bluuebunny/crossref_metadata_2025_split huggingface dataset:
PFA-100 monitoring of von Willebrand factor (VWF) responses to desmopressin (DDAVP) and factor VIII/VWF concentrate substitution in von Willebrand disease type 1 and 2
Authors: van Vliet Huub H. D. M. , Kappers-Klunne Mies C. , Michiels Jan J. , Leebeek Frank W. G. 
Published: August 2008

SummaryDose-response relationship was studied between PFA-100 closure times (PFA CTs) and factor (F)VIII-von Willebrand factor (VWF) parameters in patients with von Willebrand disease (VWD) type 1 and type 2 before and after treatment with DDAVP (n=84) or FVIII/VWF concentrate (n=38). DDAVP treatment of patients with VWD type 1 normalised the PFA CTs by increasing VWF levels to normal. Of the 14 patients with VWD type 2, PFA CTs did not normalize in eight. Haemate-P substitution in patients with VWD type 1 induced a less favourable response as compared to DDAVP, because PFA CTs did not correct in all patients. Of 12 patients with VWD type 2 treated with Haemate-P, six showed a correction of PFA CTs (<250 sec), which correlated with the normalisation of the VWF CB/ Ag ratio. In-vitro studies were performed by using whole blood of patients with VWD and adding various amounts of FVIII/VWF concentrate. Addition of Haemate-P induced an increase of the VWF CB/Ag ratio from 0.30 to 0.70 in blood of patients with VWD type 2 with correction of the PFA CTs. Immunate did not result in an increase of VWF CB/Ag ratio in blood of VWD type 2 patients, and the PFA CTs remained prolonged. We conclude that PFA-100 might be an adequate instrument not only for diagnosis but also for monitoring of DDAVP responses and FVIII/ VWF substitution of patients with VWD type 1 and 2,but this is dependent upon the type of VWD and the concentrate used.
Population pharmacokinetics and pharmacodynamics of once and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement
Authors: Borris Lars C. , Dahl Ola E. , Haas Sylvia , Huisman Menno V. , Kakkar Ajay K. , Kälebo Peter , Muelhofer Eva , Misselwitz Frank , Eriksson Bengt I. , Mueck Wolfgang 
Published: August 2008

SummaryRivaroxaban (Xarelto®) is an oral, direct factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. The aim was to compare the population pharmacokinetics (PK) and pharmacodynamics (PD) of twice-daily (bid) and once-daily (od) rivaroxaban in patients undergoing total hip replacement (THR). Blood samples were collected from patients enrolled in two phase IIb, dose-ranging studies undertaken to investigate rivaroxaban for thromboprophylaxis after THR. A sparse sampling technique was used and the samples were pooled for PK and PD analysis, which used non-linear mixed effect modelling. Rivaroxaban PK (samples from 758 patients) were well described by an oral, one-compartment model; age and renal function influenced clearance, and body surface area affected volume of distribution. When comparing the same total daily doses, maximum plasma concentrations of rivaroxaban were higher and minimum plasma concentrations were lower with od dosing, compared with bid dosing; however, the 90% intervals overlapped. The area under the plasma concentration–time curve was 18–30% higher in the od than in the bid study. Prothrombin time in seconds (samples from 1181 patients) correlated with rivaroxaban plasma concentrations in a linear fashion in both studies. In conclusion, the PK and PD of rivaroxaban were predictable when given either bid or od. These findings, along with the suggested efficacy and safety of rivaroxaban in the phase II studies, relative to enoxaparin, supported the selection of a convenient, once-daily 10 mg rivaroxaban dose for investigation in phase III studies.
Clinical implications of aspirin resistance
Authors: Zimmermann Norbert , Hohlfeld Thomas 
Published: August 2008

SummaryAspirin reduces major atherothrombotic events across a wide spectrum of patients with atherosclerotic disease. The occurrence of ischemic events despite of aspirin treatment is a failure of therapy, often denoted ‘clinical aspirin resistance’. This is distinguished from laboratory assays showing an insufficient inhibition of platelet function, which indicate ‘laboratory aspirin resistance’. Laboratory aspirin resistance has been reported in up to 60% of patients after stroke or peripheral arterial disease, up to 70% in stable coronary heart disease and even up to 80% in acute myocardial infarction. However, this data must be interpreted carefully because of small sample sizes and potential confounding factors such as compliance, co-morbidities and large differences between the laboratory methods used for detection. During the past years, evidence has accumulated that laboratory aspirin resistance is associated with an increased incidence of major atherothrombotic events, with an up to 13-fold increased risk of events in patients with cardiovascular disease. Thus, an individualized antiplatelet therapy will have to consider the possibility of aspirin resistance, and the identification of aspirin non-responders may improve antiplatelet therapy in future. Whether an increased dose of aspirin or another antiplatelet drug (e.g. clopidogrel) instead or in addition to aspirin should be given is unclear. Prospective trials are underway which address this issue. This review gives an overview on the various clinical studies that have investigated the prevalence and clinical importance of laboratory aspirin resistance. Moreover, therapeutic options, as well as future perspectives are discussed.
Intermittent intravenous urokinase for critical limb ischemia in diabetic foot ulceration
Authors: Weck Matthias , Rietzsch Hannes , Lawall Holger , Pichlmeier Uwe , Bramlage Peter , Schellong Sebastian 
Published: August 2008

SummaryPatients with diabetic foot ulceration and critical limb ischemia have a high risk of major amputation, especially if limbs can not be revascularized. Urokinase is effective in improving microcirculation in critical limb ischemia and might improve outcomes. There are no data on the efficacy and safety of urokinase treatment (survival free of major amputation, ulcer healing and the rate of minor and major bleeding). Therefore, we aimed to investigate the effect of urokinase treatment in a phase II clinical trial. We performed an open, prospective, non-controlled, multi-center phase II cohort study in 77 type-2 diabetic patients with critical limb ischemia and diabetic foot ulceration. Patients had no surgical or endovascular treatment option based on interdisciplinary consensus. Urokinase (1 Mio IU if plasma fibrinogen ≥2.5 g/l, 0.5 Mio IU if fibrinogen < 2.5 g/l) was administered for 21 days as an intravenous infusion over 30 minutes. Each patient was followed up for 12 months. Treatment for a median of 21 days resulted in 33% of patients being alive, having no major amputation and completely healed ulcers after 12 months. Total survival rate was 84.6%,amputation-free survival 69.2% and rate of major amputation 21.1%.Eighty-two percent of patients experienced at least once a complete ulcer healing within the course of study. Three serious adverse events were urokinase-related. Urokinase treatment in diabetic patients with critical limb ischemia appears to be effective, feasible and safe. Although this calls for a larger, randomized and controlled trial, the results are highly relevant for clinical practice to prevent these patients from receiving major amputation due to diabetic foot syndrome.Clinical Trial Registration No.: NCT00537498
Should female relatives of factor V Leiden carriers be screened prior to oral contraceptive use?
Authors: Smith Kenneth J. , Monsef Brenna S. , Ragni Margaret V. 
Published: August 2008

SummaryVenous thromboembolism (VTE) is three-fold higher among FV Leiden (FVL) carriers receiving oral contraceptives (OCPs) than in the general population. FVL screening, however, is not routinely performed before prescribing OCP, and the cost-effectiveness of this strategy is unknown. A decision tree model was constructed to evaluate FVL screening and prophylactic anticoagulation (AC) strategies in female relatives of FVL carriers. In the model, AC was low molecular weight heparin, given warfarin embryopathy risks. VTE morbidity, mortality, and other clinical parameters were obtained from published studies. Drug costs were based on average wholesale price, and counseling included VTE risk with OCP use and FVL status. Outcomes included medical costs, effectiveness measured as quality-adjusted-life-years (QALY), and the incremental cost-effectiveness ratio (ICER) over 30 years, with cost and effectiveness discounted at 3%/year. FVL screening and counselling without prophylactic AC cost less and was more effective than no screening in this population, but was less effective than screening, counselling,and prophylaxis during high-risk periods, which gained 0.083 QALY, for an ICER of $147/QALY gained. Screening with counselling and long-term AC cost $3,536 with minimal QALY gain and an ICER >$600,000/QALY. Screening, OCP counseling, and prophylactic AC during high-risk periods was favoured and cost <$20,000/QALY, unless: (a) high-risk prophylaxis cost >$4,231 (base $932), (b) long-term prophylaxis cost < $1199 (base $6,546), or (c)VTE relative risk reduction with prophylaxis was <21% (base 90%).In conclusion, screening, counselling and prophylactic AC during high-risk periods in female relatives of FVL carriers is an economically favourable strategy.
A multicenter evaluation of a new quantitative highly sensitive D-dimer assay for exclusion of venous thromboembolism
Authors: Palareti Gualtiero , Aguilar Carlos , Legnani Cristina , Reber Guido , Peetz Dirk , de Moerloose Philippe 
Published: August 2008

SummaryD-dimer testing is widely applied for exclusion of deep-vein thrombosis (DVT) and pulmonary embolism (PE).We report on a multicenter performance evaluation of a new particle-enhanced immuno assay Innovance™ D-Dimer. Innovance D-Dimer assay was performed in 1,543 frozen samples from outpatients suspected of DVT and/or PE enrolled in three management studies as well as in a routine clinical practice. Samples were assayed on BCS®/BCS® XP, BCT® as well as Sysmex® CA-7000, CA-1500 and CA-560 analyzers (cut-off on all analyzers: 0.5 mg/l). Stratus® CS D-Dimer and Vidas® D-Dimer Exclusion were used for comparison. The precision study indicated total coefficients of variation ranging from 2.1% to 8.4% depending on the analyzer and on the sample. Sensitivity and negative predictive values were above 99% and their lower 95% confidence interval were equal or above 97.4% and 98.6%, respectively. Specificity ranged from 38.2% to 40.4% and the respective lower 95% confidence intervals from 35.5% to 37.7%. Area under the curve was 0.90 for all assay systems except for Innovance D-Dimer with BCT (0.89).Two samples from patients with distal DVT tested negative with all assay systems. One patient with high pre-test clinical probability and proximal DVT tested negative with Vidas D-Dimer Exclusion. Our data indicate that the performances of Innovance D-Dimer, regardless of the analyzer, are similar to the reference methods, and that this assay can be used for the exclusion of venous thromboembolic disease.
Procoagulant activities of plasma factor VIIc and factor Xc are positively and independently associated with concentrations of the high-density lipoprotein apolipoprotein, apo A-II
Authors: Atta Maria , Crook David , Shafique Faria , Johnston Desmond G. , Godsland Ian F. 
Published: August 2008

SummaryThe pro- and antiatherogenic roles of apolipoproteins B andA-I, respectively, are well-established although the importance of apolipoprotein A-II remains unclear. There is extensive evidence for the involvement of plasma lipoproteins in haemostatic function. However, in-vivo studies of relationships between haemostatic variables and apolipoprotein concentrations are very limited. Plasma fibrinogen, factors VIIc and Xc (FVIIc and FXc, respectively), apolipoproteins (apo) A-I, A-II and B, triglycerides, total, low-density and high-density lipoprotein (HDL) cholesterol, and cholesterol in HDL subfractions 2 and 3 were measured in 186 apparently healthy Caucasian men (aged 26–78 years; body mass index 19.9–37.8 kg/m2).Associations between haemostatic, apolipoprotein,lipid and lipoprotein variables were explored in uni- and multivariable analyses. Fibrinogen did not correlate with any of the lipid-related variables. FVIIc and FXc were significant positive univariate correlates of total cholesterol (correlation coefficients 0.26,p<0.001 and 0.19,p<0.05,respectively) triglycerides (0.37, p<0.001 and 0.36, p<0.001), and apoB (0.21, p<0.01 and 0.17, p<0.05) and apoA-II (0.19, p<0.05 and 0.29, p<0.001). HDL2 subfraction cholesterol correlated negatively with FVIIc and FXc (-0.20, p<0.01 and –0.22, p<0.01, respectively). In multivariable analysis, only the associations of FVIIc and FXc with total cholesterol, triglycerides and apoA-II remained statistically significant. In conclusion, total cholesterol and triglycerides were the major independent lipid correlates of FVIIc and FXc. The independent and positive associations of apoA-II with FVIIc and FXc suggest a prothrombotic involvement for this apolipoprotein
Proteasome degradation of protein C and plasmin inhibitor mutants
Authors: Nishio Miwako , Nakahara Masako , Egawa Nagisa , Hirosawa Shinsaku , Koyama Takatoshi 
Published: August 2008

SummaryProtein C (PC) deficiency and plasmin inhibitor (PI) deficiency are inherited thrombotic and haemorrhagic disorders. We investigated the intracellular degradation of mutant proteins, using naturally occurring PC and PI mutants that lead to congenital deficiencies. To examine the necessity of N-linked glycosylation for the proteasomal degradation of PC and PI, PC178 and PC331 mutants treated with tunicamycin and N-glycosylation-lacking mutants, PC92Stop and PI-America were pulse chased. The analysis revealed that the speed of degradation of the tunicamycin-treated PC mutants, PC92Stop and PI-America lacking glycosylation, was slower than that of N-glycosylated mutants. Immunoprecipitation and immunoblot analysis showed that PC178 and PC331 mutants were associated with molecular chaperones, Bip, GRP94, and calreticulin. PI-America was associated with only Bip. Although degradation of mutants was mediated by proteasomes, no association with ubiquitin was detected. Co-transfection of endoplasmic reticulum (ER) degradation enhancing α-mannosidase-like protein (EDEM) accelerated the degradation of N-glycosylated PC. In the absence of autophagy using Atg5-deficient cell lines, the degradation of the PC331 mutant was mildly accelerated but that of PC178, PI-America and PI-Okinawa mutants was not influenced. While the degradation of the PC and PI mutants was facilitated by N-glycosylation moieties, they were ubiquitin-independently degraded by proteasomes, irrespective of the presence or absence of N-glycosylation. Molecular chaperone binding was influenced by the presence of N-glycosylation moieties. When the misfolded or truncated mutant proteins are functionally active, proteasome inhibitors such as bortezomib may have therapeutic potential for treatment of protein deficiencies.
The Effects of Accessory Stimuli on Information Processing: Evidence from Electrophysiology and a Diffusion Model Analysis
Authors: Jepma Marieke , Wagenmakers Eric-Jan , Band Guido P. H. , Nieuwenhuis Sander 
Published: August 2008

AbstractPeople typically respond faster to a stimulus when it is accompanied by a task-irrelevant accessory stimulus presented in another perceptual modality. However, the mechanisms responsible for this accessory-stimulus effect are still poorly understood. We examined the effects of auditory accessory stimulation on the processing of visual stimuli using scalp electrophysiology (Experiment 1) and a diffusion model analysis (Experiment 2). In accordance with previous studies, lateralized readiness potentials indicated that accessory stimuli do not speed motor execution. Surface Laplacians over the motor cortex, however, revealed a bihemispheric increase in motor activation—an effect predicted by nonspecific arousal models. The diffusion model analysis suggested that accessory stimuli do not affect parameters of the decision process, but expedite only the nondecision component of information processing. Consequently, we conclude that accessory stimuli facilitate stimulus encoding. The visual P1 and N1 amplitudes on accessory-stimulus trials were modulated in a way that is consistent with multisensory energy integration, a possible mechanism for this facilitation.
Oscillatory Correlates of Retrieval-induced Forgetting in Recognition Memory
Authors: Spitzer Bernhard , Hanslmayr Simon , Opitz Bertram , Mecklinger Axel , Bäuml Karl-Heinz 
Published: August 2008

AbstractRetrieval practice on a subset of previously studied material enhances later memory for practiced material but can inhibit memory for related unpracticed material. The present study examines the effects of prior retrieval practice on evoked (ERPs) and induced (oscillatory power) measures of electrophysiological activity underlying recognition of practiced and unpracticed words. Compared to control material, recognition of unpracticed words was characterized by reduced amplitudes of the P2 ERP component and by reduced early (200–400 msec) oscillatory theta power. The reduction in P2 amplitude was associated with decreased evoked theta power but not with decreased theta phase locking (phase-locking index). Recognition of unpracticed material was further accompanied by a reduction in occipital gamma power (&gt;250 msec). In contrast, the beneficial effects of retrieval practice on practiced words were reflected by larger parietal ERP positivity (&gt;500 msec) and by a stronger decrease in oscillatory alpha power in a relatively late time window (&gt;700 msec). The results suggest that the beneficial and detrimental effects of retrieval practice are mediated by different processes. In particular, they suggest that reduced theta (4–7 Hz) and gamma (60–90 Hz) power reflect the specific effects of inhibitory processes on the unpracticed material's memory representation.
Experience-dependent Enhancement of Linguistic Pitch Representation in the Brainstem Is Not Specific to a Speech Context
Authors: Krishnan Ananthanarayan , Swaminathan Jayaganesh , Gandour Jackson T. 
Published: August 2008

AbstractNeural representation of pitch is influenced by lifelong experiences with music and language at both cortical and subcortical levels of processing. The aim of this article is to determine whether neural plasticity for pitch representation at the level of the brainstem is dependent upon specific dimensions of pitch contours that commonly occur as part of a native listener's language experience. Brainstem frequency following responses (FFRs) were recorded from Chinese and English participants in response to four Mandarin tonal contours presented in a nonspeech context in the form of iterated rippled noise. Pitch strength (whole contour, 250 msec; 40-msec segments) and pitch-tracking accuracy (whole contour) were extracted from the FFRs using autocorrelation algorithms. Narrow band spectrograms were used to extract spectral information. Results showed that the Chinese group exhibits smoother pitch tracking than the English group in three out of the four tones. Moreover, cross-language comparisons of pitch strength of 40-msec segments revealed that the Chinese group exhibits more robust pitch representation of those segments containing rapidly changing pitch movements across all four tones. FFR spectral data were complementary showing that the Chinese group exhibits stronger representation of multiple pitch-relevant harmonics relative to the English group across all four tones. These findings support the view that at early preattentive stages of subcortical processing, neural mechanisms underlying pitch representation are shaped by particular dimensions of the auditory stream rather than speech per se. Adopting a temporal correlation analysis scheme for pitch encoding, we propose that long-term experience sharpens the tuning characteristics of neurons along the pitch axis with enhanced sensitivity to linguistically relevant variations in pitch.
Development of the Soil Moisture Index to Quantify Agricultural Drought and Its “User Friendliness” in Severity-Area-Duration Assessment
Authors: Sridhar Venkataramana , Hubbard Kenneth G. , You Jinsheng , Hunt Eric D. 
Published: August 2008

Abstract
This paper examines the role of soil moisture in quantifying drought through the development of a drought index using observed and modeled soil moisture. In Nebraska, rainfall is received primarily during the crop-growing season and the supply of moisture from the Gulf of Mexico determines if the impending crop year is either normal or anomalous and any deficit of rain leads to a lack of soil moisture storage. Using observed soil moisture from the Automated Weather Data Network (AWDN), the actual available water content for plants is calculated as the difference between observed or modeled soil moisture and wilting point, which is subsequently normalized with the site-specific, soil property–based, idealistic available water for plants that is calculated as the difference between field capacity and wilting point to derive the soil moisture index (SMI). This index is categorized into five classes from no drought to extreme drought to quantitatively assess drought in both space and time. Additionally, with the aid of an in-house hydrology model, soil moisture was simulated in order to compute model-based SMI and to compare the drought duration and severity for various sites. The results suggest that the soil moisture influence, a positive feedback process reported in many earlier studies, is unquestionably a quantitative indicator of drought. Also, the severity and duration of drought across Nebraska has a clear gradient from west to east, with the Panhandle region experiencing severe to extreme drought in the deeper soil layers for longer periods (&gt;200 days), than the central and southwestern regions (125–150 days) or the eastern regions about 100 days or less. The anomalous rainfall years can eliminate the distinction among these regions with regard to their drought extent, severity, and persistence, thus making drought a more ubiquitous phenomenon, but the recovery from drought can be subject to similar gradations. The spatial SMI maps presented in this paper can be used with the Drought Monitor maps to assess the local drought conditions more effectively.