field of industrial vision, the three-dimensional inspection of highly reflective metallic objects is still a delicate task. We deal with a new automated three-dimensional inspection system based on polarization analysis. We first present an extension of the shape-from-polarization method for dielectric surfaces to metallic surfaces. Then, we describe what we believe to be a new way of solving the ambiguity concerning the normal orientation with an active lighting system. Finally, applications to shape-defect detection are discussed, and the efficiency of the system to discriminate defects on specular metallic objects made by stamping and polishing is presented.

Algorithms↗

Results of preoperative lymphoscintigraphy for breast cancer are predictive of identification of axillary sentinel lymph nodes.

The aim of this study was to identify the variables associated with successful peroperative sentinel lymph node (SLN) localization. We studied 201 patients with T1, T2, N0 invasive breast cancer who underwent a SLN procedure from 1999 to 2003. Of these 201 patients, 55 underwent peritumoral and 146 underwent periareolar radioisotope injection before the blue dye injection. All patients were operated on by breast conservative surgery and axillary dissection after SLN biopsy. Age, weight, menopausal status, previous biopsy, localization of the tumor, results of lymphoscintigraphy, site of radiotracer injection, tumor size, tumor grade, experience of surgeons, and the number of invaded axillary nodes were analyzed to determine whether they had any significant correlation with successful identification of SLN. Variables found to have a statistically significant influence on the SLN identification rate and on preoperative lymphoscintigraphy identification were introduced into a univariate and multivariate logistic regression model. In multivariate analysis, successful lymphoscintigraphy (P < 0.0001) and the absence of metastatic axillary nodes (P < 0.005) were associated with successful identification of SLNs. The peritumoral injection of radiotracer (P < 0.001), patient age > 60 years (P < 0.003), and localization of the tumor in the upper outer quadrant (P < 0.004) were associated with failure of lymphoscintigraphic visualization of SLN. The technique of SLN detection thus appears to be better for patients with low risk of invaded axillary lymph nodes.

Adult↗

Prognostic value of C-reactive protein and cardiac troponin I in primary percutaneous interventions for ST-elevation myocardial infarction.

BACKGROUND: The rise in cardiac troponin I after ST-elevation myocardial infarction treated by primary percutaneous coronary interventions (PCIs) is predictive of infarct size and left ventricular ejection fraction (LVEF). However, the comparative value of C-reactive protein (CRP) and troponin I for infarct size evaluation and the respective relationships between these biomarkers and mortality have not been investigated. METHODS: We studied 87 patients who underwent primary PCI for ST-elevation myocardial infarction. Concentrations of troponin I and CRP were measured before and for 72 hours after PCI. Infarct size was measured by the cumulative release of alpha-hydroxybutyrate deshydrogenase during the 72 hours after PCI (QHBDH72) and by delayed radionuclide LVEF (at 4.6 +/- 1.7 weeks). RESULTS: Concentrations of CRP at peak and at 24, 48 and 72 hours, and of troponin I at 6 and 72 hours, correlated with QHBDH72 and LVEF. In single variable analysis, at a mean follow-up of 42 +/- 8 months, Killip score of 3 to 4, CRP at baseline and at 48 hours, and troponin I at 6 and 72 hours were related to mortality. By multiple variable analysis, Killip score (OR 9.9, CI 1.6-58.8) and troponin I at 72 hours (OR 9.43, CI 2.1-43.5) were the only independent predictors of mortality. CONCLUSIONS: Plasma concentrations of CRP and troponin I after PCI were related to infarct size and mortality. However, Killip class and troponin I at 72 hours were the only independent predictors of mortality at long-term follow-up.

Aged↗

Diagnostic and prognostic value of circulating D-Dimers in patients with acute aortic dissection.

OBJECTIVE: We sought to determine whether assessing D-Dimer might be helpful for the management of acute aortic dissection (AAD). DESIGN: Single-center retrospective case-control study. SETTING: University Hospital of Strasbourg France. PATIENTS: Patients were 94 consecutive patients admitted to our institution with confirmed AAD and in whom D-Dimer test had been performed at presentation. These patients were matched with 94 controls presenting with clinical suspicion of dissection, which was later ruled out. INTERVENTIONS: Patient characteristics and clinical course were analyzed. MEASUREMENTS AND MAIN RESULTS: Ninety-three (99%) patients with AAD had elevated D-Dimer (>400 ng/mL) with a median D-Dimer value of 8610 ng/mL (interquartile range, 2982-20,000 ng/mL). Receiver operating characteristic curves analysis showed that D-Dimer, but not C-reactive protein, troponin, lactate dehydrogenase, or leukocyte count, was predictive of a diagnosis of AAD, with a sensitivity and specificity of 99% and 34%, respectively. D-Dimer concentration positively correlated with the anatomical extension of the dissection to the different segments of the aorta (R = .47, p < .0001). A positive relationship was observed between D-Dimer and in-hospital mortality rate among patients with AAD (p = .037). On multivariate analysis, the independent predictors of in-hospital mortality were the presence of pericardial effusion (odds ratio, 6.80; confidence interval, 1.87-27.60), D-Dimer >5200 ng/mL (odds ratio, 5.38; confidence interval, 1.27-30.87), and female gender (odds ratio, 4.96; confidence interval, 1.39-19.95). CONCLUSIONS: D-Dimers are elevated in patients with AAD and provide valuable diagnostic and prognostic information. In patients with acute chest pain and elevated D-Dimer, a diagnosis of AAD should also be considered. D-Dimer might be a useful complementary tool to the current diagnostic work-up of patients with suspected AAD.

Acute Disease↗

Procoagulant microparticles: 'criminal partners' in atherothrombosis and deleterious cellular exchanges.

Procoagulant microparticles (MP) constitute valuable hallmarks of vascular cell damage at the crossroad of atherothrombosis processes. Detectable at low concentrations in the blood flow of healthy individuals, elevated levels of procoagulant microparticles are characteristic features of most cardiovascular risk factors. Circulating MP support cellular cross-talk leading to vascular inflammation, endothelial dysfunction, leukocyte adhesion and recruitment possibly contributing to plaque growth with consecutive development of local thrombosis and altered vasomotion. Within the plaque, MP shed by apoptotic monocytes and smooth muscle cells are major determinant of plaque thrombogenicity mainly through the presence of tissue factor (TF) activity. Besides this procoagulant potential, trapped MP could contribute to plaque vulnerability through multiple pathways including angiogenesis, extracellular matrix proteolysis, recruitment of inflammatory cells, smooth muscle cell and endothelial apoptosis. Having long been considered sufficient to initiate coagulation following plaque disruption, the role assigned to plaque-bound TF does not appear physically realistic at a macroscopic scale, the swift growth of the thrombus probably involving blood-borne TF conveyed by circulating MP. As participants in crucial steps of atherosclerotic disease, MP can now be viewed as "partners in crime" in acute ischemic syndromes.

Arteriosclerosis↗

Prognostic value of an increase in the serum thyroglobulin level at the time of the first ablative radioiodine treatment in patients with differentiated thyroid cancer.

PURPOSE: The aim of this study was to assess the prognostic factors for treatment efficacy, and in particular the increase in serum thyroglobulin (Tg) level at the time of the first ablative radioiodine treatment, in patients with differentiated thyroid carcinoma (DTC). METHODS: A retrospective chart review was performed on 407 patients treated for DTC by total thyroidectomy and (131)I ablation between 1995 and 2002, and examined 5-12 months later with diagnostic (131)I whole-body scan and serum Tg measurement after thyroid hormone treatment withdrawal. At the time of the ablative radioiodine treatment, serum Tg level was determined just before (131)I administration (TgD0) and 5 days later (TgD5); Tg variation was expressed as the ratio TgD5/TgD0. At the first post-ablation follow-up examination, unsuccessful ablation was defined by a Tg level > or =2 ng/ml and/or abnormal (131)I uptake. RESULTS: Ablation was unsuccessful in 51 patients. Univariate analysis showed high TgD0 level, low TgD5/TgD0 ratio extrathyroidal invasion, (131)I uptake in the neck (excluding the thyroid bed) during the ablative treatment and distant metastases to be significantly associated with unsuccessful ablation. On logistic multivariate analysis, TgD0 level <5 ng/ml and TgD5/TgD0 ratio > or =20 were independently associated with successful ablation. A receiver operating characteristic curve analysis determined that a TgD5/TgD0 ratio greater than 20 had a 97% positive predictive value for successful ablation. When both TgD0 and TgD5/TgD0 ratio were considered, that is, TgD0 <5 ng/ml or TgD0 > or =5 ng/ml but TgD5/TgD0 ratio >20, ablation was unsuccessful in only 12/301 patients. CONCLUSION: Our data show that the TgD5/TgD0 ratio may be used as a new prognostic indicator of (131)I treatment efficacy in patients with DTC.

Adolescent↗

Shed membrane particles from T lymphocytes impair endothelial function and regulate endothelial protein expression.

BACKGROUND: Microparticles (MPs) are membrane vesicles with procoagulant and proinflammatory properties released during cell activation. The present study was designed to dissect the effects evoked by T lymphocyte-derived MPs on vascular function. METHODS AND RESULTS: MPs were produced by treatment of the human lymphoid CEM T cell line with actinomycin D or phytohemagglutinin. Incubation of mouse aortic rings with 30 nmol/L MPs resulted in a time-dependent impairment of acetylcholine-induced relaxation of precontracted vessels, with a maximal reduction after 24 hours. MPs also impaired shear stress-induced dilatation of mouse small mesenteric arteries by affecting the nitric oxide (NO) and prostacyclin but not the endothelium-derived hyperpolarizing factor components of the response. However, neither alteration of calcium signaling in response to agonists nor reduction of cyclooxygenase-1 expression accounted for the impairment of the NO and prostacyclin components of the endothelial response. The effect of MPs was rather because of a decrease in expression of endothelial NO synthase and an overexpression of caveolin-1. Furthermore, lymphocyte-derived MPs from diabetic patients or in vivo circulating MPs from either diabetic or HIV-infected patients reduced endothelial NO synthase expression. Finally, the effects of MPs on endothelial cells were not driven through CD11a/CD18 adhesion molecules or the Fas/FasL pathway. CONCLUSIONS: MPs from T cells induce endothelial dysfunction in both conductance and resistance arteries by alteration of NO and prostacyclin pathways. MPs regulate protein expression for endothelial NO synthase and caveolin-1. These data contribute to a better understanding of the deleterious effects of enhanced circulating MPs observed in disorders with cardiovascular or immune complications.

Acetylcholine↗

Cellular microparticles: a disseminated storage pool of bioactive vascular effectors.

PURPOSE OF REVIEW: Microparticles (MP) or microvesicles are fragments shed from the plasma membrane of stimulated or apoptotic cells. Having long been considered inert debris reflecting cellular activation or damage, MP are now acknowledged as cellular effectors involved in cell-cell crosstalk. This review focuses on procoagulant MP circulating in the vascular compartment, their role in hemostasis and thrombosis, and possible impact in vascular functions. RECENT FINDINGS: Microparticles can be viewed as a "storage pool" by themselves, disseminating blood-borne tissue factor activity and procoagulant phospholipids. Increasing evidences of integrated loops involving dynamic exchanges and transfer events through multiple MP-cell interactions are summarized. SUMMARY: Microparticles can be considered true targets in the pharmacological control of thrombosis. Another challenging issue is to take advantage of their procoagulant potential for the management of hemophilia.

Apoptosis↗

Sustained elevated amounts of circulating procoagulant membrane microparticles and soluble GPV after acute myocardial infarction in diabetes mellitus.

During myocardial infarction (MI), platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP were described in diabetes mellitus (DM), and could be of particular significance in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM) patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon thrombin cleavage. Variations were compared to values measured in healthy volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and quantified by prothrombinase assay. Their cellular origin was assessed. With respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of platelet-derived MP and the correlation between procoagulant MP and sGPV, testify to the central role of thrombin-activated platelets during MI in both DM and NDM subsets. The release of platelet and endothelial cell-derived MP persisted at D6 and was more important in DM, the associated prothrombotic risk being also reflected by higher levels of sGPV. The endothelial damage revealed by endothelial-derived MP was twice that observed in NDM patients. In DM patients presenting cardio-vascular events at 6 month follow-up, MP levels were significantly higher at D1 after MI than in those without complication (24.9 +/- 4.8 vs. 12.3 +/- 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP.

Aged↗