bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral contraceptives, hormone replacement therapy, thrombophilias and risk of venous thromboembolism: a systematic review
Authors: Wu Olivia , Robertson Lindsay , Langhorne Peter , Twaddle Sara , Lowe Gordon D. O. , Clark Peter , Greaves Mike , Walker Isobel D. , Brenkel Ivan , Regan Lesley , Greer Ian A. 
Published: June 2005

SummaryCombined oral contraceptives, oral hormone replacement therapy and thrombophilias are recognised risk factors for venous thromboembolism in women. The objective of this study was to assess the risk of thromboembolism among women with thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47).Although limited by the small number of studies, the findings of this study support the presence of interaction between thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, thrombophilias with venous thromboembolism among hormone users.
Fibrillar type I collagens enhance platelet-dependent thrombin generation via glycoprotein VI with direct support of α2β1 but not αIIbβ3 integrin
Authors: Lecut Christelle , Jandrot-Perrus Martine , Feijge Marion A. H. , Cosemans Judith M. E. M. , Heemskerk Johan W. M. 
Published: June 2005

SummaryThe role of collagens and collagen receptors was investigated in stimulating platelet-dependent thrombin generation. Fibrillar type-I collagens, including collagen from human heart, were most potent in enhancing thrombin generation, in a way dependent on exposure of phosphatidylserine (PS) at the platelet surface. Soluble, non-fibrillar type-I collagen required pre-activation of integrin α2β1 with Mn2+ for enhancement of thrombin generation. With all preparations, blocking of glycoprotein VI (GPVI) with 9O12 antibody abrogated the collagen-enhanced thrombin generation, regardless of the α2β1 activation state. Blockade of α2β1 alone or antagonism of autocrine thromboxane A2 and ADP were less effective. Blockade of αIIbβ3 with abciximab suppressed thrombin generation in platelet-rich plasma, but this did not abolish the enhancing effect of collagens. The high activity of type-I fibrillar collagens in stimulating GPVI-dependent procoagulant activity was confirmed in whole-blood flow studies, showing that these collagens induced relatively high expression of PS. Together, these results indicate that: i) fibrillar type-I collagen greatly enhances thrombin generation, ii) GPVI-induced platelet activation is principally responsible for the procoagulant activity of fibrillar and non-fibrillar collagens, iii) α2β1 and signaling via autocrine mediators facilitate and amplify this GPVI activity, and iv) αIIbβ3 is not directly involved in the collagen effect.
Isolated integrin β3 subunit cytoplasmic domains require membrane anchorage and the NPXY motif to recruit to adhesion complexes but do not discriminate between β1– and β3-positive complexes
Authors: Ponsonnet Lionel , Foletti Alessandro , Alghisi Gian Carlo , Rüegg Curzio 
Published: June 2005

SummaryIntegrin adhesion receptors consist of non-covalently linked α and β subunits each of which contains a large extracellular domain, a single transmembrane domain and a short cytoplasmic tail. Engaged integrins recruit to focal structures globally termed adhesion complexes. The cytoplasmic domain of the β subunit is essential for this clustering. β1 and β3 integrins can recruit at distinct cellular locations (i.e. fibrillar adhesions vs focal adhesions, respectively) but it is not clear whether individual β subunit cytoplasmic and transmembrane domains are by themselves sufficient to drive orthotopic targeting to the cognate adhesion complex. To address this question, we expressed fulllength β3 transmembrane anchored cytoplasmic domains and truncated β3 cytoplasmic domains as GFP-fusion constructs and monitored their localization in endothelial cells. Membrane-anchored full-length β3 cytoplasmic domain and a β3 mutant lacking the NXXY motif recruited to adhesion complexes, while β3 mutants lacking the NPXY and NXXY motifs or the transmembrane domain did not. Replacing the natural β subunit transmembrane domain with an unrelated (i.e. HLA-A2 α chain) transmembrane domain significantly reduced recruitment to adhesion complexes. Transmembrane anchored β3 and cytoplasmic domain constructs, however, recruited without discrimination to β1– and β3-rich adhesions complexes. These findings demonstrate that membrane anchorage and the NPXY (but not the NXXY) motif are necessary for β3 cytoplasmic domain recruitment to adhesion complexes and that the natural transmembrane domain actively contributes to this recruitment. The β3 transmembrane and cytoplasmic domains alone are insufficient for orthotopic recruitment to cognate adhesion complexes.
Ultrasound thrombolysis
Authors: Pfaffenberger Stefan , Devcic-Kuhar Branka , Kastl Stefan P. , Maurer Gerald , Wojta Johann , Gottsauner-Wolf Michael , Huber Kurt 
Published: June 2005

SummaryCardiovascular diseases are a major cause of mortality in the developed world. Efficacy of thrombolysis plays an important role in the management of acute myocardial infarction and cerebral insult both in the acute event and in the long-term outcome of these patients. New adjunctive strategies have been tested, therefore, to make thrombolytic therapies more effective and safer. Ultrasound Thrombolysis is a technique which showed promising results under in vitro conditions and in animal studies. Now clinical trials have to prove if it is also feasible for clinical application. This report gives an overview on different technical approaches and their current performances in the clinical setting. All original articles are chronologically ordered in tables providing detailed information on each study concerning experimental design, acoustical parameters and thrombolysis outcome.
Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis
Authors: Farner Beate , Kroll Hartmut , Kohlmann Thomas , Warkentin Theodore E. , Eichler Petra , Greinacher Andreas 
Published: June 2005

SummaryImmune mediated heparin induced thrombocytopenia (HIT) is a prothrombotic adverse effect of heparin. However, only a subgroup of patients with HIT develops thromboembolic complications. We aimed to identify risk factors for developing HITassociated thrombosis. We analyzed a registry of patients with clinical suspicion of HIT who tested positive using a sensitive functional assay. Patient information was obtained by a standardized questionnaire. By multivariate analysis the association of age, gender, type of patient population, and magnitude of the platelet count decline with the frequency, type (venous or arterial), and temporal pattern of thrombotic events was assessed. In 408 HIT patients we observed predominance of venous thrombosis (2.4:1), with 40% of patients developing a pulmonary embolism. However, in the subgroup of post-cardiovascular surgery patients there was predominance of arterial thrombosis (1:8.5). The type of arterial thrombosis (limb artery thrombosis > thrombotic stroke > myocardial infarction) was the converse of that observed with typical atherothrombotic clots in non-HIT populations. In 59.8% of patients HIT-related thrombosis manifested either on the same day a platelet count decrease >50% was documented (26.3%) or before the decrease in platelet counts (33.5%).The most important risk factors for thrombosis were orthopedic/trauma surgery and the magnitude of platelet count decrease. HIT-associated thrombosis occurs in a considerable proportion of patients before platelet counts decrease by more than 50%.
Ruling out deep venous thrombosis in primary care
Authors: Moons Karel G. M. , Hoes Arno W. , Oudega Ruud 
Published: June 2005

SummaryIn primary care, the physician has to decide which patients have to be referred for further diagnostic work-up. At present, only in 20% to 30% of the referred patients the diagnosis DVT is confirmed. This puts a burden on both patients and health care budgets. The question arises whether the diagnostic work-up and referral of patients suspected of DVT in primary care could be more efficient. A simple diagnostic decision rule developed in primary care is required to safely exclude the presence of DVT in patients suspected of DVT, without the need for referral. In a cross-sectional study, we investigated the data of 1295 consecutive patients consulting their primary care physician with symptoms suggestive of DVT, to develop and validate a simple diagnostic decision rule to safely exclude the presence of DVT. Independent diagnostic indicators of the presence of DVT were male gender, oral contraceptive use, presence of malignancy, recent surgery, absence of leg trauma, vein distension, calf difference and D-dimer test result. Application of this rule could reduce the number of referrals by at least 23% while only 0·7% of the patients with a DVT would not be referred. We conclude that by using eight simple diagnostic indicators from patient history, physical examination and the result of D-dimer testing, it is possible to safely rule out DVT in a large number of patients in primary care, reducing unnecessary patient burden and health care costs.
A subpopulation of human B lymphocytes can express a functional Tissue Factor in response to phorbol myristate acetate
Authors: Mechiche Houria , Cornillet-Lefebvre Pascale , Nguyen Philippe 
Published: June 2005

SummaryTissue Factor (TF, CD142) is a transmembrane glycoprotein that belongs to the cytokine receptor superfamily. This multifunctional protein is constitutively present in most tissues. Among circulating blood cells, TF expression is known to be restricted to monocytes which do not constitutively produce TF but express TF in response to various stimuli. Here, we report that highly purified B lymphocytes can support a procoagulant activity (PCA) in response to phorbol myristate acetate (PMA).Using flow cytometry (FCM), we observed that a subpopulation of B lymphocytes (CD19+) can expressTF and anionic phospholipids in response to PMA. TF protein was identified and characterized by immunofluorescence, immunocytochemistry and electronic microscopy. Using RT-PCR, we identified the presence of TF mRNA in response to PMA. In conclusion, B lymphocytes are a potential source of functional TF in human.
Preoperative fibrin monomer measurement allows risk stratification for high intraoperative blood loss in elective surgery
Authors: Gabi Konrad , Rohner Mirjam , Gähler Anita , Szadkowski Christine , Schnider Thomas W. , Lange Jochen , Riesen Walter , Korte Wolfgang 
Published: June 2005

SummaryWe recently demonstrated that patients with increased blood loss due to intraoperative coagulopathy show a persistent pre-, intra- and postoperative increase in fibrin monomer concentration. We thus tested the hypothesis that preoperative fibrin monomer concentrations can be used as a risk indicator for intraoperative blood loss in a study designed for diagnostic test evaluation in 168 patients admitted to the surgical service of our hospital. Intraoperative blood loss increased with preoperative fibrin monomer concentration (median blood loss of 50, 100, 200 and 400 ml in preoperative fibrin monomer quartile groups 1 to 4, p<0.001,ANOVA on ranks; interquartile comparisons p < 0.05 (4/6), MannWhitney Rank Sum test). In contrast, intraoperative blood loss was unrelated to preoperative values of prothrombin time, activated partial thromboplastin time and platelet count. By multivariate (logistic regression) analysis, only fibrin monomer remained a significant predictor of intraoperative blood loss > 500 ml when age, gender, BMI, fibrin monomer and the different types of surgical procedures (tumor surgery, vascular surgery, cholecystectomy, gastric banding, varicous vein surgery and hernia repair) were included as independent variables. Most importantly, accuracy evaluation showed that preoperative fibrin monomer concentration < 3 μg/l excluded intraoperative blood loss > 500 ml with 92% sensitivity and 95% negative predictive value. These results support our hypothesis that preoperative fibrin monomer concentrations are related to intraoperative blood loss in elective surgery. Fibrin monomer should be further investigated for it’s potential to serve as a routine tool for preoperative risk stratification of intraoperative bleeding.
Bridging anticoagulation with low-molecular-weight heparin after interruption of warfarin therapy is associated with a residual anticoagulant effect prior to surgery
Authors: Woods Karen , Foster Gary A. , Crowther Mark A. , Douketis James D. 
Published: June 2005

SummaryBridging anticoagulation with low-molecular-weight heparin (LMWH) is common in patients who require temporary interruption of warfarin before surgery or a procedure, but whether such patients have a residual anticoagulant effect just before a procedure is not known. Consecutive patients who received bridging anticoagulation with LMWH had anti-Xa levels measured just before a procedure. The proportion of patients with a residual anticoagulant effect, defined as an anti-Xa level ≥0.10 IU/ml, was determined. Multivariable regression analysis identified predictors of a residual anticoagulant effect, expressed as an odds ratio (OR) and corresponding 95% confidence interval (CI). A pre-procedure residual anticoagulant effect was detected in 12 of 73 (16%) patients overall, in 11 of 37 (30%) patients who received therapeutic-dose LMWH, and in 1 of 36 patients (3%) who received low-dose LMWH. Receiving therapeutic- dose LMWH (OR = 118.8; 95% CI: 5.8, 999.9), and increasing age (OR = 4.0; 95% CI: 1.3, 12.5) were predictors of a residual pre-procedure anticoagulant effect. In patients who require bridging anticoagulation with LMWH, a residual anticoagulant effect from LMWH is detected in 1 of 6 patients, and receiving therapeutic-dose LMWH is the strongest predictor of such an effect.
Variability of anti-β2 glycoprotein I antibodies measurement by commercial assays
Authors: Tincani Angela , Sanmarco Marielle , de Moerloose Philippe , Boffa Marie-Claire , Reber Guido 
Published: June 2005

SummaryThe aim of this study was to evaluate the agreement in assay results between commercial kits for the measurement of anti- β2glycoprotein I antibodies. Ten manufacturers provided one IgG and one IgM kit to three testing centres. Samples from patients with primary (n=13) or secondary (n=3) antiphospholipid syndrome (APS), from lupus patients without APS features (n=6) and from normal individuals (n=2) were tested in the three centres according to manufacturers’ instructions. Dilutions in normal serum of a pool made from positive patients’ samples (Forum Calibrators) and dilutions of humanized monoclonal antibodies (MoAbs) were used as additional calibrators. The calibration curves obtained with each calibrator differed widely between kits. The rate of positivity of patients’ samples varied from 7 to 16 for IgG and from 2 to 17 for IgM, depending on the kit. Perfect agreement occurred in 12/22 samples for IgG and 5/22 samples for IgM. Samples from normals were found negative by all kits. Between kits, cutoff values varied up to five fold when expressed in Forum Calibrators arbitrary units and up to three fold when expressed in MoAbs equivalents. Examination of discrepant samples indicated that about half of the discrepancies, scoring 8:2 and 9:1, involved the same few kits. In highly discrepant samples, some kits appeared as high responders as compared to others. In conclusion, with the exception of a few kits, agreement in assay results was acceptable. In conclusion, additional efforts are however necessary, especially concerning the way to assess the cutoff point and the adoption of a reference calibrator, in order to improve standardization of the assays.
An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome
Authors: Shitrit David , Peled Nir , Shitrit Ariella Bar-Gil , Meidan Silvia , Bendayan Daniel , Sahar Gidon , Kramer Mordechai R. 
Published: June 2005

SummaryD-dimer, a degradation product of fibrin, is being increasingly used as a marker and prognostic factor in various thrombotic diseases. Previous reports have shown that obstructive sleep apnea is associated with platelet activation and hypercoagulability. The aim of the study was to assess the potential role of the plasma D-dimer test in patients with obstructive sleep apnea. We designed a prospective group comparison study in a tertiary- care, university-affiliated medical center. One hundred and three patients of mean age 57 years (range 50–76 years) with symptoms suggestive of obstructive sleep apnea were included. Polysomnography was performed in all cases, and blood was collected for plasma D-dimer measurement by MiniQuant turbidmetric assay. The demographic and polysomnograph data were compared between patients with normal and high (>250 ng/ml) D-dimer levels. The group with higher D-dimer values had lower mean minimal oxygen saturation (72.1±16.4 vs. 81.7±11.6%, p=0.008) and a longer mean period of oxygen saturation below 90% (84.1±86.2 vs. 38.5±70.8 minutes, p=0.032). There was no correlation of respiratory disturbance index and sleep architecture with D-dimer values. We concluded that sleep apnea syndrome is associated with fibrinolytic activity. Oxygen desaturation seems to be one of the mediatory factors in the putative connection between obstructive sleep apnea and hypercoagulability state.
Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom
Authors: Soto Mónica , Escalante Teresa , Loría Gilbert D. , Arni Raghuvir , Gutiérrez José María , Rucavado Alexandra 
Published: June 2005

SummaryThrombocytopenia and platelet dysfunction occur in patients bitten by Bothrops sp snakes in Latin America. An experimental model was developed in mice to study the effects of B. asper venom in platelet numbers and function. Intravenous administration of this venom induces rapid and prominent thrombocytopenia and ex vivo platelet hypoaggregation. The drop in platelet numbers was primarily due to aspercetin, a protein of the C-type lectin family which induces von Willebrand factor-mediated platelet aggregation/agglutination. In addition, the effect of class P-III hemorrhagic metalloproteinases on the microvessel wall also contributes to thrombocytopenia since jararhagin, a P-III metalloproteinase, reduced platelet counts. Hypoaggregation was associated with the action of procoagulant and defibrin(ogen)ating proteinases jararacussin-I (a thrombin-like serine proteinase) and basparin A (a prothrombin activating metalloproteinase). At the doses which induced hypoaggregation, these enzymes caused defibrin(ogen)ation, increments in fibrin(ogen) degradation products and D-dimer and prolongation of the bleeding time. Incubation of B. asper venom with batimastat and α2-macroglobulin abrogated the hypoaggregating activity, confirming the role of venom proteinases in this effect. Neither aspercetin nor the defibrin(ogen)ating and hypoaggregating components induced hemorrhage upon intravenous injection. However, aspercetin, but not the thrombin-like or the prothrombin-activating proteinases, potentiated the hemorrhagic activity of two hemorrhagic metalloproteinases in the lungs.
In vitro expression demonstrates impaired secretion of the γAsn319, Asp320 deletion variant fibrinogen
Authors: Kani Satomi , Terasawa Fumiko , Lord Susan T. , Tozuka Minoru , Ota Hiroyoshi , Katsuyama Tsutomu , Okumura Nobuo 
Published: June 2005

SummaryThe hypodysfibrinogenemia Otsu is caused by the two-residue deletion,γAsn319 and γAsp320. Analysis of plasma or purified fibrinogen from the heterozygous propositus revealed that the amount of variant γ-chain was lower than that of normal γ-chain. In order to examine the basis for this difference, we transfected Chinese hamster ovary cells and established stable cell lines that expressed both chains, γΔ/γN, only the normal chain, γN, and only the variant chain, γΔ. We measured fibrinogen concentration of confluent cultures by ELISA. We found the ratios of the concentrations in the media to the concentrations in the cell lysates of γΔ, γΔ/γN, and γN-cells were 0.42, 0.60, and 1.00, respectively. We measured the concentrations of the γΔ and γN chains by densitometric analysis of samples following separation by SDS-PAGE and found the fraction of γΔ-chains in cell lysates was always greater than the fraction in the respective culture media. We examined the kinetics of fibrinogen synthesis, assembly and secretion in pulse-chase experiments, and found that the γΔ-chain was assembled into intact fibrinogen at a rate similar to assembly of the γN-chain into normal fibrinogen, but was secreted into the medium at a slightly slower rate than normal fibrinogen. Considered together, these experiments indicate secretion of the variant fibrinogen was slightly impaired. These results suggest that the reduced level of γΔ319,320 fibrinogen in the plasma of the Otsu patient arises from modestly impaired secretion of this variant fibrinogen.
Servants at the Gate: Eunuchs at the Court of al-Muqtadir
Authors: El-Cheikh Nadia Maria 
Published: June 2005

AbstractThis paper investigates the eunuch's institution in the court of the Abbasid caliph al-Muqtadir and seeks, first, to delineate the variety of functions that the eunuchs held in the early fourth/tenth century Abbasid court both in the harem and in ceremonial; second, it investigates the careers of the eunuchs Sāfī al-Huramī and Muflih al-Khādim al-Aswad, exploring their sources of authority and their various networks which allowed them to exercise a high degree of political influence. Le but de ce travail est d'étudier l'institution "Eunuque" au coeur de la cour Abbaside du caliphe al-Muqtadir. En premier lieu nous soulignons les fonctions multiples que les eunuques performaient dans la cour abbaside (début 4/10ème siècle) tant au sein du harem pendant le ceremonial royal. En second lieu nous explorons plus en détail les carrières des eunuques Sāfī al-Huramī et Muflih al-Khādim al-Aswad, identifiant les sources de leur pouvoir et les réseaux differents qui leur permirent d'éxercer une veritable influence politique.