bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is Colour Doppler Ultrasound a Sensitive Screening Method in Diagnosing Deep Vein Thrombosis after Hip Surgery ?
Authors: Magnusson Marie , Eriksson Bengt I , Kãlebo Peter , Sivertsson Ramon 
Published: July 2018

SummaryPatients undergoing orthopedic surgery are at high risk of developing deep vein thrombosis. One hundred and thirty-eight consecutive patients undergoing total hip replacement or hip fracture surgery were included in this study. They were surveilled with colour Doppler ultrasound (CDU) and bilateral ascending contrast phlebography. The prevalence of proximal and distal DVT in this study was 5.8% and 20.3% respectively.CDU has a satisfactory sensitivity in patients with symptomatic deep vein thrombosis, especially in the proximal region. These results could not be confirmed in the present study of asymptomatic patients. The sensitivity was 62.5% (95% confidence interval: C.I. 24-91%) and the specificity 99.6% (C.I. 98-100%) for proximal DVT; 53.6% (C.I. 34-73%) and 98% (C.I. 96-99%) respectively for distal thrombi. The overall sensitivity was 58.1% (C.I. 39-75%) and the specificity 98% (C.I. 96-99%). The positive predictive value was 83.3% (C.I. 36-99%) and 75% (C.I. 51-91%) for proximal and distal DVT respectively. The negative predictive value was 98.9% (C.I. 98-100%) and 94.9% (C.I. 92-98%) for proximal and distal DVT respectively. The results of this study showed that even with a highly specialised and experienced investigator the sensitivity of CDU was too low to make it suitable for screening purposes in a high risk surgical population.
The Gla26 Residue of Protein C Is Required for the Binding of Protein C to Thrombomodulin and Endothelial Cell Protein C Receptor, but not to Protein S and Factor Va
Authors: Nishioka Junji , Ido Masaru , Hayashi Tatsuya , Suzuki Koji 
Published: July 2018

SummaryA functionally defective protein C (PC)-Mie, detected in the plasma of a patient with hereditary thrombophilia, has Lys substituted for γ-carboxyglutamic acid (Gla)26 residue. The activation rate of PC-Mie by Protac or thrombin in the absence of Ca2+ and that by thrombin with native thrombomodulin (TM), recombinant soluble truncated TM or on cultured endothelial cells in the presence of Ca2+ were all apparently lower than that of normal PC. The anticoagulant activity of Protac-activated PC (APC)-Mie on the plasma clotting time and the rate of inactivation of factor Va by APC-Mie in the presence of phospholipids were lower than those seen with normal APC. APC-Mie and normal APC bound equally to protein S and to biotinyl-factor Va. However, neither PC-Mie nor APC-Mie bound to phospholipids and to cultured human endothelial cells. It was similar to that observed with Gla-domainless PC/APC, but different from that seen with normal PC/APC. These results suggest that Gla26-dependent conformation is required for the binding of PC/APC to phospholipids, TM and the surface of endothelial cell PC/APC receptor, but not to protein S and factor Va.
Low Molecular Weight Heparin Is Responsible for the Anti-Xa Activity of Desmin 370
Authors: Brieger David , Dawes Joan 
Published: July 2018

SummaryDermatan sulphate does not catalyse the inactivation of factor Xa. However, the low molecular weight (LMW) dermatan sulphate Desmin 370 has been shown to generate circulating anti-Xa activity following administration to humans. Using a single batch of Desmin 370, we measured 3 U/mg of anti-Xa activity by amidolytic assay in vitro. The material responsible for this activity had a lower molecular weight range (6000 and 1800 Da) than Desmin 370 and was more highly sulphated than the bulk of the drug. Heparinase digestion of Desmin 370 eliminated 90% of the in vitro anti-Xa activity without significantly interfering with its ability to potentiate inactivation of thrombin by HCII, suggesting that the anti-Xa activity is not due to dermatan sulphate and is probably heparin. When 125I-labelled Desmin 370 together with 40 mg/kg carrier drug was administered intravenously to a rabbit, anti-Xa activity was readily detectable in the plasma for up to 10 h and had a longer half-life than the sulphated radiolabel. Most of this anticoagulant activity was recovered from the plasma by Polybrene affinity chromatography and was probably a sulphated glycosaminoglycan. Administration of the heparinase-digested drug to a rabbit resulted in 70% less anti-Xa activity than the undigested drug. We conclude that Desmin 370 contains detectable quantities of biologically active low molecular weight heparin, which is responsible for persistent anti-Xa activity following intravenous administration.
Echinomycin Suppresses the Pyrogenic Effects of Endotoxin and Interleukin- lβ in Human Endothelial Cells and Peripheral Blood Mononuclear Cells
Authors: Herbert Jean-Marc , Lalé Alain , Pereillo Jean-Marie , Derocq Jean-Marie , Casellas Pierre 
Published: July 2018

SummaryEndotoxin (LPS) and interleukin-1(3 (IL-iβ) increased in a dose-dependent manner the expression of tissue factor, an ubiquitous membrane-anchored glycoprotein that initiates blood coagulation at the surface of human umbilical vein endothelial cells (HUVEC) and human peripheral blood mononuclear cells (PBMC). Echinomycin, a cyclic octapeptide of microbial origin strongly inhibited LPS- and IL-1β-induced tissue factor expression in HUVEC and PBMC with IC50 values in the subnanomolar range at the same time it reduced LPS and IL-iβ-induced expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on HUVEC (IC50 = 0.4 ± 0.1 and 0.3 ± 0.2 nM respectively). Echinomycin also reduced LPS-induced secretion of IL-iβ and IL-6 by human PBMC (IC50 = 10 ± 2 and 3 ± 0.5 nM respectively). These observations demonstrate that echinomycin protects endothelial cells and PBMC from the pyrogenic effect of LPS and 1β.
Thrombosis in Cancer Patients Treated with Hematopoietic Growth Factors - A Meta-Analysis
Authors: Barbul T , Finazzi G , Grassi A , Marchioli R 
Published: July 2018

SummaryHematopoietic colony-stimulating factors (CSFs) are largely used in patients with cancer undergoing cytotoxic treatment to accelerate neutrophil recovery and decrease the incidence of febrile neutropenia. Clinical practice guidelines for their use have been recently established (1), taking into account clinical benefit, but also cost and toxicity. Vascular occlusions have been recently reported among the severe reactions associated with the use of CSFs, in anedoctal case reports (2, 3), consecutive case series (4) and randomized clinical trial (5, 6). However, the role of CSFs in the pathogenesis of thrombotic complications is difficult to ascertain, because pertinent data are scanty and widely distributed over a number of heterogenous investigations. We report here a systematic review of relevant articles, with the aims to estimate the prevalence of thrombosis associated with the use of CSFs and to assess if this rate is significantly higher than that observed in cancer patients not receiving CSFs.
Tissue Factor Induces Migration of Cultured Aortic Smooth Muscle Cells
Authors: Sato Yuichiro , Asada Yujiro , Marutsuka Kousuke , Hatakeyama Kinta , Sumiyoshi Akinobu 
Published: July 2018

SummaryTissue factor (TF) plays a key role as a primary initiator on the extrinsic coagulation cascade. Recently, upregulation of TF has been reported in human atherosclerotic lesions. We investigated the effects of TF on migration and proliferation of cultured smooth muscle cells (SMCs) from rabbit aortas. We tested three kinds of recombinant human TF (L-TF: the full length of TF with relipidation, NL-TF: the full length of TF without relipidation, and S-TF: a soluble form of TF1-219). Only L-TF had coagulant activity. All kinds of TF showed the chemotactic migration activity for SMCs. The migration ability of TFs was comparable to those of platelet-derived growth factor (PDGF)-BB and basic fibroblast-growth factor (bFGF), and was inhibited by anti-TF polyclonal and monoclonal antibodies. On the other hand, none of the forms of TF induced SMC proliferation. These results indicate that TF is not only a coagulation factor but also a strong chemotactic factor for vascular SMCs, and suggest that TF could play an important role in atherogenesis as well as in hemostasis and thrombosis.
“Pseudo Homozygous” Activated Protein C Resistance due to Double Heterozygous Factor V Defects (Factor V Leiden Mutation and Type I Quantitative Factor V Defect) Associated with Thrombosis: Report of Two Cases Belonging to Two Unrelated Kindreds
Authors: Simioni Paolo , Scudeller Alberta , Radossi Paolo , Gavasso Sabrina , Girolami Bruno , Tormene Daniela , Girolami Antonio 
Published: July 2018

SummaryTwo unrelated patients belonging to two Italian kindreds with a history of thrombotic manifestations were found to have a double heterozygous defect of factor V (F. V), namely type I quantitative F. V defect and F. V Leiden mutation. Although DNA analysis confirmed the presence of a heterozygous F. V Leiden mutation, the measurement of the responsiveness of patients plasma to addition of activated protein C (APC) gave results similar to those found in homozygous defects. It has been recently reported in a preliminary form that the coinheritance of heterozygous F. V Leiden mutation and type I quantitative F. V deficiency in three individuals belonging to the same family resulted in the so-called pseudo homozygous APC resistance with APC sensitivity ratio (APC-SR) typical of homozygous F. V Leiden mutation. In this study we report two new cases of pseudo homozygous APC resistance. Both patients experienced thrombotic manifestations. It is likely that the absence of normal F. V, instead of protecting from thrombotic risk due to heterozygous F. V Leiden mutation, increased the predisposition to thrombosis since the patients became, in fact, pseudo-homozygotes for APC resistance. DNA-analysis is the only way to genotype a patient and is strongly recommended to confirm a diagnosis of homozygous F. V Leiden mutation also in patients with the lowest values of APC-SR. It is to be hoped that no patient gets a diagnosis of homozygous F. V Leiden mutation based on the APC-resi-stance test, especially when the basal clotting tests, i.e., PT and aPTT; are borderline or slightly prolonged.
Antibodies to Prothrombin Imply a Risk of Myocardial Infarction in Middle-Aged Men
Authors: Vaarala Outi , Puurunen Marja , Mänttäri Matti , Manninen Vesa , Aho Kimmo , Palosuo Timo 
Published: July 2018

SummaryAntiphospholipid antibodies in patients with “antiphospholipid syndrome” may be directed at least in part against plasma phospholipid-binding proteins, such as Β2-glycoprotein I or prothrombin, which are involved in the control of thrombosis and haemostasis. IgG-class antibodies against prothrombin and Β2-glycoprotein I were measured by enzyme-linked immunoassay in initially healthy middle-aged dyslipid-aemic men (non-high-density lipoprotein >5.2 mml/1). Serum samples had been drawn at entry to a 5-year coronary primary-prevention trial with gemfibrozil from 106 subjects who experienced either a non-fatal myocardial infarction or cardiac death during the follow-up and from 106 subjects without coronary episodes, matched for treatment group (gemfibrozil/placebo) and geographical area.The antiprothrombin antibody level, as expressed in optical density units, was significantly higher in patients than in controls (0.26 ±0.17 versus 0.22 ±0.09; p<0.02). A high level of antiprothrombin antibodies (highest tertile of distribution) predicted a 2.5-fold increase in the risk (95% confidence interval 1.2-5.3) of myocardial infarction or cardiac death. The distribution of IgG-class antibodies against (Β2-glycoprotein I did not differ significantly between cases and controls. The joint effect of antiprothrombin antibodies and other factors associated with hypercoagulative state: triglyceride level, lipoprotein(a) and smoking, was multiplicative for the risk. Antiprothrombin antibodies are a new immunological predictor of myocardial infarction and the effect of these antibodies may be mediated by hypercoagulative mechanisms.
Interventional Thermal Injury of the Arterial Wall: Unfolding of von Willebrand Factor and Its Increased Binding to Collagen after 55° C Heating
Authors: Post Mark J , de Graaf-Bos Anke N , Posthuma George , de Groot Philip G , Sixma Jan J , Borst Cornelius 
Published: July 2018

Summary
Purpose. Thermal angioplasty alters the thrombogenicity of the arterial wall. In previous studies, platelet adhesion was found to increase after heating human subendothelium to 55° C and decrease after heating to 90° C. In the present electron microscopic study, the mechanism of this temperature-dependent platelet adhesion to the heated arterial wall is elucidated by investigating temperature-dependent conformational changes of von Willebrand factor (vWF) and collagen types I and III and the binding of vWF to heated collagen.
Methods. Purified vWF and/or collagen was applied to electron microscopic grids and heated by floating on a salt-solution of 37° C, 55° C or 90° C for 15 s. After incubation with a polyclonal antibody against vWF and incubation with protein A/gold, the grids were examined by electron microscopy.
Results. At 37° C, vWF was coiled. At 55° C, vWF unfolded, whereas heating at 90° C caused a reduction in antigenicity. Collagen fibers heated to 37° C were 60.3 ± 3.1 nm wide. Heating to 55° C resulted in the unwinding of the fibers, increasing the width to 87.5 ± 8.2 nm (p < 0.01). Heating to 90° C resulted in denatured fibers with an enlarged width of 85.1 ± 6.1 nm (p < 0.05). Heating of collagen to 55° C resulted in an increased vWF binding as compared to collagen heated to 37° C or to 90° C. Incubation of collagen with vWF, prior to heating, resulted in a vWF binding after heating to 55° C that was similar to the 37° C binding and a decreased binding after 90° C.
Conclusions. After 55° C heating, the von Willebrand factor molecule unfolds and collagen types I and III exhibit an increased adhesiveness for von Willebrand factor. Heating to 90° C denatures von Willebrand factor and collagen. The conformation changes of von Willebrand factor and its altered binding to collagen type I and III may explain the increased and decreased platelet adhesion to subendothelium after 55° C and 90° C heating, respectively.
Species Specificity of Anti-β2 Glycoprotein I Autoantibodies and Its Relevance to Anticardiolipin Antibody Quantitation
Authors: Arvieux J , Darnige L , Hachulla E , Roussel B , Bensa J C , Colomb M G 
Published: July 2018

SummarySome patients suspected of having antiphospholipid antibody syndrome (APS) were found to be positive for anti-β2 glycoprotein I (β2GPI) antibodies despite negative results for antibodies to cardiolipin (ACA). Since the major source of β2GPI in the ACA assay is animal (usually bovine) serum, we studied the influence on ACA quantitation of the species specificity of anti-β2GPI antibodies from patients with various autoimmune disorders, mostly systemic lupus erythematosus and primary APS. Ninety-seven sera were selected based on IgG (n = 76) or IgM (n = 64) positivity by ELISA using γ-irradiated plates coated with human or bovine purified β2GPI. A higher proportion of IgM (43.7%) than IgG (7.9%) reacted to human, but not bovine, β2GPI. Furthermore, from the samples reactive to both proteins, the ratio of antibody level against bovine to that against human β2GPI was 1.08 ± 0.58 for IgG and 0.58 ± 0.3 for IgM (p <10−5). IgG and IgM ACA were detected in 78 and 40 sera, respectively; concordance between the two ELISAs for ACA and anti-β2GPI antibodies was 94% for IgG and 75% for IgM. Out of 28 IgM showing recognition restricted to human β2GPI, 21 were missed by the ACA assay, possibly because of lower concentrations of β2GPI in those patients’ sera. The antibody reactivity pattern towards human and bovine β2GPI of individual sera showed no variation with time and was related to the relative antibody avidity for each protein. A murine anti-human β2GPI monoclonal antibody, 9G1, that cross-reacts with bovine β2GPI, competed to a large extent with the patients’ anti-β2GPI antibody binding sites whatever isotype involved or protein recognized. Therefore, anti-β2GPI antibodies of IgM isotype display a marked preference for human compared to bovine β2GPI responsible for frequent inconsistencies in the ACA assay.
Evaluation of a Low Molecular Weight Modulator of Human Plasminogen Activator Inhibitor-1 Activity
Authors: Charlton Peter A , Faint Richard W , Bent Fiona , Bryans Justin , Chicarelli-Robinson Inês , Mackie Ian , Machin Samuel , Bevan Paul 
Published: July 2018

SummaryA critical component in the regulation of thrombus formation and clearance is the balance between tissue plasminogen activator (tPA) and plasminogen activator inhibitor type-1 (PAM). An increase in the plasma concentration of PAH has been proposed as a risk factor in thrombotic disease. Inhibition of PAI-1 activity may have utility in the treatment of thromboembolic disease. We report here the evaluation of three diketopiperazine-based low molecular weight inhibitors of PAI-1 activity (XR334, XR1853 and XR5082). In vitro these compounds reversed the inhibitory effects of PAI-1 against both tPA and urokinase (UK) (IC50:5 to 80 μM). In contrast, other serpin-serine protease interactions, including α1-antitrypsin-trypsin, α2-antiplasmin-plasmin and antithrombin-thrombin, were not affected, neither did these inhibitors affect global tests of haemostasis. In the light of this promising in vitro profile these compounds were evaluated in a standard radioisotopic assay of clot lysis in whole rat blood following intravenous administration. In this assay these compounds dose-dependently enhanced fibrinolysis ex vivo. After intravenous bolus administration XR334, XR1853 and XR5082 at 5 mg/kg increased clot lysis by 32.0 ± 5.1% SEM (n = 25, p <0.01), 36.7 ± 3.5% SEM (n = 36, p <0.01) and 60.0 ± 2.8% SEM (n = 17, p <0.01) respectively compared to vehicle. Intravenous infusion of these compounds (1 mg/kg/min for 20 min) significantly prolonged (approximately twofold) the time to blood vessel occlusion in the rat electrically-stimulated carotid artery thrombosis model. Thus, these low molecular weight inhibitors of PAI-1 activity enhanced fibrinolysis ex vivo and protected against thrombus formation in the rat.
Development of Large Platelet Aggregates from Small Aggregates as Determined by Laser-light Scattering: Effects of Aggregant Concentration and Antiplatelet Medication
Authors: Tohgi Hideo , Takahashi Hiroaki , Watanabe Katsumi , Kuki Hiroyuki , Shirasawa Yoshiaki 
Published: July 2018

SummaryParticle-counting methods that employ light scattering (LS) quantify changes in the number of platelet aggregates of different sizes after the application of an aggregating stimulus. Using the LS method, we studied the effects of aggregant concentration, aspirin administration, and ticlopidine administration on aggregate formation and compared the results with those obtained using the conventional optical density (OD) method. Subjects were 47 controls, 31 patients treated with aspirin (330 mg/day), and 37 patients treated with ticlopidine (200 mg/day). Platelet aggregation after stimulation by 0.5, 1.0 or 5.0 μM ADP, or 0.5, 1.0 or 2.0 μg/ml collagen was determined using both methods. Using the LS method, small (9-25 μm), medium (25-50 μm), and large (50-70 μm) aggregates were counted. In patients untreated with antiplatelet medication, greater concentrations of ADP or collagen generated larger aggregates. Generation of small and medium-sized aggregates showed a significant positive correlation with OD levels after stimulation with 0.5 or 1.0 μM ADP, or 0.5 or 1.0 μg/ml collagen. In patients treated with aspirin, the development of small aggregates into large aggregates was inhibited. Thus, the number of small aggregates increased. Inhibition induced by aspirin was more effective against aggregation after stimulation with collagen than with ADP. In patients treated with ticlopidine, small and medium-sized aggregate formation was inhibited after stimulation with low concentrations of ADP or collagen, but was promoted after stimulation with high aggregant concentrations. The capability of the LS method to quantify different sizes of aggregates after stimulation with low concentration agonists may facilitate investigation of the aggregation process, and of how this process is affected by antiplatelet agents.
Influence of Metabolic Control on Thromboxane Biosynthesis and Plasma Plasminogen Activator Inhibitor Type-1 in Non-insulin-dependent Diabetes mellitus
Authors: Davì Giovanni , Belvedere Mario , Vingneri Sergio , Catalano Isabella , Giammarresi Carlo , Roccaforte Salvatore , Consoil Agostino , Mezzetti Andrea 
Published: July 2018

SummaryWe have previously shown that tight metabolic control by insulin therapy reduced thromboxane-dependent platelet activation in noninsulin-dependent diabetes mellitus (NIDDM) patients. The present study was undertaken to determine whether a similar effect could be obtained without switching diabetics in secondary failure to insulin treatment. For this purpose, we gave strict diet and exercise advise program and adjusted on a weekly basis the oral antidiabetic therapy (glipizide) that 26 patients with NIDDM had been given over the previous months.Basal measurements of urinary ll-dehydro-TXB2 and PAI-1 confirmed previous findings of enhanced levels of these parameters in NIDDM patients with macrovascular disease in comparison to age-and sex-matched controls. After 2-6 weeks, 16 patients achieved tight metabolic control associated with significant reduction of both thromboxane biosynthesis and PAI-1 levels; 10 patients remained in poor control and no significant decrease of both parameters was observed.We conclude that reduction of in-vivo platelet activation and PAI-1 antigen levels after metabolic improvement obtained by frequent reassessment of sulphonylurea therapy together with strict diet and exercise programs may have beneficial effects on the progression of diabetic micro- and macrovascular disease.
Factor V Leiden, Antiphospholipid Antibodies and Thrombosis in Systemic Lupus Erythematosus
Authors: Fijnheer R , Horbach D A , Donders R C J M , Vilé H , Oort E v , Nieuwenhuis H K , Gmelig-Meijling F H J , de Groot Ph G , Derksen R H W M 
Published: July 2018

SummaryThromboembolic complications are frequently observed in patients with systemic lupus erythematosus (SLE). Significant associations have been reported between these complications and the presence of antiphospholipid antibodies, notably the lupus anticoagulant and anti-cardiolipin antibodies. Factor V Leiden is a genetic disorder associated with an increased risk of venous thrombosis. We studied these factors in 173 patients with SLE in relation to both arterial and venous thrombosis. The frequency of factor V Leiden in SLE patients is comparable to that in the Dutch population (5%) and a risk factor for venous thrombosis (odds ratio 4.9; Cl 1.2-19.6), but not for arterial thrombosis. The lupus anticoagulant is a risk factor for both arterial thrombosis (odds ratio 7.1; Cl 2.9-17.4) and venous thrombosis (odds ratio 6.4; Cl 2.7-15.4). From multivariate analysis, both the lupus anticoagulant and factor V Leiden appeared independent risk factors for venous thrombosis.