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Biomedical subjects

L Drouet

Publications and source records attributed to L Drouet.

At least 19 recordsLinked to original sources
PubMed2006

Embolic and bleeding events after modified Bentall procedure in selected patients.

AIM: As valve-sparing procedures gain increasing popularity, the long-term results of the total aortic root replacement (TARR) were evaluated using mechanical valve grafts in selected patients. METHODS AND RESULTS: From January 1993 to December 2003, 100 patients (87 men), aged >65 years (mean 51 (SD 10.4 years), presenting with isolated aortic root dilatation with or without aortic valve insufficiency, undergoing elective root replacement using a mechanical valve graft were reviewed. The aetiology of aortic root disease was degenerative in 69 patients and related to the bicuspid aortic valve in 31 patients. In 11 patients, concomitant coronary artery bypass graft was performed. Hospital mortality was 4%. Overall survival was 93.9% (2.4%), 89.1% (3.5%) and 83.2% (5.2%) at 1, 5 and 7 years, respectively. 14 patients experienced 45 embolic events (3.21 (2.64) events/patient; range: 1-10 events). Thus, the linearised rate of embolic events was 10.3 per 100 patient-years (95% confidence interval (CI) 7.29 to 13.31). The actuarial embolism-free survival was 96.6% (1.9%), 77.1% (6%) and 74.3% (6.4%) at 1, 5 and 7 years, respectively. The linearised rate of bleeding events was 2.2 per 100 patient-years (95% CI 0.87 to 3.71). Actuarial bleeding free survival was 95.6% (2.1%), 93.2% (2.6%) and 87.7% (5.8%) at 1, 5 and 7 years. respectively. None of the patients required reoperation and no cases of structural or non-structural valve dysfunction were observed. CONCLUSIONS: TARR using mechanical valve grafts yields excellent survival results in selected patients. However, a high rate of minor thromboembolic events was recorded. Aspirin in combination with oral anticoagulants might be of potential interest in these patients.

Adolescent↗
PubMed2006

Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice.

A correlation between high plasma serotonin levels and total pulmonary resistance was reported in more than 80% of pulmonary hypertensive patients. When submitted to chronic hypoxia (10% O(2) for more than 3 weeks), wild-type mice develop lung vascular remodeling and pulmonary hypertension. We previously reported that, in contrast, the development of these hypoxia-dependent alterations is totally abolished in mice with permanent (genetic) or transient (pharmacologic) inactivation of the serotonin 5-hydroxytryptamine (5-HT)(2B) receptor. In the present study, we asked whether 5-HT(2B) receptors could be involved in the control of plasma serotonin levels. Further investigating the chronic hypoxic mouse model of pulmonary hypertension, we first show that in wild-type mice, plasma serotonin levels and 5-HT(2B) receptors expression were significantly increased after chronic exposure to hypoxia. This increase appeared before significant changes in remodeling factors could be detected and persisted when the pathology was established. Conversely, in mice with either genetically or pharmacologically inactive 5-HT(2B) receptors, plasma serotonin levels were not modified by chronic hypoxia. We then confirmed that 5-HT(2B) receptors can control plasma serotonin levels by providing in vivo evidence that an acute agonist stimulation of 5-HT(2B) receptor triggers a transient increase in plasma serotonin that is serotonin transporter dependent and blocked by 5-HT(2B) receptor-selective antagonist or genetic ablation. Our data support the notion that a 5-HT(2B) receptor-dependent regulation of serotonin uptake is implicated in the control of plasma serotonin levels.

Animals↗
PubMed2005

[rFVIIa administration in patient with a left ventricular assistance patient].

We report the case of a left ventricular mechanical assistance (Incor Berlinheart) in a woman that experienced a postoperative non-surgical haemorrhagic complication following a reconstructive pedicled omentoplasty for implanted materials infection. After massive substitutive therapy failure at reducing blood loss and because of an hypovolaemic shock, high dosage (70 microg/kg twice) of recombinant activated factor VII (r-VIIa) was administrated resulting in spectacular cessation of bleeding and haemodynamic restoration. Continuous repeated clinical evaluation, cardiac echography and electronic monitoring of the axial pump device characteristic did not reveal any thromboembolic accident. This observation brings some indirect arguments for safe rFVIIa treatment in this type of pathology with a high thromboembolic risk.

Aged↗
PubMed2005

Metabolic syndrome is associated with markers of subclinical atherosclerosis in a French population-based sample.

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). The relation of MetS with early stages of atherosclerosis, more important from a prevention perspective, has not been evaluated extensively. We examined the association of MetS, using WHO and NCEP definitions, with number of carotid and femoral plaques; carotid intima-media thickness (IMT); pulse wave velocity (PWV) in a random population-based sample of 1153 French adults (35-65 year). Impact of inflammatory factors (C-reactive protein and soluble intercellular adhesion molecule-1) on these parameters was also evaluated. Prevalence of MetS was 14.5 (CI: 12.3-16.0) and 17.5 (CI: 15.1-20.2)%, using NCEP and WHO definitions, respectively. MetS significantly predicted number of plaques, IMT, and PWV after adjustment for traditional risk factors (P<0.05). Inflammatory factors predicted peripheral plaques only. The risk of subclinical atherosclerosis was considerably increased with MetS (P<0.05); odds ratios ranged 1.80-2.15 with NCEP definition, and 1.48-1.97 with WHO definition. Individuals meeting both NCEP and WHO definitions had slightly greater risk of increased plaques, IMT, and PWV. MetS was strongly associated with subclinical atherosclerosis and aortic stiffness, and can be used as a surrogate marker for high CVD risk, deserving aggressive treatment.

Adult↗
PubMed2005

Lack of association between ADH3 polymorphism, alcohol intake, risk factors and carotid intima-media thickness.

OBJECTIVE: We assess the relationships between alcohol dehydrogenase 3 (ADH3) polymorphism, alcohol consumption and cardiovascular risk factor levels. METHODS: In a representative population sample from Southwestern France (614 men, 567 women, age 49.7+/-8.5 years), alcohol intake was assessed by questionnaire. RESULTS: Alcohol consumption was significantly related with higher levels of total and HDL cholesterol, triglycerides, apolipoprotein A-I in men and with higher levels of HDL cholesterol in women. Also, an inverse relationship between alcohol consumption and intima-media thickness was found in men. Conversely, in both genders, no differences were found between ADH3 genotypes regarding all cardiovascular risk factors studied and carotid intima-media thickness. Also, in both genders, no significant ADH3xalcohol interaction was found for all variables, and further adjustment on age, body mass index, educational level, smoking status or after excluding subjects on hypolipidemic or antihypertensive drug treatment did not change the results. CONCLUSION: We found no interaction between the ADH3 polymorphism and alcohol intake on cardiovascular risk factor levels and atherosclerotic markers in Southwestern France.

Adult↗
PubMed2005

[Blood activation during long-term mechanical circulatory support].

Mechanical circulatory support has become an approved treatment option for patients with cardiogenic shock or end-stage heart failure. However, recipients of heart assist devices are prone to high incidences of bleeding, thrombo-embolic and infectious complications. The occurrence of these complications is favoured by systemic alterations of coagulation and fibrinolysis, inflammation and immune responses. Several studies have evaluated these pathophysiological changes in patients undergoing long term circulatory support with pulsatile devices. However, the systemic consequences of the more recently introduced rotary blood pumps remain largely unknown. The present review focuses on the systemic consequences of long term circulatory support with pulsatile and non-pulsatile devices.

Assisted Circulation↗
PubMed2005

Rationale for the use of antifactor Xa in the treatment and prevention of venous and arterial thromboembolic events.

The design and synthesis of new antithrombotic agents have led to numerous recent clinical trials to investigate their efficacy and safety. Analysis of the data from these trials, especially when the results were not totally expected, has provided interesting information, allowing a better understanding of the pathophysiology of thrombosis in various clinical situations. The aim of the present manuscript is to present the hypotheses on thrombogenesis generated by some of these recent clinical trials, notably those investigating the antithrombotic efficacy of a new synthetic and selective factor Xa inhibitor, fondaparinux. The antithrombotic efficacy of fondaparinux was recently investigated in a number of trials in the prevention and treatment of venous and arterial thrombotic disorders. In each case, the concept of the clinical efficacy of a selective factor Xa inhibitor has been proven. These trials have also clarified the implication and mode of action of factor Xa in these various types of thrombotic events. In the light of these trials, we discuss the clinical efficacy of such a selective factor Xa inhibitor, and other specific points such as the apparent lack of dose-dependency of its antithrombotic effect.

Anticoagulants↗
PubMed2005

Paracetamol: a haemorrhagic risk factor in patients on warfarin.

AIM: To quantify the effect of paracetamol on the anticoagulant effect of warfarin under normal clinical conditions. PATIENTS AND METHODS: In a prospective double-blind, cross-over, placebo-controlled study, 11 patients on stable warfarin therapy received in random order two 14-day regimens of paracetamol 4 g day(-1) or placebo, with a 14-day or more wash-out period in between, time necessary to fulfil the inclusion criteria. RESULTS: In patients on paracetamol, the mean maximum increase in the International Normalized Ratio (INR) observed was 1.04 +/- 0.55 vs. 0.20 +/- 0.32 in those on placebo (P = 0.003). The mean maximum INR observed was significantly higher with paracetamol than with placebo (3.47 vs. 2.61, P = 0.01). In patients receiving paracetamol, the mean observed INR was significantly increased after 4 days (+ 0.6 +/- 0.6, P < 0.001). CONCLUSION: Paracetamol at 4 g day(-1) induces a significant increase in INR in patients receiving a stable regimen of warfarin, increasing the risk of bleeding associated with warfarin.

Acetaminophen↗
PubMed2004

Activity of a synthetic hexadecasaccharide (SanOrg123781A) in a pig model of arterial thrombosis.

The activity of SanOrg123781A, a new synthetic antithrombotic drug inhibiting both factor Xa and thrombin through antithrombin (AT), was compared to that of unfractionated heparin (UFH) and of the synthetic pentasaccharide (fondaparinux, SP) in an ex vivo arterial thrombosis model in the pig. Six groups of four pigs were administered intravenously with SanOrg123781A (1, 3, 10 and 30 nmol kg(-1)), UFH (30 nmol kg(-1)) or SP (30 nmol kg(-1)). In this arterial model in which platelet thrombus was formed on a thrombogenic surface under a constant high shear rate, UFH and SP had moderate antithrombotic effects while SanOrg123781A exhibited a strong, dose-dependent inhibitory activity on platelet adhesion and platelet thrombus formation. In contrast to UFH, SanOrg123781A did not modify the activated partial thromboplastin time (aPTT) even at 30 nmol kg(-1), but strongly inhibited thrombin generation. At the same dose, despite a lower antithrombotic activity than SanOrg123781A, UFH significantly affected all the coagulation parameters. Taken together, these results show that SanOrg123781A, due to its potent and selective antifactor Xa and antifactor IIa activities is a promising new antithrombotic agent even in arterial setting.

Animals↗
PubMed2003

No alteration in platelet function or coagulation induced by EGb761 in a controlled study.

Some cases of spontaneous bleeding have been reported in patients treated with Ginkgo biloba. A prospective, double-blind, randomized, placebo-controlled study was carried out in 32 young male healthy volunteers to evaluate the effect of three doses of Ginkgo biloba extract (120, 240 and 480 mg/day for 14 days) on hemostasis, coagulation and fibrinolysis. This study did not reveal any alteration of platelet function or coagulation. This suggests that the reported clinical bleeding events in patients receiving Ginkgo biloba extract are not related to pharmacological properties of EGb761.

Adenosine Diphosphate↗
PubMed2002

Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension.

Primary pulmonary hypertension is a progressive and often fatal disorder in humans that results from an increase in pulmonary blood pressure associated with abnormal vascular proliferation. Dexfenfluramine increases the risk of pulmonary hypertension in humans, and its active metabolite is a selective serotonin 5-hydroxytryptamine 2B (5-HT(2B)) receptor agonist. Thus, we investigated the contribution of the 5-HT(2B)receptor to the pathogenesis of pulmonary hypertension. Using the chronic-hypoxic-mouse model of pulmonary hypertension, we found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-beta levels, and that these parameters are potentiated by dexfenfluramine treatment. In contrast, hypoxic mice with genetically or pharmacologically inactive 5-HT(2B)receptors manifested no change in any of these parameters. In both humans and mice, pulmonary hypertension is associated with a substantial increase in 5-HT(2B) receptor expression in pulmonary arteries. These data show that activation of 5-HT(2B) receptors is a limiting step in the development of pulmonary hypertension.

Animals↗
PubMed2002

D-dimer: a characteristic of the coagulation state of each patient with chronic atrial fibrillation.

BACKGROUND AND OBJECTIVE: It is accepted that patients with atrial fibrillation (AF) are characterised by increased levels of plasmatic D-dimers, with a wide inter-individual variability depending on the patients and therapeutic characteristics, but it has not been established if this level was predictive of the risk of arterial thromboembolic event. In order to answer such a question, it has to be established if the D-dimer level in a given patient is characteristic of such a patient (stable over time) if also fluctuating with time (and useless to characterise the patient). METHODS AND RESULTS: One hundred thirty clinically stable patients with chronic AF were recruited (anticoagulant: group 1, antiaggregant aspirin: group 2, no antithrombotic: group 3). During the follow-up of patients without clinical events (n=63), it is notable that in patients with D-dimer levels <500 ng/ml, these remained <1000 ng/ml, in patients with levels between 500 and 1000 ng/ml, these did not reach 1590 ng/ml, and in those with D-dimers >1000 ng/ml, the levels remained relatively stable. Mean age and D-dimer levels were lower in group 1 (74.4 years and 509.1 ng/ml, respectively) than in group 2 (82.4 years, p=0.0003 and 1015.7 ng/ml, p<0.0001, respectively) and in group 3 (79.3 years and 1289.3 ng/ml, p<0.0001, respectively). The effect of the antithrombotic therapy was independent of the age of patients (p=0.017). CONCLUSION: D-dimer levels in patients with chronic AF remain in the same range over time. They are lower on anticoagulant therapy than on antiaggregant or no antithrombotic therapy, irrespective of age. Thus, D-dimers appear to be a useful parameter for assessing the degree of hypercoagulability of patients whatever their age.

Age Factors↗
PubMed2002

Clopidogrel-induced qualitative changes in thrombus formation correlate with stent patency in injured pig cervical arteries.

Thienopyridines (ticlopidine or clopidogrel) alone or in combination with aspirin are now the reference antiplatelet therapy after stent implantation. To better understand the high efficacy and low risk of bleeding with these agents, we tested clopidogrel alone or with aspirin in an acute ex vivo flow chamber model and in a subacute in vivo arterial thrombosis model. Clopidogrel induced a dose-dependent increase in bleeding time (BT), inhibited ADP-induced platelet aggregation and in the flow chamber reduced thrombus size, and changed thrombus structure to broad-based structure composed of nondegranulated loosely attached platelets contrasting with the tight clumps of degranulated platelets seen without clopidogrel. The in vivo model involved angioplasty and stenting at the site of a preinduced arterial lesion and thrombosis in pig carotid arteries. Clopidogrel alone or with aspirin (but not aspirin alone) decreased the number of stented vessels occluded for more than 24 h and conversely reduced the number of occluding thrombus. At 96 h after stenting, 100% and 90% of the arteries were patent with clopidogrel/aspirin and clopidogrel alone, respectively (vs. 67% and 44% with aspirin and saline, respectively). Clopidogrel destabilizes thrombus without complete abolishment of platelet reactivity.

Animals↗
PubMed2002

Coagulation abnormalities associated with extensive venous malformations of the limbs: differentiation from Kasabach-Merritt syndrome.

Confusion in the nomenclature of vascular malformations has been a major obstacle to the understanding of these conditions, so that misdiagnosis and treatment inconsistencies are common. Coagulation abnormalities occurring in combination with venous malformations (VM) have been misdiagnosed as Kasabach-Merritt syndrome (KMS), despite marked differences in clinical features, pathology and treatment. A homogenous group of 24 patients with diffuse limb VM was entered into a retrospective chart review study. The VM affected an upper limb in 12 patients, a lower limb in 10 and both in two. Localized intravascular coagulation (LIC) was characterized by a decrease in fibrinogen (0.5-1 g/l), an increase in d-dimers (2-64 micro g/ml) and presence of soluble complex of fibrin (+ to +++). Platelet counts were normal or slightly decreased. Higher VM severity scores were associated with more severe LIC. A number of events such as sclerotherapy, surgery, bone fracture, prolonged immobilization and pregnancy or menstruation triggered conversion of the LIC to disseminated intravascular coagulation (DIC), with bleeding related to factor consumption and multiorgan failure related to disseminated microvascular thrombosis. Clinical symptoms associated with worsening of LIC were pain, thrombosis and bleeding at wound sites or during surgery. None of the patients had the large ecchymotic and inflammatory tumours seen in KMS. Graded permanent elastic compression with heparin therapy was the only effective treatment. In conclusion, VM-associated LIC is a distinctive lifelong coagulopathy that must be differentiated from KMS, which is characterized by platelet trapping within a vascular tumour of infancy. The treatment of the two conditions is very different.

Adult↗
PubMed2002

Pulmonary arterial hypertension and type-I glycogen-storage disease: the serotonin hypothesis.

A case of pulmonary arterial hypertension in a patient with type-Ia glycogen-storage disease, a rare autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase is reported in this study. It has been suggested that the occurrence of pulmonary arterial hypertension in type-Ia glycogen-storage disease could be due to an abnormal production of vasoconstrictive amines such as serotonin. To test this hypothesis, plasma serotonin concentrations were prospectively measured in 13 patients with type-Ia glycogen-storage disease, one patient with severe pulmonary hypertension and type-Ia glycogen-storage disease, 16 patients displaying severe pulmonary arterial hypertension, and 26 normal healthy controls. Elevated plasma serotonin concentrations were found in patients with either severe pulmonary arterial hypertension (38.8+/-7.3 nmol x L(-1)) or type-Ia glycogen-storage disease (36.8+/-11.5 nmol x L(-1)), as compared with controls (8.8+/-0.6 nmol x L(-1), p<0.001). Plasma serotonin was dramatically elevated in the patient with type-Ia glycogen-storage disease and pulmonary arterial hypertension (113.4 nmol x L(-1)). It is concluded that type-Ia glycogen-storage disease may be another condition in which abnormal handling of serotonin is one event in a multistep process leading to severe pulmonary arterial hypertension.

Adolescent↗
PubMed2002

[Fibrinogen: factor and marker of cardiovascular risk].

Most cardiovascular events result from a thrombotic complication in patients with atherosclerosis. Inflammation plays a central role both in the pathogenesis of atherosclerosis and in the development of complications (particularly plaque rupture). Fibrinogen is both a marker of inflammation and a major determinant of thrombosis and hemorrheology. Clinical data corroborate with epidemiological data showing that higher serum fibrinogen level (compared with matched controls) is predictive of both the risk of primary cardiovascular events in the general population and the risk of secondary events among patients. Fibrinogen level, determined by both environmental and genetic factors, is a good example of gene-environment interaction. The rise in fibrinogen level indicative of significantly increased risk is actually very small, lying within the normal range. This explains why epidemiological data cannot be used to establish cardiovascular risk for individual patients in routine practice (excepting very high elevations rarely encountered). To date, fibrinogen is the only compound formally recognized as both a risk factor and a marker of cardiovascular risk. Other compounds, including CRP, von Willebrand factor, and more recently the CD40-CD40 ligand system, have also been shown to play a double role as predictors and markers. These new developments shed new light on fibrinogen as a risk marker/factor for atherothrombotic ischemic events.

Alternative Splicing↗