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Biomedical subjects

B Jude

Publications and source records attributed to B Jude.

At least 19 recordsLinked to original sources
PubMed2005

[Polycythemia vera and pregnancy: difficulties for diagnosis and treatment].

Polycythemia vera is a myeloproliferative syndrome. This clonal disorder involves a pluripotent stem cell capable of differentiating into red blood cells, granulocytes, and platelets. Polycythemia vera is characterized by the overproduction of mature red blood cells in the bone marrow. Myeloid and megakaryocytic elements are also often increased. Polycythemia vera (PV) is rarely associated with pregnancy. About 20 cases have been reported. Prognosis of PV is not influenced by pregnancy. Conversely, pregnancy outcome is poor, due to the occurrence of gestational hypertension, stillbirth and induced prematurity. During pregnancy, clinical management needs to be close including a collaborative approach between obstetricians, hematologists and anesthesists. The risk of poor outcome may be reduced by the association of antiaggregant and anticoagulant therapy. Phlebotomy can be provided in order to maintain hemoglobin level under 42%.

Adult↗
PubMed2005

The specific thromboxane receptor antagonist S18886: pharmacokinetic and pharmacodynamic studies.

OBJECTIVES AND PATIENTS: We conducted a multicenter double-blind pharmacokinetic/pharmacodynamic (PK/PD) study of the new oral thromboxane receptor antagonist S18886 in 30 patients with peripheral artery disease, who were randomized to receive five different oral dosages of S18886 (1, 2.5, 5, 10 or 30 mg) for 12 weeks (83 days). Primary objective was to determine the effect of S18886 on platelet aggregation ex vivo. RESULTS: Pharmacokinetics of S18886 was linear, with peak plasma levels being reached between 30 min and 2 h and a terminal half-life of 5.8-10 h. No significant accumulation of S18886 in plasma was observed after repeated dosing. The relationship between the S18886 concentration and platelet inhibition was examined in terms of U46619-induced platelet aggregation. Over the range of doses studied, there was a predictable relation between the plasma drug concentration and the degree of platelet inhibition at each dose. Maximal inhibition of U46619-induced platelet aggregation was achieved within 1 h with all oral doses of S18886, and this effect was maintained for at least 12 h. The PK/PD relationship was direct, and U46619-induced platelet aggregation was strongly inhibited by S18886 plasma concentrations above 10 ng mL(-1). This concentration was thus the minimal effective antiplatelet level in this population, and was maintained only by the dosages of 10 and 30 mg. The safety profile of S18886 was excellent, whatever the unit dose, with no attributable adverse events. CONCLUSION: The results of this study, which included modeling and simulation, help identify the minimal effective plasma concentration of S18886 required for potent antiplatelet efficacy in patients with stable peripheral arterial disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2005

Relevance of tissue factor in cardiovascular disease.

Overexpression and exposition of tissue factor (TF) in atherosclerotic plaques and/or arterial thrombi are critical events in atherothrombosis. TF, the receptor for factor VII (FVII) and activated factor VII (FVIIa), is the principal initiator of blood coagulation and induces thrombin generation leading to fibrin formation and platelet activation. TF also plays a major role in cell migration and angiogenesis. TF activity is downregulated by Tissue Factor Pathway Inhibitor (TFPI), a Kunitz-type inhibitor, which forms a neutralizing complex with TF, FVIIa and activated factor X. In physiological conditions, TF is absent from vascular cells which come into contact with flowing blood and is present as an inactive pool in fibroblasts and smooth muscle cells (SMC). In contrast, TF is widely expressed in atherosclerotic plaques and is found in macrophages, SMCs, and foam-cells and also in extracellular matrix and acellular lipid-rich core. TF expression is up-regulated by inflammatory cytokines and oxidized lipids. Plaque thrombogenicity is directly correlated to their TF content. After fibrous cap disruption, TF is exposed on plaque surface and triggers thrombus formation leading to arterial lumen occlusion and/or downstream embolization. In coronary and carotid plaques, TF content was found to be higher in plaques from symptomatic than asymptomatic patients. Soluble forms of TF and microparticles of monocyte and platelet origin, and bearing TF, constitute "blood-born TF". The contribution of this TF pool to arterial thrombosis is still under discussion. TF pathway is a target for new therapeutic agents that can decrease TF activity, such as active site-inactivated factor VIIa, recombinant TFPI and antibodies against TF or peptides interfering with TF-FVIIa complex activity.

Arteriosclerosis↗
PubMed2004

[Monitoring of heparin therapy during extracorporeal bypass: what are the remaining questions?].

Cardiac surgery with extracorporeal circulation induces major alterations of haemostasis and requires high level of anticoagulation, usually achieved by unfractionated heparin infusion. Optimization of anticoagulant regimen, through adapted biological monitoring, can probably improve postoperative course, at least for postoperative haemostatic status. Despite increasing knowledge on extracorporeal circulation-induced haemostatic abnormalities and the development of new biological devices for heparin monitoring, the optimal level of anticoagulation remains matter of debate, as well as the monitoring procedures. This critical review presents the current available data on heparin anticoagulation and monitoring in this specific context, and underlines the pending issues about anticoagulation management during extracorporeal bypass.

Anticoagulants↗
PubMed2004

[Hormone replacement therapy and venous thromboembolism].

Venous thromboemboembolism is a multigenic and a multifactorial disease. Several genetic risk factors have been identified: antithrombin, protein C and protein S deficiencies, and molecular defects in factor V gene (factor V Leiden) or factor II gene (G 20210A transition). Retrospective and prospective studies have demonstrated that hormone replacement therapy (HRT) in women is associated with a 2-3-fold increase of venous thromboembolism events. To minimize this risk, it seems desirable to carefully evaluate the individual clinical risk factors. Prescribing HRT should clearly be avoided in women with previous thromboembolic events. In case of familial thrombophilia, HRT should probably be prescribed with caution. Recent data suggest that transdermal HRT would induce a lower increase in thrombotic risk, but additional studies are needed to determine whether they can be safely used in women at risk. In each case, the net balance of risk and benefit of HRT use must consider the potential beneficial health effects, the most evident being the relief of climacteric symptoms.

Estrogen Replacement Therapy↗
PubMed2003

[Cell therapy to treat heart failure].

INTRODUCTION: Systolic heart failure is mainly due to a decreased left ventricular systolic function after myocardial infarction. Despite significant improvements in medical management of heart failure, the prognostic remains poor, with a 5-years survival only of 30%. PURPOSE: Current treatments are only able to delay progression toward end-stage heart failure. Heart transplantation is accessible only for selected patients. Thus, in the context of post-myocardial infarction, cell therapy appears to be a new original technique, available for the majority of patients and potentially non-invasive. CONCLUSION: After promising results in experimental models, a phase I clinical trial has been conducted in France, showing the feasibility of intracardiac autologous skeletal myoblast implantation. Other studies in Europe and USA are currently testing a variety of cells and delivery systems. A phase II-trial will begin in France.

Animals↗
PubMed2003

[Placing an endoprosthesis to maintain arterial canal permeability in lamb neonates].

Placing an endoprosthesis in the arterial canal in order to maintain permeability is a possible alternative to performing a modified Blalock-Taussig type surgical systemico-pulmonary anastomosis. This was studied in an animal model. Twelve newborn lambs, weighing from 1.8 to 3.5 kg, were catheterised in the neonatal period in order to place a stent. Three had a partial ligature of the pulmonary artery in utero. During the initial angiography, the canal was occluded in ten of them. Different types of coronary endoprosthesis were used: Multi link tetra TM and RX Herculink TM (Guidant Europe SA), Niroyal (Boston Scientific International), Bx Velocity (Cordis, Johnson and Johnson), Jostent (Jomed). The length of the endoprostheses varied from 12 to 18 mm and the diameter from 3.5 to 6 mm. Implantation was successful 10 out of 12 times: in one case, implantation was complicated by a fatal haemopericardium, and in another by pulmonary artery embolism. Nine animals out of 10 were followed up for 1 to 2 months. At autopsy verification, the canal was permeable in 7 cases with the development of a neointima and zones of moderate stenosis with intimal hyperplasia. In 2 animals the canal was occluded at the aortic level in a zone not covered by the endoprosthesis. Three animals died after implantation: the 2 implantation failures. A third animal with a well inserted prosthesis and a permeable canal died on day 1 from an unknown cause. Placing a stent in the arterial canal is a possible alternative to performing an aorto-pulmonary shunt. Coronary stents seem well adapted and this study does not allow any conclusions to be made at this time on the best type of stent. Further studies will be necessary in order to validate this concept before its use in congenital cardiopathies.

Animals↗
PubMed2001

Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity.

Proteoglycans that modulate the activities of growth factors, chemokines, and coagulation factors regulate in turn the vascular endothelium with respect to processes such as inflammation, hemostasis, and angiogenesis. Endothelial cell-specific molecule-1 is mainly expressed by endothelial cells and regulated by pro-inflammatory cytokines (Lassalle, P., Molet, S., Janin, A., Heyden, J. V., Tavernier, J., Fiers, W., Devos, R., and Tonnel, A. B. (1996) J. Biol. Chem. 271, 20458-20464). We demonstrate that this molecule is secreted as a soluble dermatan sulfate (DS) proteoglycan. This proteoglycan represents the major form either secreted by cell lines or circulating in the human bloodstream. Because this proteoglycan is specifically secreted by endothelial cells, we propose to name it endocan. The glycosaminoglycan component of endocan consists of a single DS chain covalently attached to serine 137. Endocan dose-dependently increased the hepatocyte growth factor/scatter factor (HGF/SF)-mediated proliferation of human embryonic kidney cells, whereas the nonglycanated form of endocan did not. Moreover, DS chains purified from endocan mimicked the endocan-mediated increase of cell proliferation in the presence of HGF/SF. Overall, our results demonstrate that endocan is a novel soluble dermatan sulfate proteoglycan produced by endothelial cells. Endocan regulates HGF/SF-mediated mitogenic activity and may support the function of HGF/SF not only in embryogenesis and tissue repair after injury but also in tumor progression.

Amino Acid Sequence↗
PubMed2001

Factor VII, tissue factor pathway inhibitor, and monocyte tissue factor in diabetes mellitus: influence of type of diabetes, obesity index, and age.

Changes of the tissue factor (TF) pathway of blood coagulation have been described in diabetes and could be involved in its vascular complications. In order to evaluate the influence of the type of diabetes and of the obesity index and age on these changes, factor VII coagulant activity, factor VII antigen, activated factor VII, monocyte TF expression, and plasma Tissue Factor Pathway Inhibitor (TFPI) were examined in 18 Type 1 and 16 Type 2 diabetic patients compared to non-diabetic control subjects matched for age, sex, and obesity index (Types 1 and 2 controls, respectively). Multicomplicated patients were excluded. FVIIc, FVIIAg, and FVIIa were higher in Type 2 diabetic patients and controls than in Type 1 diabetic patients and controls (P< .03). However, FVIIc and FVIIAg were lower in diabetic patients than in their matched controls (P< .03). Monocyte expression of TF was not different between Types 1 and 2 diabetic patients and their matched controls except for LPS-stimulated monocyte TF activity which was lower in Type 2 diabetic patients than in Type 2 controls (P< .05). Plasma TFPI was slightly but significantly higher in Type 1 diabetic patients than in Type 1 controls (P= .01) and was correlated to glycemia. However, both in Type 2 diabetic patients and controls, TFPI was higher than in Type 1 controls and was correlated with BMI (P< .0003). These results indicate that in not multicomplicated patients, the increase of FVII and TFPI was highly dependent on obesity index and age rather than on diabetes by itself.

Adult↗
PubMed2001

PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages.

BACKGROUND: Monocytic tissue factor (TF) expression may contribute to thrombogenicity associated with plaque rupture and may propagate thrombus formation at the site of vascular lesions. Induction of monocytic TF expression by endotoxin is mediated by the activation of transcription factors such as AP-1 and NF-kappaB. Both these signaling pathways are modulated by peroxisome proliferator-activated receptor-alpha (PPARalpha). Therefore, we have studied the effects of fibrates and other PPARalpha agonists on the expression of TF. METHODS AND RESULTS: We show that PPARalpha protein, like primary human monocytes, is also expressed in the human monocytic THP-1 cell line. Fenofibric acid, WY14643, and GW2331 inhibited TF mRNA upregulation after stimulation of THP-1 cells with lipopolysaccharide or interleukin-1ss. In primary human monocytes and macrophages, the lipopolysaccharide- or interleukin-1ss-mediated induction of TF activity was also inhibited by fenofibric acid, WY14643, or GW2331. CONCLUSIONS: These data indicate that activation of PPARalpha results in the downregulation of the TF gene. Our results suggest a novel role for PPARalpha in the control of atherosclerotic plaque thrombogenicity through its effects on TF expression in monocytes and macrophages.

Butyrates↗
PubMed2001

Preclinical phase of polycythemia vera in pregnancy.

BACKGROUND: In some cases, complications of pregnancy are related to thrombophilia. We describe a preclinical phase of polycythemia vera. CASE: A woman, who experienced perinatal deaths in her first two pregnancies, was diagnosed with polycythemia vera during antenatal counseling for a third pregnancy. During this pregnancy, phlebotomies, low molecular weight heparin, and low-dose aspirin treatments resulted in the delivery of a healthy baby. CONCLUSION: Polycythemia vera is a rare condition in women of childbearing age and can exist in a preclinical phase for many years. During pregnancy, it can cause severe but preventable thrombotic complications of placental origin.

Counseling↗
PubMed2001

Beneficial effect of glycoprotein IIb/IIIa inhibitor (AZ-1) on endothelium in Escherichia coli endotoxin-induced shock.

OBJECTIVE: To investigate the effects of AZ-1, a murine monoclonal antiglycoprotein-IIb/IIIa antibody, on endothelium and on hemostasis in a rabbit endotoxic shock model. DESIGN: Prospective laboratory study. SETTING: University laboratory. SUBJECTS: Thirty-five male New-Zealand rabbits. INTERVENTIONS: In vitro vascular reactivity, endothelium CD31-PECAM1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor determination were performed 1 day and/or 5 days after onset of endotoxic shock (0.5 mg/kg, intravenous bolus,Escherichia coli lipopolysaccharide) with or without treatment by AZ-1 (0.5 mg/kg intravenously) given 1 hr after lipopolysaccharide injection. MEASUREMENTS AND MAIN RESULTS: Metabolic acidosis and coagulation activation confirmed the presence of shock. AZ-1 treatment improved endothelial-dependent relaxation at 1 day (maximal effect = 87.2 +/- 4.0% vs. 60.9 +/- 5.2% in the nontreated group, p <.05) and at 5 days (maximal effect = 84.5 +/- 3.5% vs. 56.6 +/- 8.2% in the nontreated group, p <.05). Endotoxin-induced endothelial injury was decreased significantly by AZ-1 at 1 day (6.4 +/- 1.9% vs. 10.3 +/- 0.8% in the nontreated group, p <.05) and at 5 days (6.3 +/- 2.0% vs. 20.2 +/- 1.2% in the nontreated group, p <.05). Monocyte tissue factor expression was significantly reduced at 5 days. CONCLUSIONS: These data indicate that potent inhibition of platelet function via antiglycoprotein-IIb/IIIa receptor blockade can inhibit coagulation activation and protect against endothelial dysfunction and histologic injury in endotoxin-induced shock.

Animals↗
PubMed2001

[Peripheral arterial revascularization: which antithrombotic agents?].

Thrombotic occlusion after vascular reconstructive surgery is a frequent complication, specially when low-flow arteries and arterial prostheses are involved. Heparin therapy is usually administered in acute arterial insufficiency, and also during the perioperative period, in order to limit thrombus formation or propagation at the surgical or the cross-clamp application sites. The overall benefit of antiplatelet agents, specially aspirin, during the pre, peri and postoperative periods has been clearly demonstrated for arterial prostheses, and is probably useful in venous bypasses. Aspirin therapy also prevents thrombotic complication in other vascular beds, and reduces long-term cardiovascular morbidity and mortality. Oral anticoagulation by vitamin K antagonists, alone or combined with aspirin is perhaps an appropriate choice in selected patients with high risk of graft thrombosis, but cannot be recommended for routine treatments because of an increased risk of hemorrhage.

4-Hydroxycoumarins↗
PubMed2000

Association between anticardiolipin antibodies and mortality in patients with peripheral arterial disease.

PURPOSE: Anticardiolipin antibodies may be associated with recurrent thromboembolic events in patients with myocardial infarction or stroke. We sought to determine the prevalence of anticardiolipin antibodies in patients with peripheral arterial disease and their association with subsequent thromboembolic events and mortality. METHODS: We ascertained anticardiolipin antibodies using a standardized enzyme-linked immunosorbent assay (immunoglobulin G [IgG] anticardiolipin > or =15 GPL units or IgM anticardiolipin > or =15 MPL units) in 232 patients with peripheral arterial disease and 100 control subjects. Patients were observed to determine overall and cardiovascular mortality, and incident thromboembolic events. RESULTS: IgG anticardiolipin antibodies were significantly more common in the patients with peripheral arterial disease (36 of 232 [16%]) than in the controls (7 of 100 [7%], P = 0.03). During a median follow-up of 3.5 years, 3 of the 232 patients were lost to follow-up and 56 (24%) died. Overall mortality was significantly greater in the IgG anticardiolipin-positive patients (16 of 35 [46%]) compared with those who were IgG anticardiolipin-negative (40 of 194 [21%], P = 0.0003), largely due to an increase in cardiovascular mortality among the IgG anticardiolipin-positive patients. In a multivariate proportional hazards analysis, IgG anticardiolipin antibodies were an independent risk factor for overall mortality (hazard ratio [HR] = 2.1, 95% confidence interval [CI]: 1.2 to 4.0) and cardiovascular mortality (HR = 4.4, 95% CI: 1.6 to 12). CONCLUSIONS: IgG anticardiolipin antibodies are common in patients with peripheral arterial disease and are associated with an increased risk of overall and cardiovascular mortality.

Aged↗
PubMed2000

Basic fibroblast growth factor increases tissue factor expression in circulating monocytes and in vascular wall.

BACKGROUND: Basic fibroblast growth factor (bFGF) promotes vascular repair and angiogenesis and can induce in vitro tissue factor (TF), a potent agent initiating thrombogenesis, which probably plays a role in angiogenesis. We investigated whether bFGF administration induced TF expression by monocytes and vascular cells. METHODS AND RESULTS: We studied TF expression in normally fed (n=16) and cholesterol-fed (2% for 6 weeks, n=16) rabbits. Animals were then randomized to receive intravenous bFGF (2.5 microg twice weekly for 3 weeks) or saline injections. TF expression was evaluated in mononuclear cells from arterial blood and in aortic sections by an immunohistochemical assay using a monoclonal anti-rabbit TF antibody (activator protein 1). Monocyte TF expression was increased by bFGF administration in both normal and hypercholesterolemic rabbits (129+/-45 versus 19+/-3 mU TF/1000 monocytes, P<0.05, and 31+/-12 versus 7+/-1 mU TF/1000 monocytes, P<0.005, respectively) and was further increased by stimulation of monocytes by endotoxin in vitro. TF expression was lower in hypercholesterolemic rabbits than in normal rabbits. In the media of the vascular wall, bFGF induced strong TF expression in normal rabbits and only weak TF expression in hypercholesterolemic ones. CONCLUSIONS: This study demonstrates that systemic administration of bFGF induces an impressive increase of TF expression in circulating monocytes and in the vascular wall in normal and to a lower extent in hypercholesterolemic rabbits. The significance of this observation in terms of inducing thrombosis in vivo needs clarification.

Animals↗
PubMed2000

[G20210A transition in the prothrombin gene and venous thromboembolic disease].

INTRODUCTION: Genetic predisposition to venous thrombosis can be due to coagulation inhibitor deficiencies (antithrombin, protein C or protein S) or to activated protein C resistance resulting from factor V Leiden mutation (FV Leiden). Poort et al. recently identified a new polymorphism in the 3'-untranslated region of the prothrombin gene, the G20210A transition (FII G20210A), which was found to be associated with an increased risk of venous thrombosis. EXEGESIS: The prevalence of the A allele is approximately 1 to 4% in the general population, and 5 to 7% in patients with venous thrombosis. Heterozygous carriers have a three to five times increased risk of thrombosis. The diagnosis is based on a polymerase chain reaction technique and restriction enzyme digestion from genomic DNA. Recent studies aim to determine the relative risk of thrombosis and the clinical features which are associated with the mutation (age of first thrombosis, recurrence). The thrombotic risk seems to be higher when FII G20210A transition is associated with the FV Leiden mutation. CONCLUSION: The presence of heterozygous FII G20210A transition does not modify the management of acute thrombotic events but can lead to an increase in the duration of the anticoagulant treatment. When such a genetic abnormality is identified, thorough information of the patient is needed, including on the prophylactic heparin in high-risk situations and caution on the prescription of oral contraceptives containing estrogens.

Factor V↗
PubMed2000

A single endotoxin injection in the rabbit causes prolonged blood vessel dysfunction and a procoagulant state.

OBJECTIVES: To determine the duration of vascular blood vessel dysfunction and coagulation abnormalities after administration of endotoxin in a nonlethal septic rabbit model. DESIGN: Randomized, controlled, interventional trial. SETTING: University animal laboratory. SUBJECTS: A total of 30 male New Zealand White rabbits, randomly assigned to one of two groups. INTERVENTIONS: Male New Zealand White rabbits were randomly divided into control or lipopolysaccharide (LPS) (0.5 mg/kg iv bolus Escherichia coli endotoxin)-treated groups. Metabolic acidosis and coagulation activation confirmed the presence of septic shock. The abdominal aorta was removed at 24 hrs (day 1), day 5, or day 21 after LPS injection. Immunohistochemical staining for an endothelial cell marker (PECAM-1/CD31) was performed to assess endothelial injury. Endothelium-dependent vascular relaxation was analyzed by in vitro vascular reactivity studies. Responses to acetylcholine, to calcium ionophore (A-23187), and to sodium nitroprusside were studied. In addition, arterial blood samples were collected on day 1, day 5, and day 21 for measurement of clotting factors and tissue factor activity. MEASUREMENTS AND MAIN RESULTS: LPS injection resulted in endothelial injury, with loss of approximately 25% of the endothelial area on day 5, which disappeared on day 21. LPS injection also caused a significantly reduced relaxation response to acetylcholine (44.9% +/-9.9% vs. 76.5%+/-5.4% for the control group; p < .005), which was restored on day 21. In contrast, vascular relaxation in response to A-23187 and sodium nitroprusside was not altered. A significant decrease in the platelet count was observed on day 1, associated with a decrease in factors II and V. On day 5, platelet count and factors II and V were corrected in conjunction with an elevated monocyte tissue factor activity in LPS-injected rabbits. On day 21, coagulation abnormalities were corrected. CONCLUSIONS: A single endotoxin injection in the rabbit was responsible for prolonged aortic endothelial cell dysfunction, as well as a prolonged procoagulant state. The latter is a potential trigger for disseminated intravascular coagulation. Importantly, these features are associated with normalization of conventional biological evidence of septic shock.

Animals↗