bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory and Procoagulant Mediator Interactions in an Experimental Baboon Model of Venous Thrombosis
Authors: Wakefield Thomas W , Greenfield Lazar J , Rolfe Mark W , DeLucia Alphonse , Strieter Robert M , Abrams Gerald D , Kunkel Steven L , Esmon Charles T , Wrobleski Shirley K , Kadell Amy M , Burdick Marie D , Taylor Fletcher B 
Published: July 2018

SummaryTheoretic and in vitro evidence suggests that thrombosis and inflammation are interrelated. The purpose of the present study was to define the relationship between inflammation and deep venous thrombosis (DVT) in an in vivo model. Initiation of DVT was accomplished by administration of antibody to protein C (HPC4, 2 mg/kg) and tumor necrosis factor (TNF, 150 μg/kg); stasis; and subtle venous catheter injury. Thrombosis was assessed by thrombin-antithrombin assay (TAT), 125I-fibrinogen scanning (scan) over both the proximal and distal iliac veins, and ascending venography. Cytokines TNF, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8) were measured along with differential white blood cell counts, platelet counts, fibrinogen (FIB), and erythrocyte sedimentation rates (ESR). Baboon pairs were sacrificed on day 3 (T + 3d), T + 6d, and T + 9d and veins removed. All animals developed inferior vena cava and left iliofemoral DVT by venography; no right DVT was found. TAT was elevated by T + 1hr and peaked at T + 3hrs. Left iliofemoral DVT was found at T + 1hr by scan and reached a 20% uptake difference between the affected left and nonaffected right side at T + 3hrs. TNF peaked at T + 1hr; MCP-1 peaked at T + 6hrs; IL-8 and IL-6 peaked on T + 2d; all cytokines declined to baseline. TNF and TAT elevations were found to correlate with all cytokines; elevations in IL-8 were correlated with elevations in MCP-1 and IL-6 (p <0.05). Correlation between cytokines and scan revealed a significant (p <0.05) relationship only between elevations in IL-6 and distal iliac fibrin accumulation; no significant correlation was found between IL-8 and MCP-1 and scan. Increased mature polymorphonuclear leukocytes were found by T + 2d; immature forms were prominent at T + 3hrs, T + 6hrs, and T + 2d. Increased monocytes were noted by T + 4d; increased lymphocytes and platelets by T + 8d. ESR and FIB were elevated by T + 3d. Histopathologic study revealed venous inflammation at T + 3d, with beginning thrombus organization by T + 6d. MCP-1 localized to areas of thrombus and phlebitis. The development of DVT in this model involves inflammatory as well as coagulant activity. We conclude that this model allows studies on the role of inflammatory mediators in the development and natural history of DVT.
A Database of Polymorphisms in the von Willebrand Factor Gene and Pseudogene
Authors: Sadler J Evan , Ginsburg David 
Published: July 2018

SummaryNucleotide sequence polymorphisms in the von Willebrand factor (vWF) gene are useful for genetic studies in von Willebrand disease (vWD). This database describes 33 known vWF polymorphisms distributed throughout the vWF gene. DNA sequence information is available for 21 of these sites. The most informative system is a tetranucleotide repeat polymorphism in vWF intron 40. Sixteen of these polymorphisms are within vWF exons, and approximately half of them also alter the encoded amino acid sequence. Many occur close to mutations that cause vWD. The high prevalence of vWF polymorphisms must be considered in the analysis of candidate vWD mutations. In addition to the vWF gene on chromosome 12, there is a partial unprocessed vWF pseudogene on chromosome 22 that corresponds to vWF exons 23 to 34. Three polymorphisms have been assigned to the vWF pseudogene. Because the vWF gene and pseudogene have diverged only ∼3.1% in DNA sequence, correct assignment of polymorphisms to either locus can be difficult in the region of homology. This problem has been solved in some cases by comparison of the published sequences and predicted restriction maps for the gene and pseudogene.
Ultraschalluntersuchungen der hirnversorgenden Arterien Bedeutung für Diagnostik und Therapie
Authors: Widder B. 
Published: July 2018

ZusammenfassungDie Dopplersonographie der extrakraniellen hirnversorgenden Arterien hat sich in den vergangenen Jahren als zuverlässige Methode zur Erkennung höhergradiger Stenosen und Verschlüsse bewährt. In Kombination mit der Schnittbild-Untersuchung (Duplex-Scan) können auch geringgradige Stenosen erfaßt werden, und die transkranielle Dopplersonographie erweitert das Untersuchungsspektrum auf die großen Hirnbasisarterien. In jüngster Zeit kommt den Ultraschallmethoden zunehmende Bedeutung bei der Therapieplanung zu: Die Bestimmung der Autoregulationsreserve mit dem Doppler-C02-Test eignet sich zur Erfassung hämodynamisch kritischer Verschlußprozesse der A. carotis, und die Einführung echomorphologischer Parameter bei der DuplexUntersuchung ermöglicht Aussagen über subintimale Blutungen bei Karotisstenosen mit dadurch erhöhtem embolischen Risiko. Weiterhin gibt die transkranielle Dopplersonographie Auskunft über die Funktionsfähigkeit intrakranieller Kollateralen, gibt Hinweise auf das Clamping-Risiko in der Karotischirurgie, und trägt bei Subarachnoidalblutungen durch Verlaufskontrollen des Vasospasmus zu einer individuell angepaßten operativen und konservativen Therapie bei.
Wirkung von Knoblauch (Allium sativum L.), insbesondere rheologische und hämostaseologische Effekte
Authors: Jung F. , Mrowietz C. , Wenzel E. , Kiesewetter H. 
Published: July 2018

ZusammenfassungEs werden die Wirkungen von Knoblauch auf Theologische und hämostaseologische Variablen, Lipide und den Blutdruck sowohl aus eigenen Untersuchungen als auch aus der Literatur zusammengestellt. Erste deutlich dosisabhängige Effekte werden nach Einmaldosen von 300 mg bzw. Tagesdosen von 600 mg gefunden. Der maximale Wirkzeitpunkt liegt zwischen 4 und 6 Stunden nach der Einnahme. Knoblauch reduziert die spontane und die induzierte Thrombozytenaggregation, die Plasmaviskosität, den Hämatokritwert und läßt die fibrinolytische Aktivität, den Durchmesser präkapillärer Arteriolen und die Mikrozirkulation ansteigen. Eine signifikante lipidsenkende Wirkung ist bislang in kontrollierten klinischen Studien mit 423 Patienten belegt. Milde Blutdrucksenkungen sind in mehreren Untersuchungen beobachtet worden. Bei einer täglichen Dosis von 900 mg treten bei bis zu 25% der Patienten knoblauchbedingt Geruchsbelästigungen auf. Darüber hinaus werden von 5% der Patienten gastrointestinale Beschwerden, bei starker Überdosierung Blutdruckabfälle (in seltenen Fällen bis zum Kollaps) angegeben. Ein Wirksamkeitsnachweis im Sinne einer Antiatherosklerosewirkung liegt bisher nicht vor, eine Gehstrekkensteigerung konnte für die periphere arterielle Verschlußkrankheit in einer Pilotuntersuchung gezeigt werden.
Extra-Cranial Bleeding and Other Symptoms due to Low Dose Aspirin and Low Intensity Oral Anticoagulation
Authors: Meade T W , Roderick P J , Brennan P J , Wilkes H C , Kelleher C C 
Published: July 2018

SummaryData from the early stages of the thrombosis prevention trial (TPT) have been used to establish and quantify the risk of extracranial bleeding due to low dose aspirin (75 mg) and low intensity oral anticoagulation with warfarin (international normalised ratio, INR, 1.5) singly or in combination, in men aged between 45 and 69 who are at high risk of ischaemic heart disease (IHD). The design of the trial is factorial, the four treatments being combined low dose aspirin and low intensity anticoagulation (WA), low intensity anticoagulation alone (W), low dose aspirin alone (A) and double placebo treatment (P). The trial is being carried out through the Medical Research Council’s General Practice Research Framework, with participating practices throughout the United Kingdom. Results are based on the first 3,667 men entered. The risk of major gastrointestinal bleeding due to active treatment is probably about 1 in 500 man-years of treatment, there currently being no difference between the three active regimes (WA, W, A). Intermediate and minor bleeding episodes occur more frequently with WA than with W or A on their own, the excess being mainly due to minor nose bleeds and bruises. In turn, both W and A on their own cause more such minor episodes than placebo treatment, P. There is no evidence that any of the three active regimes increases the risk of peptic ulceration, nor do they increase reports of indigestion. Aspirin increases reports of constipation and reduces reports of blurred vision. Minor bleeding occurs less frequently in smokers than in non-smokers but is not influenced by age. The antithrombotic regimes used are feasible and acceptable. So far, combined treatment and treatment with warfarin alone are not associated with more frequent serious hazards than low dose aspirin on its own, a regime that is increasingly used in clinical practice. The results provide a measure of reassurance for further trials of low intensity oral anticoagulation with warfarin alone or in combination with low dose aspirin.
Subcutaneous Low Molecular Weight Heparin versus Subcutaneous Unfractionated Heparin in the Treatment of Deep Vein Thrombosis: a Polish Multicenter Trial
Authors: Lopaciuk S , Meissner A J , Filipecki S , Zawilska K , Sowier J , Ciesielski L , Bielawiec M , Glowinski S , Czestochowska E ,   others
Published: July 2018

SummaryIn a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen’s score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p <0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/ 68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis.
Granulocyte Elastase, Tumor Necrosis Factor-α and Urokinase Levels as Prognostic Markers in Severe Infection
Authors: Philippé J , Dooijewaard G , Offner F , Turion P , Baele G , Leroux-Roels G 
Published: July 2018

SummaryWe have examined the prognostic value of the levels in the blood of granulocyte elastase-α1-proteinase inhibitor (E-α1-PI) complex, tumor necrosis factor-α (TNF-α) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died.No differences for E-α1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value.TNF-α levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p <0.05). TNF-α was not detectable by bioassay.Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p <0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p <0.05). TNF-α correlated with u-PA Ag (r = 0.38, p <0.05) and with u-PA# (r = 0.47, p <0.01).In a stepwise logistic regression analysis, documentation of infection and plasma levels of u-PA Ag contributed most significantly to prediction of patient outcome. Serum levels of TNF-α did not. These results suggest that, in addition to a number of other clinical and laboratory parameters, u-PA Ag can be used as a prognostic marker in patients with severe infection admitted to an Intensive Care Unit.
Screening for Fibrin Specific Monoclonal Antibodies: The Development of a New Procedure
Authors: Tymkewycz P M , Creighton-Kempsford L J , Hockley D , Gaffney P J 
Published: July 2018

SummaryThe acquisition of monoclonal antibodies specific for human fibrin has been impaired by the similarity in chemical composition between fibrinogen and fibrin and the conformational difference between immobilised and soluble fibrinogen. Five monoclonal antibodies (mabs) with a known affinity for fibrin have been subjected to screening procedures which involved the presentation of different forms of both fibrinogen and fibrin to the test mabs. It was observed by scanning electron microscopy that dried fibrin (denoted fibrin D), immobilised on the wells of PVC plates was morphologically similar to the fibrin found in human clots whereas PVC-immobilised fibrin monolayers (fibrin M) and a homogenised form of fibrin (fibrin FF) presented two very different morphological appearances. It was shown that lack of cross reactivity of a mab with an antigen (e.g. fibrinogen) was validly demonstrated only when both mab and antigen were present in the soluble state. These findings have allowed the generation of a screening procedure which involves the use of fibrin D on PVC plates in conjunction with whole human plasma incubated with the test antibody. This screening procedure has been validated using two mabs, one of which has an exclusive fibrin affinity while the other has a broad spectrum crossreactivity with both fibrinogen and fibrin. This procedure would ensure the acquisition of all the five fibrin-specific mabs used in this study while other less reliable screening procedures might not.
A Collaborative Study on the Measurement of Protein S Antigen in Plasma
Authors: Hubbard Anthony R , Wong Man Yu 
Published: July 2018

SummaryA collaborative study on the measurement of protein S (PS) antigen (total and free) in a freeze-dried ampouled test plasma by assay against local house standard plasmas was carried out in eleven laboratories. Potency estimates of total PS showed good agreement between laboratories with a geometric coefficient of variation (gcv) of 5.9% and an overall combined potency of 0.84 units per ml. Potency estimates of free PS antigen in the test sample were associated with increased variability between laboratories resulting from the polyethylene glycol (PEG) precipitation step which is used to separate free PS from PS bound to the C4b binding protein. Free PS in the test could be expressed relative to either total PS in the house standards (e. g. 0.28 units per ml) or relative to free PS in the house standards following PEG precipitation (e. g. 0.71 units free PS per ml).
Inhibition by D-MePhe-Pro-Arg-H (GYKI-14766) of Thrombus Growth in Experimental Models of Thrombosis
Authors: Bagdy Dániel , Szabó Gabriella , Barabás Éva , Bajusz Sándor 
Published: July 2018

SummaryThe antithrombotic action of the highly effective synthetic thrombin inhibitor D-MePhe-Pro-Arg-H (GYKI-14766) was studied in various models of experimental thrombosis. The compound administered to rats and rabbits by i. v. bolus injections, continuous i. v. infusions, subcutaneously and orally, respectively, induced significant decrease in thrombus weight (i) in a quantitative venous thrombosis model with stasis based on vascular lesion in rats, (ii) in an extracorporeal arterio-venous shunt model in rabbits, and (iii) prevented the occlusion of the vessel in arterial thrombosis induced by mechanical damage in rats. By using the arterio-venous shunt model in rabbits the inhibitory effect on thrombus growth could be demonstrated as a function of dose and time in self-controlled experiments. Blood level of the inhibitor determined by a bioassay varied between 0.09-0.67 µg/ml whole blood when doses of 15 and 20 mg/kg were administered orally. A correlation was found between thrombin time, platelet aggregation induced by thrombin ex vivo and the weight of thrombi formed.
Vampire Bat Salivary Plasminogen Activator Promotes Robust Lysis of Plasma Clots in a Plasma Milieu Without Causing Fluid Phase Plasminogen Activation
Authors: Hare Timothy R , Gardell Stephen J 
Published: July 2018

SummaryVampire bat salivary plasminogen activator (BatPA), human tissue-type plasminogen activator (tPA) or streptokinase (SK) were incubated in human citrated plasma containing a plasma clot that was radiolabelled with iodine-125 fibrin(ogen). Complete clot dissolution by BatPA (30 nM) was associated with slight activation of “fluid phase” plasminogen; the plasma levels of functional fibrinogen and α2-antiplasmin decreased by only 8 and 19%, respectively. Addition of SK (3,600 IU/ml) to the clot-containing plasma caused complete clot lysis and massive activation of the “fluid phase” plasminogen, leading to >60 and 96% decreases of the functional levels of fibrinogen and α2-antiplasmin, respectively. Incubation of tPA (30 nM) in clot-containing plasma caused complete clot lysis as well as substantial activation of “fluid phase” plasminogen; the plasma levels of functional fibrinogen and α2-antiplasmin decreased by 45 and 79%, respectively. The profound degradation of fibrinogen in the SK and tPA but not BatPA-containing samples was confirmed by immunoblot analysis. Additional experiments showed that the presence of soluble clot lysate in plasma containing tPA enhanced the extent of fibrinogen degradation from 25% to >60%; the addition of soluble clot lysate to the plasma containing BatPA did not prompt further fibrinogen degradation. Finally, studies using exogenous α2-antiplasmin suggested that plasmin generated via tPA-mediated activation of “fluid phase” plasminogen does not play an important role in clot dissolution.
Lysine-Binding Heterogeneity of Lp(a): Consequences for Fibrin Binding and Inhibition of Plasminogen Activation
Authors: Leerink C Bas , Duif Pieter F C C M , Gimpel Joke A , Kortlandt Wouter , Bouma Bonno N , Rijn Herman J M van 
Published: July 2018

SummaryLipoprotein(a) [Lp(a)] is recognized as an independent risk factor for atherosclerosis. Lp(a) consists of a LDL-like moiety with an additional glycoprotein, apo(a), linked to apolipoprotein B-100. Apo(a) has a high homology with plasminogen (Pg). In vivo, Pg is activated on a fibrin surface by tissue Pg activator (tPA). We prepared Lp(a) from plasma by sequential ultracentrifugation followed by lysine-sepharose affinity chromatography. We found that a changing (donor dependent) fraction of the Lp(a) did not bind to lysine-sepharose. This fraction, designated Lp(a)lys–, was further purified using gel filtration. Bound Lp(a) [Lp(a)lys+] was eluted with 0.2 M EACA. Apo(a) isoforms in both fractions were identical. In contrast Lp(a)lys+ inhibited Pg activation by tPA in vitro (IC50% 20 mg/1), whereas Lp(a)lys– did not. In addition Lp(a)lys– did not bind to CNBr-digested fibrinogen whereas Lp(a)lys+ did (K
d, app = 0.2 nM). Therefore we conclude that a changing donor dependent fraction of human plasma Lp(a) does not inhibit Pg activation in vitro and does not bind to CNBr-digested fibrinogen.
Transient Expression of Recombinant Glycoprotein Ibα Polypeptides in COS Cells that Inhibit von Willebrand Factor Binding to the Platelet Glycoprotein Ib/IX Complex
Authors: Petersen Eefke , Handin Robert I 
Published: July 2018

SummaryThe cDNA encoding the glycoprotein Ibα polypeptide has been expressed in COS cells. Transfection with full-length cDNA and a cDNA truncated at an internal Xbal site produced a recombinant polypeptide doublet with estimated molecular weights of 48 and 46 kDa (rGpIbαL318) which could be resolved into a single band of molecular weight 36 kDa following digestion with endoglycosidase F. A portion of the truncated polypeptide was retained in the endoplasmic reticulum of COS cells and slowly released. A second fraction was rapidly secreted into COS cell-conditioned medium and could be used for functional studies. Soluble rGpIbαL318 harvested from COS cell-conditioned medium inhibited ristocetin-dependent binding of [125I]-vWF to fixed washed human platelets (IC50 20 nM). Binding was inhibited by reduction and alkylation of “rGpIbαL318” suggesting the need for a critical disulfide bond to maintain biological activity of the recombinant polypeptide. We conclude that the recombinant polypeptides produced by transfection of GpIbα cDNA into heterologous cells are secreted, soluble, and can inhibit vWF binding to platelet GpIb/IX.
Geburtshilfliches Vorgehen beim HELLP-Syndrom
Authors: Loos W. , Rath W. , Kuhn W. , Graeff H. 
Published: July 2018

ZusammenfassungDas HELLP-Syndrom ist eine atypische Verlaufsform der Präeklampsie mit ungewöhnlicher Symptomatik. Es geht mit einer beträchtlichen mütterlichen und perinatalen Mortalität einher. Bisher wurden an den Frauenkliniken der Universität Göttingen und der TU München 23 Schwangere mit einem HELLP-Syndrom behandelt. Die rasche Entbindung durch Kaiserschnitt erscheint gerechtfertigt durch die akute mütterliche Symptomatik und die häufig auftretende intrauterine Gefährdung des Feten.
Adolescent's Hair Loss due to Levetiracetam
Authors: Hamd Rola S. , Hasbini Dana A. 
Published: July 2018

AbstractHair loss is a known complication observed with the intake of many medications including a few antiepileptic drugs. We report, in this article, a 13-year-old girl with epilepsy who developed hair loss, which was noted within 2 months of starting levetiracetam. To our knowledge, this is the first case report of hair loss induced by levetiracetam in this age group.
Boron Neutron Capture Therapy for High-Grade Skull-Base Meningioma
Authors: Takeuchi Koji , Hiramatsu Ryo , Matsushita Yoko , Tanaka Hiroki , Sakurai Yoshinori , Suzuki Minoru , Ono Koji , Miyatake Shin-Ichi , Kuroiwa Toshihiko , Kawabata Shinji 
Published: July 2018

Objectives Boron neutron capture therapy (BNCT) is a nuclear reaction-based tumor cell-selective particle irradiation that occurs when nonradioactive Boron-10 is irradiated with low-energy neutrons to produce high-energy α particles (10B [n, α] 7Li). Possible complications associated with extended surgical resection render high-grade meningioma (HGM) a challenging pathology and skull-base meningiomas (SBMs) even more challenging. Lately, we have been trying to control HGMs using BNCT. This study aims to elucidate whether the recurrence and outcome of HGMs and SBMs differ based on their location.
Design Retrospective review.
Setting Osaka Medical College Hospital and Kyoto University Research Reactor Institute.
Participants Between 2005 and 2014, 31 patients with recurrent HGM (7 SBMs) were treated with BNCT.
Main Outcome Measures Overall survival and the subgroup analysis by the anatomical tumor location.
Results Positron emission tomography revealed that HGMs exhibited 3.8 times higher boron accumulation than the normal brain. Although tumors displayed transient increases in size in several cases, all lesions were found to decrease during observation. Furthermore, the median survival time of patients with SBMs post-BNCT and after being diagnosed as high-grade were 24.6 and 67.5 months, respectively (vs non-SBMs: 40.4 and 47.5 months).
Conclusions BNCT could be a robust and beneficial therapeutic modality for patients with high-grade SBMs.