bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular risk factors and global risk of fatal cardiovascular disease are positively correlated between partners of 802 married couples from different European countries
Authors: Castelnuovo Augusto Di , Quacquaruccio Gianni , Jozef Arnout , Cappuccio Francesco Paolo , Lorgeril Michel de , Dirckx Carla , Donati Maria Benedetta , Krogh Vittorio , Siani Alfonso , van Dongen Marten , Zito Francesco , Gaetano Giovanni de , Iacoviello Licia ,   European Collaborative Group of the IMMIDIET Project
Published: October 2007

SummaryShared environmental factors may confer to spouses a similar risk for cardiovascular disease. We aimed at investigating in pairs the concordance in risk factors for cardiovascular disease and in global risk of cardiovascular events. In the framework of the IMMIDIET Project, married couples, recruited randomly from general practice, were studied. One thousand six hundred and four apparently healthy subjects aged 25–74 years from three different European populations were enrolled. Individual cardiovascular risks were estimated using SCORE risk equations. Age was strongly correlated within couples (r=0.86, P<0.0001). In multivariate model, within-pair correlation was high for social status (r=049; percentage of explained variation=24%) and percent of calories from lipids (r=0.34; 12%). Concerning conventional metabolic risk factors, percentage of explained variation varied from 0.5% (triglycerides) to 11% (glucose). Among new risk factors, activated factor VII showed the strongest correlation (r=0.28) and C-reactive protein the lowest (r=0.13). Either total, coronary or non-coronary risk estimates at 10 years were strongly correlated within pairs: the risk of a member explained about two thirds of the cardiovascular risk of the partner. Spouse pairs share common lifestyle habits, common and new metabolic risk factors and the predicted global risk of cardiovascular events. If the individual risk of a person is influenced by the risk of his/her partner, decreasing the risk in a member of the pair should also decrease the risk in the partner. These concepts may have important public health consequences in targeting screening or disease prevention measures towards partners of people with cardiovascular risk.
Activated protein C downregulates p38 mitogen-activated protein kinase and improves clinical parameters in an in-vivo model of septic shock
Authors: Nold-Petry Claudia , Fischer Doris , Richter Bernd , Blaheta Roman , Pfeilschifter Josef , Muhl Heiko , Schranz Dietmar , Veldman Alex , Nold Marcel 
Published: October 2007

SummaryDespite the success of the anti-coagulant protease protein C (PC) in treating septic shock in humans, the signaling pathways used are still unclear. To explore the effects of treatment with PC zymogen and its activated form aPC in a setting of sepsis, we employed a piglet model of endotoxic shock. In the aPC group, we observed a 65%-90% reduction in plasmaTNF-alpha levels and a concomitant clinical improvement. Unexpectedly, administration of aPC also resulted in stabilization of the plasma pH above 7.2. Moreover, phosphorylated p38 mitogen-activated protein kinase (p38MAPK) was virtually absent in the livers of those piglets receiving aPC. In cultured human umbilical vein endothelial cells, we observed that nanomolar concentrations of PC and aPC inhibited the phosphorylation of p38MAPK. Furthermore, we showed that the regulation of the pro-apoptotic cell cycle regulator p53 by PC and aPC is dependent on the reduction of p38MAPK activation. The transduction of these effects involves all three receptors associated with protein C signaling, namely endothelial protein C receptor, protease-activated receptor 1, and sphingosine 1-phosphate receptor 1. Ultimately, this study elucidates novel signaling pathways regulated by protein C and emphasises the pivotal importance of its multiple modes of action beyond anticoagulation. APC’s clinical success may, in part, be due to p38MAPK inhibition.
Polymorphisms in the endothelial protein C receptor gene and thrombophilia
Authors: Medina Pilar , Navarro Silvia , Estellés Amparo , España Francisco 
Published: October 2007

SummaryThe protein C anticoagulant pathway plays a crucial role as a regulator of the blood clotting cascade. Protein C is activated on the vascular endothelial cell membrane by the thrombin-thrombomodulin complex. Once formed, activated protein C (APC) down-regulates thrombin formation by inactivating factors (F)Va and FVIIIa. Endothelial protein C receptor (EPCR) is able to bind protein C and increase the rate of protein C activation. Normal APC generation depends on the precise assemblage, on the surface of endothelial cells, of thrombin, thrombomodulin, protein C and EPCR.Therefore, any change in the efficiency of this assemblage may cause reduced/increased APC generation and modify the risk of thrombosis. This review highlights the different mutations/polymorphisms reported in the EPCR gene and their association with the risk of thrombosis.
Invasive procedures in the outpatient setting: Managing the short-acting acenocoumarol and the long-acting phenprocoumon
Authors: Hutten Barbara , Péquériaux Nathalie , de Vries-Goldschmeding Hanneke , Räkers Emmy , Levi Marcel , van Geest-Daalderop Johanna 
Published: October 2007

SummaryTreatment with vitamin K antagonists (VKAs) has to be interrupted when invasive procedures are planned. We compared various methods of interruption in patients on acenocoumarol or phenprocoumon in a prospective study. In patients on acenocoumarol (n=141), 99 stopped three days before the intervention and 42 stopped two days before. All patients on phenprocoumon (n=111) received vitamin K two days before the intervention, and 55 of these patients discontinued phenprocoumon, whereas 56 did not stop. In a subset of 30 patients we determined International Normalized Ratios (INRs) and coagulation factors II,VII, X and protein C. The mean INR after stopping acenocoumarol for three days was significantly lower than after two days (1.1 vs. 1.3, p=<0.0001), but its clinical relevance may be trivial. In patients using phenprocoumon, the mean INR on the day of the intervention was only slightly lower after stopping the VKAs (1.5 vs. 1.6, p=0.0407), but a similar proportion of patients had an INR ≤1.4. On the day of the intervention, in the acenocoumarol group mean plasma levels of all coagulation factors were higher than 50% and in the phenprocoumon group higher than 25%. We conclude that acenocoumarol can be stopped two days before an invasive procedure that is associated with a low or moderate bleeding risk and three days before an intervention with a higher bleeding risk. For phenprocoumon, administration of vitamin K two days before an intervention results in an acceptable INR during the intervention, regardless whether phenprocoumon is interrupted or not.
Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis
Authors: Falcó Cristina , Simó María , Ferrando Fernando , Mira Yolanda , Todolí José , España Francisco , Corella Dolores , Vayá Amparo 
Published: October 2007

SummaryIt is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT).We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed. After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases than in controls (P=0.013; P=0.012; P=0.013; P=0.028, respectively). When the risk of DVT associated with these variables (using cut-offs that corresponded to the mean plus one SD of the control group) was estimated, EA>8.2 and PV>1.28 mPa·s were significantly associated with DVT even further adjustment for lipids and obesity (OR=2.78, P=0.004; OR=1.91, P=0.024, respectively). However, PV did not remain statistically significant after additional adjustment for Fg. When we consider together all the analyzed variables in order to control every variable for each other, TG>175 mg/dl (OR=3,2,P=0.004) and BMI>30 kg/m2 (OR=3.5, P=0.003), were also independently associated with a greater risk of DVT. Our results suggest that increased EA constitute an independent risk factor for DVT. However, when associated to hyperlipidaemia and obesity it further increases thrombotic risk.
Platelet-associated LIGHT (TNFSF14) mediates adhesion of platelets to human vascular endothelium
Authors: Stellos Konstantinos , May Andreas , Shankar Vijay , Kurz Kerstin , Katus Hugo , Celik Sultan , Langer Harald , Gawaz Meinrad , Dengler Thomas 
Published: October 2007

SummaryLIGHT (TNFSF 14) belongs to the tumor necrosis factor super-family and is expressed by different types of immune cells. Recently, LIGHT was found to be associated with platelets and released upon activation. Activation of endothelial cells by recombinant LIGHT results in pro-inflammatory and pro-thrombotic changes, qualitatively comparable to effects of CD40 ligand. Given the important role of platelet-associated CD40 ligand in vascular inflammatory responses we investigated the role of LIGHT for activation of endothelium and adhesion of platelets to endothelial cells. Expression of LIGHT was detected on thrombocytes upon exposure to ADP or TRAP-1. The expression of the LIGHT receptors TR2 and LTβR on native human endothelial cells was confirmed by FACS analysis. LIGHT mediated adhesion of platelets to endothelium significantly, occurring both under static and dynamic flow conditions. This interaction was inhibited by a monoclonal antibody to LIGHT but not a control IgG. Moreover, in-vitro stimulation of endothelial cells with recombinant soluble human LIGHT (rhLIGHT) resulted in significantly increased transcriptional and translational upregulation of inflammatory markers ICAM-1, tissue factor (TF) and IL-8. This activation of endothelial cells by LIGHT was mediated by NFκB activation and qualitatively comparable to that induced by membrane-bound CD40-ligand on transfected cells. Furthermore, plasma levels of patients with myocardial infarction, in those with ST-elevation myocardial infarction (STEMI), showed increased plasma levels of LIGHT compared with healthy controls. In conclusion, platelet-associated LIGHT is involved in adhesion of platelets to endothelium while soluble LIGHT induces a pro-inflammatory state in vascular endothelial cells. LIGHT may thus be implicated in the pathogenesis of atherosclerosis and acute coronary syndrome, as evidenced by serum levels.
A two adenine insertion polymorphism in the 3’ untranslated region of factor VII gene is associated with peripheral arterial disease but not with venous thrombosis
Authors: Serve Emilie , Reny Jean-Luc , Akhavan Sepideh , Emmerich Joseph , Fischer Anne-Marie , Tapon-Bretaudière Jacqueline 
Published: October 2007

SummaryPolymorphic variants of genes encoding blood coagulation proteins have been extensively studied as risk factors for venous or arterial thrombosis A variation in the 3' untranslated region (UTR) involved in the post-transcriptional regulation of factor VII (FVII) gene has been recently identified, a two adenine insertion/deletion at nucleotide 11293. In this study, we investigated its effect on the risk of thrombosis in the frame of two case-control studies, including patients suffering from peripheral arterial disease (PAD) or venous thromboembolic (VTE) disease. The 3’UTR FVII gene polymorphism was investigated i) in 181 patients who had symptomatic atherosclerotic disease of the lower limbs, ii) in 178 patients who had had at least one episode of objectively diagnosed deep venous thrombosis and iii) in controls matched for age and sex. Plasma FVII antigen (FVII:Ag) levels were lower in the presence of the 3’UTR 2A insertion (68.4 ± 12.3%, 81.3 ± 14.5% and 89.5 ± 13.7% in 2A/2A, 2A/0 and 0/0 subjects respectively, p<0.0001). No significant relationship was found with VTE disease. In the contrary we observed a lower risk of PAD for the 2A/2A compared to the 0/0 genotype after adjustment for traditional risk factors (hypercholesterolemia, smoking status, diabetes and hypertension), with an OR of 0.24 [95% CI 0.06–0.99]. In conclusion, the 2 adenine insertion in the 3’UTR of FVII gene, related to lower plasma FVII levels, is a genetic variation that may contribute to reduce the risk of PAD.
Prevalence of deep vein thrombosis (DVT) in non-surgical patients at hospital admission
Authors: Hoffmanns Wibke , Hoffmanns Phillip , Rapp Uli , Ames Michael , Pira Alessandro , Paar Dieter , Bramlage Peter , Diehm Curt , Lawall Holger 
Published: October 2007

SummaryVenous thromboembolism (VTE) is known as a common complication in surgical and non-surgical patients. We hypothesized that according to the underlying risk factors and the acute illness, the prevalence of VTE in non-surgical patients admitted to hospital is widely underestimated. For three months each patient admitted to the department of internal medicine with an acute illness, but without known deep venous thrombosis (DVT) was investigated by ultrasound compression sonography. Patients’ history, risk factors and extent of immobilisation were documented. In patients with newly detected DVT D-dimer and fibrinogen were measured as well as computer tomography scans performed. Follow-up investigations of the DVT population were performed at four weeks and three months. Six hundred seventeen patients (49.3% men) were included. In 16 patients (men=7) a previously unknown thrombosis (2.6%) was detected, mainly in patients with acute cardio-pulmonary disease (56%) and the elderly (mean age 75.6 years). Eight patients had femoro-popliteal (50.0%), four a femoral (25.0%), and four a popliteal vein thrombosis (25.0%). Five had pulmonary embolism (31.3%). In patients with DVT D-dimer was 875 ± 1,228 mg/l, fibrinogen 568 ± 215 mg/dl and C-reactive-protein 58.54 ± 73.65 mg/dl. One patient died from sepsis during hospitalisation, one died from sudden cardiac death at home. None of the other 14 surviving patients relapsed. The study shows a 2.6% risk for DVT in outpatients with acute illness admitted to the department of internal medicine. These data demonstrate the high risk of DVT is in non-surgical patients. Early prophylaxis has to be considered in internal medicine patients especially in the elderly.
Adrenomedullin and endothelial barrier function
Authors: Temmesfeld-Wollbrück Bettina , Hocke Andreas , Suttorp Norbert , Hippenstiel Stefan 
Published: October 2007

SummaryAlthough loss of endothelial barrier function is a hallmark of every acute inflammation and contributes to fatal loss of organ function during severe infections, there is no sufficient therapy for stabilization of endothelial barrier function. Endogenous peptide adrenomedullin (AM) serum levels were shown to be increased during severe infection including sepsis and septic shock. In different in-vitro and in-vivo models AM acted as a potent therapeutic endothelial barrier function-stabilizing agent. Activation of specific receptors by AM results in elevation of second messenger cAMP. AM inhibits actin-myosin based endothelial cell contraction and junctional disassembly, thereby preventing paracellular permeability and oedema formation. The peptide furthermore possesses several protective cardiovascular qualities, including protection of the microcirculation during inflammation, and was proven as an efficient counter-regulatory molecule in various models of sepsis and septic shock. Overall, AM may be an attractive molecule to combat against cardiovascular malfunction during severe infection.
Factor V Leiden and the etiology of inflammatory bowel disease
Authors: ten Kate Fiebo , te Velde Anje , Spek Arnold 
Published: October 2007

SummaryInflammatory bowel disease (IBD) refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn’s disease. Patients suffering from IBD have a threefold increased risk of venous thrombosis compared with matched controls. Importantly, thromboembolic disease is a significant cause of morbidity and mortality in patients with IBD. However, despite several supporting observations it is still elusive whether activation of the blood coagulation cascade is involved in the etiology and pathogenesis of IBD. To confirm or refute the hypothesis that activated blood coagulation aggravates the development of IBD, we subjected wildtype and homozygous FV Leiden mice to a model of DSS-induced colitis. Experimental colitis led to a reduction in body weight, shortening of the colon and increased colon weight. In addition, DSS treatment led to ulcerations, edema formation, crypt loss, fibrosis and the influx of inflammatory cells into the colon. However, the FV Leiden genotype had no significant effect on any of the DSS-induced symptoms of colitis. We therefore conclude that the FV Leiden allele has no effect in murine colitis and we thus question the importance of activated blood coagulation in the etiology or pathogenesis of IBD.
Clinical outcome of patients with venous thromboembolism and renal insufficiency
Authors: Falgá Conxita , Capdevila Josep Antón , Soler Silvia , Rabuñal Ramón , Muñoz-Torrero Juan Francisco Sánchez , Gallego Pedro , Monreal Manuel ,   the RIETE Investigators
Published: October 2007

SummaryThere is little information on the clinical outcome of patients with venous thromboembolism and renal insufficiency. RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE). In this analysis we analyzed the three-month outcome in patients with creatinine clearance (CrCl) <30 ml/min. As of March 2007, 1,037 of the 18,251 (5.7%) patients enrolled in RIETE had CrCl <30 ml/min. During the three-month study period these patients had an increased incidence of fatal bleeding, fatal PE, and overall death compared to those with CrCl >30 ml/min. Of the 579 patients presenting with clinically overt PE, 52 (9.0%) died of the initial PE, 13 (2.2%) of recurrent PE, and nine (1.6%) died of bleeding complications. During the first 15 days of therapy the 10% incidence of fatal PE was 10-fold their 1.0% of fatal bleeding. From day 16 to 90, the 1.0% rate of fatal PE was not significantly higher than the 0.5% of fatal bleeding. Of the 458 DVT patients with CrCl <30 ml/min, 14 (3.1%) had fatal bleeding and only one (0.2%) died of PE. In patients with CrCl <30 ml/min presenting with clinically overt PE the main threat is PE itself. On the contrary, in those with DVT the main threat is bleeding.
ProTime self-management yielding improvement of fluency and quality of life
Authors: Völler Heinz , Taborski Uwe , Dovifat Clemens , Hartwig Ines , Kadar Janos , Wegscheider Karl , LaDuca Frank , Ansell Jack , Zucker Marcia 
Published: October 2007

SummaryPatient self-management (PSM), as the standard of care for vitamin K-antagonist therapy management in Germany requires a detailed, point-of-care (POC) device-specific training program to ensure quality patient care. In a multi-center trial using the ProTime System (Training program plus POC device), 105 patients were enrolled to evaluate efficacy of training, knowledge retention, patient satisfaction and quality of life (QoL). Patients returned to the centers 1, 3 and 6 months after training to complete questionnaires and demonstrate INR test proficiency. Training assessment employed self-evaluation and comparison of POC results between PSM and professional operators. Patient satisfaction and QoL were assessed using a modification of the questionnaire described by Sawicki and the SF12v2 QoL Survey, respectively. Patients demonstrated statistically significant improvements in knowledge post training (p<0.001) and retained the acquired information (p=NS vs. post-training; N=45) after 6 months. Trained patients yielded equivalent INR results to professional operators (r=0.92) with little or no bias across all clinic visits. Compliance with weekly testing improved from 1 to 3 months (p = 0.03), remaining at the required weekly frequency through 6 months. Average patient satisfaction improved significantly during the first month and remained constant thereafter. There was a statistically significant improvement in the Physical Component Summary of SF12 between baseline and 3/6 month assessments in all centers. In conclusion, PSM requires a comprehensive system including appropriate disease and POC device training. Such a system fosters compliance, improved knowledge about underlying disease, patient satisfaction and QoL.Footnote:Portions of this trial were presented on November 15, 2005 at the American Heart Association Scientific Sessions 2005 in Dallas, TX, USA.
Factors with conformational effects on haemostatic serpins: Implications in thrombosis
Authors: Hernández-Espinosa David , Ordóñez Adriana , Vicente Vicente , Corral Javier 
Published: October 2007

SummarySerpins are key actors of systems involving proteolytic reactions, such as the haemostatic system, as they are irreversible suicide inhibitors of serine proteases. The structural flexibility and physical properties of serpins that are required for their efficient inhibitory mechanism also make them especially vulnerable to even minor factors that induce conformational changes in the native form of these molecules, leading to a number of inactive conformations, such as latent, cleaved or polymers. Increasing numbers of conformational mutations affecting haemostatic serpins, mainly antithrombin, the main endogenous anticoagulant, have been described. These mutations cause circulating deficiencies of the molecules, in most cases due to intracellular retention, which may be associated with a hyper-coagulable state. Indeed, conformational mutations in antithrombin have been identified in patients with severe venous thrombosis,which has led to the hypothesis that these disorders might be included in the group of conformational diseases. Moreover,we have recently demonstrated that other factors,including both drugs,such as the treatment with L-asparaginase,or environmental factors, such as high temperatures or hyperlipidemia, may also have conformational consequences on hepatic antithrombin,thus resulting in intracellular aggregation and plasma deficiency, which may increase the risk of thrombosis. In this study,we review the causes of deficiency of haemostatic serpins that may be explained by conformational mechanisms, and their association with an increased risk of venous thrombosis.
Effector functions of pathogenic Yersinia species
Authors: Trasak Claudia , Ruckdeschel Klaus , Aepfelbacher Martin 
Published: October 2007

SummaryPathogenic species of the genus Yersinia suppress and reorient the immune system to infect lymphatic tissues, inner organs and at times also the vasculature. For this purpose yersiniae employ a type III secretion system to translocate effector proteins (Yersinia outer proteins;Yops) into immune cells.Yops often exert unique biochemical activities for modulating the activity of Rho GTP-binding proteins, focal adhesion proteins, inflammatory pathways and cell survival/apoptosis. In this review we will put emphasis on the biochemistry, cell- and infection biology ofYersinia effector Yops.