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Biomedical subjects

P de Moerloose

Publications and source records attributed to P de Moerloose.

At least 19 recordsLinked to original sources
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

Aspirin inhibits endothelial cell activation induced by antiphospholipid antibodies.

BACKGROUND: Antiphospholipid antibodies (APLA) have been shown to activate endothelial cells (EC) in vitro, as documented by an increased expression of tissue factor as well as leukocyte adhesion molecules such as intercellular adhesion molecule-1, vascular cell adhesion molecule (VCAM)-1 and E-selectin. Currently, treatment of patients with the antiphospholipid syndrome includes aspirin, particularly for women with recurrent fetal loss. OBJECTIVE: The present study was undertaken to investigate whether aspirin interferes with EC activation induced by APLA in vitro. METHODS: IgG from 14 patients with APLA, and suffering from thrombotic complications and/or pregnancy morbidity, and control IgG were tested for their ability to modify the expression of VCAM-1 in human umbilical vein endothelial cells. VCAM-1 antigen was measured by flow cytometry and its mRNA by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: Incubation of EC with IgG from most of the patients led to a higher VCAM-1 expression compared with incubation with control IgG. The effect of aspirin was studied for the eight IgG samples that induced a more than 50% increase in VCAM-1. Aspirin (10 mm) treatment of the cells significantly reduced the VCAM-1 response to these APLA. CONCLUSIONS: Our results indicate that besides its antiplatelet properties, aspirin exerts a protective effect towards APLA at the EC level by decreasing leukocyte adhesion molecule expression at the cell surface.

Antibodies, Antiphospholipid↗
PubMed2004

Analysis of biological phenotypes from 42 patients with inherited factor VII deficiency: can biological tests predict the bleeding risk?

BACKGROUND AND OBJECTIVES: Inherited factor VII (FVII) deficiency is a rare bleeding disorder characterized by a poor relationship between reported FVII clotting activity (FVII:C) and bleeding tendency. Our study was aimed at defining biological parameters that are possibly predictive for bleeding risk in this condition. DESIGN AND METHODS: Forty-two FVII-deficient patients (FVII:C <30%) were classified into two opposite clinical groups defined as severe and non-or-mild bleeders. For each patient, plasma samples were collected and then investigated for FVII:C (using a sensitive method and human recombinant thromboplastin as the reagent), FVII antigen, activated FVII coagulant activity (FVIIa:C) and the free-form of tissue factor pathway inhibitor. RESULTS: None of these tests could be used as highly accurate predictors of bleeding. Nevertheless, both FVII:C and FVIIa:C differed significantly between the two clinical groups. Using ROC-curve analysis, two critical values of 8% and 3mIU/mL for FVII:C and FVIIa:C, respectively, could be proposed to discriminate between severe bleeders and non-or-mild bleeders. INTERPRETATION AND CONCLUSIONS: A highly accurate diagnostic test for predicting bleeding tendency in inherited FVII deficiency still eludes definition, highlighting the fact that factors other than FVII itself interfere with the expression of bleeding phenotypes in this condition. Nevertheless, potential critical values using sensitive FVII:C and FVIIa:C methods may be useful in clinical laboratories for FVII-deficient patients. Those patients with FVII:C levels higher than 8% FVII:C or FVIIa:C higher than 3 mIU/mL, with no other hemostatic defect, seem to have a minimal risk of severe bleeding. Extended clinical studies are needed to support these findings.

Adolescent↗
PubMed2003

Is measurement of D-dimer useful in the diagnosis of cerebral venous thrombosis?

BACKGROUND: The diagnosis of cerebral venous thrombosis (CVT) is a challenge because its clinical presentation is variable, brain CT may be normal, and MRI is not always available. Furthermore, early treatment may be effective. As D-dimer (DD) measurement is a sensitive test for the exclusion of venous thromboembolism, the authors studied whether this test could be useful in the diagnosis of CVT. METHODS: A prospective study of 54 consecutive patients with headaches suggestive of CVT was conducted between October 2000 and September 2002. DD levels were tested for all patients in the emergency room before brain CT or MRI was performed. RESULTS: Twelve (22%) of the 54 patients had CVT, and 10 (83%) of these 12 patients had DD level of >500 ng/mL (sensitivity of 83% and negative predictive value of 95%). Two patients with confirmed CVT and DD of <500 ng/mL had a history of chronic headache of >30 days' duration. In the 42 patients without confirmed CVT, only 4 patients had DD level of >500 ng/mL (specificity of 90% and positive predictive value of 71%). CONCLUSIONS: DD test is useful in the diagnosis of acute CVT. A value below 500 ng/mL makes acute thrombosis unlikely.

Adult↗
PubMed2003

Effects of statins on adhesion molecule expression in endothelial cells.

BACKGROUND: Inhibitors of HMG-CoA reductase are widely used to prevent atherosclerosis progression. The expression of adhesion molecules on activated endothelial cells (EC) is an important step in the initiation and progression of atherosclerosis. OBJECTIVES: We investigated whether adhesion molecule expression on activated EC is influenced by simvastatin, fluvastatin and pravastatin and, if so, by which mechanisms. METHODS: Human EC from umbilical veins or saphenous veins were pretreated overnight with statins with or without mevalonate, and also for simvastatin or fluvastatin with the isoprenoid intermediates, farnesyl pyrophosphate (FPP), or geranylgeranyl pyrophosphate (GGPP). After 4-6 h activation with tumor necrosis factor (TNF)-alpha or lipopolysaccharide (LPS), surface adhesion molecule expression was evaluated by ELISA and by flow cytometry. The same experiments were performed with selective inhibitors of geranylgeranyltransferase (GGTI-286) and farnesyltransferase (FTI-277). RESULTS: Pretreatment with simvastatin, fluvastatin or pravastatin potentiated the TNF-alpha and LPS-induced expression of E-selectin and VCAM-1, and mevalonate reversed the potentiating effect of these statins. GGPP also reversed the potentiating effect of simvastatin or fluvastatin on adhesion molecule expression, while FPP only partially reversed this effect. Furthermore, GGTI-286, but not FTI-277, mimicked the effect of simvastatin by increasing the TNF-alpha-mediated overexpression of E-selectin. CONCLUSIONS: Statins increase E-selectin- and VCAM-1-induced expression on vascular endothelial cells stimulated with TNF-alpha or LPS. The inhibition of geranylgeranylated proteins could contribute to this effect.

Cell Adhesion Molecules↗
PubMed2003

Severe thrombocytopenic purpura due to rubella infection in a patient with systemic lupus erythematosus.

We report the case of a woman suffering from systemic lupus erythematosus who developed a severe thrombocytopenic purpura (platelet count < 1 x 10(9)/l) secondary to rubella infection. The search for antiplatelet antibodies revealed transient circulating anti-GPIIb-IIIa and anti-GPIb-IX platelet antibodies. After a few weeks, bound anti-GPIIb-IIIa antiplatelet antibodies were still detectable and they persisted several months after recovery, probably in relation to a mild autoimmune thrombocytopenia related to systemic lupus erythematosus. To our knowledge, this is the first case report of severe thrombocytopenic purpura due to rubella in an adult with systemic lupus erythematosus.

Adult↗
PubMed2002

[Diagnosis of deep venous thrombosis of the lower limbs: performance of diagnostic tests].

Deep-vein thrombosis is a frequent affection that needs precise diagnosis. Indeed, the clinical complications (from post-thrombotic syndrome to fatal pulmonary embolism) as well the risk of anticoagulant treatment require a precise diagnosis. Since clinical evaluation cannot assure reliably diagnosis by lack of sensitivity and specificity, complementary exams are needed. However, clinical assessment is an important part to decide further examinations. D-dimers assessment allows to role out the diagnosis of deep-vein thrombosis in a number of cases. Plethysmography and continuous Doppler are progressively given up. Compressive venous ultrasonography is now the exam of first choice. Scintigraphy, scanner and RMI must still be validated. Phlebography remains the gold standard in case of negative compressive venous ultrasonography and a high clinical probability.

Enzyme-Linked Immunosorbent Assay↗
PubMed2001

Performance of helical computed tomography in unselected outpatients with suspected pulmonary embolism.

BACKGROUND: Helical computed tomography (CT) is commonly used to diagnose pulmonary embolism, although its operating characteristics have been insufficiently evaluated. OBJECTIVE: To assess the sensitivity and specificity of helical CT in suspected pulmonary embolism. DESIGN: Observational study. SETTING: Emergency department of a teaching and community hospital. PATIENTS: 299 patients with clinically suspected pulmonary embolism and a plasma D -dimer level greater than 500 microgram/L. INTERVENTION: Pulmonary embolism was established by using a validated algorithm that included clinical assessment, lower-limb compression ultrasonography, lung scanning, and pulmonary angiography. MEASUREMENTS: Sensitivity, specificity, and likelihood ratios of helical CT and interobserver agreement. Helical CT scans were withheld from clinicians and were read 3 months after acquisition by radiologists blinded to all clinical data. RESULTS: 118 patients (39%) had pulmonary embolism. In 12 patients (4%), 2 of whom had pulmonary embolism, results of helical CT were inconclusive. For patients with conclusive results, sensitivity of helical CT was 70% (95% CI, 62% to 78%) and specificity was 91% (CI, 86% to 95%). Interobserver agreement was high (kappa = 0.823 to 0.902). The false-negative rate was lower for helical CT used after initial negative results on ultrasonography than for helical CT alone (21% vs. 30%). Use of helical CT after normal results on initial ultrasonography and nondiagnostic results on lung scanning had a false-negative rate of only 5% and a false-positive rate of only 7%. CONCLUSION: Helical CT should not be used alone for suspected pulmonary embolism but could replace angiography in combined strategies that include ultrasonography and lung scanning.

Adult↗
PubMed2001

Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 G-->T.

Our recent studies on the molecular basis of the autosomal recessive disorder congenital afibrinogenemia showed that the most common mutation is a donor splice mutation in FGA intron 4, IVS4 + 1 G-->T, accounting for approximately half of disease alleles. The effect of this mutation on messenger RNA (mRNA) splicing, however, remained unproven. COS-7 cells transfected with a normal plasmid construct produced 100% mRNA molecules with correct splicing, whereas cells transfected with a mutant construct produced multiple aberrant mRNAs, due to utilization of cryptic donor splice sites situated in exon 4 and intron 4. One particular site situated 4 base pairs (bp) downstream of the normal site was used in 85% of transcripts causing afibrinogenemia by a 4-bp insertion-frameshift, leading to premature alpha-chain truncation. Our results confirm the utility of transfecting COS-7 cells to study mRNA splice-site mutations and demonstrate that the common FGA IVS4 variant is a null mutation leading to afibrinogenemia.

Afibrinogenemia↗
PubMed2001

Point of care and central laboratory determinations of the aPTT are not interchangeable in surgical intensive care patients.

PURPOSE: The objective of the study was to compare a bedside whole blood activated partial thromboplastin time (aPTT) performed by a point of care (POC) apparatus (CoaguCheck(R) Pro) in surgical intensive care (SIC) patients with a conventional aPTT obtained from the central laboratory. METHODS: The prospective concomitant measurements of the two aPTT were performed in 233 samples from 46 consecutive patients admitted after cardiovascular or major abdominal surgery. RESULTS: Inter-operator, inter-instrument and inter-cartridge variability of the new device measured in three healthy volunteers and in nine patients in stable condition (controls) was low (F test: P=0.86). The agreement by Bland and Altman between POC and central laboratory aPTT (-20.2 +/- 18.8 sec) was not satisfactory. The agreement between POC and central laboratory aPTT in patients after surgery was worst (-17 +/- 33.1 sec). Heparin treatment or timing of blood sampling after intensive care admission (<48 hr vs >48 hr) did not influence the agreement. The correlation between POC or central laboratory aPTT and anti-factor Xa activity was poor (r(2) 0.077 and 0.181 respectively). The test which correlated the best to heparin doses was anti-factor Xa activity (r(2) 0.714). CONCLUSION: POC aPTT and central laboratory aPTT showed a poor agreement in SIC patients admitted after surgery, although in healthy volunteers or in control patients, this agreement was better. The best test to monitor heparin treatment in this setting was anti-factor Xa activity.

Abdomen↗
PubMed2001

Molecular analysis of the fibrinogen gene cluster in 16 patients with congenital afibrinogenemia: novel truncating mutations in the FGA and FGG genes.

Congenital afibrinogenemia is an autosomal recessive disorder characterized by the complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease in a non-consanguineous Swiss family. These were homozygous deletions of approximately 11 kb of the fibrinogen alpha chain gene (FGA). Our subsequent study revealed that the majority of cases were attributable to truncating mutations in FGA, with the most common mutation affecting the donor splice site in FGA intron 4 (IVS4+1 G-->T). Here, we report 13 further unrelated patients with mutations in FGA, confirming the relative importance of this gene compared with FGG and FGB in the molecular aetiology of afibrinogenemia. Three other patients were homozygous for mutations in FGG. Eight novel mutations were identified: five in FGA and three in FGG. Sufficient mutation data is now available to permit an effective strategy for the genetic diagnosis of congenital afibrinogenemia.

Afibrinogenemia↗