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Biomedical subjects

B Jude

Publications and source records attributed to B Jude.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of L-arginine on endothelial injury and hemostasis in rabbit endotoxin shock.

To investigate whether impaired endothelial function was related to alteration of nitric oxide (NO) formation during endotoxic shock, we studied the effects of supplementation of L-arginine (L-Arg), D-arginine (D-Arg), and N(G)-nitro-L-arginine methyl ester (L-NAME), on endothelial function and structure in a rabbit model. Endotoxic shock was induced by a single lipopolysaccharide bolus (0.5 mg/kg i.v., Escherichia coli endotoxin). Coagulation factors and expression of monocyte tissue factor were determined by functional assays. Endothelium-dependent vascular relaxation was assessed by in vitro vascular reactivity. Immunohistochemical staining (CD31) was performed to assess damaged endothelial cell surface of the abdominal aorta. These parameters were studied 5 days after the onset of endotoxic shock and were compared under three conditions: in absence of treatment, with L-Arg or D-Arg supplementation, or with L-NAME. Both L-Arg and D-Arg significantly improved endothelium-dependent relaxation and endothelial morphological injury. L-NAME did not alter endothelial histological injury induced by lipopolysaccharide. These data indicate that arginine supplementation nonspecifically prevents endothelial dysfunction and histological injury in rabbit endotoxic shock. Moreover, L-Arg has no effect on coagulation activation and expression of monocyte tissue factor induced by endotoxic shock.

Acetylcholine↗
PubMed2000

Pentoxifylline prevents upregulation of monocyte tissue factor in renal transplant recipients undergoing post-graft complications.

Pentoxifylline (PTX) has been demonstrated to improve graft survival in renal transplant recipients undergoing post graft complications. As activated monocytes are possible initiators of vascular damage through tissue factor (TF) expression, we evaluated the monocyte TF expression and endothelium activation markers in 140 consecutive patients receiving cadaveric kidney grafts, randomized in a double-blind study comparing PTX versus placebo. Monocyte TF expression and plasma von Willebrand factor, tissue plasminogen activator, thrombomodulin and tumor necrosis factor-alpha (TNF-alpha) levels were determined before transplantation and each month after. Additional samplings were realized in case of acute rejection. TF and TNF-alpha expression were significantly modified after graft. In patients with complications, PTX prevented the increase of TF expression at month one, and after rejection episodes. Endothelium activation markers were significantly modified after graft and in patients with complications but PTX had no significant effect on their plasma levels. These results suggest that the protective effect of PTX on graft survival could be related to the prevention of monocyte TF upregulation associated with complications.

Adult↗
PubMed1999

Monocyte tissue factor response is decreased in patients with hyperlipidemia.

Monocytes are potent regulators of blood coagulation through the expression of tissue factor (TF) on stimulation and of tissue factor pathway inhibitor (TFPI), a selective inhibitor of TF pathway. As hyperlipidemia can modify some monocyte functions, we compared the TF and TFPI expression by circulating monocytes and the plasma TFPI levels between 65 healthy normolipemic controls and 38 nontreated hyperlipemic patients. TF and TFPI relationships with plasma lipoproteins are also examined. TF and TFPI expression were evaluated in peripheral mononuclear cells after isolation from blood by density gradient centrifugation and after short culture with or without lipopolysaccharide (LPS). TF and TFPI activity and antigen were measured in mononuclear cell lysates using amidolytic assay and enzyme-linked immunosorbent assay, respectively. TFPI activity and antigen were measured in plasma using the same methods. Plasma factor VII (FVII) activity and antigen were also determined. LPS-stimulated monocyte TF activity and antigen were lower in hyperlipidemic patients than in controls (0.0001<p<0.03). This decrease of monocyte TF expression in hyperlipidemic patients was not related to an increase of monocyte TFPI. Monocyte TF activity was negatively correlated to atherogenic fractions and positively correlated to protective fractions, specially after ex vivo LPS stimulation. Increased TFPI and FVII plasma levels were found in hyperlipidemic patients compared to controls. These results indicate an impairment of TF production by circulating monocytes from hyperlipidemic subjects, which is linked to the increase of atherogenic lipoprotein fractions. Further studies are required to elucidate the mechanism of this inhibition.

Adult↗
PubMed1999

Are there specific haemostatic abnormalities in children surviving septic shock with purpura and having skin necrosis or limb ischaemia that need skin grafts or limb amputations?

UNLABELLED: More than 10% of children surviving septic shock with purpura have skin necrosis or limb ischaemia (SNLI.). Among 44 children consecutively admitted to our pediatric intensive care unit, 35 (80%) survived, 6 of them (17%) developed SNLI (defined as the need of a surgical procedure). Two timed haemostasis measurements included the determination of coagulation factors, protein C (PC), protein S (PS), C4b binding protein (C4bBP), antithrombin (AT), and plasminogen activator inhibitor 1 (PAI-1). Two severity scores and CRP levels were determined at admission. Children with SNLI and without SNLI were compared. On admission, severity scores, and AT, PC, PS, C4bBP levels were similar in both groups with and without SNLI. Prothrombin time (23% vs 34%; P < 0.01), factor VII+X (20% vs 31%; P = 0.05) and factor VII (0% vs 19%; P < 0.01) were lower in the group with SNLI. The 2nd sample showed no difference between the two groups. Kinetics of haemostatic abnormalities were no different between the two groups. CONCLUSION: In this series, the only difference between the two groups was lower factor VII levels in children with skin necrosis or limb ischaemia. This suggests the benefit of tissue factor pathway inhibitor administration as an adjunctive therapy to prevent skin necrosis or limb ischaemia. Further studies including more children are needed to determine the potential effects of treatments such as protein C, antithrombin, and plasminogen activator inhibitor antibody administration, and to advocate tissue factor pathway inhibitor in preventing skin necrosis or limb ischaemia.

Adolescent↗
PubMed1998

Enhanced monocyte tissue factor response after experimental balloon angioplasty in hypercholesterolemic rabbit: inhibition with dietary L-arginine.

BACKGROUND: There is evidence that tissue factor (TF) is a major contributor to the thrombogenicity of a ruptured atherosclerotic plaque. Nitric oxide (NO) has antiatherogenic and antithrombotic properties. We investigated whether L-arginine (L-arg), the endogenous precursor of NO, might affect the ability of monocytes to produce TF. METHODS AND RESULTS: We studied TF expression in 18 rabbits with atherosclerosis induced by bilateral iliac damage and 10 weeks of a 2% cholesterol diet. Six weeks after the initiation of the diet, an angioplasty was performed. After angioplasty, the surviving rabbits (n=15) were randomized to receive L-arg (2.25%) supplementation in drinking water (L-arg group, n=8) or no treatment (untreated group, n=7). TF expression was evaluated in mononuclear cells from arterial blood in the presence and absence of endotoxin stimulation. Monocyte TF expression, as assessed with an amidolytic assay, did not differ significantly before or after the induction of atherosclerotic lesions (87+/-15 versus 70+/-12 mU of TF/1000 monocytes, P=NS). Endotoxin-stimulated TF activity increased significantly 4 weeks after angioplasty (138+/-22 versus 70+/-12 mU of TF/1000 monocytes, P=0.02). This increase was blunted by L-arg (43+/-16 mU of TF/1000 monocytes, P=0.01). CONCLUSIONS: This study demonstrates that angioplasty-induced plaque rupture is associated with a marked increase in monocyte TF response that is blunted by the oral administration of L-arg. This suggests that the documented antithrombotic properties of NO may be related in part to an inhibitory effect on monocyte TF response.

Angioplasty, Balloon↗
PubMed1998

Improvement in the outcome of rejection with pentoxifylline in renal transplantation: a randomized controlled trial.

BACKGROUND: Pentoxifylline (PTX), a methylxantine phosphodiesterase inhibitor commonly used to treat peripheral vascular disease, has been shown to decrease the production of proinflammatory cytokines and reactive oxygen species and to reduce the toxic effects of cyclosporine. Thus, administration of PTX to transplant patients, as an adjunct to immunosuppressive therapy, could prevent numerous posttransplantation complications. METHODS: One hundred forty consecutive patients receiving cadaveric kidney grafts were registered in a randomized double-blind study comparing PTX at a dose of 800 mg/day, then 1200 mg/day, versus placebo during the first 6 months after transplantation. All patients were followed up for 1 year. RESULTS: Rejection episodes were validated as the only independent risk factor for graft loss in this study. We compared graft survival rates in each group according to the presence or absence of acute rejection. Acute rejection reduced graft survival in the control group (graft survival rate at 1 year, 59% vs. 97%, P < 0.001), but this adverse effect was blunted in the PTX group (72% vs. 89%, NS). This improvement was confirmed by multivariate analysis for risk factors, with graft survival rates being described at best as the interaction between rejection and treatment (PTX vs. placebo, P = 0.045). CONCLUSION: Although PTX does not modify the incidence of any posttransplant complications, it weakens the consequences of rejection on graft survival.

Adult↗
PubMed1998

Relationships between severe neonatal thrombocytopenia and maternal characteristics in pregnancies associated with autoimmune thrombocytopenia.

In pregnant women with antecedents of autoimmune thrombocytopenia (AITP), no predictive factor for severe fetal thrombocytopenia has been identified. We evaluated the relationships between the course of the maternal disease before and during pregnancy and the risk of severe fetal thrombocytopenia, in 64 pregnant women with known chronic AITP antecedents, over a 12-year period. 28 pregnant women had undergone splenectomy before pregnancy and 17 experienced severe thrombocytopenia (< 50 x 10(9)/l) during pregnancy (monthly determination). Eight infants presented with severe thrombocytopenia at birth (12.5%), and four in the following days (6.25%). No severe haemorrhage was observed. Severe thrombocytopenia at birth was present in 57% (CI 95% 18-90%) of the infants born to mothers with severe pregnancy-associated thrombocytopenia and splenectomy antecedents, and in 0% (CI 95% 0-15%) of the infants born to mothers who presented none of these antecedents (P=0.001). In thrombocytopenic mothers the infant platelet counts at birth were positively correlated to the nadir maternal platelet count during the index pregnancy (r=0.42, P=0.0075). These results suggest that severe autoimmune disease is a risk factor for severe fetal thrombocytopenia, and that pregnant women with no antecedent of splenectomy nor severe thrombocytopenia during pregnancy have a very low risk of severe fetal thrombocytopenia.

Chronic Disease↗
PubMed1997

Effects of coronary angioplasty on monocyte tissue factor response in patients with stable or unstable angina.

Balloon coronary angioplasty is a revascularization procedure which increases the luminal diameter at a site of arterial stenosis, leading to mechanical disruption of the atherosclerotic plaque and to stretching of the vascular wall (1). This procedure can be complicated by thrombosis or restenosis, which occur in 5% and 30% of the cases respectively (2). These complications probably result from exposure of blood to components of atherosclerotic plaque, subendothelium and components of vascular wall, leading to activation of coagulation (thrombin generation) and platelets (3,4). Recent data point to simultaneous increase of leukocyte adhesive receptors, indicating an additional process of leukocyte activation, which could play a key role in the vascular healing process after angioplasty (5). These elements could also play a role in the thrombotic and stenotic complications.

Aged↗
PubMed1997

Clinical features in 36 patients homozygous for the ARG 506-->GLN factor V mutation.

We analyzed the clinical features of 36 patients homozygous for the Arg 506 to Gln factor V mutation and found a circumstantial event at risk for thrombosis in 29 of the 31 patients with thrombosis. The most frequent predisposing factors were the post-partum period and the use of oral contraceptives in women, and surgery in both sexes. Venous thrombosis recurred in 48% of the patients. One patient had a myocardial infarction at age 33 years, and also had an antiphospholipid syndrome. Homozygous Gln 506 mutation leads to far less severe thrombotic complications than homozygous protein C and protein S deficiencies and does not seem to predispose patients to arterial thrombosis.

Adult↗
PubMed1996

Prevalence and clinical significance of antiphospholipid antibodies in heart valve disease: a case-control study.

The purposes of this study were (1) to assess the prevalence of antiphospholipid (aPL) antibodies in patients with non-specific heart valve disease referred for valve replacement and (2) to determine whether the presence of aPL antibodies carries a risk for thrombotic events during a postoperative follow-up in a prospective cohort. The sera of 89 consecutive patients and 80 matched control subjects were tested for antibodies to cardiolipin (immunoglobulin G and immunoglobulin M) and for lupus anticoagulant. The prevalence of aPL antibodies was significantly higher in patients (19 [21%] of 89) than in control subjects (7 [9%] of 80) (p < 0.05). Patients were divided into two subgroups according to the presence (subgroup A) or the absence (subgroup B) of aPL antibodies. No significant difference in age or sex ratio was observed between the two subgroups. A history of arterial thrombosis was more frequent in subgroup A (8 [42%] of 19) than in subgroup B (8 [11%] of 70) (p < 0.01). No significant difference with respect to the occurrence of thrombotic events was observed during a median follow-up period of 8.7 months. Thus a high prevalence of aPL antibodies was found in patients referred for heart valve replacement compared with matched control subjects. No increased risk has been demonstrated in the patients with aPL antibodies.

Antibodies, Anticardiolipin↗
PubMed1996

Liver transplantation without the use of fresh frozen plasma.

In orthotopic liver transplantations (OLT), fresh frozen plasma (FFP) is classically used to normalize coagulation factor concentrations. In this study, 28 OLT were performed without the use of FFP. According to their preoperative factor V (FV) levels, two groups of patients were defined: Group 1 (13 patients, FV > 10% and < 60%) and Group 2 (15 patients, FV > 60%). Spontaneous evolution of coagulation factors, concentration, and bleeding were observed during OLT and up to 48 h after surgery. Total intraoperative bleeding was similar in both groups (3460 +/- 2700 mL and 3470 +/- 2110 mL in Groups 1 and 2, respectively). Levels of clotting factors were not different between groups after the anhepatic stage. The lowest values were noted after reperfusion. Thirty-six hours after surgery, all levels of clotting factors in both groups were more than 50%, with FV level increasing the most rapidly. Hematocrit from the subhepatic drainage liquid was 1.8% and less than 1% at 24 and 48 h, respectively, after surgery. No reintervention for bleeding was necessary. These results suggest that, in OLT, correct hemostasis can be assumed without FFP use when hyperfibrinolysis, platelet count, fibrinogen rate, and hemodynamic status are controlled.

Adult↗
PubMed1996

Homozygous variant of antithrombin with lack of affinity for heparin: management of severe thrombotic complications associated with intrauterine fetal demise.

Patients with homozygous heparin-binding-site (HBS) qualitative antithrombin deficiencies are at significant risk of venous and arterial thrombosis. We report on the eighth case of homozygous HBS deficiency, and the fourth case concerning the Arg 47-Cys mutation. The proposita is a 25 year old, without known thrombotic antecedent, despite an oral contraceptive therapy for 7 years. After 25 weeks of a first pregnancy, she presented an intrauterine fetal demise complicated with deep vein thrombosis and pulmonary embolism. Heparin therapy was inefficient (no clinical nor angiographic improvement, no biological hypocoagulability). Heparin cofactor activity was < 10%, antigen concentration was normal. The crossed immunoelectrophoresis of patient's plasma, with and without heparin, showed a typical profile of qualitative HBS antithrombin deficiency. The molecular analysis revealed an homozygous Arg 4-Cys mutation. Antithrombotic therapy was achieved with continuous infusion of antithrombin concentrates (80 IU/kg/day) and unfractionated heparin (500 IU/kg/day) during 12 days, leading to clinical improvement, and followed by treatment with vitamin K antagonists. This observation emphasizes the risk of intrauterine fetal demise and the inefficiency of heparin therapy without antithrombin infusion in type II HBS homozygous deficiency. The management of a future pregnancy will probably require repeated infusions of antithrombin.

Adult↗
PubMed1996

First case of sporadic protein S deficiency due to a novel candidate mutation, Ala 484-->Pro, in the protein S active gene (PROS1).

In a series of 16 propositi with symptomatic protein S deficiency and a protein S gene mutation, we identified a sporadic case of a novel mutation that probably affects gene expression. The mutation, a G to C transversion leading to the substitution of Ala 484 by Pro, was not found in the protein S gene of the patient's parents. Transmission of the paternal and maternal protein S alleles was apparently normal, on the basis of the frequent polymorphism in exon XV. We also checked the transmission of chromosomal material by analysing protein C gene polymorphisms, beta-globin gene frameworks and four variable number of tandem repeats (VNTRs). By combining the results of these analyses, we were able to rule out nonpaternity and to confirm the de novo nature of the mutation.

Alanine↗
PubMed1996

[Pulmonary embolism disclosing activated protein C resistance].

Resistance to the activation of protein C is a recently discovered constitutional anomaly of coagulation which is responsible for thromboembolic events in young subjects. We report a case in a 26 year old man who presented with pulmonary embolus. Laboratory data was characterised by an absence of any lengthening of the activated cephaline time after adding purified activated exogenous Protein C. The confirmation of this anomaly is provided by the evidence of a mutation Arg 506 to Gln of Factor 5. The outcome is favourable with treatment by Heparin then by anti-Vitamin K.

Adult↗