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We studied the value of serum amyloid A (SAA), a first-class acute-phase protein, as a marker for coronary heart disease (CHD) in a middle-aged male population. In a working population of 16 307 men (age, 35-59 years), 446 cases had a history of CHD or prominent Q:QS waves on electrocardiogram. For each case, two matched controls were investigated. SAA, measured by immunonephelometry, was correlated with other acute-phase proteins, cardiovascular risk factors, and infectious serology markers. SAA concentrations were significantly higher in the cases than in controls (P < 0.05) and correlated with serum C-reactive protein (CRP) (r = 0.61), plasma fibrinogen (r = 0.39), serum haptoglobin (r = 0.26), and body mass index (r = 0.13) (P < 0.001). Serum CRP is a better marker for CHD than SAA, which showed discriminative power only in a univariate model comparing highest versus lowest tertile (odds ratio, 1.39; 95% confidence interval, 1.03-1.87). Neither SAA nor other acute-phase proteins correlated with Chlamydia pneumoniae immunoglobulin (Ig)G, Helicobacter pylori IgG and IgA, and cytomegalovirus IgG. In conclusion, although SAA has a discriminative value for CHD, serum CRP is to be preferred as a first-class acute-phase reactant for detection of the disease. © 2002 Elsevier Science Ireland Ltd. All rights reserved., SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: le.j, info:eu-repo/semantics/published

A qualitative (Instantia®) and a quantitative (VIDAS D-Dimer®) D- Dimer test have been evaluated and compared with an ELISA method (Asserachrom D-D®) in a population of 74 patients suspected of presenting a deep vein thrombosis. Among the thirty-two patients presenting a deep vein thrombosis on phlebography, there were 16 (50%) proximal vein thrombosis and 16 (50%) distal vein thrombosis. Sensitivity and negative predictive value for proximal thrombosis were 100% in all three tests. For distal vein thrombosis, sensitivity and negative predictive value were respectively 8 1% and 8 1% for Asserachrom D-DI® 75% and 76% for VIDAS D-Dimer® and 63% and 82% for Instantia®. In conclusion, this study shows that these D-Di assays are a useful tool to exclude proximal vein thrombosis, at least for patients who are not under anticoagulant therapy., SCOPUS: ar.j, info:eu-repo/semantics/published

The molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency, with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type II AT deficiency was occasionally diagnosed. DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intron-exon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion, known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect., SCOPUS: ar.j, info:eu-repo/semantics/published

The CD40 molecule expressed on endothelial cells has been shown to transduce activation signals resulting in upregulation of adhesion molecules. Herein, we studied the impact of CD40 engagement on the induction of tissue factor (TF)-dependent procoagulant activity (PCA) at the surface of human umbilical vein endothelial cells (HUVECs). First, we found that co-incubation of HUVECs with 3T6 fibroblasts transfected with the CD40L gene (3T6-CD40L) resulted in a clear induction of PCA which was not observed with control untransfected fibroblasts. The specificity of this finding was established by inhibition experiments using monoclonal antibodies (mAbs) blocking CD40 or CD40L. PCA induced by CD40 ligation was TF-related as it was not observed in factor VII-deficient plasma and was associated with the accumulation of TF mRNA. To investigate the role of CD40/CD40L interactions in the induction of endothelial cell PCA by lymphocytes, interferon (IFN)-gamma-stimulated EC were incubated with T cells in the absence or presence of anti-CD40 or anti-CD40L mAb. The 60-70% inhibition of PCA induced by these mAbs but not their isotype-matched control indicated that the CD40 pathway is involved in the induction of PCA resulting from interactions between activated HUVECs and T cells. We conclude that activation signals elicited by CD40 engagement on endothelial cells result in the induction of TF-dependent PCA. The CD40/CD40L pathway might therefore be involved in the development of prothrombic states during diseases associated with endothelial cell and T cell activation., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/nonPublished

A case of angiosarcoma arising in the setting of transplantation is reported. This rare and malignant tumor of the endothelial system is seldom observed in allograft recipients, with only seven cases having been previously reported. What is interesting about the present observation is that the tumor is thought to have developed in the vicinity of a Dacron graft and that it showed prominent erythrophagocyte-like activity. This activity was associated with a particular clinical syndrome that shared some attributes with infection-associated hemophagocytic syndrome., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

A particular case of marginal zone B-cell lymphoma (MZBCL) presenting with leukemic lymphocytes is reported. In the present observation, the leukemic cells not only displayed a remarkable morphological fluctuation but also had an unusual phenotype, changing with time. These phenotypic features, which have been functionally investigated by in vitro assays, might simply reflect an activation state depending on the microenvironment. Because of its disconcerting similarities with hairy cell leukemia (HCL) and splenic lymphoma with villous lymphocytes (SLVL), this case relaunches the debate about whether close relationships might exist between the splenic marginal zone, SLVL and HCL., SCOPUS: ar.j, info:eu-repo/semantics/published

Antiphospholipid antibodies are associated with venous and arterial thromboembolism and with fetal loss. These associations are found either in autoimmune disease or without any other associated disease. In the first case one will speak of secondary antiphospholipid syndrome and in the second of primary antiphospholipid syndrome. The detection techniques of these antibodies have been improved these last years, although they remain difficult to standardize. The treatment of thromboembolism is based on the use of heparin and oral anticoagulants. Several therapeutic options exist to treat fetal losses, among which corticosteroids, subcutaneous heparin and aspirin are the most frequently used., SCOPUS: sh.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: The benefit of performing chemotherapy on soft tissue sarcomas remains controversial. The present study deals with the in vitro characterisation of the influence of 3 antitumoral agents on the growth of 8 sarcoma cell lines. MATERIALS AND METHODS: Cell growth was monitored by means of the MTT colorimetric assay, which was further validated by a direct cell counting method. The three drugs tested included doxorubicin (ADR), cisplatin (DDP) and dacarbazine (DTIC). ADR was tested at 10(-5) M, 10(-6) M and 10(-7) M; DDP at 10(-5) M, 10(-6) M and 10(-7) M; and DTIC at 10(-3) M, 10(-4) M and 10(-5) M. A combination of the three drugs was also tested in order to ascertain whether a synergistic effect on cell growth inhibition could be obtained. A potential antineoplastic agent-induced influence on cell growth was determined 3 days after the addition of the diverse drug(s) to the culture media. The cell concentration was specifically adapted to each cell line. The 8 cell lines included 3 leiomyosarcomas, 1 malignant mixed Müllerian tumour, 3 rhabdomyosarcomas and 1 fibrosarcoma. RESULTS: The results show that of the three drugs tested, ADR was the most efficient in terms of the level of cell growth inhibition obtained and the number of cell lines whose growth was significantly inhibited. Of the three drugs, the least active was DDP. A significant synergistic effect was observed when the three drugs were added together to the culture medium. This synergistic effect was evident at the lowest doses tested for each drug. Whatever the histopathological type, the 8 cell lines exhibited a wide range of response to chemotherapy. CONCLUSIONS: The present study shows that the inhibition induced by 10(-7) M ADR, 10(-7) M DDP and 10(-5) M DTIC on sarcoma cell line growth is significantly more efficient than if each agent is tested individually. The in vitro methodology used here fits in with clinical reality because it enables sarcoma cell heterogeneity to be taken into acc, Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: ar.j, info:eu-repo/semantics/published

info:eu-repo/semantics/published

Very high-dose chemotherapy with autologous blood stem cell (BSC) rescue becomes more and more widely performed. In order to simplify the technique, a large volume apheresis programme combined with an uncontrolled rate cryopreservation at –80°C was developed. Twenty-six patients suffering from multiple myeloma (n = 8), non-Hodgkin's lymphoma (n = 7), dysgerminoma (n = 4), breast cancer (n = 3), Hodgkin's disease (n = 2), acute lymphoblastic leukaemia (n = 1) and acute myelocytic leukaemia (n = 1) were autografted after a classical high-dose chemotherapy regimen. A single large volume apheresis was sufficient to obtain the threshold value of CD34+ BSC in 24/26 transplantations. The haematological recovery was favourably comparable with the previously published data obtained with controlled rate frozen BSC: median time to granulocytes > 1000/μL and to a self-supporting platelet count > 20,000/μL, respectively, 10.5 and 12 d. The treatment-related mortality was confined to 1/26 BSCT. These results indicate that this easy and cost-saving policy of BSCT is efficacious and safe: sustained long-term haematopoiesis, reduced morbidity and mortality were observed., SCOPUS: ar.j, FLWIN, info:eu-repo/semantics/published