bluuebunny/crossref_metadata_2025_split huggingface dataset:
Significant association with location of central venous line placement and risk of venous thrombosis in children
Authors: Male Christoph , Julian Jim A. , Massicotte Patricia , Gent Michael , Mitchell Lesley ,   for the PROTEKT Study Group
Published: July 2005

SummaryVenous thromboembolic events (VTE) in children are frequently associated with central venous lines (CVL). Identifying risk factors related to CVL management could potentially minimize CVL-related thrombotic complications. The objectives of the study were to assess whether CVL location, type, size, and duration of placement are associated with the incidence of VTE in children. The study was a prospective, multicentre cohort study in a general pediatric population requiring CVL. Data on CVL characteristics were documented prospectively using standardized case report forms. Outcome assessments were by i) clinical monitoring for symptomatic VTE which were confirmed by appropriate objective test, or ii) screening by venography at study exit. Among 158 children, 21 (13%) hadVTE. The incidence of VTE was increased with femoral CVL (32%) and subclavian CVL (27%) compared to brachial CVL (12%) and jugular CVL (8%;p=0.01). The incidence ofVTE was independent of CVL type (peripherally inserted central catheters, untunneled CVL, tunneled exteriorized CVL, subcutaneous ports; p=0.90), and CVL size (CVL diameter, p=0.42; number of CVL lumen, p=0.58). The incidence of VTE did not increase with duration of CVL placement: 0–5 days (17% VTE), 6–20 days (19%), 21–35 days (10%), and 36–50 days (11%,p=0.68). The incidence of CVL-relatedVTE may be reduced by preferred placement of CVL in brachial or jugular veins. The choice of CVL type and size does not significantly influence the risk of VTE. Short-term CVL are associated with a similar risk of VTE as longer-term CVL.
Quantification of thrombin activatable fibrinolysis inhibitor (TAFI) gene polymorphism effects on plasma levels of TAFI measured with assays insensitive to isoform-dependent artefact
Authors: Frère Corinne , Emmanuel Morange Pierre , Saut Noémie , Tregouet David Alexandre , Grosley Mariana , Beltran Jérôme , Juhan-Vague Irène , Alessi Marie-Christine 
Published: July 2005

SummaryReports have reappraised the genotype-dependent variation of Thrombin Activatable Fibrinolysis Inhibitor (TAFI), demonstrating that, in some enzyme-linked immunosorbent assays (ELISA), decreased antibody reactivity towards the TAFI 325 Ile isoform led to erroneous TAFI levels. Assays free of this artefact are required to evaluate the contribution of theTAFI gene polymorphisms toTAFI level variability.TAFI levels were measured in 209 individuals with both immunological and functional assays. Each assay was characterized, in particular for its reactivity towards the 325 Thr and Ile isoforms. Two ELISAs were found to have a lower reactivity towards the Ile isoform, leading to an overesti-mate of the magnitude of variation between two different genotypes. In contrast, one ELISA, as well as functional assays, was found to be free of genotype-dependent artefact constituting a reliable method to detect true quantitative variations of TAFI levels. Using these reliable methods, univariate and haplotype analyses revealed that TAFI gene polymorphisms explain 25% of TAFI level variability. This effect seems to be the consequence of the joint independent action of two polymorphisms, one in the 5’ (G-1102T) and the other in the 3’ region (T+1583A) of the TAFI gene.
Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction
Authors: Saldanha Carlota , Monteiro José , Perdigão Carlota , Martins e Silva J. , Sargento Luis 
Published: July 2005

SummaryThe objective of this study was to evaluate the long-term predictive value of the haemostatic,inflammatory and haemorheologic disturbances in transmural myocardial infarction (MI). Sixty-four (59 male) consecutive survivors of a MI, with a mean age of 58.3 ± 12.0 years, were followed over a period of 36 months. Eighteen patients had a cardiovascular event defined as the composite of death, non-fatal MI, unstable angina and stroke. The haemostatic (protein C activity-PtC, antithrombin III, plasminogen activator inhibitor-1), haemorheologic (blood fluidity and components, erythrocyte membrane fluidity) and inflammatory (polymorphonuclear elastase, leukocyte count) profiles were determined at hospital discharge, using standard methodology. Our results can be summarized as follow: (i) at hospital discharge, the subgroup of patients with events had higher leuko-cyte count (7833.0 ± 1696.0 vs. 10294.0 ± 3129.0; p= 0.011), lower PtC (100.65 ± 19.08 vs.81.25 ± 19.95;p = 0.002),and lower erythrocyte aggregation (14.26 ± 5.94 vs.11.47 ± 3.45;p = 0.031) in relation to the ones without events;(ii) By Cox regression the protein C activity lower tertile (OR 0.169; 0.045 – 0.628; p=0.008); erythrocyte membrane outer layer fluidity upper tertile (OR 0.067; 95% CI 0.011 – 0.393; p=0.003); and erythrocyte aggregation lower tertile (OR 0.182; 0.038 – 0.876; p= 0.034) were independent predictors of the composite endpoint. We can conclude that some haemostatic, haemorheologic and inflammatory disturbances,at hospital discharge,are long-term independent predictors of recurrent cardiovascular events in transmural myocardial infarction survivors.
Genotype-specific increase in plasma concentrations of activated coagulation factor VII in response to experimental inflammation
Authors: Held Claes , Ericsson Carl-Göran , Silveira Angela , Hamsten Anders , Tornvall Per , Bennermo Marie 
Published: July 2005

SummaryThere is evidence that infection and inflammation might trigger an acute coronary event, but the mechanisms are unclear. Activated factor VII (FVIIa) is a potent coagulant that is under genetic control and a potential determinant of the outcome of acute myocardial infarction. This study investigated the acute FVIIa response to experimental inflammation. Forty healthy men and women were vaccinated with 1 ml of Salmonella Typhii vaccine. Plasma levels of FVIIa, FVII antigen (FVIIag), tissue factor (TF) activity and thrombin-antithrombin complex (TAT) were measured at baseline and up to 24 hours after inoculation. All subjects were genotyped for the FVII gene Arg353Gln polymorphism. Plasma concentrations of FVIIa, but not FVIIag, increased significantly with a peak at 10 hrs after vaccination. At 24 hrs FVIIa levels had returned to baseline. The FVIIa response to vaccination was significantly greater in subjects with the ArgArg genotype compared with ArgGln subjects.TAT increased, butTF activity was unchanged after vaccination. The results are of interest from a mechanistic viewpoint, since one explanation for the link between infection and acute myocardial infarction might be activation of coagulation. However, there is a need for further studies of the role of infection and inflammation in haemostasis.
The antiplatelet effect of clopidogrel is not attenuated by statin treatment in stable patients with ischemic heart disease
Authors: Vinholt Pernille , Korsholm Lars , Risom Kristensen Søren , Hallas Jesper , Damkier Per , Mickley Hans , Svenstrup Poulsen Tina 
Published: July 2005

SummaryRecent studies suggest that cytochrome P450 (CYP) 3A4 metabolized statins attenuate the antiaggregatory effect of clopidogrel. We evaluated how CYP3A4 metabolized statins and non- CYP3A4 metabolized statins influence platelet aggregation when given concomitantly with clopidogrel. Sixty-six stable patients with ischemic heart disease were included in this parallel group study. All patients were on clopidogrel and aspirin. Thirty-three patients received a CYP3A4 metabolized statin (simvastatin or atorvastatin), and 33 were treated with a non- CYP3A4 metabolized statin (pravastatin). The antiplatelet effect of clopidogrel was assessed at inclusion and 21 days after statin discontinuation. Platelet function was evaluated by two methods 1) optical platelet aggregometry after stimulation with 20 and 30 μM ADP, and 2 and 4 mg/l collagen, respectively, 2) a Platelet FunctionAnalyzer-100. The primary effect measure was final platelet aggregation after stimulation with 20 μM ADP. No difference was observed between patients treated with a CYP3A4 metabolized statin and patients receiving a non-CYP3A4 metabolized statin (30% point (7–42) versus 20% point (9–32), p=0.83). Platelet aggregation was not improved by discontinuation of statins for 21 days. Indeed, we found that statin treatment given concomitantly with clopidogrel resulted in an improved platelet inhibition when compared to clopidogrel given alone. The antiplatelet effect of clopidogrel is not attenuated by concomitant treatment with a CYP3A4 metabolized statin in patients with clinical stable ischemic heart disease.
Tissue factor is regulated by epidermal growth factor in normal and malignant human endometrial epithelial cells
Authors: Kato Sumie , Pinto Mauricio , Carvajal Andrés , Espinoza Natalia , Monsó Carolina , Bravo Loreto , Villalon Manuel , Cuello Mauricio , Quest Andrew F. , Suenaga Akihiko , Brosens Jan J. , Owen Gareth I. 
Published: July 2005

SummaryTissue Factor (TF), the initiator of the extrinsic coagulation cascade, is overexpressed in a variety of cancers. TF is also expressed in normal human endometrium but little is known about its expression or regulation in endometrial cancer. We demonstrate herein that TF is expressed in the endometrial adenocarcinoma cell line Ishikawa. Furthermore, epidermal growth factor (EGF) induces a rapid and sustained increase in TF expression. Estradiol and progesterone had no effect on basal or EGF-induced TF expression in Ishikawa cells. In contrast to the pronounced and sustained upregulation at the protein level,EGF treatment elicited only a modest and transient increase in TF mRNA levels. This activity corresponded to the response observed from an exogenous TF promoter construct. However, the induction of TF was abrogated by cycloheximide as well as actinomycin-D, inhibitors or protein- and mRNA-synthesis, re-spectively, demonstrating that EGF mediates its effect through activation of the TF gene. Fractionation experiments showed that EGF increases TF presence in caveolin-1 containing membrane fractions. Coagulation and invasion assays were used to explore the physiological implications of TF regulation. The results demonstrate that EGF-mediated induction of TF increases the procoagulant activity and invasive potential of Ishikawa cells. Furthermore, immunocytochemistry confirmed that TF is regulated by EGF in primary cultures of normal endometrial epithelial cells and malignant tumor cells. In conclusion, EGF-mediated upregulation ofTF results in accumulation of this glycoprotein in caveolae-like membrane fractions and increased coagulative and invasive potential. Our results suggest that TF may play an integral role in endometrial carcinogenesis.
Prognostic factors for recurrence of venous thromboembolism (VTE) or bleeding during long-term secondary prevention of VTE with ximelagatran
Authors: Lundström Torbjörn , Wåhlander Karin , Billing Clason Solveig , Schulman Sam , Eriksson Henry ,   for the THRIVE III Investigators
Published: July 2005

SummaryThe oral direct thrombin inhibitor ximelagatran (24 mg twice daily) has been shown to significantly reduce the incidence of recurrent venous thromboembolism (VTE) vs. placebo over 18 months, with no significant influence on bleeding (THRIVE III). The influence of potential prognostic factors on the risk of recurrent VTE or major and/or minor bleeding and their impact on ximelagatran treatment was evaluated in theTHRIVE III study population. The effect of sex, age, body weight, renal function, malignancy, type of initialVTE event, and history of previousVTE events was investigated in the intention-to-treat population using Cox proportionate hazard modelling. Ximelagatran was administered to 612 patients and placebo to 611 patients. Within the placebo group, risk of recurrent VTE was higher among men than women (hazard ratio [HR]: 2.50,95% confidence interval [CI] 1.49, 4.17), and in patients with one or more than one previous VTE event (HR: 1.73, 95% CI 1.00, 2.99). There was a higher risk of bleeding among women than men in both the ximelagatran (HR: 1.49, 95% CI 1.06, 2.09) and placebo (HR: 1.48, 95% CI 1.01, 2.15) groups, and in placebo-treated patients with an initial pulmonary embolism (HR: 1.53, 95% CI 1.06, 2.23) compared to those with initial deep vein thrombosis. There were no significant interactions between treatment effect and any of the potential prognostic factors. In conclusion, the superior efficacy of ximelagatran vs. placebo was maintained in all subgroups. Long-term use of oral ximelagatran, without coagulation monitoring or dose adjustment, should be feasible and well tolerated in a wide cross-section of patients for the secondary prevention of VTE.
Congenital erythropoietin over-expression causes “anti-pulmonary hypertensive” structural and functional changes in mice, both in normoxia and hypoxia
Authors: Manz Daniel , Buchspies Daniela , Keller Stephan , Mehling Tanja , Voswinckel Robert , Quanz Karin , Ghofrani Hossein A. , Schermuly Ralph T. , Fink Ludger , Seeger Werner , Gassmann Max , Weissmann Norbert 
Published: July 2005

SummaryAcute alveolar hypoxia causes pulmonary vasoconstriction that matches lung perfusion to ventilation to optimize gas exchange. Chronic alveolar hypoxia induces pulmonary hypertension, characterized by increased muscularization of the pulmonary vasculature and right ventricular hypertrophy. Elevated erythropoietin (EPO) plasma levels increase hematocrit and blood viscosity and may affect structure and function of the pulmonary circulation. To differentiate between the direct effects of hypoxia and those linked to a hypoxia-induced increase in EPO/hematocrit levels, we investigated the lung vasculature in transgenic mice constitutively over-expressing EPO (termed tg6) upon exposure to normoxia and chronic hypoxia. Despite increased hematocrit levels (∼0.86),tg6 mice kept in normoxia did not develop selective right ventricular hypertrophy. The portion of vessels with a diameter of 51–95 μm and >155 μm was increased whereas the portion of small vessels (30–50 μm) was decreased. Pulmonary vascular resistance and the strength of hypoxic vasoconstriction measured in isolated perfused lungs were decreased. Vasoconstrictions induced by the thromboxane mimetic U46619 tended to be reduced. After chronic hypoxia (FiO2 = 0.10, 21days), vascular resistance and vasoconstrictor responses to acute hypoxia and U46619 were reduced in tg6 mice compared to wildtype controls. Chronic hypoxia increased the degree of pulmonary vascular muscularization in wildtype but not in tg6 mice that already exhibited less muscularization in normoxia. In conclusion, congenital over-expression of EPO exerts an “anti-pulmonary hypertensive” effect, both structurally and functionally, particularly obvious upon chronic hypoxia.
Endocytosis and storage of plasma factor V by human megakaryocytes
Authors: Suehiro Youko , Veljkovic Dragoslava Kika , Fuller Nola , Motomura Yasuaki , Massé Jean Marc , Cramer Elisabeth M. , Hayward Catherine P. M. 
Published: July 2005

SummaryFactor V is an essential coagulation cofactor that circulates in plasma and platelet α-granules where it is stored complexed to multimerin 1 (MMRN1). To gain insights into the origin and processing of human platelet factor V, and factor V-MMRN1 complexes, we studied factor V in cultured megakaryocytes. Factor V mRNA was detected in all megakaryocyte cultures. However, like albumin, IgG and fibrinogen, factorV protein was detectable only in megakaryocytes cultured with exogenous protein. The amount of factor V associated with megakaryocytes was influenced by the exogenous factorV concentration. Similar to platelet factor V, megakaryocyte factor V was proteolyzed and complexed with megakaryocyte-synthesized MMRN1. With secretagogues, megakaryocytes released factorV, IgG, fibrinogen and MMRN1. Immunofluorescent and electron microscopy confirmed factorV uptake by endocytosis and its trafficking to megakaryocyte α-granules. These data provide direct evidence that human megakaryocytes process plasma-derived factor V into α-granules and generate factor V-MMRN1 complexes from endogenously and exogenously synthesized proteins.
The post-thrombotic syndrome: incidence and prognostic value of non-invasive venous examinations in a six-year follow-up study
Authors: Heijer Martin den , Janssen Mirian C. H. , Vleuten Carine van der , Thien Theo , Wollersheim Hub , Roumen-Klappe Edith M. 
Published: July 2005

SummaryThe ability to predict severity of the post-thrombotic syndrome (PTS) early after acute deep-vein thrombosis (DVT) is limited. The aim of our study was to examine the incidence of PTS prospectively and to evaluate the predictive value of non-invasive venous examinations shortly after DVT for the development of PTS. In 93 patients with DVT thrombosis score (TS), reflux, venous outflow resistance (VOR) and calf muscle pump dysfunction (CMP) were examined prospectively. After one, two and six years patients were evaluated for PTS using the clinical scale of the CEAP-classification (PTS present ≥3 on a scale from 0 to 6). Area under the curves (AUC) were used to evaluate the predictive value of the non-invasive examinations at one and three months after diagnosis of DVT for future PTS. The cumulative incidence of PTS increased from 49% (32/65) after one year to 55% (36/65) and 56% (27/48) after two and six years, whereas the incidence of patients with PTS class 4 progressed from 20% after two years to 33% after six years. The prognostic value to predict PTS was highest for the combination of TS, VOR and reflux measured three months after diagnosis and showed anAUC of 0.77 (0.65−0.90) for PTS after one year. In conclusion, the incidence of PTS after DVT did not increase significantly after one year, whereas during longer follow-up the severity of PTS rose in patients with PTS. Moreover, measurement of TS, VOR and reflux three months after DVT could predict, with reasonable accuracy, the risk of PTS after one year of follow-up.
The contribution of the endothelium to the development of coagulation disorders that characterize Ebola hemorrhagic fever in primates
Authors: Hensley Lisa E. , Geisbert Thomas W. 
Published: July 2005

SummaryRecently, there have been substantdevelopments ial in the understanding of Ebola hemorrhagic fever pathogenesis, but there are still major gaps. These infections occur in underdeveloped areas of the world,and much of our knowledge of naturally occurring disease is derived from sporadic outbreaks that occurred decades in the past. Recently conducted laboratory animal studies have provided insight into Ebola pathogenesis and may help guide clinical investigations of disease using contemporary methodologies that were not available previously. A better understanding of the relevant host and viral factors that influence clinical and virologic outcome will be critical to our ability to combat this aggressive pathogen. This article reviews the most relevant information relating to the postulated pathogenesis of this disease, focusing on the role of the endothelium in contributing to the coagulation disorders that characterize Ebola hemorrhagic fever in primates. Some of the remaining and key unanswered questions relating to the role of the vascular system in the pathogenesis of this disease, that need to be addressed in further research, are highlighted.
Ethanol inhibits pulse pressure-induced vascular smooth muscle cell migration by differentially modulating plasminogen activator inhibitor type 1, matrix metalloproteinase-2 and -9
Authors: Cullen John P. , Sayeed Shariq , Kim Youngrin , Theodorakis Nicholas G. , Sitzmann James V. , Cahill Paul A. , Redmond Eileen M. 
Published: July 2005

SummaryWe investigated the effect of ethanol on the pulse pressure-induced expression of PAI-1 and MMP-2/9 in human smooth muscle cells (SMC). Human SMC were exposed to static or pulse pressure (25 mL/min; pulse pressure 106/50 mm Hg) conditions for 24 h in the absence or presence of ethanol (0.1-100 mM). SMC migration was then measured byTranswell migration assay. SMC exposed to pulse pressure demonstrated a significant increase in PAI-1 mRNA and protein expression (∼4-fold and ∼3-fold) concomitant with a 3- and 8-fold increase in MMP-2 and MMP-9 protein, respectively. Ethanol dose-dependently inhibited the pulse pressure-induced SMC migration with complete inhibition observed at 20 mM. There was no effect of ethanol on basal PAI-1 or MMP-2/9 in SMC under static conditions. However, ethanol significantly enhanced the pulse pressure- induced PAI-1 mRNA and protein expression (2.2±0.52 fold and 2.5±0.27 fold, for 10 mM), respectively. In contrast, ethanol dose-dependently inhibited the pulse pressure-induced increases in MMP-9 protein and pro-MMP-9 activity and to a lesser extent MMP-2 mRNA and protein and pro-MMP-2 activity, with significant inhibition observed at 1 mM. These data provide a molecular mechanism mediating the inhibitory effect of ethanol on pulse-pressure-induced SMC migration and may be relevant to the cardioprotective effects of ethanol in vivo.
Interleukin-1 gene cluster variants and abdominal aortic aneurysms
Authors: Marculescu Rodrig , Sodeck Gottfried , Domanovits Hans , Hobusch Gerhard , Exner Markus , Heinzl Harald , Huber Kurt , Mannhalter Christine , Minar Erich , Wagner Oswald , Schillinger Martin 
Published: July 2005

SummaryInflammation is a key factor in the pathogenesis of abdominal aortic aneurysms (AAA). Interleukin 1 (IL-1), a fundamental regulator of the inflammatory cascade, has been shown to be involved in this process. Several functional polymorphisms in the IL-1 gene cluster are known. In this matched case-control study, we investigated a potential association between six genetic variants in IL-1 and IL-1 receptor antagonist (IL-1 RN) withAAA. We enrolled 405 individuals, 135 consecutive patients with AAA were individually age- and sex-matched to 270 patients with coronary artery disease (CAD). Traditional cardiovascular risk factors and IL-1 genotypes were determined, and the distribution of six single nucleotide polymorphisms were compared between patients and controls by multivariable conditional logistic regression analysis: IL-1A (-889) C>T, IL-1A (+4845) G>T, IL-1B (-511) C>T, IL-1B (-31) C>T, IL-1B (+3954) C>T and IL-1RN (+2018) C>T. IL-1A (-889) C>T and IL-1A (+4845) G>T (kappa 0.98, 95% CI 0.96 to 1.00), and IL-1B (-511) C>T and IL-1B (-31) C>T (kappa 0.98, 95% CI 0.96 to 1.00) were closely linked, therefore IL-1A (-889) C>T and IL-1B (-31) C>T were not considered for further analyses. None of the 4 remaining polymorphisms showed a significant association with AAA: IL-1RN (+2018) C>T (p=0.061), IL-1B (+3954) C>T (p=0.51), IL-1B (-511) C>T (p=0.61) and IL-1A (+4845) G>T (p=0.81). No significant first-degree interactions between the genetic variants andAAA were detected. In conclusion, these six genetic variants in the interleukin-1 gene cluster do not seem to play a clinically relevant role in the pathogenesis of AAA, although we cannot rule out the existence of higher degree gene-gene or gene-environment interactions.