bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis
Authors: Gayet Stéphane , Alessi Marie-Christine , Audrain Marie , de Maistre Emmanuel , Gris Jean-Christophe , de Groot Philip , Hachulla Eric , Harlé Jean-Robert , Sié Pierre , Boffa Marie-Claire , Sanmarco Marielle 
Published: June 2007

SummaryA multicenter study was set up to evaluate the prevalence, clinical and biological significance of antiphosphatidylethanolamine antibodies (aPE) in thrombotic patients with or without the main known clinical and biological risk factors for thrombosis. APE and antibodies, defined as the laboratory criteria of antiphospholipid syndrome (APS) -lupus anticoagulant, anticardiolipin and anti-beta2-GPI antibodies were measured in 270 patients with thrombosis (234 venous and 37 arterial) and 236 matched controls. APE were found in 15% of thrombotic patients compared to 3% of controls (p<0.001) with no predominant isotype, no association with the main known clinical or biological risk factors for thrombosis neither with a type of thrombosis, arterial or venous. In a multivariate logistic regression analysis of antibodies, aPE showed the highest association with thrombosis (odds ratio [OR]: 4.2, p<0.001). Moreover, using a multivariate analysis in a case-control subgroup study on 158 patients, IgGaPE were found to be significantly associated with venous thrombosis (OR:6;p=0.005). Interestingly, 25 of the 40 aPE-positive patients (63%) were negative for the APS laboratory criteria. Most of them (21/25) had venous thrombosis, recurrent in ten of them. Four patients also suffered from early or late miscarriages. Our results underline the strength of the association between the presence of aPE and thrombosis and suggest their measurement in thrombotic patients, especially when lupus anticoagulant, anticardiolipin or anti-beta2-GPI antibodies are absent.
Differential impact of conventional and low-dose oral hormone therapy (HT), tibolone and raloxifene on functionality of the activated protein C system
Authors: Liestøl Sigurd , Mowinckel Marie-Christine , Hemker H. Coen , Sandset Per-Morten , Eilertsen Anette 
Published: June 2007

SummaryRecent studies have shown that hormone therapy (HT) is associated with an acquired resistance to activated protein C (APC). The aims of the present study were to evaluate a possible dose-response relationship and differential effects of different HT regimens on functionality of the APC system. Two hundred two healthy women were randomly assigned to receive treatment for 12 weeks with tablets containing either low-dose HT containing 1 mg 17β-oestradiol + 0.5 mg norethisterone acetate (NETA) (n=50), conventional-dose HT containing 2 mg 17β-oestradiol and 1 mg NETA (n=50), 2.5 mg tibolone (n=51), or 60 mg raloxifene (n=51). Normalized APC system sensitivity ratios (nAPCsr) were determined in plasma collected at baseline and after 12 weeks using a thrombin generation-based APC resistance test probed with either recombinant APC (rAPC) or thrombomodulin (rTM). NAPCsr increased in both the conventional- and low-dose HT groups, consistent with reduced sensitivity to APC. The increase was slightly more pronounced in the conventional-dose group, but the difference between the two HT groups was not statistically significant. The sensitivity to APC was only marginally altered in those allocated to tibolone. Consequently, tibolone showed a different phenotype as compared with the low-dose HT group. A small increase in nAPCsr with both rAPC and rTM was seen in the raloxifene-group, but the increase was less than in the low-dose HT group. Our findings indicate that oestrogen-progestin therapy induces an APC resistant phenotype, which may be related to dose, whereas tibolone and raloxifene only marginally alter the sensitivity to APC.
Clinically suspected acute recurrent pulmonary embolism: A diagnostic challenge
Authors: Kwakkel-van Erp Hanneke , Söhne Maaike , Tick Lidwine , Kruip Marieke , Ullmann Eric , Kramer Mark , Büller Harry , Prins Martin , Leebeek Frank , Huisman Menno , Nijkeuter Mathilde 
Published: June 2007

SummaryIt is unknown whether strategies validated for diagnosing pulmonary embolism (PE) are valid in patients with a history of PE. It was the objective of this study to investigate whether a diagnostic algorithm consisting of sequential application of a clinical decision rule (CDR), a quantitative D-dimer test and computed tomography (CT) safely ruled out a clinical suspicion of acute recurrent PE. Data were obtained from a diagnostic outcome study of patients suspected of PE. Acute recurrent PE was ruled out by an unlikely probability of PE (CDR score ≤4 points) combined with a normal D-dimer test (≤500 ng/ml) or by a normal CT in all other patients. The primary outcome was the incidence of acute recurrent venous thromboembolism during three months of follow-up in patients with normal tests and not treated with anticoagulants. Of 3,306 patients suspected of acute PE, 259 patients (7.8%) had a history of PE of whom 234 were not treated with anticoagulants. The probability of PE was unlikely in 82 of 234 patients (35%), and 42 had a normal D-dimer test (18%), excluding recurrent PE. None of these patients had a thrombotic event during follow-up (0%, 95%CI: 0–6.9). A CT was indicated in all other patients (192) and ruled out recurrent PE in 127 patients (54%). Only one patient with a negative CT had a fatal recurrent PE during follow-up (0.8%; 95%CI: 0.02–4.3). In conclusion, this prospective study demonstrates the safety of ruling out a clinical suspicion of acute recurrent PE by a simple diagnostic algorithm in patients with a history of PE.
Activated coagulation factors in human malignant effusions and their contribution to cancer cell metastasis and therapy
Authors: Lühr Inke , Kunze Thomas , Mundhenke Christoph , Maass Nicolai , Erhart Tobias , Denker Momme , Beckmann Dennis , Tiemann Markus , Schulte Christoph , Dohrmann Peter , Cavaillé Françoise , Godeau François , Gespach Christian , Gieseler Frank 
Published: June 2007

SummaryWe have shown that the thrombin G-protein coupled receptors (GPCR) designated as protease-activated receptors (PAR-1) are expressed in primary cancer cells isolated from peritoneal and pleural malignant effusions. Here, our main goal was to evaluate several coagulation and thrombin activation effectors and markers in a series of 136 malignant effusions from cancer patients with gastrointestinal, lung and mammary carcinomas. All these patients present a highly activated coagulation system in blood and their malignant effusions, as indicated by high levels of prothrombin F1.2 fragments and D-dimers. Notably, we detected in the effusions all the coagulation factors of the tissue factor pathway inducing thrombin activation, namely factorsVII, V, X and II, as well as high VEGF levels and IGF-II in mature and precursor forms. Fibrin clot formation also correlated with higher levels of free ionized calcium (iCa), suggesting that iCa and its binding protein albumin are regulatory factors for fibrinogenesis in effusions. Consequently, thrombin,VEGF and IGFII appear to converge in the promotion of survival and invasivity of the metastatic cancer cells from blood to the malignant effusions. Thus, we add new insights on the interconnections between blood coagulation disorders in cancer patients and thrombin activation in malignant effusions, including their functional interaction with PAR in metastatic cancer cells. Based on these data we propose to counteract the metastatic cascades by targeted invalidation of key effectors of the coagulation system. Therefore, potential therapeutic approaches include the application of thrombin protease inhibitors, VEGF-blocking antibodies, and drugs targeting the VEGF and thrombin signaling pathways, such as tyrosine kinase or GPCR inhibitors.
Hyperresponsiveness of platelets in ischemic stroke
Authors: Tomandl Bernd , Sander Dirk , Stellos Konstantinos , Geisler Tobias , Langer Harald , Walton Kodwo , Handschu Rene , Garlichs Christoph , Daniel Werner , Fateh-Moghadam Suzanne , Htun Patrik , Gawaz Meinrad 
Published: June 2007

SummaryPlatelet activation and aggregation are critical in the pathogenesis of acute ischemic cerebrovascular diseases. The aim of our study was to characterize platelet function in patients with acute ischemic stroke or transient ischemic attack (TIA), and to evaluate the effect of platelet activation on clinical outcome. One hundred thirty-eight consecutive patients with TIA (n=74) or stroke (n=64) were enrolled in this study. Platelet aggregation in response to ADP, epinephrine, arachidonic acid, or collagen, and expression of platelet activation receptors (CD62P, CD63, LIBS-1 and PAC-1) in the acute phase and at three months follow-up were evaluated. Platelets derived from stroke patients were more hyperaggregable in response to agonists in the acute phase compared to TIA patients (p[ADP]=0.002, p[arachidonic acid]=0.047, p[epinephrine]=0.020). Platelet activation was enhanced in the acute phase irrespective of the severity of the disease (stroke or TIA) and returned to baseline levels three months later. Persistent elevated platelet activation at three months follow-up (PAC-1) was associated with increased incidence of recurrent stroke (median, [interquartile range] 3.4, [3.0–5.2] versus 2.9, [2.3–4.0], p=0.048). In conclusion, platelets are hyperactive in acute stroke compared with TIA. A more intensified dual antiplatelet therapy may be of benefit for stroke patients.
A novel P2Y12 adenosine diphosphate receptor antagonist that inhibits platelet aggregation and thrombus formation in rat and dog models
Authors: Vincelette Jon , Cunha Valdeci , Martin-McNulty Baby , Mallari Cornell , Fitch Richard , Alexander Serene , Islam Imadul , Buckman Brad , Yuan Shendong , Post Joseph , Subramanyam Babu , Vergona Ronald , Sullivan Mark , Dole William , Morser John , Bryant Judi , Wang Yi-Xin 
Published: June 2007

SummaryIrreversible platelet inhibitors, such as aspirin and clopidogrel, have limited anti-thrombotic efficacy in the clinic due to their bleeding risk. We have developed an orally active reversible P2Y12 receptor antagonist, BX 667.The aim of this study was to determine if the reversible antagonist BX 667 had a greater therapeutic index than the irreversible P2Y12 receptor antagonist clopidogrel. Since BX 667 is rapidly converted to its active metabolite BX 048 in rats,we first injected BX 048 intravenously (iv) in a rat arterial venous (A-V) shunt model of thrombosis.BX 048 dose- and concentration-dependently attenuated thrombosis. When administered orally, BX 667 and clopidogrel had similar efficacy, but BX 667 caused less bleeding than clopidogrel. In a rat model of a platelet-rich thrombus induced by vessel injury with FeCl2, both BX 667 and clopidogrel exhibited higher levels of thrombus inhibition after oral administration compared to their potency in the A-V shunt model.Again, BX 667 caused less bleeding than clopidogrel. In a dog cyclic flow model, iv injection of either BX 667 or clopidogrel dose-dependently reduced thrombus formation with lower bleeding for BX 667 than clopidogrel. Inhibition of thrombosis was highly correlated with inhibition of ADP-induced platelet aggregation in these animal models. In dogs pre-treated with aspirin, BX 667 maintained its wider therapeutic index, measured by inhibition of platelet aggregation over bleeding, compared to the aspirin-clopidogrel combination.These data demonstrate that the reversible P2Y12 receptor antagonist, BX 667, has a wider therapeutic index than clopidogrel in experimental models of thrombosis.
Three reactive compartments in venous malformations
Authors: Bartnick Katja , Dörge Hilmar , Becker Jürgen , Schweigerer Lothar , Ebenebe Chinedu , Diehl Stefanie , Wilting Jörg 
Published: June 2007

SummaryVascular malformations affect 3% of neonates. Venous malformations (VMs) are the largest group representing more than 50% of cases. In hereditary forms of VMs gene mutations have been identified, but for the large group of spontaneous forms the primary cause and downstream dysregulated genes are unknown. We have performed a global comparison of gene expression in slow-flow VMs and normal saphenous veins using human whole genome micro-arrays.Genes of interest were validated with qRT-PCR. Gene expression in the tunica media was studied after laser micro-dissection of small pieces of tissue. Protein expression in endothelial cells (ECs) was studied with antibodies.We detected 511 genes more than four-fold down- and 112 genes more than four-fold up-regulated. Notably, chemokines, growth factors, transcription factors and regulators of extra-cellular matrix (ECM) turnover were regulated. We observed activation and “arterialization” of ECs of the VM proper, whereas ECs of vasa vasorum exhibited up-regulation of inflammation markers. In the tunica media, an altered ECM turnover and composition was found. Our studies demonstrate dysregulated gene expression in tunica interna, media and externa of VMs, and show that each of the three layers represents a reactive compartment.The dysregulated genes may serve as therapeutic targets.
Chemokines in cardiovascular risk prediction
Authors: Yndestad Arne , Smith Camilla , Ueland Thor , Gullesta Lars , Damås Jan , Aukrust Pål 
Published: June 2007

SummaryIn consideration of the important role of inflammation in plaque progression and stability, recent work has focused on whether plasma markers of inflammation can non-invasively diagnose and predict coronary artery disease (CAD) and other forms of atherosclerotic disorders. Although several studies support an important pathogenic role of chemokines in atherogenesis and plaque destabilization, potentially representing attractive therapeutic targets in atherosclerotic disorders,this does not necessarily mean that chemokines are suitable parameters for risk prediction. In fact, the ability to reflect up-stream inflammatory activity, stable levels in individuals and high stability of the actual protein (e.g. long half-life and negligible circadian variation), are additional important criteria for an ideal biomarker in cardiovascular disease. Although plasma/serum levels of certain chemokines (e.g. interleukin 8 and monocyte chemoattractant protein- 1) have been shown to be predictive for future cardiac events in some studies, independent of traditional cardiovascular risk factors and C-reactive protein,and although certain gene polymorphisms of chemokines/chemokine receptors (e.g. fractalkine receptor) have been shown to be predictive of future atherosclerotic disease, further prospective studies, including a larger number patients,are needed to make any firm conclusion. While the demonstrations of an association between chemokines and CAD are a necessary first step, such studies do not establish the full clinical utility of a biomarker, which is a more demanding process that requires validation in multiple cohorts, and clear demonstration of incremental prognostic value over traditional risk models. If successful, such new biomarker will be a useful indicator for better risk assessment,diagnosis,and prognosis, as well as monitoring pharmacological treatments for atherosclerosis.
International Registry on Factor XIII Deficiency: A basis formed mostly on European data
Authors: Seitz Rainer , Kohler Hans , Schroeder Verena , Muszbek Laszlo , Ariens Robert , Seifried Erhard , Oldenburg Johannes , Ivaskevicius Vytautas ,   and The Study Group
Published: June 2007

SummaryFXIII deficiency is known as one of the rarest blood coagulation disorders. In this study, the phenotypic and in part genotypic data of 104 FXIII-deficient patients recorded from 1993 – 2005 are presented. The most common bleeding symptoms were subcutaneous bleeding (57%) followed by delayed umbilical cord bleeding (56%), muscle hematoma (49%), hemorrhage after surgery (40%), hemarthrosis (36%), and intracerebral bleeding (34%). Prophylactic treatment was initiated in about 70% of all patients. FXIII-B subunit-deficient patients had a milder phenotype than patients with FXIII-A subunit deficiency. The most frequent mutation affecting the F13A gene was a splice site mutation in intron 5 (IVS5–1G>A). This mutation was found in eight (17%) of 46 analyzed families. The haplotype analysis of patients carrying the IVS5–1A allele was consistent with a founder effect. The international registry (http://www.f13-database.de) will provide clinicians and scientists working on FXIII deficiency with a helpful tool to improve patient care and direct future studies towards better understanding and treatment of the disease.
Chemokines as mediators of angiogenesis
Authors: Mehrad Borna , Keane Michael , Strieter Robert 
Published: June 2007

SummaryChemokines were originally described as cytokines that mediate leukocyte recruitment to sites of inflammation. Members of a subgroup of chemokines, the CXC family, also play a critical role in both physiologic and pathologic angiogenesis, including in the context of chronic inflammation, fibrosis, and malignancy.A unique feature of this family of cytokines is that, on the basis of their structure and receptor binding, individual ligands display either angiogenic or angiostatic biological activity in the regulation of angiogenesis. In this review, we summarize the key literature in this growing field.
Chemokines at large: In-vivo mechanisms of their transport, presentation and clearance
Authors: Colditz Ian , Schneider Martin , Pruenster Monika , Rot Antal 
Published: June 2007

SummaryCompelling evidence implicates chemokines in the induction of leukocyte emigration from blood into tissues.This arguably most fundamental effect of chemokines is accomplished by triggering cognate classical G-protein-coupled chemokine receptors on the leukocyte surface. In vitro, these same receptors mediate leukocyte migration; however, the mechanisms of chemokine-induced migration differ between in-vivo and in-vitro settings. Leukocyte egress from blood is greatly influenced by haemodynamic conditions and requires full cooperation of endothelial cells.The behaviour of chemokines in their“native habitat” in vivo is controlled by their interaction with several accessory molecules which influence immobilisation, transport, clearance and degradation of chemokines and thereby determine the sites and duration of their action. Here we discuss peculiarities of the invivo actions of chemokines,the mechanisms of chemokine interaction with receptors and auxiliary molecules including interceptors, glycosaminoglycans and enzymes and illustrate how these interactions influence the outcome of chemokine activities in vivo.
Circulating P-selectin and the risk of recurrent venous thromboembolism
Authors: Hron Gregor , Eichinger Sabine , Wagner Oswald , Kyrle Paul 
Published: June 2007

SummaryThe clinical relevance of high P-selectin levels in venous thrombosis is unknown. We prospectively followed 544 patients with first unprovoked venous thromboembolism (VTE) after cessation of anticoagulation and evaluated P-selectin as a risk factor of recurrent VTE. VTE recurred in 63 (12%) patients. Patients with recurrence had significantly higher P-selectin levels than those without (45.8 mg/dl ± 16.4 vs. 40.1 mg/dl ± 13.3; p = 0.006). After four years, the probability of recurrence was 20.6% (95% confidence interval [CI] 12.6–28.5) among patients with P-selectin values above the 75th percentile of the patient population and was 10.8% (95% CI 7.2–14.3) among patients with lower values (p = 0.046). Compared to patients with low P-selectin, adjusted risk of recurrence was 1.7-fold (95% CI 1.0–2.9, p = 0.045) increased among patients with P-selectin levels exceeding the 75th percentile. We conclude that high circulating P-selectin is a risk factor of recurrent VTE.
The effect of measurement method on static weight distribution to all legs in dogs using the Quadruped Biofeedback System
Authors: Ramos V. , Shires P. K. , Werre S. R. , Phelps H. A. 
Published: June 2007

SummaryAn application to measure static quadruped load distribution would be highly beneficial in the assessment of rehabilitation and lameness in many small animal patients. The scope of this study was to analyze the effects of confinement, location and local environment on the measurement of static quadruped load distribution as measured by the Quadruped Biofeedback System in normal dogs in order to better prescribe the use of this system. A prospective study of 20 healthy adult dogs was performed to evaluate effects on measurement on quadruped load distribution. Data collection in the form of mean load per extremity was recorded four times in five positions for a total of 20 measurements for each limb. A replicated cross-over design in which a mixed effect, repeated measures analysis of variance was used to test for main effects of treatment and end as well as their interaction. The effects of right vs. left within each end and for each end was analyzed for each treatment and significance of p<0.01 was established. Measurements were taken from 20 healthy adult dogs with no obvious lameness at the time of data collection. Analysis by end suggests that measurements were affected in similar manners in comparable locations. Each method demonstrated consistency in measurement without any significant influence by day or session, suggesting that one standardized method be established for measurement. With standardization, the Quadruped Biofeedback System has potential use as a reliable instrument for the measurement of quadruped load distribution in dogs.
Measurement differences between three versus five photocells during collection of ground reaction forces in dogs
Authors: Punke J. P. , Speas A. L. , Reynolds L. R. , Andrews C. M. , Budsberg S. C. 
Published: June 2007

SummaryThe differences between velocities and accelerations obtained from three and five photocells were examined when obtaining ground reaction force (GRF) data in dogs. Ground reaction force data was collected 259 times from 16 different dogs in two experimental phases. The first phase compared velocities and accelerations reported by the two systems based on trials accepted by the three photocell system. The second phase accepted trials based on data from five photocells. Three photocell data were calculated mathematically in the second phase in order to compare the values of both systems. The velocity and acceleration values obtained from each system were significantly different (at the hundredth of a meter per second). Differences in measured values did not result in acceptance of data by the three photocell system that would not have been acceptable with the five photocell system (false positives), but did result in rejection of acceptable data by the three photocell system (11% false negative rate). Given the small differences between the two systems, GRF data collected should not be significantly different, though the three photocell system is less efficient in gathering data due to the number of trials rejected as false negatives.
Evaluation of clinical, radiographical and cytological findings compared to arthroscopic findings in shoulder joint lameness in the dog
Authors: Sjöström L. , Åkerblom S. 
Published: June 2007

SummaryForty-two dogs with lameness emanating from the shoulder joint were studied by clinical examination, radiographic examination, joint fluid analysis, and arthroscopic examination, following a set protocol. Dogs with mild clinical signs, absent or mild radiographic signs of osteoarthrosis, and without or with very mild changes in the synovial fluid, may still have moderate to severe degenerative pathological changes in the shoulder joint.