bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Evaluation of Hepatitis B 1762T/1764A Mutations on Hepatocellular Carcinoma Development in Shanghai, China
Authors: Yuan Jian-Min , Ambinder Alex , Fan Yunhua , Gao Yu-Tang , Yu Mimi C. , Groopman John D. 
Published: February 2009

Abstract
Chronic infection with the hepatitis B virus (HBV) is the most important risk factor for hepatocellular carcinoma (HCC). However, determinants of HCC risk in infected individuals are not well understood. We prospectively evaluated the association between acquired HBV 1762T/1764A double mutations and HCC risk among 49 incident HCC cases and 97 controls with seropositive hepatitis B surface antigen at baseline from a cohort of 18,244 men in Shanghai, China, enrolled during 1986 to 1989. Compared with HBV carriers without the mutations, chronic HBV carriers with the HBV 1762T/1764A double mutations experienced an elevated risk of HCC (odds ratio, 2.47; 95% confidence interval, 1.04-5.85; P = 0.04). Risk increased with increasing copies of the double mutations; men with ≥500 copies/μL serum had an odds ratio of 14.57 (95% confidence interval, 2.41-87.98) relative to those without the double mutations (Ptrend = 0.004). Thus, the HBV 1762T/1764A double mutation is a codeterminant of HCC risk for people chronically infected with HBV. (Cancer Epidemiol Biomarkers Prev 2009;18(2):590–4)
Antidepressant Medications and Change in Mammographic Density in Postmenopausal Women
Authors: Chubak Jessica , Bowles Erin J.A. , Terry Mary Beth , Trentham-Dietz Amy , Buist Diana S.M. 
Published: February 2009

Abstract
Background: Several studies suggest antidepressant medications can increase prolactin levels. Some, but not all, studies suggest prolactin levels are positively associated with mammographic breast density, an established risk factor for breast cancer.
Methods: We evaluated 29,284 women with two routine screening mammograms 9 to 28 months apart between 1996 to 2006 to examine whether antidepressant use was associated with changes in mammographic breast density. Mammographic breast density was assigned by radiologists and coded according the Breast Imaging Reporting and Data System classification. Exposure to antidepressants was ascertained based on electronic pharmacy dispensing data, including dispensings from claims data. We used polytomous logistic regression to estimate the odds of an increase or decrease in density categories between mammograms associated with antidepressant initiation, continuation, and discontinuation compared with nonusers of any antidepressants.
Results: Initiation, continuation, and discontinuation of antidepressant medications were not associated with changes in mammographic density.
Conclusions: The lack of association between antidepressant use and breast density is consistent with recent studies that do not suggest an association between antidepressant use and breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(2):676–9)
Risk Factors for Pancreatic Cancer Mortality: Extended Follow-up of the Original Whitehall Study
Authors: Batty G. David , Kivimaki Mika , Morrison David , Huxley Rachel , Smith George Davey , Clarke Robert , Marmot Michael G. , Shipley Martin J. 
Published: February 2009

Abstract
Given the well-established links between diabetes and elevated rates of pancreatic cancer, there are reasons to anticipate that other markers of metabolic abnormality (increased body mass index, plasma cholesterol, and blood pressure) and their correlates (physical activity and socioeconomic status) may also confer increased risk. However, to date, the results of a series of population-based cohort studies are inconclusive. We examined these associations in the original Whitehall cohort study of 17,898 men. A maximum of 38 years of follow-up gave rise to 163 deaths due to carcinoma of the pancreas. Although Poisson regression analyses confirmed established risk factor–disease associations for increasing age, smoking, and type II diabetes, there was essentially no evidence that body mass index (rate ratio, 1.01; 95% confidence interval per 1 SD increase, 0.86-1.18), plasma cholesterol (0.91; 0.78-1.07), diastolic blood pressure (0.93; 0.78-1.09), systolic blood pressure (0.98; 0.83-1.15), physical activity (sedentary versus high: 1.37; 0.89-2.12), or socioeconomic status [clerical (low) versus professional/executive, 0.95; 0.59-1.51] offered any predictive value for pancreatic cancer mortality. These results were unchanged following control for a range of covariates. (Cancer Epidemiol Biomarkers Prev 2009;18(2):673–5)
Will a once-weekly anticoagulant for the treatment and secondary prevention of thromboembolism improve adherence?
Authors: Maillardet Louise , Yavin Yshai , Cohen Alexander T. 
Published: February 2009

SummaryOral anticoagulation, most commonly with warfarin once daily, has long been the main form of long-term treatment and secondary prevention of thromboembolism. The efficacy of warfarin has been established in clinical trials, but problems with unstable anticoagulation with international normalized ratios (INRs) outside the recommended range due to incorrect dosing, drug and food interactions, and with adherence and persistence have been reported in practice. Poor adherence and persistence are serious problems because they result in out-of-range INRs. Many new thromboembolic events, such as strokes, occur when INRs are out-of-range or after warfarin discontinuation. Among the new anticoagulants currently being investigated, some offer the possibility of more stable anticoagulation and weekly administration. Less frequent dosing schedules generally improve adherence. In many cases, such as bisphosphonate treatment for osteoporosis, and the long-term treatment of depressive disorders or multiple sclerosis, adherence to, and persistence with, weekly dosing is improved compared with daily dosing, and most patients prefer weekly dosing. The advent of novel anticoagulants such as idraparinux with its long half-life offers hope for improved adherence with anticoagulation, and ultimately improved outcomes.
Contribution of (sub)domains of Staphylococcus aureus fibronectin-binding protein to the proinflammatory and procoagulant response of human vascular endothelial cells
Authors: Heying Ruth , Gevel Joke van de , Que Yok-Ai , Piroth Lionel , Moreillon Philippe , Beekhuizen Henry 
Published: February 2009

SummaryThe Staphylococcus aureus fibronectin (Fn) -binding protein A (FnBPA) is involved in bacterium-endothelium interactions which is one of the crucial events leading to infective endocarditis (IE). We previously showed that the sole expression of S. aureus FnBPA was sufficient to confer to non-invasive Lactococcus lactis bacteria the capacity to invade human endothelial cells (ECs) and to launch the typical endothelial proinflammatory and procoagulant responses that characterize IE. In the present study we further questioned whether these bacterium-EC interactions could be reproduced by single or combined FnBPA subdomains (A, B, C or D) using a large library of truncated FnBPA constructs expressed in L. lactis. Significant invasion of cultured ECs was found for L. lactis expressing the FnBPA subdomains CD (aa 604–877) or A4+16 (aa 432–559). Moreover, this correlates with the capacity of these fragments to elicit in vitro a marked increase in EC surface expression of both ICAM-1 and VCAM-1 and secretion of the CXCL8 chemokine and finally to induce a tissue factor-dependent endothelial coagulation response. We thus conclude that (sub)domains of the staphylococcal FnBPA molecule that express Fn-binding modules, alone or in combination, are sufficient to evoke an endothelial proinflammatory as well as a procoagulant response and thus account for IE severity.
Assessment of coagulation and fibrinolysis in families with unexplained thrombophilia
Authors: Tanck Michael W. T. , Meijers Joost C. M. , Lisman Ton , Reitsma Pieter H. , Rosendaal Frits R. , Büller Harry R. , Middeldorp Saskia , Wichers Iris M. 
Published: February 2009

SummaryDespite knowledge of various inherited risk factors associated with venous thromboembolism (VTE), no definite cause can be found in about 50% of patients. The lack of an intermediate phenotype in VTE impedes the discovery of new familial risk factors. We set out to define an intermediate phenotype for VTE by performing global coagulation analyses in unexplained thrombophilic families. Families were selected through a proband with VTE but without one of the known thrombophilic defects and at least one 1st or two 2nd degree family members with VTE. Clinical data were collected using a standardized questionnaire. Blood samples were collected for overall haemostasis assays (i.e. thrombin generation time [TGT], endogenous thrombin potential [ETP], prothrombin fragment 1+2 [F1+2] and activated protein C-sensitivity ratio [APC-sr] and clot lysis time [CLT]). Data were analysed using logistic regression. Coagulation assays were performed in 353 individuals of whom 41 (12%) had a history of VTE; these belonged to 17 thrombophilic families. Of the tested variables only the ETP was associated with VTE (odds ratio [OR] 1.03 for each % increase, 95% confidence interval [CI] 1.01–1.05). However, the relatively low number of cases does not firmly exclude the other assays as candidate intermediate phenotypes for venous thrombosis. We found that an increased ETP may serve as an intermediate phenotype for VTE and may be used to discover novel inherited risk factors by genetic linkage analysis.
Diluted Russell viper-venom time improves identification of antiphospholipid syndrome in a lupus anticoagulant-positive patient population
Authors: Ferrard-Sasson Gisele , Dubucquoi Sylvain , Hachulla Eric , Prin Lionel , Hatron Pierre-Yves , Goudemand Jenny , Boffa Marie-Claire , Caron Claudine , Lambert Marc 
Published: February 2009

SummaryThe objective of this retrospective study was to evaluate the potential ability of diluted Russell viper-venom time (dRVVT) to identify antiphospholipid syndrome (APS) in a lupus anticoagulant (LA)-positive patient population, already selected by other LA clotting tests. Our cohort of positive LA patients was first identified in our outpatients population by the following sensitive LA-detecting tests: Rosner index, diluted prothrombin time (dPT) and Rosove index. Then the 227 consecutive LA-positive patients were tested for dRVVT with the same blood sample. Anticardiolipin (aCL) and anti-β2-glycoprotein-I (β2GPI) autoantibodies assays were also performed. APS using Sapporo clinical criteria revised at Sydney, was found in 116 of these 227 consecutive LA-positive patients. Results of the different tests were analysed statistically. Using univariate analysis, dRVVT, dPT, IgG aCL and IgG anti-β2GPI autoantibodies were significantly associated with APS. The receiver operating-characteristics (ROC) curve defined the best cut-off value for dRVVT ratio at 1.61 with a good specificity (78%) and a lower sensitivity (53%). A multivariate analysis using a binary logistic procedure, retained the dRVVT ratio (≥ 1.61) and IgG anti-β2GPI autoantibodies (> 15 USG) as being associated with APS (p = 0.018; odds ratio [OR] 2.39; 95% confidence interval [CI] 1.2–4.7, and p = 0.0001; OR 3.2; 95% CI 1.5–6.5, respectively). To conclude, these results agree with the need for LA criteria favouring specificity over sensitivity. The use of a threshold around 1.6 for dRVVT ratio should help discriminate APS from non-APS patients.
Cell-based therapy facilitates venous thrombus resolution
Authors: Ballmoos Moritz Wyler von , Diehm Nicolas , Völzmann Jan , Baumgartner Iris , Santo Stefano Di , Tepper Oren M. , Kalka Christoph 
Published: February 2009

SummaryEndothelial progenitor cells (EPC) are involved in many healing processes in cardiovascular diseases and can be found in spontaneously resolving venous thrombi. The purpose of the present study was to investigate whether the therapeutic administration of EPC might enhance the resolution of venous thrombi. For this purpose, venous thrombosis was induced in the infrarenal inferior vena cava (IVC) in 28 athymic nude rats. Culture expanded EPC derived from human peripheral blood mononuclear cells were injected intravenously two and four days after thrombus induction. Recanalisation of the IVC and thrombus organisation were assessed by laser Doppler measurements of the blood flow and immunohistochemical detection of endothelialised luminal structures in the thrombus. EPC transplantation resulted in significantly enhanced thrombus neovascularisation (capillary density: 186.6 ± 26.7/HPF vs. 78 ± 12.3/HPF, p<0.01; area covered by capillaries: 8.9 ± 1.7 µm2 vs. 2.5 ± 1.3 µm2, p<0.01) and was accompanied by a substantial increase in intrathrombus blood flow (perfusion ratio: 0.7 ± 0.07 vs. 0.3 ± 0.08, p<0.02). These results were paralleled by augmented macrophage recruitment into resolving thrombi in the animals treated with EPC (39.4 ± 4.7/HPF vs. 11.6 ± 1.9/HPF, p<0.01). Our data suggest that EPC transplantation might be of clinical value to facilitate venous thrombus resolution in cases where current therapeutic options have limited success.
Rapid molecular diagnosis of von Willebrand disease by direct sequencing. Detection of 12 novel putative mutations in VWF gene
Authors: Corrales Irene , Ramírez Lorena , Altisent Carme , Parra Rafael , Vidal Francisco 
Published: February 2009

SummaryMolecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal von Willebrand factor gene (VWF) is large and highly polymorphic, and there is a highly homologous (>96%) partial pseudogene in chromosome 22. Because of these difficulties, application of molecular study of VWD to the clinical routine has been considerably delayed. Recent advances in sequencing technology and bioinformatics could convert direct sequencing of the complete VWF into a routine diagnostic tool for VWD, which is especially desirable in types 1 and 3. This study describes a highly optimized procedure in which all the coding and intronic flanking regions of VWF are amplified under identical thermocycling parameters in a ready-to-use PCR plate format. The entire sequencing procedure, from blood extraction to mutation identification, can be done within 24 hours, resulting in a simple, versatile, cost-effective strategy with little hands-on time requirements. To validate the method, we performed full-length VWF sequencing of 21 index cases including seven of each VWD type. A total of 30 VWF genetic variations were identified. Twelve of these sequence variations are new, including four missense, one nonsense, one insertion, the first insertion-deletion described in VWF, and 5 potential splice site mutations. To our knowledge, this is the fastest and most efficient protocol designed to date for complete sequencing of the VWF coding region in the molecular diagnosis of VWD.
Levels of inflammatory markers and the development of the post-thrombotic syndrome
Authors: Shbaklo Hadia , Holcroft Christina A. , Kahn Susan R. 
Published: February 2009

SummaryThe post-thrombotic syndrome (PTS) occurs frequently after deep venous thrombosis (DVT) despite appropriate anticoagulant therapy. A close relationship between inflammation and thrombosis exists. While the inflammatory process at the time of DVT appears to improve thrombus resolution, it may promote destruction of venous valves, valvular reflux and subsequent development of PTS. We prospectively evaluated the association between levels of four cytokines (IL-6, IL-8, IL-10 and MCP-1), two adhesion molecules (ICAM-1 and VCAM-1) and the development of PTS in a well-defined cohort of patients with DVT. The study population consisted of 387 patients with objectively diagnosed symptomatic DVT who were followed for two years to determine the incidence of PTS. At the end of follow-up, plasma samples frozen at the four-month visit in 307 study patients were thawed and analyzed for the above inflammatory markers using the Luminex beads technology. Mean levels of IL-6 were significantly higher in patients with PTS compared to patients without PTS (7.35 pg/ml ± 14.26 [SD] vs. 4.60 pg/ml ± 4.90;p=0.03). Logistic regression analyses showed significant associations between PTS and levels above vs. below the median of IL-6 [odds ratio (OR) 1.66; 95% confidence interval (CI) 1.05, 2.62 (p=0.03)] and ICAM-1 [OR 1.63; 95% CI 1.03, 2.58 (p=0.04)]. None of the other markers showed any association with PTS. Our study suggests the presence of significant associations between markers of inflammation such as IL-6 and ICAM-1 and the development of PTS. Further work is needed to evaluate this relationship and to analyse other candidate markers that could be implicated etiologically in the association between DVT and PTS. If confirmed, this could lead to identification of new therapeutic targets for preventing PTS after DVT.
Cell-derived microparticles in haemostasis and vascular medicine
Authors: Burnier Laurent , Fontana Pierre , Kwak Brenda R. , Angelillo-Scherrer Anne 
Published: February 2009

SummaryConsiderable interest for cell-derived microparticles has emerged, pointing out their essential role in haemostatic response and their potential as disease markers, but also their implication in a wide range of physiological and pathological processes. They derive from different cell types including platelets – the main source of microparticles – but also from red blood cells, leukocytes and endothelial cells, and they circulate in blood. Despite difficulties encountered in analyzing them and disparities of results obtained with a wide range of methods, microparticle generation processes are now better understood. However, a generally admitted definition of microparticles is currently lacking. For all these reasons we decided to review the literature regarding microparticles in their widest definition, including ectosomes and exosomes, and to focus mainly on their role in haemostasis and vascular medicine.
Venous thromboembolism in pregnancy: diagnosis, management and prevention
Authors: Bates Shannon M. , Chunilal Sanjeev D. 
Published: February 2009

SummaryA pregnant woman has a two- to five-fold higher risk of venous thromboembolism (VTE) than a non-pregnant woman of the same age and, in developed countries, she is more likely to die from fatal pulmonary embolism (PE) than from obstetric haemorrhage. The increased VTE risk is mediated through normal physiological changes of pregnancy including alterations in haemostasis that favour coagulation, reduced fibrinolysis and pooling and stasis of blood in the lower limbs. Thrombophilia, smoking, obesity, immobility and postpartum factors such as infection, bleeding and emergency surgery (including emergency caesarian section) also increase the risk of pregnancy-related VTE. The diagnosis of VTE can be safely established with acceptable radiation exposure to the fetus using readily available imaging modalities such as ultrasound, ventilation perfusion lung scanning and computed tomographic pulmonary angiography. However, the optimal diagnostic strategies still remain to be determined. If there is no contraindication to anticoagulation, commencing treatment prior to objective confirmation should be strongly considered. For the mother and fetus, effective and safe treatment is readily available with low-molecular-weight heparin (LMWH), but optimal dosing of these agents in pregnancy remains controversial. Emerging data support antepartum LMWH prophylaxis for women with previous VTE if the event was unprovoked or in the presence of thrombophilia. On the other hand, women with prior provoked VTE and no thrombophilia or women with asymptomatic thrombophilia (but a family history of VTE) can safely be managed with antepartum surveillance. Postpartum prophylaxis is recommended for women with prior VTE or thrombophilia (and a family history of VTE).
International normalised ratio (INR) measured on the CoaguChek S and XS compared with the laboratory for determination of precision and accuracy
Authors: Larsen Torben B. , Jensen Claus , Maegaard Marianne , Sørensen Benny , Christensen Thomas D. 
Published: February 2009

SummaryOral anticoagulation therapy is monitored by the use of international normalised ratio (INR). Patients performing self-management estimate INR using a coagulometer, but studies have been partly flawed regarding the estimated precision and accuracy. The objective was to estimate the imprecision and accuracy for two different coagulometers (CoaguChek® S and XS). Twenty-four patients treated with coumarin were prospectively followed for six weeks. INR’s were analyzed weekly in duplicates on both coagulometers, and compared with results from the hospital laboratory. Statistical analysis included Bland-Altman plot, 95% limits of agreement, coefficient of variance (CV), and an analysis of variance using a mixed effect model. Comparing 141 duplicate measurements (a total of 564 measurements) of INR, we found that the CoaguChek S and CoaguChek XS had a precision (CV) of 3.4% and 2.3%, respectively. Regarding analytical accuracy, the INR measurements tended to be lower on the coagulometers, and regarding diagnostic accuracy the CoaguChek S and CoaguChek XS deviated more than 15% from the laboratory measurements in 40% and 43% of the measurements, respectively. In conclusion, the precision of the coagulometers was found to be good, but only the CoaguChek XS had a precision within the predefined limit of 3%. Regarding analytical accuracy, the INR measurements tended to be lower on the coagulometers, compared to the laboratory. A large proportion of measurement of the coagulometers deviated more than 15% from the laboratory measurements. Whether this will have a clinical impact awaits further studies.
Subtherapeutic oral anticoagulant therapy: Frequency and risk factors
Authors: Rombouts Eva K. , Rosendaal Frits R. , van der Meer Felix J. M. 
Published: February 2009

SummarySubtherapeutic anticoagulation levels increase both the risk and severity of thromboembolism. The aim of this study was to determine the cumulative incidence of subtherapeutic international normalised ratios (INRs) and to identify risk factors associated with a low INR. We performed a cohort study in 7,419 patients from a Dutch anticoagulation clinic. Patients who started a first treatment with oral anticoagulants between January 2000 and December 2005 and who were stably anticoagulated (4 consecutive INRs in the therapeutic range) were included. Within the cohort a nested case control study was performed to identify risk factors of subtherapeutic INRs and to determine how often a subtherapeutic INR is the result of medical interference in case of invasive procedures, hospital admissions, haemorrhage or overanticoagulation. In patients with a stable anticoagulation, the median time to a first low INR was 40 weeks. A subtherapeutic INR occurred twice as often in patients using acenocoumarol as in those using phenprocoumon (hazard ratio [HR] 2.1, 95% confidence interval [95%CI]:2.0 – 2.3) and was more common in patients with a high therapeutic range compared to a low therapeutic range (HR 1.8, 95%CI:1.5 – 2.2). Occurrence of a low INR also depended on indication for anticoagulant therapy, with the highest risk in patients who used anticoagulants as prophylaxis and the lowest risk in patients with mechanical heart valves. In 30% of cases the subtherapeutic INR was preceded by an event necessitating vitamin K or discontinuation of the anticoagulant drug.