bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of psychological factors and healthcare use with the discrepancy between subjective and objective respiratory-health complaints in the general population
Authors: Selinheimo Sanna , Vasankari Tuula , Jokela Markus , Kanervisto Merja , Pirkola Sami , Suvisaari Jaana , Paunio Tiina 
Published: March 2018

AbstractBackgroundWe examined the prevalence of self-perceived respiratory symptoms (SRS) in the absence of any objective findings of respiratory pathology, and the association of such prevalence with psychological factors and healthcare use in the general population.MethodsThe study was conducted among a nationally representative sample of Finnish adults (BRIF8901). Respiratory functioning was measured by a spirometry test. Structured questionnaires were used to measure SRS, physician visits and psychological factors of alexithymia, sense of coherence, illness worry and common mental disorders. Individuals with a diagnosed respiratory disease or a severe psychiatric disorder, determined in a diagnostic interview, were excluded, giving a sample comprising 4544 participants.ResultsTwenty-six per cent of the general population and 36% of those with no diagnosed severe psychiatric disorder or respiratory disease experienced SRS despite a normal spirometry result. Psychological factors were associated with SRS (0.0001 < p < 0.032), and on the number of physician visit explaining 42.7% of the difference in visits between individuals with and without SRS, respectively. Illness worry was associated most strongly with SRS [odds ratio (OR) 1.29, 95% confidence interval (CI) 1.19–1.41, p < 0.0001] and higher numbers of physician visits (OR 1.35, CI 1.32–1.38, p < 0.00001), even after several adjustments.ConclusionsRespiratory symptoms without objective findings are common in the general population. The study results underline the role of psychological factors in the reporting of respiratory symptoms and the associated medical burden, thereby indicating the functional nature of the symptomatology.
Some Patients with Antiphospholipid Syndrome Express hitherto Undescribed Antibodies to Cardiolipin-binding Proteins
Authors: Rampazzo P. , Biasiolo A. , Garin J. , Rosato A. , Betterle C. , Ruffatti A. , Pengo V. 
Published: March 2018

SummaryContrary to infective anticardiolipin (aCL) antibodies, autoimmune aCL antibodies react with phospholipids (PL) mainly via binding to the plasma glycoprotein cofactor β2-Glycoprotein I (β2GPI). While there is a well-documented link between the risk of thrombosis and the presence of β2GPI-dependent anticardiolipin antibodies, the pathological impact of other antiphospholipid antibodies is less clear. By means of cardiolipin affinity-chromatography, we isolated and identified 3 CL-binding proteins, complement component C4, complement factor H and a kallikrein-sensitive glycoprotein, and tested for the presence of autoantibodies against these proteins in patients with antiphospholipid syndrome (APS), systemic lupus erythematosus (SLE) and other autoimmune diseases. High titers of autoantibodies to C4 as compared to age- and sex-matched healthy controls were present in 3 of 26 patients with APS, and weak titers were found in 2 of 26 patients with SLE and in none of 26 patients with other autoimmune diseases. Autoantibodies to complement factor H were found in 4 APS, 3 SLE and none of the other autoimmune patients. Autoantibodies to kallikrein-sensitive glycoprotein were detected in 6 APS patients, 1 SLE patient, and 1 patient with another autoimmune disease. A close relationship between these antibodies was found, suggesting their origin from a common macromolecular complex. However, no relationship with anti-β2GPI antibodies was found, with the three patients with higher levels of autoantibodies having a low titer of anti-β2GPI antibodies. In conclusion, some patients with APS harbor circulating antibodies to other CL-binding proteins which might be useful to further characterize these patients.
High Levels of Adhesion Molecules Are Associated with Impaired Endothelium-dependent Vasodilation in Patients with Peripheral Arterial Disease
Authors: Martone Vincenzo , de Cristofaro Tiziana , Corrado Salvatore , Silvestro Antonio , Di Donato Anna Maria , Bucur Roxana , Scopacasa Francesco , Brevetti Gregorio 
Published: March 2018

SummarySoluble intercellular adhesion molecule-1 (sICAM-1) and vascular cellular adhesion molecule-1 (sVCAM-1) were measured alongside flow-mediated vasodilation (FMD) in 34 patients with intermittent claudication and 14 control subjects. Patients with plasma sICAM-1 >253 ng/mL (median value) showed lower FMD than those with sICAM-1 <253 ng/mL (5.6 ± 1.8% vs 9.6 ± 4.2%, p <0.01). Similarly, in the 17 patients with plasma sVCAM-1 >414 ng/mL, FMD was lower than in the remaining 17 patients (6.1 ± 1.9% vs 9.2 ± 4.5%, p <0.05). Additionally, when endothelial dysfunction was defined as FMD ≤5.5%, patients with FMD below this value had higher plasma concentrations of sICAM-1 and sVCAM-1 than those with FMD >5.5%. Therefore, our findings indicate a close association between elevated plasma levels of adhesion molecules and endothelial dysfunction. As impaired endothelial function is one of the first steps in atherogenesis, our findings have clinical relevance since they serve as the basis for further evaluation of sICAM-1 and sVCAM-1 as potential plasma markers for progression of atherosclerosis in a population at high risk.
Functional Properties of Factor V and Factor Va Encoded by the R2-gene
Authors: Hoekema Lico , Castoldi Elisabetta , Tans Guido , Girelli Domenico , Gemmati Donato , Bernardi Francesco , Rosing Jan 
Published: March 2018

SummaryCarriership of the factor V (FV) gene marked by the R2-haplotype, a series of linked polymorphisms encoding several amino acid changes in FV, is associated with mild resistance to activated protein C (APC) and with an increased risk of thrombosis. We compared the functional properties of normal FV(a) and R2-FV(a) in model systems and in plasma. FV and R2-FV were equally well activated by thrombin and expressed identical cofactor activities in prothrombin activation. Rate constants of APC-catalyzed inactivation of FVa and R2-FVa were similar both with and without protein S. However, significant differences were observed between haemostatic parameters determined in plasma from homozygous carriers of the R2-gene (n = 5) and age-matched non-carriers (n = 19). Plasma from R2-carriers contained significantly lower FV levels and the ratio of the two FV isoforms (FV1 and FV2) was shifted in favor of FV1. The FV2/FV1 ratio was 1.4 (95% CI = 1.3-1.5) in homozygous carriers of R2 and 2.8 (95% CI = 2.5-3.1) in controls (p <0.00001). In an APC resistance test which quantifies the cofactor activity of FV in APC-catalyzed FVIII(a) inactivation, homozygous R2-carriers had significantly lower (p <0.00001) APC sensitivity ratios (APCsr = 1.54, 95% CI = 1.48-1.60) than controls (APCsr = 2.17, 95% CI = 2.05-2.28). This indicates that R2-FV has reduced cofactor activity in APC-catalyzed FVIII(a) inactivation. The changes of the relative amounts of FV1 and FV2 in carriers of the R2-gene will result in increased thrombin formation in the presence of APC and may provide a mechanistic explanation for the increased thrombotic risk associated with the R2-haplotype.
Relationship of Coagulation Test Abnormalities to Tumour Burden and Postoperative DVT in Resected Colorectal Cancer
Authors: Thorlacius-Ussing O. , Iversen L. H. 
Published: March 2018

SummaryIn a prospective study, coagulation test results were compared in 137 patients with colorectal cancer (CRC) and 39 subjects with benign colorectal diseases. Prothrombin fragment 1+2 (F1+2), thrombinantithrombin complex (TAT), and soluble fibrin (SF) were measured in plasma before and after surgery. CRC patients presented with significantly higher values of F1+2 and TAT than controls. Patients with localised CRC had elevated values of F1+2 and TAT, whereas patients with advanced CRC also had elevated SF values. TAT and SF levels correlated with tumour spread, and normal values virtually excluded advanced cancer. Postoperative deep venous thrombosis (DVT) was diagnosed by phlebography in 20% of the CRC patients. Preoperative values of the markers did not predict postoperative DVT, but postoperative values did.
Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery
Authors: Larson G. , Lindahl T. L. , Andersson C. , Frison L. , Gustafsson D. , Bylock A. , Eriksson B. I. , Wåhlander K. 
Published: March 2018

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.
Aberrant Splicing and Premature Termination of Transcription of the FVIII Gene as a Cause of Severe Canine Hemophilia A: Similarities with the Intron 22 Inversion Mutation in Human Hemophilia
Authors: Hough Christine , Kamisue Seiki , Cameron Cherie , Notley Colleen , Tinlin Shawn , Giles Alan , Lillicrap David 
Published: March 2018

SummaryWe have identified the causative mutation in the hemophilia A dog colony at Queen’s University, Canada and have observed a striking similarity with the intron 22 inversion found in ∼45% of severely affected hemophilia A patients. The canine hemophilia A phenotype arises from aberrant splicing and premature termination of transcription of the FVIII gene, resulting in a polyadenylated transcript lacking exons distal to 22 and terminating with a novel sequence element (NSE). In dogs and other species including humans, this NSE is present in low copy number. One copy of these sequences in the canine genome is within intron 22 and reveals differences in the hybridization banding patterns between normal and hemophilic DNA, suggestive of a large genomic rearrangement. The mutation mechanism may not be uncommon, as identical mutant transcripts were isolated from two hemophilia A littermates that are unrelated to the Queen’s colony and from hemophiliac dogs in the colony at Chapel Hill.
Cholesterol-induced Thrombogenicity of the Vessel Wall: Inhibitory Effect of Fluvastatin
Authors: Camera Marina , Toschi Vincenzo , Comparato Carmen , Baetta Roberta , Rossi Francesca , Fuortes Michele , Ezekowitz Michael , Paoletti Rodolfo , Tremoli Elena 
Published: March 2018

SummaryHigh cholesterol levels are a known risk factor for coronary events. The molecular links between high serum cholesterol and the increased thrombogenicity of the arterial wall are still matter of investigation. In the present study we investigate the relationship between plasma cholesterol, thrombus formation and TF expression in a atherosclerotic rabbit model.Hypercholesterolemic rabbits showed a pronounced TF staining as well as NF-κB activation in the aortic arch. A consistent vessel wall platelet deposition was also observed. Treatment with fluvastatin reduced lipid accumulation, TF overexpression (-60%), NF-κB activation, and platelet deposition (-56%). In vitro studies showed that the drug upregulated IκBa in unstimulated as well as in TNFa-stimulated cells and also impaired the TNF-α-induced Cdc42 prenylation, indicating that fluvastatin interferes with the transcriptional activation of TF gene.These results indicate that the prothrombotic phenotype of arterial wall, associated with elevated serum cholesterol levels, is mediated by TF overexpression. Fluvastatin treatment reduces the prothrombotic tendency by inhibiting TF synthesis.
Laboratory Diagnosis of Lupus Anticoagulants
Authors: Chantarangkul Veena , Clerici Marigrazia , Bressi Caterina , Mannucci Pier , Tripodi Armando 
Published: March 2018

SummaryResidual platelets in plasma are considered detrimental after freezing-thawing, as phospholipids released from ruptured platelets may quench lupus anticoagulants (LA). We aimed at assessing the effect of residual platelets after freezing-thawing plasmas tested with two procedures for LA. Blood from 52 patients suspected of having LA were centrifuged at 2,500 g. Plasmas were subdivided into 2 aliquots. One was filtered to remove residual platelets and both were frozen and stored at –70° C. Silica clotting time (SCT) at low and high phospholipid concentrations and Staclot® LA with and without Hexagonal phospholipids were performed on thawed plasmas. Plasmas were considered LA-positive when both SCT and Staclot® LA performed on filtered plasmas were diagnostic for LA. Forty-two of 52 plasmas fulfilled the diagnostic criteria and were retained for subsequent analysis. SCT on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) percentage correction recorded after phospholipids addition for filtered plasmas, i. e., 67% (36%-83%) was reduced to 54% (25%-81%) for non-filtered plasmas (p <0.001), it was still above the cut-off (i. e., 20.9%). Staclot® LA on non-filtered plasmas was diagnostic for LA in 42 of 42 plasmas. Though the median (range) clotting time difference recorded after phospholipid addition for filtered plasmas, i. e., 40.8 (10-103.5) s was reduced to 31.7 (2.8-88.8) s for non-filtered plasmas (p <0.001), it was still above the cut-off (i. e., 1.7 s). In conclusion, residual platelets do not affect the diagnostic efficacy of SCT and Staclot® LA. However, the fact that the percentage correction for SCT and the clotting time difference for Staclot® LA are reduced by residual platelets, suggests that weak LA may be lost upon freezing-thawing non-filtered plasmas.
Platelet Activation by the apoB/E Receptor-binding Domain of LDL
Authors: Gorter G. , van Rijn J. M. H. , Akkerman N. J.-W. , Relou I. A. M. 
Published: March 2018

SummaryLow density lipoprotein (LDL) increases the sensitivity of human platelets for agonists by activating p38MAPK. Antibody 4G3 disturbs apoB100 binding to the classical apoB/E receptor and inhibits LDLinduced p38MAPK activation, whereas an antibody against a distal domain on apoB100 has no effect. Peptide RLTRKRGLKLA mimics the binding domain of apoB100 called the B-site and activates platelet p38MAPK. Activation by B-site peptide is dose-dependent, transient and followed by desensitization, in accordance with receptor-mediated signalling. A scrambled peptide and a partially homologous peptide RKLRKRLLRDA mimicking the apoB/E receptor binding site of apoE in high density lipoprotein (HDL) also activate p38MAPK albeit 40% weaker, but an uncharged peptide lacks p38MAPK activating capacity. LDL and B-site peptide bind to the same binding sites and initiate similar signalling to p38MAPK and cytosolic phospholipase A2. Thus, LDL and to a lesser extent HDL activate platelets via specific domains in the protein moiety that recognize receptors of the LDL receptor family.
Pharmacokinetics of New Synthetic Heparin Mimetics
Authors: Hérault J. P. , Bernat A. , Roye F. , Michaux C. , Schaeffer P. , Bono F. , Petitou M. , Herbert J. M. 
Published: March 2018

SummaryPharmacokinetics of oligosaccharides displaying various affinities for antithrombin (AT) allowed us to show that there was a close relationship between the plasma half-life of these antithrombotic oligosaccharides and their affinity for AT. Recently, we have described new heparin mimetics comprising an AT binding domain and a thrombin binding domain separated by a neutral methylated saccharide sequence. These compounds displayed strong anti-Xa and anti-IIA activities and, in contrast to heparin, escaped neutralisation by platelet factor 4. The aim of this work was to compare the pharmacokinetics of several of these heparin mimetics in rats. These compounds differed by their length, charge and affinity for AT (AT-binding domain). The results obtained indicate that the prolongation of the AT binding domain did not modify significantly their affinities for AT. However, an increase in the number of charges leads to a decrease in the half-life. When a methylated spacer was added in order to minimise the non-specific interactions to other proteins, half-lives of the heparin mimetic were in the same range than that of the pentasaccharide used as an AT binding domain.In conclusion, this study shows the influence of the charge of the oligosaccharides on their pharmacokinetics and underlines the importance of minimising their non-specific binding to plasma proteins in order to obtain compounds with predictive pharmacokinetics.
Local tissue factor pathway inhibitor release in the human forearm
Authors: Burggraaf Jacobus , Schoemaker Rik , Cohen Adam , Kluft Cornelis , Chia Stanley , Webb David , Newby David , Kemme Michiel 
Published: March 2018

SummaryNineteen healthy men received unilateral brachial artery infusions of either unfractioned heparin (0.3-100 IU/min), saline or the endothelium-dependent vasodilators substance P (2-8 pmol/min) and bradykinin (100-1000 pmol/min), and the endothelium-independent vasodilator sodium nitroprusside (2-8 µg/min). Heparin caused a dose-dependent increase in plasma TFPI concentrations in both arms (ANOVA, p <0.0001). Estimated net forearm TFPI release was 7 ± 16, 29 ± 20 and 138 ± 72 ng/100 mL tissue/min during 10, 30 and 100 IU/min of heparin respectively (ANOVA, p <0.0001). Compared to the systemic circulation, the forearm sensitivity to heparin induced TFPI release was 3.6-fold lower (166 ± 67 ng/IU vs. 596 ± 252 ng/IU: t-test, p = 0.004). Substance P, bradykinin and sodium nitroprusside all caused substantial dose-dependent increases in blood flow (ANOVA, p <0.001 for all) without affecting plasma TFPI concentrations. There are important regional differences in endothelial TFPI release, with the forearm circulation being relatively insensitive to heparin.
Prothrombin G20210A mutation and oral contraceptive use increase upper-extremity deep vein thrombotic risk
Authors: Mira Yolanda , Mateo Jose , Falco Cristina , Villa Piedad , Estelles Amparo , Corella Dolores , Fontcuberta Jordi , Aznar Justo , Vayá Amparo 
Published: March 2018

SummaryThe role played by a hypercoagulable state, either inherited or acquired, in the pathogenesis of upper-extremity deep vein thrombosis (UEDVT) remains a question of debate. We performed a case-control study including 79 patients with a first objectively confirmed episode of UEDVT, 31 secondary and 48 primary, and 165 healthy controls. Nine patients (11.4%) with UEDVT were carriers of the prothrombin G20210A mutation vs. six (3.7%) in controls; P = 0.025, OR: 3.39 (95% CI 1.16 to 9.88). No statistical difference was observed between cases and controls for the factor V Leiden mutation, AT, protein C or protein S deficiency and anticardiolipin antibodies (ACAs). Thirteen (35.1%) UEDVT patients were oral contraceptive (OC) users vs. 12 (16%) controls; P = 0.020, OR: 2.89 (95% CI 1.16-7.21). When secondary UEDVT patients were compared with controls, no differences were observed in any of the risk factors analysed. On the other hand, when primary UEDVT was considered, six (12.5%) patients were carriers of the prothrombin G20210A mutation vs. six (3.7%) controls; P = 0.031, OR: 3.76 (95% CI 1.15-12.26). Regarding ACAs, a borderline statistical significance was observed when primary UEDVT was compared with controls, P = 0.048; OR: 4.88 (95% CI 1.05-22.61). In primary UEDVT, 52% of the fertile women were OC users vs. 16% of controls; P = 0.001, OR:5.78 (95% CI 2.13-15.67). When the interaction of both factors, i.e. prothrombin G20210A mutation and OC intake, were considered, the risk increased markedly, indicating a synergistic effect as observed with other thrombotic locations. In patients with primary UEDVT screening for antithrombin, protein C and protein S deficiency and APC resistance would not be justified, although it might be reasonable to determine the carrier status of the prothrombin G20210A mutation only in OC users.
A quantitative measure of the efficacy of factor VIII in hemophilia A mice
Authors: Parker Ernest , Lollar Pete 
Published: March 2018

SummaryWe developed a quantitative method to study the efficacy of intravenously delivered human factor VIII in hemophilia A mice. Mortality was assessed after tail transection under conditions in which there were no survivors in untreated hemophilia A mice. Blood loss was significantly greater in untreated hemophilia A mice compared to normal C57BL/6 mice, and in hemophilia A non-survivors that were treated with subtherapeutic doses of factor VIII. The up-and-down method for small samples yielded an estimated dose of factor VIII producing survival in 50% of the mice (ED50) of 58 units/kg (95% confidence interval: 42.4 - 78.5 units/kg). This method should be useful in the evaluation and comparison of novel factor VIII products delivered either parenterally or in a gene therapy setting.
Effects of antioxidant vitamins C and E on endothelial function and thrombosis/fibrinolysis system in smokers
Authors: Antoniades Charalambos , Tentolouris Costas , Toutouza Marina , Marinou Kyriakoula , Goumas George , Tsioufis Costas , Toutouzas Pavlos , Stefanadis Christodoulos , Tousoulis Dimitris 
Published: March 2018

SummarySmoking is associated with endothelial dysfunction and abnormalities in thrombosis/fibrinolysis system, possibly through increased oxidative stress. In this study we investigated the effect of combined antioxidant treatment with vitamins C and E on endothelial function and plasma levels of plasminogen activator inhibitor (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA) and factor VII (fVII), in smokers. Forty-one healthy smokers were randomly divided into 4 groups receiving vitamin C 2g/day (group A), vitamin C 2g/day plus vitamin E 400IU/day (group B), vitamin C 2g/day plus vitamin E 800IU/day (group C) or no antioxidants (controls, group D), for 4 weeks. Forearm blood flow was measured using venous occlusion strain-gauge plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to sublingual nitroglycerin administration (NTG%) were considered as indexes of endothelium dependent or independent dilation respectively. After treatment, RH% was increased only in groups B (p <0.05) and C (p <0.001) but not in groups A and D. Plasma levels of PAI-1 and vWF were decreased only in group C (p <0.05 for both), while PAI-1/tPA ratio was significantly decreased in both groups B and C (p <0.05 for both). NTG% and plasma levels of tPA and fVII remained invariable in all groups. In conclusion, combined administration of vitamin C and vitamin E at high dosages, improved endothelial function and decreased plasma levels of PAI-1, vWF and PAI-1/tPA ratio in chronic smokers.