bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of venous thromboembolism with vitamin K antagonists: patients’ health state valuations and treatment preferences
Authors: Bossuyt Patrick , Stalmeier Peep , Sprangers Mirjam , van Dongen Carlo , Middeldorp Saskia , Bank Ivan , van der Meer Jan , Hamulyák Karly , Prins Martin , Locadia Mirjam 
Published: November 2004

SummaryDetermining the optimal duration of vitamin K antagonist (VKA) therapy for patients with venous thromboembolism (VTE) requires a weighting of the benefits and risks of treatment. The objectives of our study were to investigate patient variability in health state valuations associated with VKA therapy and treatment preferences, and to investigate the extent to which valuations and treatment preferences are associated with prior experience with these health states and other patient characteristics. Valuations of outcomes after VTE scaled from 0 (tantamount to death) to 1 (tantamount to perfect health) were elicited from 53 patients who had experienced VTE, 23 patients who had experienced major bleeding during treatment, and 48 patients with the post-thrombotic syndrome. In addition, patients’ treatment preferences were evaluated using treatment trade-off questions. Median health state valuations ranged from 0.33 for ‘non-fatal haemorrhagic stroke’ to 0.96 for ‘no VKA treatment’. Variability between patients was substantial. Patients’ treatment preferences also varied: 25% of patients chose cessation of treatment, regardless of the probability of recurrent VTE presented, whereas 23% of patients were never willing to choose cessation of treatment. Differences in valuations and treatment preferences were not associated with type of event experienced. Due to the substantial and unpredictable variability in valuations and treatment preferences, recommendations regarding treatment duration should be tailored to patients’ specific values and concerns.
Genetic variation in Fcγ receptor IIa protects against advanced peripheral atherosclerosis
Authors: van der Meer Irene , Hofman Albert , Kluft Cornelis , de Maat Moniek , Witteman Jacqueline 
Published: November 2004

SummaryImmune processes play a substantial role in atherosclerotic disease. The role in atherosclerosis of Fcγ receptor IIa (FcγRIIa), a receptor for immunoglobulin G and for the inflammatory mediator C-reactive protein, is not yet clear. Since the R/H131 polymorphism in the FcγRIIa gene strongly influences binding to FcγRIIa, we investigated the association of the R/H131 polymorphism with advanced peripheral atherosclerosis. Within the Rotterdam Study, a population-based cohort study, we determined FcγRIIa genotype in 430 subjects with advanced peripheral atherosclerosis as indicated by the ankle-arm index, and 411 controls. Heterozygous and homozygous carriers of the H131 allele were protected against advanced peripheral atherosclerosis (age- and gender-adjusted odds ratio (OR) 0.77 (0.54–1.12) and 0.65 (0.44–0.98), respectively, P trend=0.04). This effect was most pronounced in subjects with modestly elevated levels of inflammation as indicated by the leukocyte count (OR 0.52 (0.29–0.93) and 0.45 (0.23–0.86), for heterozygotes and H131 homozygotes, respectively; P trend=0.02). This is the first study showing that the H131 allele of FcγRIIa protects against advanced peripheral atherosclerosis.
Proinflammatory properties of murine aortic endothelial cells exclusively expressing a non cleavable form of TNFα
Authors: Canault Matthias , Peiretti Franck , Mueller Christoph , Deprez Paule , Bonardo Bernadette , Bernot Denis , Juhan-Vague Irène , Nalbone Gilles 
Published: November 2004

SummarySoluble (sTNF) and transmembrane (tmTNF) forms of TNFα (TNF) have distinct proinflammatory effects. We investigated whether tmTNF altered the synthesis of some proinflammatory proteins involved in atherothrombosis, in murine aortas and aortic endothelial cells (MAEC). Samples were obtained from wild-type (WT) mice and TNF-deficient mice that express a mutated non cleavable tmTNF transgene (tmTNFnc).The levels of secreted MCP-1, RANTES, IL-6, PAI-1, soluble ICAM-1, and soluble TNF receptor type 1 (TNFR1; CD120a) antigens, MMP-9 activity and of cell surface ICAM-1 were not significantly different between the two types of MAEC.The magnitude of endotoxin-stimulated production of RANTES, MCP-1 and IL-6 was similar in the two types of cells. Of note, the amount of synthesized TNF receptor type 2 (TNFR2; CD120b), measured by its secreted (in aorta and MAEC), intracellular and mRNA levels (in MAEC), was significantly 4-fold lower in tmTNFnc than in WT mice, both in basal and endotoxin-stimulated conditions. A neutralizing anti-TNF antibody or the recombinant murine TNF did not modify the magnitude of the difference in TNFR2 production between the two types of cells, suggesting a preponderant role of tmTNF in the down-regulation of TNFR2 synthesis. Macrophages of tmTNFnc mice also produced less TNFR2 than WT macrophages (−30%). Plasmas of tmTNFnc mice contained significantly less sTNFR2 than WT mice (−75%). In conclusion, an increase in tmTNF levels, rather than the lack of sTNF, significantly down-modulated TNFR2 synthesis in aortic endothelial cells, but had no major influence on the synthesis of some major pro-inflammatory and pro-atherothrombotic proteins.
Platelet morphology, soluble P selectin and platelet P-selectin in acute ischaemic stroke
Authors: Nadar Sunil , Blann Andrew , Lip Gregory 
Published: November 2004

SummaryThe pathophysiology of ischaemic stroke involves the platelet. In this study, we hypothesised that abnormalities in platelet morphology, as well as soluble (sPsel) and total platelet P-selectin (pPsel) levels would be present in patients presenting with an acute ischaemic stroke, and that these changes would improve at ≥ 3 months’ follow-up. We studied 59 hypertensive patients (34 male; mean age 68± 12 years) who presented with an acute ischaemic stroke (ictus< 24 hours), and compared them with 2 groups: (i) age-, sex-and ethnic-origin matched normotensive healthy controls; and (ii) uncomplicated ‘ high risk’ hypertensive patients as ‘ risk factor control’ subjects. Platelet morphology (volume and mass) was quantified, and sPsel (plasma marker of platelet activation) was measured (ELISA) in citrated plasma. The mass of P-selectin in each platelet (pPsel) was determined by lysing a fixed number of platelets and then determining the levels of P-selectin in the lysate. Results show that patients who presented with a stroke had significantly higher levels of sPsel and pPsel (both p< 0.001), compared to the normal controls and the hypertensive patients. Patients with an acute stroke had lower mean platelet mass (MPM) and mean platelet volume (MPV) as compared to the uncomplicated hypertensive patients, who had significantly higher mean MPM and MPV values, as compared to normal controls. On follow-up, the levels of both sPsel (p = 0.011), pPsel (< 0.001) and MPV (p = 0.03) were significantly lower. Mean MPM levels remained unchanged. We conclude that patients presenting with an acute ischaemic stroke have activated platelets, as evident by the increased levels of soluble and platelet P-selectin. Further study of platelet activation and the role of P-selectin is warranted.
Conformational Asn187Asp/Lys antithrombin variants and thrombosis
Authors: Bauters Anne , Khairy Mahnouch , Ochat Nadège , Jude Brigitte , Aiach Martine , Alhenc-Gelas Martine , Picard Véronique 
Published: November 2004

SummaryAntithrombin Rouen VI (N187D) is a rare conformational thermolabile variant.The unique symptomatic carrier reported in the literature developed 3 thrombotic events during pregnancy, in each case in a context of pyrexial infection. In fresh plasma, antithrombin activity and antigen level were normal but in vitro experiments demonstrated the presence of a thermolabile variant, suggesting that fever could be a trigger for thrombosis in N187D carriers.The RouenVI variant was further found in two asymptomatic brothers. In these subjects, it was associated with normal antigen level but reduced activity. In order to better delineate the functional and clinical consequences of the N187 variants,we have studied a series of seven subjects from two distinct families heterozygous for the Rouen VI mutation. Antithrombin levels were normal or borderline in these patients. Thermostability of plasma antithrombin was normal. We have also studied six subjects heterozygous for a new mutation, 6462C>G,which results in an asparagine to lysine substitution at residue 187. In these patients, the N187K mutation is associated with a clear type II deficiency and decreased thermostability of the plasma protein has been demonstrated. That the N187D mutation has milder consequences on plasma antithrombin activity than the N187K mutation is in agreement with structural predictions. About 50% of the N187 carriers studied have suffered venous thrombotic events, strongly suggesting that both mutations are risk factors for thrombosis, but none occurred during pyrexial infections.
Synthesis of Nickel Nanocrystallites with Hexagonal Flake-like Morphology from Nickel Dimethylglyoximate
Authors: Ni Xiaomin , Chen Lifu , Zheng Huagui , Zhang Dongen , Zhao Qingbiao , Song Jimei 
Published: November 2004

Abstract
Nickel nanocrystallites with hexagonal flake-like morphology with a side length of 200–400 nm and a thickness of 20–30 nm were prepared by reduction of nickel dimethylglyoximate with hydrazine hydrate in a solution. Selected area electron diffraction (SAED) pattern revealed that the flakes were single crystals. It was found that the precursor, nickel dimethylglyoximate, played an important role for the formation of these flakes. Magnetic properties of the product were measured by a vibration sample magnetometer (VSM).
Factors associated with nonunion in conservatively-treated type-II fractures of the odontoid process
Authors: Koivikko M. P. , Kiuru M. J. , Koskinen S. K. , Myllynen P. , Santavirta S. , Kivisaari L. 
Published: November 2004

In type-II fractures of the odontoid process, the treatment is either conservative in a halo vest or primary surgical stabilisation. Since nonunion, requiring prolonged immobilisation or late surgery, is common in patients treated in a halo vest, the identification of those in whom this treatment is likely to fail is important. We reviewed the data of 69 patients with acute type-II fractures of the odontoid process treated in a halo vest. The mean follow-up was 12 months. Conservative treatment was successful, resulting in bony union in 32 (46%) patients. Anterior dislocation, gender and age were unrelated to nonunion. However, nonunion did correlate with a fracture gap (> 1 mm), posterior displacement (> 5 mm), delayed start of treatment (> 4 days) and posterior redisplacement (> 2 mm). We conclude that patients presenting with these risk factors are unlikely to achieve bony union by treatment in a halo vest. They deserve careful attention during the follow-up period and should also be considered as candidates for primary surgical stabilisation.
Fractures of the calcaneum
Authors: Paul M. , Peter R. , Hoffmeyer P. 
Published: November 2004

We have assessed the long-term results after operative and non-operative treatment of undisplaced and displaced calcaneal fractures. At a mean of 6.5 years, we reviewed 70 patients with a calcaneal fracture who were divided into four groups: group 1, 18 patients with undisplaced fractures and a normal Böhler’s angle (BA) who had been treated non-operatively; group 2, 23 with intra-articular fractures and a BA < 10° who had been treated non-operatively; group 3, 13 with intra-articular fractures and a BA > 10° who had been treated surgically; and group 4, 16 with intra-articular fractures and a BA < 10° who had been treated surgically. The results were assessed by a clinical score considering pain, return to work, return to physical activity, change in shoe-wear and the requirement for subtalar arthrodesis. Patients with undisplaced calcaneal fractures had a good outcome. Those with displaced fractures treated surgically who presented at follow-up with a BA > 10° had a satisfactory functional outcome and those with displaced fractures who had non-operative treatment had a poor outcome. The poorest outcome was consistently seen in patients who were treated operatively without restoration of BA. Open reduction and internal fixation of intra-articular calcaneal fractures can only be expected to benefit those patients in whom nearly anatomical reconstruction is obtained.
Mild phenotype in two unrelated patients with a partial deletion of 21q22.2‐q22.3 defined by FISH and molecular studies
Authors: Ehling Daniela , Kennerknecht Ingo , Junge Annelore , Prager Bettina , Exeler Rita , Behre Beate , Horst Juergen , Schmitt‐John Thomas , Bartsch Oliver , Wirth Jutta 
Published: November 2004

AbstractWe describe two unrelated patients with cytogenetically visible deletions of 21q22.2‐q22.3 and mild phenotypes. Both patients presented minor dysmorphic features including thin marfanoid build, facial asymmetry, downward‐slanting palpebral fissures, depressed nasal bridge, small nose with bulbous tip, and mild mental retardation (MR). FISH and molecular studies indicated common deleted areas but different breakpoints. In patient 1, the breakpoint was fine mapped to a 5.2 kb interval between exon 5 and exon 8 of the ETS2 gene. The subtelomeric FISH probe was absent on one homologue 21 indicating a terminal deletion spanning ∼7.9 Mb in size. In patient 2, the proximal breakpoint was determined to be 300–700 kb distal to ETS2, and the distal breakpoint 2.5–0.3 Mb from the 21q telomere, indicating an interstitial deletion sized ∼4.7–7.3 Mb. The 21q‐ syndrome is rare and typically associated with a severe phenotype, but different outcomes depending on the size and location of the deleted area have been reported. Our data show that monosomy 21q of the area distal to the ETS2 gene, representing the terminal 7.9 Mb of 21q, may result in mild phenotypes comprising facial anomalies, thin marfanoid build, and mild MR, with or without signs of holoprosencephaly. © 2004 Wiley‐Liss, Inc.
Phase separation structure in the polymer blend of fluorocarbon elastomer and hydrogenated nitrile rubber
Authors: Hirano Kousei , Suzuki Ken , Nakano Kenji , Tosaka Masatoshi 
Published: November 2004

AbstractHydrogenated nitrile rubber (HNBR) and a ternary copolymer of vinylidene fluoride, tetrafluoropropylene, and perfluoromethyl vinyl ether (FKM) were blended and vulcanized rubbers that have the excellent low temperature characteristics and oil resistance were successfully obtained. The results of dynamic mechanical analysis demonstrated the great improvement of low temperature characteristics for one of the polymer blend materials (FKM/HNBR = 30/70). Subsequently, the structures of the polymer blends were analyzed by using atomic force microscopy (AFM) and transmission electron microscopy (TEM). The results of AFM and TEM showed that the polymer blend materials have phase‐separated structures with the sea‐island morphology. The sea regions were HNBR and the island regions were FKM for the samples containing less than 50% of FKM. On the other hand, the sea region was FKM for the sample containing 70% of FKM. Even in the stretched polymer blend, no gap or crazing was observed at the interface of FKM and HNBR. Therefore, some kind of strong bonding was presumed to exist between the two types of phases. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 149–156, 2005
Chondrocyte terminal differentiation, apoptosis, and type X collagen expression are downregulated by parathyroid hormone
Authors: Harrington Erik Kern , Lunsford Leif E. , Svoboda Kathy K.H. 
Published: November 2004

AbstractParathyroid hormone (PTH) regulates calcium and phosphate homeostasis through the endocrine system. Parathyroid hormone‐related peptide (PTHrP) is a heterogeneous polypeptide with sequence homology to PTH in its first 13 amino acid residues. Both bind and activate a common receptor, the type 1 PTH/PTHrP receptor (PTH1R). Activation of this G‐protein‐coupled receptor by PTHrP has been shown to regulate chondrogenesis in a manner that attenuates chondrocyte hypertrophy. Here, we report the dose‐response (10−7 to 10−15 M) effects of PTH on chondrogenesis using an avian sternal organ culture model. PTH increased cartilaginous tissue length and downregulated the deposition of type X collagen and its mRNA expression. In addition, PTH increased chondrocyte cell diameter in prehypertrophic and proliferative regions while decreasing chondrocyte apoptosis in the hypertrophic zone. In conclusion, these experiments demonstrate that PTH regulates cartilage growth, chondrocytic apoptosis, deposition of type X collagen protein, and expression of type X collagen mRNA. Type X collagen mRNA expression was downregulated by PTH in this organ culture model, but cell size, another marker for terminal differentiation, increased. © 2004 Wiley‐Liss, Inc.
No influence of 20 and 400 µT, 50 Hz magnetic field exposure on cognitive function in humans
Authors: Delhez Marie , Legros Jean‐Jacques , Crasson Marion 
Published: November 2004

AbstractThe aim of the present study was to investigate cognitive effects of a continuous, vertical extremely low frequency (ELF) magnetic field (MF) of 20 and 400 µT 50 Hz in healthy young men during performance on cognitive tests. Thirty‐two volunteers (20–30 years old, mean 22.6 ± 2.2 years) participated in this double blind study. The test protocol consisted of a set of tests: divided attention, flexibility, memory updating, digit span, digit span with articulary suppression, and time perception. The total duration of the exposure was 65 min. Participants were assigned four sessions: three conditions in the helmet (sham exposure, 20 and 400 µT) and one condition out of the helmet (to control the expectancy effect). No effect of MF exposure was observed on performance. Bioelectromagnetics 25:592–598, 2004. © 2004 Wiley‐Liss, Inc.
Theoretical and experimental analysis of analyte transport in a fiber‐optic, protein C immuno‐biosensor
Authors: Tang Liang , Kwon Hyun J. , Kang Kyung A. 
Published: November 2004

AbstractProtein C (PC) is an important anticoagulant in human blood plasma, and early diagnosis of PC deficiency is critical for preventing dangerous thromboembolic complications. A fiber‐optic PC immuno‐biosensor has been under development in our research group for real‐time PC‐deficiency diagnosis. The sensor has demonstrated a good sensitivity and specificity for quantifying PC in buffered solutions. However, for plasma samples, with a limited sample reaction time, the sensor produced only 30% of the signal intensity of PC in buffer. The high plasma viscosity (1.9 cP) was speculated as the major reason for signal intensity reduction. In this investigation, the sensing performance of the fiber‐optic PC biosensor is systematically characterized in terms of physical and chemical properties of the sample media. Theoretical and experimental analyses indicate that the reduced diffusion rate of PC molecules in viscous samples caused the sensing system to be more mass‐transfer‐limited. Convective flow of sample/reagent solutions during immunoreactions can increase the rate of the analyte mass transport from the bulk solution to the sensor surface, with reaction kinetics changing from mass‐transfer‐limited to reaction‐limited as flow velocity increases. It was shown that PC sensor performance was significantly improved for plasma samples with convection. The effect of the flow velocity and incubation times for samples and reagents on the sensor performance was also systematically analyzed to optimize the assay protocol for PC sensing. Currently, a 6‐cm‐long immuno‐biosensor is capable of quantifying PC in plasma (1 mL) in the heterozygous PC deficiency range (0.5 to 2.5 μg/mL) within 5 minutes, at an average signal‐to‐noise ratio of 50. © 2004 Wiley Periodicals, Inc.
Fast Detection of Single Nucleotide Polymorphisms (SNPs) by Primer Elongation with Monitoring of Supercritical‐Angle Fluorescence
Authors: Krieg Alexander , Laib Stephan , Ruckstuhl Thomas , Seeger Stefan 
Published: November 2004

AbstractWe describe the rapid detection of single nucleotide polymorphisms (SNPs) by real‐time observation of primer elongation. The enzymatic elongation of surface‐bound primers is monitored by detecting the increase of surface‐bound fluorescence caused by the incorporation of Cy5‐labelled deoxycytidine 5′‐triphosphate residues (Cy5‐dCTPs) into the corresponding strand. In order to discriminate against the fluorescence from unbound Cy5‐dCTPs, the detection volume was restricted to the surface by collecting supercritical‐angle fluorescence. The efficiency of enzymatic double‐stranded DNA synthesis is governed by the complementarity of the primer and template. An SNP in the sequence of the primer obstructs its elongation increasingly with decreased distance of the mismatch to the 3′ end of the primer. By real‐time fluorescence detection during primer elongation, SNPs can be detected within a few minutes, which is significantly faster than in experiments where the fluorescence is measured after completion of the reaction. We demonstrate the efficiency of the method by detecting an SNP in the ErbB2 gene that is involved in causing a higher risk of breast cancer.
Pax6 guides a relay of pioneer longitudinal axons in the embryonic mouse forebrain
Authors: Nural Hikmet F. , Mastick Grant S. 
Published: November 2004

AbstractWe have characterized a system of early neurons that establish the first two major longitudinal tracts in the embryonic mouse forebrain. Axon tracers and antibody labels were used to map the axon projections in the thalamus from embryonic days 9.0–12, revealing several distinct neuron populations that contributed to the first tracts. Each of the early axon populations first grew independently, pioneering a short segment of new tract. However, each axon population soon merged with other axons to form one of only two shared longitudinal tracts, both descending: the tract of the postoptic commissure (TPOC), and, in parallel, the stria medullaris. Thus, the forebrain longitudinal tracts are pioneered by a relay of axons, with distinct axon populations pioneering successive segments of these pathways. The extensive merging of tracts suggests that axon–axon interactions are a major guidance mechanism for longitudinal axons. Several axon populations express tyrosine hydroxylase, identifying the TPOC as a major pathway for forebrain dopaminergic projections. To start a genetic analysis of pioneer axon guidance, we have identified the transcription factor Pax6 as critical for tract formation. In Pax6 mutants, both longitudinal tracts failed to form due to errors by every population of early longitudinal axons. Taken together, these results have identified potentially important interactions between series of pioneer axons and the Pax6 gene as a general regulator of longitudinal tract formation in the forebrain. J. Comp. Neurol. 479:399–409, 2004. © 2004 Wiley‐Liss, Inc.