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B Jude

Publications and source records attributed to B Jude.

At least 55 records · Page 3Linked to original sources
PubMed1995

Detection of monocyte tissue factor after endotoxin stimulation: comparison of one functional and three immunological methods.

Monocyte procoagulant activity is mainly due to tissue factor (TF) expression, but functional assays may not be sufficiently accurate in clinical use, making useful a determination of TF antigen level. The aim of this study was to compare the results of one functional and three immunological TF assays (ELISA, immunocytochemical staining on slides and flow immuno cytometric analysis), in normal monocytes, after standardized stimulation by endotoxin. TF expression was determined in blood mononuclear cells isolated by gradient centrifugation and cultured, with or without various concentrations of endotoxin. On lysed cells, TF activity was determined by amidolytic assay and TF antigen level was determined, after triton extraction, by ELISA (Imubind, American Diagnostica). Mouse monoclonal antibody against TF (4508, American Diagnostica) was used for 1) immunocytochemical (ICC) staining on cytocentrifuge slides (Avidine-Biotine-peroxidase-Complex revelation) and 2) flow cytometric analysis using indirect labeling (Fab'2 Fluoresceine Isothyocyanate revelation). The determination of TF activity and TF antigen by ELISA method were equally sensitive to low concentration of endotoxin (0.005 EU/ml) and well correlated in the presence of higher concentrations of endotoxin. ICC led to a qualitative detection with a similar sensitivity to endotoxin stimulation. Flow cytometric analysis was poorly sensitive to increasing stimulation of monocytes. Of note, the functional, ELISA and immunocytochemical assays for monocyte TF expression were sensitive to endotoxin concentrations as low as 0.005 EU/ml.

Adult↗
PubMed1995

Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM.

Because multiple risk factors in one patient may increase the clinical expression of thrombophilia, we assessed the presence in protein C-deficient patients of the factor V Arg 506 Gln mutation responsible for activated protein C resistance. Using a strategy allowing rapid screening of factor V exon 10, we studied 113 patients with protein C deficiency and 104 healthy volunteers. We detected the Arg 506 Gln mutation in 15 patients (14%) and in one healthy subject (1%). We identified a previously unpublished sequence variation leading to an Arg 485 Lys substitution in three normal subjects and seven protein C-deficient patients. A significant difference in the allelic frequency of the Arg 506 Gln factor V mutation was found between protein C-deficient patients heterozygous for an identified protein C mutation (n = 84; allelic frequency, 4.8%) and protein C-deficient patients with no identified mutation in the protein C gene coding regions (n = 25; allelic frequency, 14%). The results demonstrate that a significant subset of thrombophilic patients has multiple genetic risk factors although additional secondary genetic risk factors remain to be identified for the majority of symptomatic protein C-deficient patients.

Adolescent↗
PubMed1995

Identification of 15 different candidate causal point mutations and three polymorphisms in 19 patients with protein S deficiency using a scanning method for the analysis of the protein S active gene.

To screen for point mutations causing protein S deficiency, we used a sequence of techniques specifically for the study of the protein S active gene, PS alpha. This strategy comprises amplification of exons and intron/exon junctions by means of the polymerase chain reaction (PCR) and electrophoresis of the amplified fragments in polyacrylamide gel containing a gradient of denaturing agents (denaturing gradient gel electrophoresis). Only fragments with altered melting behavior are sequenced after asymmetric PCR. Beside the frequent polymorphism already described on Pro 626, we detected 18 different sequence variations by studying exons II, IV, V, VIII, X, and XV in 19 of 100 consecutive patients with protein S deficiency. Fifteen were candidate causal mutations, 4 of which were associated with a qualitative deficiency (type IIa or IIb). The remaining three sequence variations were probably polymorphisms.

Base Sequence↗
PubMed1994

First de novo mutations in the protein C gene of two patients with type I deficiency: a missense mutation and a splice site deletion.

In a series of 40 patients with symptomatic protein C deficiency, we identified two sporadic cases with novel mutations that probably affect gene expression. The mutations, a 5-bp deletion of the donor splice site of intron f (nucleotides 3455 to 3459) and a mutation of nucleotide 8523 in exon IX leading to the substitution of Ser 270 by Pro, were not found in the protein C gene of the patients' parents. Transmission of the paternal and maternal protein C alleles was apparently normal on the basis of frequent polymorphisms in exons I, VI, and VIII. We also checked the transmission of the chromosomal material by analyzing the beta-globin gene frameworks and three variable number of tandem repeats (VNTRs). By combining the results of intragenic polymorphism, VNTR and beta-globin gene framework analyses, we were able to exclude nonpaternity and confirm the de novo origin of the mutation.

Adult↗
PubMed1994

Evidence for time-dependent activation of monocytes in the systemic circulation in unstable angina but not in acute myocardial infarction or in stable angina.

BACKGROUND: Platelet activation plays a pivotal role in the pathogenesis of acute coronary disease. Monocytes are involved in the progression of atherosclerosis and are potent activators of blood coagulation through their ability to synthesize tissue factor (TF). The aim of this study was to compare markers of monocyte and coagulation activation in the systemic blood of patients with unstable angina, acute myocardial infarction, or stable angina. METHODS AND RESULTS: We studied 26 patients with unstable angina (10 +/- 5 hours after the onset of the last episode of pain), 18 patients with acute myocardial infarction (5 +/- 4 hours after the onset of pain), and 34 patients with stable angina. We measured levels of TF expression in peripheral blood mononuclear cells (isolated by gradient centrifugation and incubated for 16 hours, with or without endotoxin stimulation), levels of plasma prothrombin fragment 1 + 2 (F1 + 2), and levels of fibrinogen in peripheral blood. In patients with unstable angina, both stimulated and unstimulated cells exhibited higher levels of TF expression than in patients with stable angina (P = .0001). In patients with acute myocardial infarction, monocyte TF activity did not differ from that in patients with stable angina. Mean levels of F1 + 2 and of fibrinogen did not differ significantly between groups. Only in the unstable angina group, a modest correlation was found between fibrinogen (r = .72, P = .005) and F1 + 2 levels (r = .54, P = .001) levels and the degree of monocyte TF expression. In patients with unstable angina, monocyte TF expression (both stimulated and unstimulated, assessed by biological activity and by antigen techniques) and fibrinogen levels were correlated with the time elapsed from the beginning of the most recent episode of pain (.61 < r < .72, .02 < P < .0001). By contrast, there was no correlation between these variables and the time from onset of pain in patients with acute myocardial infarction. CONCLUSIONS: A time-dependent activation of systemic monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings provide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether monocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations between platelet and monocyte activation in these circumstances.

Adult↗
PubMed1993

Compound heterozygosity in a family with protein C deficiency illustrating the complexity of the underlying molecular mechanism.

The association of two missense mutations, a Leu 223 to Phe and an Ile 403 to Met, is described in a family presenting with various protein C deficiency phenotypes. In this family, two subjects were compound heterozygotes with protein C levels of about 25%, the other members being heterozygous for only one of the mutations. The Leu 223 to Phe mutation was also found in 9 members of 3 other families and, in all cases but one, resulted in protein C levels below 60% associated with a high incidence of thrombotic complications. The other mutation, an Ile 403 to Met, was identified in those of the family' members who presented with borderline protein C concentrations. In such a family, the genomic DNA analysis represents the only way to differentiate between the genetic status of each family member. The results highlight the importance of the genotype determination and the poor discriminative power of the plasma assays currently used.

Adolescent↗
PubMed1993

Percutaneous transluminal venous angioplasty in occlusive iliac vein thrombosis resistant to thrombolysis.

Systemic thrombolysis is less than optimal in total occlusions of the iliac vein in which patency is 20% or less. We describe an interventional therapeutic procedure that may be effective in such cases. We selected 18 patients (average age, 29.5 years; range, 16 to 71 years) with complete iliac vein occlusion that persisted after 24 to 48 hours of systemic thrombolysis (streptokinase 100,000 U/hr). The ipsilateral femoral vein was punctured, and a guide wire was gently advanced through the thrombus into the inferior vena cava. Multiple inflations were performed with a balloon catheter that was advanced on the wire. A temporary vena cava filter was placed as a protection against possible embolic migration. Systemic thrombolysis was administered for 24 to 48 hours. Control venography and pulmonary angiography were performed. Venography showed good recanalization in seven cases, incomplete recanalization in five cases, and failure in six cases. Patency was maintained for a long time (15.6 months). In conclusion, (1) percutaneous transluminal venous angioplasty is a valuable adjunct to systemic thrombolysis when the latter alone fails; (2) segmental flow and mechanical obstruction were the critical factors, since the pharmaceutical factors were held constant, and (3) a more aggressive incremental interventional strategy warrants consideration.

Adolescent↗
PubMed1992

[Incidence and clinical expressions of microvascular complications in patients receiving kidney graft and treated with cyclosporine].

Reported cases of HUS/TTP (hemolytic uremic syndrome/thrombotic thrombopenic purpura) with cyclosporin (CsA) are more and more frequent, which led us to evaluate the incidence of microangiopathic process in kidney graft patients. In our first retrospective study we noted 9.4 percent of HUS/TTP among 117 patients. We tried to detect infraclinical hemolytic events prospectively in 40 new patients by systematic measurement of haptoglobin levels after introduction of CsA. The incidence of falls in haptoglobin levels was 25 percent. The immunological context was always noted: rejection crisis in 5 cases, cytomegalovirus infection in 3 cases, isolated markers of lymphocyte-activity in 2 cases. We never found a clinical or infraclinical form of microangiopathic process without a symptomatic or asymptomatic immunological complication. Monitoring haptoglobin levels make it possible to detect early endothelial injuries which could be linked to the future arteriolopathy described with CsA therapy.

Cyclosporine↗
PubMed1992

Myocardial infarction after FEIBA therapy in a hemophilia-B patient with a factor IX inhibitor.

A case of myocardial infarction (MI) in a hemophilia B patient with a factor IX (FIX) inhibitor (6 BU) is described. MI occurred after two infusions of FEIBA concentrate. Unexpectedly, these infusions resulted in a neutralization of the inhibitor and a consistent plasma FIX activity which may have increased the thrombotic risks. Four days later, a psoas hematoma was suspected. At that time the inhibitor remained undetectable, allowing a therapy with purified FIX concentrates. No recurrence of thrombotic complication was observed. This is an additional illustration of the thrombotic risks associated with the use of activated prothrombin complex concentrates, especially in patients having pre-existing risk factors for thrombosis. The management of bleeding episodes in hemophilia B patients with inhibitor represents an especially difficult challenge.

Adult↗
PubMed1992

Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases.

We studied, in 40 children (mean age: 52 months) with severe infectious purpura, the relationships between protein C (PC) and protein S (PS) levels, and shock, disseminated intravascular coagulation (DIC) and outcome. We determined, on admission, PC antigen (ELISA) and activity (chromogenic test), and total PS (ELISA). Results were expressed as % of normal adult values. Statistical analysis was performed with SAS. Thirty children were in shock, 20 had DIC. All children with DIC, and 10 without DIC were in shock. Of 20 children who were in shock and had DIC, 7 died and 3 had an amputation. PC antigen was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.05). PC activity was significantly decreased in shock children (p less than 0.05), in children with DIC (p less than 0.0005), and in non-survivors (p less than 0.005). Total PS was not decreased in shock children, but was significantly decreased in children with DIC (p less than 0.005), and in non-survivors (p less than 0.005). We conclude that PC and PS levels were decreased in our children, and that PC levels were significantly decreased in the presence of shock, DIC, and fatal outcome. PC and antithrombin III (AT III) supplementation, should be evaluated in children with severe infectious purpura with shock and DIC.

Adolescent↗
PubMed1992

Incidence and clinical profile of microvascular complications in renal allografted patients treated with cyclosporine.

The incidence of cyclosporine (CsA) vascular toxicity is open to debate. We attempted to evaluate the incidence of hemolytic accidents in our series of patients taking all clinical forms into consideration. From January, 1989, to December, 1990, 117 patients received kidneys from cadaver donors and were treated with CsA. Five patients presented hemolytic uremic syndrome (HUS) accompanied by a rejection crisis; 6 patients presented hemolytic anemia associated in 2 cases with marked thrombocytopenia without any evidence of rejection. Cytomegalovirus (CMV) infection was diagnosed in 2 patients and bacterial infection preceded hemolysis in 2 other cases, suggesting a triggering factor. In addition, when we systematically determined haptoglobin levels after introduction of CsA treatment, we found asymptomatic hemolytic episodes more frequently. Our incidence of hemolytic accidents was approximately 10%. Hemolysis could indicate ischemic vascular damage leading to arteriolar medial hyalinosis preceding fibrosis in CsA nephrotoxicity. Thus, it would be interesting to detect asymptomatic forms of hemolysis by monitoring haptoglobin levels. This approach could lead to a reduction of the CsA dose in patients presenting low haptoglobin levels, even in the absence of evidence of nephrotoxicity.

Adult↗
PubMed1992

[Preventive treatment of systemic embolic complications of atrial fibrillation].

Non-valvular atrial fibrillation multiplies the risk of presumed embolic events by a factor of four. The hemorrhagic risk of anticoagulant treatment varies considerably and its prophylactic efficacy was not tested in any randomised trial before the end of 1989. The recommendations of experts at that time recognised that data were inadequate. The publication since of four randomised trials involving 3,049 patients has provided a more objective base for management decisions, highly in favour of the anticoagulation of cases of non-isolated atrial fibrillation in the absence of contraindications.

Anticoagulants↗
PubMed1991

[Hemostasis anomalies and prognosis during severe infectious purpura in children. Retrospective study in 69 cases].

In 69 children with severe infectious purpura (SIP), anomalies of hemostasis on admission were studied retrospectively. Forty-four children presented with disseminated intravascular coagulation (DIC) and 18 with factor VII deficiency +/- thrombocytopenia +/- antithrombin III deficiency. Seven patients were free of hemostasis anomalies. In 5 children, purpura was necrotic on admission, whereas in 9 additional patients skin necrosis occurred subsequently (5 patients with and 4 without DIC). Among the 18 children (26%) who died, 16 were in the DIC group. Factors II and V, fibrinogen and platelet counts were lower in children who died and were correlated with the prognostic score. In the DIC group, however, factor VII + X level was not correlated with the prognostic score and was equally low in fatal and non-fatal cases. Antithrombin III level was markedly decreased in patients who subsequently developed necrosis. These results indicate that factor VII level decreases early in the course of SIP and that consumption of physiologic coagulation inhibitors probably plays a central part in the development of necrotic purpura.

Adolescent↗
PubMed1990

[Arterial thromboses and essential thrombocythemia in young patients].

The authors report two cases of essential thrombocythemia (ET) which occurred in young subjects (25 and 33 years) and revealed by arterial thromboses. The first case was one of myocardial infarction: in the second case, ischemic signs in the left leg led to cutaneous necrosis. Thrombotic signs are commonplace in ET and are generally considered to be attributable to an impaired underlying vascular territory. The cases reported by the authors conflict with these data and it would seem, therefore, that the onset of thrombosis in the absence of any associated cardiovascular risk can be envisaged. With regard to therapy, if thrombotic signs occur, myelosuppressive treatment must be undertaken; in asymptomatic patients, due to the potential and unpredictable risk of thrombosis, this treatment should be initiated if the platelet count rises above 800 x 10(9)/l. Hydroxyurea is generally prescribed (particularly in young patients) since it is generally considered to be devoid of any leukemogenic potential.

Adult↗
PubMed1989

Distinctive features of procoagulant response of monocytes from diabetic patients.

The procoagulant activity (PCA) of disrupted monocytes was examined in 32 diabetic patients (26 with insulin-dependent and 6 with non-insulin-dependent diabetes) versus 30 control subjects. Diabetes monocytes exhibited a weak PCA before any incubation, associated in 10 cases with a significant amount of factor VII activity. Incubation led to a significant rise in PCA in diabetes cells, when stimulated with lipopolysaccharide or not, and in control cells only after stimulation. In incubated diabetes cells, PCA was prothrombinase-like when factor VII was associated with the freshly isolated cells, and tissue factor-like (as in the controls) when no factor VII was associated with the cells. The characteristics of PCA were not correlated with clinical features or with the type of diabetes. Our study suggests that diabetes monocytes exhibit a higher level of PCA than control ones, possibly corresponding to an in vivo stimulation, or at least a higher responsiveness to stimuli occurring in vitro.

Adult↗