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Biomedical subjects

J Y Borg

Publications and source records attributed to J Y Borg.

At least 37 records · Page 2Linked to original sources
PubMed1997

[The vascular risk of third generation contraceptive pills].

The new progestative molecules have allowed the reduction of the doses of steroids in estroprogestative pills. They have a reduced androgenic activity allowing the positive effects of ethinylestradiol on lipid metabolism with decreased myocardial infarct, ischemic or hemorrhagic stroke. However it is necessary to consider the woman's entire risk factor profile when prescribing oral contraceptives. Unfortunately, combined estroprogestatives containing low-dose estrogen and the progestagens desogestrel or gestodene are associated with an increased risk for nonfatal venous thromboembolic disease. The occurrence of venous thromboembolic disease in a woman with oral contraceptive requires to search for a hereditary abnormality especially a resistance to the anticoagulant effect of activated protein C. Conversely it seems necessary to screen for the factor V Leiden mutation in women starting oral contraceptives who have a history of a familial venous thrombosis story.

Blood Coagulation Factors↗
PubMed1997

Evaluation of sensitivity and specificity of a standardized procedure using different reagents for the detection of lupus anticoagulants. The Working Group on Hemostasis of the Société Française de Biologie Clinique and for the Groupe d'Etudes sur I'Hémostase et la Thrombose.

This study was designed to test the sensitivity and specificity of a combination of 3 phospholipid-dependent assays performed with various reagents, for the detection of lupus anticoagulant (LA). Plasmas containing an LA (n = 56) or displaying various confounding pathologies [58 intrinsic pathway factor deficiencies, 9 factor VIII inhibitors, 28 plasmas from patients treated with an oral anticoagulant (OAC)] were selected. In a first step, the efficiency of each assay and reagent was assessed using the Receiving Operating Characteristic (ROC) method. Optimal cut-offs providing both sensitivity and specificity > or = 80% were determined. The APTT assay and most of the phospholipid neutralization assays failed to discriminate factor VIII inhibitors from LA. In a second step, using the optimal cut-offs determined above, the results of all the possible combinations of the 3 assays performed with 4 different reagents were analyzed. Thirteen combinations of reagents allowed > or = 80% of plasmas of each category (LA, factor deficiency or OAC) to be correctly classified (3/3 positive test results in LA-containing plasmas and 0/3 positive results in LA-negative samples).

Evaluation Studies as Topic↗
PubMed1996

[Venous thromboembolic disease and pregnancy].

Venous thrombo-embolic disease is the most common cause of maternal death during pregnancy. Haemodynamic, anatomical and biological changes support the notion that normal pregnancy in a prethrombotic state. But thrombotic events remain unusual episodes. A pre-thrombotic disease has to be investigated in such cases. Accurate diagnosis of deep vein thrombosis or pulmonary embolism is imperative, using non-invasive approaches. Heparin is the anticoagulant of choice to treat objective thrombosis. Thrombo-embolism prophylaxis using compression stockings and heparin has to be discussed in hypercoagulable disorders.

Female↗
PubMed1996

Activated protein C sensitivity ratio in pregnant women at delivery.

We studied activated protein C sensitivity ratio (APC-SR), factors V and VIII activity and von Willebrand antigen in control women, women using oral contraceptives, and pregnant women at delivery. The mean APC-SR of 2.4 in pregnant women was significantly lower than the mean APC-SR value of 3.5 for both the other groups and 45% of pregnant women had a ratio below the 5th percentile of the control group. None of them carried the R506-->Q mutation. This decreased ratio at delivery appeared to be connected, at least in part, with increased VIII activity. Thus, APC-SR at delivery should not be used to detect APC resistance.

Adult↗
PubMed1996

[Pseudothromboangiitis obliterans and qualitative protein C deficiency: report of a case].

Thromboangiitis obliterans is a segmental obliterating inflammatory arteritis, usually found in young (below 40) smoking males. Its diagnosis relies on patient history, clinical features, arterial angiography, and more rarely on pathological findings, though none of these is specific of the disease, and on the absence of other diseases such as early atheroma, thromboembolic processes, vascular malformation, trauma, collagen or blood disorders. Raynaud's phenomenon, digital arteritis, superficial and often migrating venous thromboses are further arguments for the disease. However, such associations can also occur during other diseases, especially congenital or acquired deficits in coagulation factors (antiphospholipid syndrome, S protein deficiency...). In our patient with suspected thromboangiitis obliterans, the occurrence of superior longitudinal and right lateral sinus thrombosis led to the discovery of a qualitative C protein defect. This observation stresses the need for careful elimination of a coagulation disorder before confirming the diagnosis of thromboangiitis obliterans.

Adult↗
PubMed1996

Five novel mutations of the protein S active gene (PROS 1) in 8 Norman families.

To further elucidate the molecular basis for hereditary thrombophilia, we screened the protein S active gene in 11 families with type I deficiency, using a strategy based on denaturing gradient gel electrophoresis (DGGE) of all the coding sequences. Fragments with an abnormal DGGE pattern were sequenced, and 5 novel mutations were identified in 8 families. The mutations were a 7-nucleotide deletion in exon II, a 4-nucleotide deletion in exon III, a T insertion in exon VII, a C to T transition transforming Leu 259 into Pro and a T to C transition transforming Cys 625 into Arg in 4 families. These mutations were the only sequence variations found in the propositus' gene exons and co-segregated with the plasma phenotype. A total of 28 members of these 8 families were heterozygous for one of the 5 mutations. Twenty-four (58,5%) of the 41 deficient subjects over 18 years of age had clinical thrombophilia, whereas the 13 subjects under 18 were asymptomatic. Of the 28 subjects, 6 (21,5%) were also found to bear the factor V Arg 506 Gln mutation.

Adolescent↗
PubMed1996

[Portal thrombosis disclosing antiphospholipid syndrome. 2 cases].

The presence of serum antiphospholipid antibodies is associated with arterial and venous thrombosis. We report two cases of portal vein thrombosis associated with serum antiphospholipid antibodies. In our two patients, systemic lupus erythematosus, chronic liver disease, hepatocellular carcinoma, myeloproliferative disorders and coagulation inhibitor deficiency were excluded after extensive tests were performed to diagnose portal vein thrombosis and after a follow-up period of 6 and 7 years, respectively. The test for serum antiphospholipid antibodies was positive on two occasions in both patients. Both patients were treated with endoscopic sclerotherapy for bleeding esophageal varices and with long term anticoagulant therapy for the prevention of recurrent thrombosis. These two cases suggest that serum antiphospholipid antibodies should be investigated in patients with portal vein thrombosis of unexplained etiology.

Adult↗
PubMed1996

[Acquired autoantibodies against human factor VIII: a new case].

The finding of a prolonged partial thromboplastin time and a normal prothrombin time localized the coagulation defect to the intrinsic or contact activation limb of the coagulation cascade. Because the situation is a source of hemorrhage, a rational and rapid approach is necessary with measure of factors of intrinsic limb of coagulation (especially factors VIII and IX, for the diagnosis of classic hemophilia), study of von Willebrand factor and search of coagulation factor inhibitors. We report the case of a 25-year old woman with high titer postpartum antibody against factor VIII for illustrating the diagnosis approach.

Adult↗
PubMed1995

Two novel antithrombin variants, Asn187Asp and Asn187Lys, indicate a functional role for asparagine 187.

Three unrelated families have been identified with mutations involving asparagine 187. Two of these families are asymptomatic and were identified during the screening of random blood donors, whilst the third has a history of recurrent thromboembolic disease. In two families the mutation (6460 AAC-->GAC) results in an asparagine to aspartate substitution and is associated with normal immunological levels of antithrombin but a reduction in functional activity. In the third family the mutation (6462 AAC-->AAA) results in an asparagine to lysine substitution at residue 187 and is associated with a parallel reduction in both immunological and functional antithrombin levels. Asparagine 187 is located in the middle of the F helix of antithrombin and forms the major link between the F helix and strand 3 of the A sheet. The F helix is seen to overlie the A sheet of the molecule and moves with strands 2 and 3 of this sheet as they open to allow entry of the reactive site loop to form strand 4. Substitutions of asparagine 187 are, therefore, likely to disrupt this sliding movement leading to a loss of inhibitory activity.

Adult↗
PubMed1995

Co-segregation of thrombosis with the factor V Q506 mutation in an extended family with resistance to activated protein C.

The activated protein C (APC) resistance phenotype results from a mutation at one of the cleavage sites of factor V by APC (Q506). We describe a large family with an APC resistance phenotype and without any other detectable coagulation defect, including eight subjects who had developed deep venous thrombosis (mean age of the first thrombosis episode 29 years; range 17-55 years). The factor V Q506 mutation was detected in the seven patients with thrombosis who could be tested and in 13 asymptomatic subjects (mean age 17 years; range 5-33 years). The APC resistance was detectable in only 10 heterozygotes among the 19 tested. These data suggest that, in affected families, the risk for the factor V Q506 mutation carriers to develop thrombosis may be very high and that factor V genotyping must be performed in patients with thrombosis even without any detectable APC resistance phenotype.

Adult↗
PubMed1995

Catastrophic antiphospholipid syndrome with fatal acute course in rheumatoid arthritis.

A 34-year old woman, with a 3 yr history of severe seropositive rheumatoid arthritis (RA) with lupus anticoagulant and anticardiolipin antibodies, developed a massive anterior myocardial infarction and ischemia of the lower extremities, with disseminated intravascular coagulation resulting from extensive tissue damage. Seven days after admission, she died of severe heart failure complicated by ventricular fibrillation. To our knowledge, this is the first documented case of fatal acute antiphospholipid syndrome in RA.

Adult↗
PubMed1994

Resistance to activated protein C: evaluation of three functional assays.

Resistance to Activated Protein C (APC) was evaluated using 3 different methods: two of them were based on the prolongation of the Activated Partial Thromboplastin Time (APTT) using 2 different APTT reagents in the presence of APC, whereas the third method was based on the prolongation of prothrombin time when APC is added. The three methods were significantly correlated. APTT-based assays were sensitive to factor XII deficiency, whereas thromboplastin-based assay was sensitive to factor VII deficiency (< 0.5 UI/ml), which surestimates the response to APC. In contrast, an increase in factor VIII (F. VIII) level is associated with a decreased response to APC, when APTT-based assays are used, whereas thromboplastin-based assay is unmodified. During pregnancy, a decreased response to APC is observed, which is not only due to the increase in F. VIII, since thromboplastin-based assay is also modified. In Protein S (PS) immuno-depleted plasma, the low response to APC is corrected by addition of free PS: the thromboplastin-based assay was the most sensitive one to PS deficiency. However, in patients with congenital PS deficiency, there was no correlation between APC-resistance and free PS level. In patients with lupus anticoagulant, discrepancies were observed between the 3 methods, but with a high frequency of low response to APC. For the 3 assays, there was a good differentiation and correlation between normal and pathological results, the thromboplastin-based assay being perhaps the most discriminating. However, 3 unrelated thrombophilic patients showed normal results using thromboplastin-based assay, although they were APC-resistant using APTT-based assays. For 2 patients, this discrepancy can be explained by high levels of F. VIII. For the last patient, an abnormal F. VIII, resistant to APC can be suspected.

Adult↗
PubMed1994

Thromboembolic disease due to thermolabile conformational changes of antithrombin Rouen-VI (187 Asn-->Asp)

A new variant of antithrombin (Rouen-VI, 187 Asn-->Asp) with increased heparin affinity was shown to have normal inhibitory activity which decreased slowly at 4 degrees C and rapidly at 41 degrees C. On electrophoresis the freshly isolated variant had an anodal shift relative to native antithrombin due to the mutation. A further anodal transition occurred after either prolonged storage at 4 degrees C or incubation at 41 degrees C due to the formation of a new inactive uncleaved component with properties characteristic of L-form (latent) antithrombin. At the same time, polymerization also occurred with a predominance of di-, tri-, and tetra-mers. These findings fit with the observed mutation of the conserved asparagine (187) in the F-helix destabilizing the underlying A-sheet of the molecule. Evidence of A-sheet perturbation is provided by the increased rate of peptide insertion into the A-sheet and by the decreased vulnerability of the reactive loop to proteolysis. The spontaneous formation of both L-antithrombin and polymers is consistent with our crystal structure of intact antithrombin where L-form and active antithrombin are linked together as dimers. The nature of this linkage favors a mechanism of polymerization whereby the opening of the A-sheet, to give incorporation of the reactive center loop, is accompanied by the bonding of the loop of one molecule to the C-sheet of the next. The accelerated lability of antithrombin Rouen-VI at 41 versus 37 degrees C provides an explanation for the clinical observation that episodes of thrombosis were preceded by unrelated pyrexias.

Adult↗
PubMed1994

[Protein S deficiency in necrotizing cellulitis of the penis].

INTRODUCTION: The pathogenesis of necrotizing cellulitis remains uncertain. Factors that enhance clot formation may contribute to tissue necrosis. CASE REPORT: A case of necrotizing cellulitis of the penis in a patient with a transient protein S deficiency, is reported. CONCLUSION: The responsibility of this transient hypercoagulable state in the occurrence of tissue necrosis in this patient is discussed.

Adult↗