bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Gemfibrozil and Ciprofibrate on Plasma Levels of Tissue-type Plasminogen Activator, Plasminogen Activator Inhibitor-1 and Fibrinogen in Hyperlipidaemic Patients
Authors: Kockx Maaike , de Maat Moniek P M , Knipscheer Haye C , Kastelein John J P , Kluft Cornelis , Princen Hans M G , Kooistra Teake 
Published: July 2018

SummaryEvaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different way. Fibrinogen antigen levels were elevated by 17.6% (p <0.05) and 24.3% (p <0.001) with gemfibrozil after six and twelve weeks, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional fibrinogen levels were decreased by 10.1% (p <0.001) and 10.5% (p <0.0001), respectively on the basis of Clauss mechanical and by 14.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen.Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen.
High Antibody Levels to Prothrombin Imply a Risk of Deep Venous Thrombosis and Pulmonary Embolism in Middle-aged Men
Authors: Palosuo Timo , Virtamo Jarmo , Haukka Jari , Taylor Philip R , Aho Kimmo , Puurunen Marja , Vaarala Outi 
Published: July 2018

SummaryAntibodies against phospholipid-binding plasma proteins, such as β2-glycoprotein I (β2-GPI) and prothrombin, are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins β2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis. The antibodies were measured in stored serum samples from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register.The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchitis, myocardial infarction and heart failure at baseline, the odds ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes.In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes.
Effect of Oxidized Low Density Lipoprotein on Thrombomodulin Expression by THP-1 Cells
Authors: Oida Koji , Tohda Gen , Ishii Hidemi , Horie Shuichi , Kohno Mitsuyuki , Okada Eiko , Suzuki Jinya , Nakai Jsuguhiko , Miyamori Isamu 
Published: July 2018

SummaryWe have investigated the effects of oxidized low density lipoproteins (oxidized LDL) on the expression of TM by THP-1 monocytic cells. TM antigen levels and its cofactor activity for thrombin-dependent protein C activation were increased by oxidized LDL and accompanied by an increase in TM mRNA levels. Incubation of THP-1 cells with 300 μg/ml oxidized LDL for 24 h resulted in an 80% increase of cellular TM antigen levels. Native LDL and acetylated LDL did not affect the TM expression by these cells. The resultant aqueous phase after extraction of oxidized LDL by chloroform/methanol increased the TM antigen levels as well as oxidized LDL. Phorbol 12-myristate 13-acetate (PMA) also increased the TM antigen level 2.1 times the control and was accompanied by the adhesion of cells to plastic dishes and increasing macrophage cell surface antigen CD 14 levels. In contrast, oxidized LDL did not induce differentiation to the macrophage. The present results indicate that oxidized LDL increases cellular TM antigen without cellular differentiation and that up-regulation of TM by oxidized LDL in monocytes may have some implication in atherosclerosis.
An in vivo Model for the Assessment of Acute Fibrinolytic Capacity of the Endothelium
Authors: Newby David E , Wright Robert A , Ludlam Christopher A , Fox Keith A A , Boon Nicholas A , Webb David J 
Published: July 2018

SummaryThe effects on blood flow and plasma fibrinolytic and coagulation parameters of intraarterial substance P, an endothelium dependent vasodilator, and sodium nitroprusside, a control endothelium independent vasodilator, were studied in the human forearm circulation. At subsystemic locally active doses, both substance P (2-8 pmol/min) and sodium nitroprusside (2-8 μg/min) caused dose-dependent vasodilatation (p <0.001 for both) without affecting plasma concentrations of PAI-1, von Willebrand factor antigen or factor VIII:C activity. Substance P caused local increases in t-PA antigen and activity (p <0.001) in the infused arm while sodium nitroprusside did not. At higher doses, substance P increased blood flow and t-PA concentrations in the noninfused arm. We conclude that brief, locally active and subsystemic infusions of intraarterial substance P cause a rapid and substantial local release of t-PA which appear to act via a flow and nitric oxide independent mechanism. This model should provide a useful and selective method of assessing the in vivo capacity of the forearm endothelium to release t-PA acutely.
Testing for Occult Cancer in Patients with Idiopathic Deep Vein Thrombosis – A Decision Analysis
Authors: Barosi Giovanni , Marchetti Monia , Dazzi Luisella , Quaglini Silvana 
Published: July 2018

SummaryObjective. To determine the effectiveness and cost-effectiveness of testing for occult cancer in idiopathic deep vein thrombosis (IDVT). Design. Threshold analysis was performed on the risk-adjusted cancer prevalence in a cost-effectiveness model of ideal testing for selecting cancers with potentially desirable utility (candidate cancers). Decision analysis was employed to compare different testing programs for candidate cancers with that of no testing. Life expectancy (LE) of early- and late-detected cancers and costs of testing were the dimensions of utility. Cost-effectiveness was expressed as marginal cost per year of life saved. The perspective of the third payer was adopted, and a discount rate of 3% was applied to both costs and benefits. Data sources. Risk of cancer in IDVT, testing policies, test characteristics, and LE were gathered from literature. Costs were provided from our hospital rate book and accounting service. Results. Ideal testing would support a gain of LE of 40 days or more for prostate, colon and bladder cancer in males and for colon, breast and endometrium cancer in females aged from 60 to 69 years. Testing females with colonoscopy and mammography in any sequence provides 70 days of life gained. Testing males with colonoscopy provides 27 days of life gained. Lower and older ages reduce testing effectiveness. The qualitative results are stable over plausible ranges of test characteristics, while variations in the value of benefit for early cancer diagnosis may modify the strategy. Incremental cost-effectiveness ranges from $ 1,789 to $ 6,979 per year of life gained. Conclusions. According to the effectiveness criterion adopted, the only worthwhile investigation strategy includes colon and breast cancer in females. Testing for colon cancer in males is desirable at a lower criterion of effectiveness. All the strategies are cost effective.
Endothelial Marker Proteins in Hyperhomocysteinemia
Authors: Jong Sylvia C de , Stehouwer Coen D A , Berg Michiel van den , Vischer Ulrich M , Rauwerda Jan A , Emeis Jef J 
Published: July 2018

SummaryHyperhomocysteinemia is associated with severe, premature atherosclerosis and thromboembolism. The mechanisms involved in the atherogenic and thrombotic complications of hyperhomocysteinemia are not understood. It has been suggested that hyperhomocysteinemia predisposes to atherosclerosis by injuring the vascular endothelium. Whether hyperhomocysteinemia is independently associated with changed endothelial function, either in the absence or the presence of clinically manifest atherosclerotic disease, is, however, not known. Therefore we investigated, both in patients with peripheral arterial occlusive disease and in healthy individuals, whether plasma protein markers of endothelial function differed between subjects with, and subjects without hyperhomocysteinemia. We studied 80 individuals under the age of 56 years: healthy individuals with (n = 20) and without (n = 20) hyperhomocysteinemia and patients with peripheral arterial occlusive disease with (n = 20) and without (n = 20) hyperhomocysteinemia. The following endothelium-derived proteins were measured as markers of endothelial cell function: von Willebrand factor (vWf) and von Willebrand factor propeptide (vWf: Agll), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), cellular fibronectin (cFN) and thrombomodulin ™. In addition we assessed C-reactive protein (CRP). vWf, vWf: Agll, tPA and CRP were significantly higher in the patients with peripheral arterial occlusive disease than in the healthy individuals. No differences in marker protein plasma levels were found between individuals with, and those without hyperhomocysteinemia, apart from vWf, which was significantly raised in hyperhomocysteinemic as compared to normohomocysteinemic patients. We did not find any evidence for an independent association between hyperhomocysteinemia and protein markers of endothelial cell function in healthy subjects.
A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A
Authors: Aygören-Pürsün Emel , Scharrer Inge ,   German Kogenate Study Group
Published: July 2018

SummaryIn this open multicenter study the safety and efficacy of recombinant factor VIII (rFVIII) was assessed in 39 previously treated patients with hemophilia A (factor VIII basal activity ≤15%).Recombinant FVIII was administered for prophylaxis and treatment of bleeding episodes and for surgical procedures. A total of 3679 infusions of rFVIII were given. Efficacy of rFVIII as assessed by subjective evaluation of response to infusion and mean annual consumption of rFVIII was comparable to that of plasma derived FVIII concentrates. The incremental recovery of FVIII (2.4 ± 0,83%/IU/kg, 2.12 ± 0.61%/IU/kg, resp.) was within the expected range. No clinical significant FVIII inhibitor was detected in this trial. Five of 16 susceptible patients showed a seroconversion for parvovirus B19. However, the results are ambiguous in two cases and might be explained otherwise in one further case. Thus, in two patients a reliable seroconversion for parvovirus B19 was observed.
Antivasoconstrictor and Antiaggregatory Activities of Picotamide Unrelated to Thromboxane A2 Antagonism
Authors: Vezza Roberta , Spina Domenico , Tallarida Ronald J , Nathan Malevika , Page Clive P , Gresele Paolo 
Published: July 2018

SummaryPicotamide is a dual thromboxane (Tx) A2 receptor antagonist/Tx synthase inhibitor although some observations suggest an anti-vasoconstrictor effect independent of TxA2 inhibition/antagonism. The aim of our study was to assess whether picotamide antagonises vascular contractions induced by different vasoactive substances in vitro. Picotamide inhibited competitively the contraction of rabbit aortic rings induced by the TxA2 mimetic U46619 (pA2 = 3.59) but also the contractions induced by phenylephrine (pA2 = 3.93) and serotonin (5-HT) (pA2 = 5.81) although in a not competitive way. Picotamide did not inhibit potassium-induced contractions, thus excluding aspecific effects on vascular smooth muscle. Picotamide inhibited 5-HT-induced platelet aggregation in vitro with an IC50 (212 μM) similar to that found when other aggregating stimuli are used, but it did not affect shape change (IC50> 1 mM) suggesting that the effects of picotamide can not be ascribed to 5-HT2-receptor antagonism; in the same experimental conditions neither a Tx-receptor antagonist (BM13.177) nor a dual Tx-receptor antagonist/synthase inhibitor (ridogrel) affected 5-HT-induced platelet responses.Our studies demonstrate that picotamide exerts antivasoconstrictor and platelet inhibitory effects unrelated to TxA2 antagonism. This activity may contribute to the anti-thrombotic/anti-ischaemic effects of the drug in vivo.
Platelet Activation Markers in Patients with Peripheral Arterial Disease
Authors: Gresele Paolo , Catalano Mariella , Giammarresi Carlo , Volpato Raul , Termini Rosanna , Ciabattoni Giovanni , Nenci Giuseppe G , Davì Giovanni 
Published: July 2018

SummaryPeripheral vascular disease (PVD) is an indicator of diffuse atherosclerosis and is associated with a greatly increased incidence of coronary heart and cerebrovascular disease. Although several studies have assessed whether in vivo platelet activation takes place in patients with PVD, no data are available comparing different platelet function tests in this patient population.We have compared prospectively four tests for the measurement of in vivo platelet activation (plasma βTG, plasma PF4, intraplatelet (βTG and urinary excretion of 11-dehydro-TXB2) and one in vitro platelet function test (ADP-induced platelet aggregation) in 63 well-characterized patients with intermittent claudication and in 18 age- and sex- matched healthy volunteers.No statistically significant difference was found between patients and controls for plasma βTG (20.0 ± 11.8 vs. 18.8 ± 9.0 ng/ml, respectively), plasma PF4 (5.2 ± 2.9 vs. 6.3 ± 3.5 ng/ml), βTG/PF4 ratio (4.0 ± 2.9 vs. 3.6 ± 1.8), intraplatelet pTG (4503 ± 1482 vs. 4059 ± 1065 ng/ml), and threshold aggregatory concentration of ADP (1.7 ± 0.72 vs. 1.45 ± 0.56 μM).Urinary 11-dehydro-TXB2 was instead significantly higher in the PVD group (55.4 ± 27.5 vs. 26.7 ± 7.0 ng/h, p <0.001).Our study shows that urinary 11-dehydro-TXB2 is a more sensitive index of in vivo platelet activation than the measurement of either platelet specific proteins or of in vitro platelet aggregation in patients with PVD.
Systemic Coagulation and Fibrinolysis in Patients with or at Risk for the Adult Respiratory Distress Syndrome
Authors: Groeneveld A B J , Kindt I , Raijmakers P G H M , Hack C E , Thijs L G 
Published: July 2018

SummaryThe authors sought to evaluate the pathogenetic and prognostic role of a procoagulant and hypofibrinolytic state in the adult respiratory distress syndrome (ARDS). Twenty-two consecutive patients admitted to the intensive care unit (ICU) for respiratory monitoring (n = 2) or mechanical ventilation (n = 20) were studied, of whom 13 had ARDS and 9 were at risk for the syndrome. Plasma levels of thrombin-anti- thrombin III complexes (TAT), the plasmin-α2-antiplasmin complexes (PAP), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1) were measured within 48 h after admission, together with respiratory variables allowing computation of the lung injury score (LIS), and pulmonary microvascular permeability [67Gallium-transferrin pulmonary leak index (PLI)], as measures of pulmonary dysfunction. Blood was also sampled 6-hourly until 2 days after admission. The LIS and PLI were higher in ARDS than at risk patients, in the presence of similar systemic morbidity and mortality. TAT complexes were elevated in a minority of patients of both groups, whereas the PAP, tPA and PAI levels were elevated above normal in the majority of ARDS and at risk patients, but groups did not differ. Neither circulating coagulation nor fibrinolysis variables correlated to either LIS or PLI. Furthermore, the course of haemostatic variables did not relate to outcome. These data indicate that systemic activation of coagulation and impaired fibrinolysis do not play a major role in ARDS development and outcome in patients with acute lung injury.
von Willebrand Factor Mediates Increased Platelet Retention in Recurrent Thrombotic Thrombocytopenic Purpura
Authors: Karpman Diana , Lethagen Stefan , Kristoffersson AnnCharlotte , Isaksson Christina , Holmberg Lars 
Published: July 2018

SummaryThe plasma cryoprecipitate of two brothers with recurrent thrombotic thrombocytopenic purpura (TTP) was previously found to mediate increased platelet retention and contain ultra-large von Willebrand factor (vWF) multimers during remissions. We conducted this study to examine if vWF is involved in the increased platelet retention in TTP. Platelet retention decreased when the patients’ plasma was incubated with a monoclonal antibody directed to the vWF epitope which interacts with the platelet receptor glycoprotein Ib or when incubated with a Fab-fragment directed to the platelet receptor glycoprotein IIb/IIIa. Replacement of patient vWF with an equivalent concentration of a factor VIII/vWF concentrate containing no ultra-large vWF multimers was accompanied by a normalization of platelet retention. These results indicate that vWF is involved in the increased platelet retention. Analysis of polymorphic markers in the vWF gene demonstrated that a recessive mutation in this gene is unlikely.
A Study of Platelet Activation during Human Cardiopulmonary Bypass and the Effect of S-Nitrosoglutathione
Authors: Langford Edward J , Parfitt Andrew , de Beider Adam J , Marrinan Michael T , Martin John F 
Published: July 2018

SummaryCardiac surgery is complicated by the occurrence of post-operative bleeding due to platelet dysfunction. This is largely caused by platelet activation and consumption during cardiopulmonary bypass. Patients undergoing cardiac surgery requiring cardiopulmonary bypass were studied to determine whether early platelet changes due to bypass could be inhibited using the platelet-selective nitric oxide donor S-nitroso-glutathione (GSNO). Flow cytometry was used to measure platelet surface expression of P-selectin (an α-granule protein) and glycoproteins (GP) IIb/IIIa and Ib (mediators of aggregation and adhesion) before and 5 and 10 min after commencing cardiopulmonary bypass, in 6 controls and 6 patients receiving GSNO 50 μg/min. Platelet P-selectin expression increased during bypass both in controls and patients receiving GSNO. Glycoproteins IIb/IIIa and Ib fell during bypass in control and GSNO-treated patients. There was no difference between control and GSNO-treated groups. Thus no significant platelet inhibition by S-nitrosoglutathione was demonstrated under these conditions.
The Development of Heuristics for Evaluation of Dashboard Visualizations
Authors: Dowding Dawn , Merrill Jacqueline 
Published: July 2018

Background Heuristic evaluation is used in human–computer interaction studies to assess the usability of information systems. Nielsen's widely used heuristics, first developed in 1990, are appropriate for general usability but do not specifically address usability in systems that produce information visualizations.
Objective This article develops a heuristic evaluation checklist that can be used to evaluate systems that produce information visualizations. Principles from Nielsen's heuristics were combined with heuristic principles developed by prior researchers specifically to evaluate information visualization.
Methods We used nominal group technique to determine an appropriate final set. The combined existing usability principles and associated factors were distributed via email to a group of 12 informatics experts from a range of health care disciplines. Respondents were asked to rate each factor on its importance as an evaluation heuristic for visualization systems on a scale from 1 (definitely don't include) to 10 (definitely include). The distribution of scores for each item were calculated. A median score of ≥8 represented consensus for inclusion in the final checklist.
Results Ten of 12 experts responded with rankings and written comments. The final checklist consists of 10 usability principles (7 general and 3 specific to information visualization) substantiated by 49 usability factors. Three nursing informatics experts then used the checklist to evaluate a vital sign dashboard developed for home care nurses, using a task list designed to explore the full functionality of the dashboard. The experts used the checklist without difficulty, and indicated that it covered all major usability problems encountered during task completion.
Conclusion The growing capacity to generate and electronically process health data suggests that data visualization will be increasingly important. A checklist of usability heuristics for evaluating information visualization systems can contribute to assuring high quality in electronic data systems developed for health care.