bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient radiation exposure during diagnostic and therapeutic interventional neuroradiology procedures
Authors: Alexander M D , Oliff M C , Olorunsola O G , Brus-Ramer M , Nickoloff E L , Meyers P M 
Published: December 2009

PurposeIncreasing in number and complexity, interventional neuroradiology (INR) procedures are becoming an important source of radiation exposure for patients. In accordance with the ALARA principle, radiation exposure during INR procedures should be curtailed as much as possible while reaching successful treatment outcomes. Moreover, the extent of radiation exposure should be one outcome measure used to assess new technologies and procedural efficacy, and training programs should include techniques for exposure limitation. This study provides a methodology and preliminary data to assess radiation exposure during different INR procedure types.Materials and methodsAll patients undergoing endovascular procedures in two biplanar dedicated neuroangiography suites at a major academic medical center were monitored according to procedure type, pathological indication, fluoroscopy time and machine-generated patient dose estimates between April 2006 and July 2008.Results1678 patients underwent cerebral arteriography during the study period. Women (62.1%) accounted for the majority of patients, but men (38.9%) were more likely to undergo an interventional procedure than women (32.8%). Diagnostic studies accounted for 64.9% of procedures. Variable exposures were found between diagnostic and interventional procedures. Exposure differed depending on indications for the procedure and procedure type.ConclusionRadiation exposure is an increasingly important consideration in the development of minimally invasive neurological procedures including cerebral angiography and INR. The type of procedure and lesion type allow the practitioner to estimate radiation exposure. Such information informs the clinical decision making process. Normative data should be collected and used for comparison purposes as one measure of technical and procedural success.
Influence of spatial positioning within stream networks on fish assemblage structure in the Kansas River basin, USA
Authors: Thornbrugh Darren J. , Gido Keith B. 
Published: December 2009

We found that riverine confluences had localized effects (within 20 km) on stream fish assemblages of the Kansas River basin. The majority of variation in fish assemblages occurred from east to west and along a stream size gradient. After controlling for the influences of longitude and stream size, distance of sample sites from streams ≥ 5th order accounted for a small proportion of taxonomic variability. However, species richness was significantly higher and assemblage structure was different in tributary stream segments directly connected to larger-ordered streams, suggesting that the effects of spatial position within this stream network were greatest in close proximity to tributary–mainstem confluences. Fish collections from three intensively sampled tributaries also indicated an abrupt change in species assemblages between mainstem river sites and tributary sample sites above confluences, followed by a gradual taxonomic change with increasing distance up to 20 km from the confluence. Changes in fish assemblages were associated with the reduced abundance of adult stream species near the confluence with the mainstem, rather than the occurrences of riverine species in the tributary.
What is the appropriate approach to prevention of thromboembolism in heart failure?
Authors: Schumaecker Matthew , Homma Shunichi , Freudenberger Ronald 
Published: December 2009

SummaryMany studies suggest a higher incidence of thromboembolic syndromes such as stroke, peripheral arterial thrombosis and pulmonary embolism in patients with heart failure (HF), particularly those with left ventricular systolic dysfunction. As a result, some clinicians have chosen to treat patients with HF with anticoagulants as primary prevention against thromboembolic events. However, this practice is not well-supported by scientific data. Retrospective analyses of large HF trials have yielded contradictory results and randomised trials designed to specifically address this question have been under-populated and under-powered. As a result, there is no general consensus among professional societies in either recommending or advising against anticoagulants in HF. We hope that ongoing clinical trials, WARCEF in particular, will yield results that will guide clinicians in deciding for or against routine use of anticoagulants in HF.
Loss of high-molecular-weight von Willebrand factor multimers mainly affects platelet aggregation in patients with aortic stenosis
Authors: Eslam Roza Badr , Schneller Alexandra , Kaider Alexandra , Koren Daniela , Eichelberger Beate , Rosenhek Raphael , Budde Ulrich , Lang Irene , Panzer Simon 
Published: December 2009

SummarySevere aortic stenosis is associated with a haemostatic abnormality that resembles acquired von Willebrand syndrome type 2. It is assumed that high shear conditions render large von Willebrand factor (VWF) multimers accessible to cleavage by ADAMTS-13. However, whether loss of these large multimers affects platelet function by impairing adhesion, aggregate formation, or both has not been evaluated in clinical studies. We prospectively enrolled 47 patients with severe aortic stenosis, and studied them prior to aortic valve surgery and at a median of six months after valve replacement. We investigated levels of large VWF multimers, platelet function under high shear conditions, and residual response to suboptimal concentrations of ADP to express P-selectin. As expected, there was a significant reduction of VWF large multimers before surgery that resolved thereafter in most patients (p<0.0001). The closure time of the ADP cartridge of the PFA-100 was also corrected in most patients after the operation (p<0.0001). We used the cone and plate(let) analyser Impact-R to differentiate between adhesion and aggregation. Both adhesion (p=0.03) and ADP-inducible platelet aggregation (p=0.002) improved considerably after valve replacement. Consequently, ADP-inducible expression of P-selectin was higher after valve replacement (p=0.001). We conclude that reduced levels of large VWF multimers associated with aortic stenosis lead to impairment of both adhesion and, especially, ADP-inducible platelet aggregation.
Impaired thrombin generation and fibrin clot formation in patients with dilutional coagulopathy during major surgery
Authors: Schols Saskia , Lancé Marcus , Feijge Marion , Damoiseaux Jan , Marcus Marco , Hamulyák Karly , Cate Hugo ten , van Pampus Elisabeth , Heemskerk Johan 
Published: December 2009

SummaryPatients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53–60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38–41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88–93% of the patients with (persistent) bleeding, but only in 40–53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.
Sulfated, low-molecular-weight lignins are potent inhibitors of plasmin, in addition to thrombin and factor Xa: Novel opportunity for controlling complex pathologies
Authors: Henry Brian , Aziz May Abdel , Zhou Qibing , Desai Umesh 
Published: December 2009

SummaryRecently we prepared sulfated, low-molecular-weight lignins (LMWLs) to mimic the biological activities of heparin and heparan sulfate. Chemo-enzymatically prepared sulfated LMWLs represent a library of diverse non-sugar, aromatic molecules with structures radically different from the heparins, and have been found to potently inhibit thrombin and factor Xa. To assess their effect on the fibrinolytic system, we studied the interaction of LMWLs with human plasmin. Enzyme inhibition studies indicate that the three sulfated LMWLs studied inhibit plasmin with IC50 values in the range of 0.24 and 1.3 μM, which are marginally affected in the presence of antithrombin. Similarly, plasmin degradation of polymeric fibrin is also inhibited by sulfated LMWLs. Michaelis-Menten kinetic studies indicate that maximal velocity of hydrolysis of chromogenic substrates decreases nearly 70% in the presence of LMWLs, while the effect on Michaelis constant is dependent on the nature of the substrate. Competitive binding studies indicate that the sulfated LMWLs compete with full-length heparin. Comparison with thrombin-heparin crystal structure identifies an anionic region on plasmin as a plausible sulfated LMWL binding site. Overall, the chemoenzymatic origin coupled with coagulation and fibrinolysis inhibition properties of sulfated LMWLs present novel opportunities for designing new pharmaceutical agents that regulate complex pathologies in which both systems are known to play important roles such as disseminated intravascular coagulation.
Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with moderate renal impairment undergoing total knee or hip replacement
Authors: Roskell Neil , Plumb Jonathan , Clemens Andreas , Noack Herbert , Robinson Paul , Dolan Gerry , Brenkel Ivan , Wolowacz Sorrel 
Published: December 2009

SummaryOral dabigatran etexilate is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing total knee replacement or total hip replacement. We investigated the cost-effectiveness of the 150 mg once daily (od) dose recommended for patients aged over 75 or with moderate renal impairment, from a United Kingdom National Health Service perspective. Dabigatran etexilate was compared with subcutaneous enoxaparin 40 mg od, using a decision model. Risks for VTE and bleeding were derived from subgroup analyses of the phase III trials. Dabigatran etexilate was less costly than enoxaparin; cost savings varied from £62 to £274 (base-case analyses) and were primarily due to differences in administration costs. Results were robust across a range of sensitivity analyses. Dabigatran etexilate 150 mg od is cost saving compared with enoxaparin 40 mg od in patients aged over 75 years and in patients with moderate renal impairment, with comparable efficacy and safety.
Contribution of exosite occupancy by heparin to the regulation of coagulation proteases by antithrombin
Authors: Yang Likui , Manithody Chandrashekhara , Qureshi Shabir , Rezaie Alireza 
Published: December 2009

SummaryHeparin promotes the antithrombin (AT) inactivation of factors IXa (fIXa) and Xa (fXa) through a conformational activation of the serpin and also by a template mechanism in the presence of physiological levels of Ca2+. Recently, it was reported that heparin induces conformational changes in the active-sites of fIXa and fXa, raising the possibility that heparin also modulates the reactivity of these proteases with AT by this mechanism. To test this possibility, we prepared an AT mutant in which four critical heparin-binding residues of the serpin (Arg-45, Arg-46, Lys-114, and Arg-129) were replaced with non-basic residues. This mutant lost its affinity for heparin, but retained its normal reactivity with coagulation proteases. Thus, the high-affinity AT-binding pentasaccharide fragment of heparin had no cofactor effect on the reactivity of the AT mutant with coagulation proteases. Full-length heparinconcentration dependence of the AT inhibition of fIXa and fXa revealed that in contrast to a greater than 4–5 orders of magnitude accelerating effect for heparin on the AT inhibition of fIXa and fXa, heparin exhibits a negligible cofactor effect (<2-fold) on the mutant AT inhibition of these proteases. The same results were obtained for the mutant AT inhibition of thrombin and factor VIIa, however, heparin accelerated the mutant AT inhibition of factor XIa ~10-fold. We conclude that, with the exception of factor XIa, heparin-mediated conformational modulation of the active-sites of coagulation proteases makes a minor contribution to the regulation of these proteases by AT.
Oxygen-Wasting Effect of Inotropy
Authors: Müller Stig , How Ole-Jakob , Jakobsen Øyvind , Hermansen Stig Eggen , Røsner Assami , Stenberg Thor Allan , Myrmel Truls 
Published: December 2009

Background—We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient.Methods and Results—Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 μg/kg loading and 0.04 μg · kg−1· min−1infusion) or an equipotent dose of dobutamine (1.25 μg · kg−1· min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 μg · kg−1· min−1and 48 μg/kg loading with 0.2 μg · kg−1· min−1infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine;P=0.007 for levosimendan as assessed by pressure-volume area).Conclusion—Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.
A highly efficient short hairpin RNA potently down-regulates CCR5 expression in systemic lymphoid organs in the hu-BLT mouse model
Authors: Shimizu Saki , Hong Patrick , Arumugam Balamurugan , Pokomo Lauren , Boyer Joshua , Koizumi Naoya , Kittipongdaja Panyamol , Chen Angela , Bristol Greg , Galic Zoran , Zack Jerome A. , Yang Otto , Chen Irvin S. Y. , Lee Benhur , An Dong Sung 
Published: December 2009

AbstractInhibiting the expression of the HIV-1 coreceptor CCR5 holds great promise for controlling HIV-1 infection in patients. Here we report stable knockdown of human CCR5 by a short hairpin RNA (shRNA) in a humanized bone marrow/liver/thymus (BLT) mouse model. We delivered a potent shRNA against CCR5 into human fetal liver-derived CD34+ hematopoietic progenitor/stem cells (HPSCs) by lentiviral vector transduction. We transplanted vector-transduced HPSCs solidified with Matrigel and a thymus segment under the mouse kidney capsule. Vector-transduced autologous CD34+ cells were subsequently injected in the irradiated mouse, intended to create systemic reconstitution. CCR5 expression was down-regulated in human T cells and monocytes/macrophages in systemic lymphoid tissues, including gut-associated lymphoid tissue, the major site of HIV-1 replication. The shRNA-mediated CCR5 knockdown had no apparent adverse effects on T-cell development as assessed by polyclonal T-cell receptor Vβ family development and naive/memory T-cell differentiation. CCR5 knockdown in the secondary transplanted mice suggested the potential of long-term hematopoietic reconstitution by the shRNA-transduced HPSCs. CCR5 tropic HIV-1 infection was effectively inhibited in mouse-derived human splenocytes ex vivo. These results demonstrate that lentiviral vector delivery of shRNA into human HPSCs could stably down-regulate CCR5 in systemic lymphoid organs in vivo.
Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience
Authors: Adès Lionel , Guerci Agnes , Raffoux Emmanuel , Sanz Miguel , Chevallier Patrice , Lapusan Simona , Recher Christian , Thomas Xavier , Rayon Consuelo , Castaigne Sylvie , Tournilhac Olivier , de Botton Stephane , Ifrah Norbert , Cahn Jean-Yves , Solary Eric , Gardin Claude , Fegeux Nathalie , Bordessoule Dominique , Ferrant Augustin , Meyer-Monard Sandrine , Vey Norbert , Dombret Herve , Degos Laurent , Chevret Sylvie , Fenaux Pierre ,   for the European APL Group
Published: December 2009

AbstractAcute promyelocytic leukemia (APL) is highly curable with the combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy (CT), but very long-term results of this treatment, when CT should be added to ATRA and the role of maintenance treatment, remain uncertain. In our APL93 trial that included 576 newly diagnosed APL patients, with a median follow-up of 10 years, 10-year survival was 77%. Maintenance treatment significantly reduced 10-year cumulative incidence of relapses, from 43.2% to 33%, 23.4%, and 13.4% with no maintenance, maintenance using intermittent ATRA, continuous 6 mercaptopurine plus methotrexate, and both treatments, respectively (P < .001). Maintenance particularly benefited patients with white blood cell (WBC) count higher than 5 × 109/L (5000/μL). Early addition of CT to ATRA significantly improved 10-year event-free survival (EFS), but without significant effect on overall survival (OS). The 10-year cumulative incidence of deaths in complete response (CR), resulting mainly from myelosuppression, was 5.7%, 15.4%, and 21.7% in patients younger than 55, 55 to 65, and older than 65 years, respectively, supporting the need for less myelosuppressive treatments, particularly for consolidation therapy. This study is registered at http://clinicaltrials.gov as NCT00599937.
DDIT3/CHOP and the sarcoma fusion oncoprotein FUS-DDIT3/TLS-CHOP bind cyclin-dependent kinase 2
Authors: Bento Christoffer , Andersson Mattias K , Åman Pierre 
Published: December 2009

Abstract

Background
The DDIT3 gene encodes a transcription factor belonging to the CCAAT/enhancer binding protein (C/EBP) family. It is normally expressed at very low levels but is activated by cellular stress conditions and induces G1 arrest and, in some cell types, apoptosis. DDIT3 is found as a part of the fusion oncogene FUS-DDIT3 that is causal for the development of myxoid/round-cell liposarcomas (MLS/RCLS).

Results
In the present study, we searched for putative interaction partners of DDIT3 and the oncogenic FUS-DDIT3 among G1 cyclins and cyclin-dependent kinases. We found that FUS-DDIT3 and the normal DDIT3 bind CDK2. In addition, CDK2 showed an increased affinity for cytoskeletal proteins in cells expressing FUS-DDIT3 and DDIT3.

Conclusions
We conclude that DDIT3 binds CDK2 and that many of the observed biological effects of DDIT3 may involve interaction with CDK2.
Whole genome transcript profiling from fingerstick blood samples: a comparison and feasibility study
Authors: Robison Elizabeth H , Mondala Tony S , Williams Adam R , Head Steven R , Salomon Daniel R , Kurian Sunil M 
Published: December 2009

AbstractBackgroundWhole genome gene expression profiling has revolutionized research in the past decade especially with the advent of microarrays. Recently, there have been significant improvements in whole blood RNA isolation techniques which, through stabilization of RNA at the time of sample collection, avoid bias and artifacts introduced during sample handling. Despite these improvements, current human whole blood RNA stabilization/isolation kits are limited by the requirement of a venous blood sample of at least 2.5 mL. While fingerstick blood collection has been used for many different assays, there has yet to be a kit developed to isolate high quality RNA for use in gene expression studies from such small human samples. The clinical and field testing advantages of obtaining reliable and reproducible gene expression data from a fingerstick are many; it is less invasive, time saving, more mobile, and eliminates the need of a trained phlebotomist. Furthermore, this method could also be employed in small animal studies, i.e. mice, where larger sample collections often require sacrificing the animal. In this study, we offer a rapid and simple method to extract sufficient amounts of high quality total RNA from approximately 70 μl of whole blood collected via a fingerstick using a modified protocol of the commercially available Qiagen PAXgene RNA Blood Kit.ResultsFrom two sets of fingerstick collections, about 70 uL whole blood collected via finger lancet and capillary tube, we recovered an average of 252.6 ng total RNA with an average RIN of 9.3. The post-amplification yields for 50 ng of total RNA averaged at 7.0 ug cDNA. The cDNA hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips had an average % Present call of 52.5%. Both fingerstick collections were highly correlated with r2values ranging from 0.94 to 0.97. Similarly both fingerstick collections were highly correlated to the venous collection with r2values ranging from 0.88 to 0.96 for fingerstick collection 1 and 0.94 to 0.96 for fingerstick collection 2.ConclusionsOur comparisons of RNA quality and gene expression data of the fingerstick method with traditionally processed sample workflows demonstrate excellent RNA quality from the capillary collection as well as very high correlations of gene expression data.
A novel anti-mycobacterial function of mitogen-activated protein kinase phosphatase-1
Authors: Cheung Benny KW , Yim Howard CH , Lee Norris CM , Lau Allan SY 
Published: December 2009

Abstract

Background

Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumor necrosis factor-α (TNF-α), which is pivotal in the development of protective granulomas. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterium used as a model to investigate the immune response against MTB, stimulates the induction of TNF-α via mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK phosphatase-1 (MKP-1) is known to regulate MAPK activities, we examined whether MKP-1 plays a role in BCG-induced MAPK activation and cytokine expression.

Results
Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression. Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, the induction of MKP-1 was regulated by p38 MAPK and extracellular signal-regulated kinase 1 and 2 (ERK1/2). Surprisingly, when MKP-1 expression was blocked by its specific siRNA, there was a significant decrease in the levels of phospho-MAPK (p38 MAPK and ERK1/2) and TNF-α inducible by BCG.

Conclusions
Since TNF-α is pivotal in granuloma formation, the results indicated an unexpected positive function of MKP-1 against mycobacterial infection as opposed to its usual phosphatase activity.