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  1. Rinoplastia em paciente com doença de Von Willebrand: relato de caso Rinoplastia en paciente con enfermedad de Von Willebrand: relato de caso Rhinoplasty in a patient with Von Willebrand disease: case report

    Directory of Open Access Journals (Sweden)

    Roberto Martins Matos Junior

    2007-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Os pacientes portadores da doença de von Willebrand apresentam sangramento anormal após ferimentos e procedimentos cirúrgicos, já que esta afeta a hemostasia primária e secundária devido à alteração do fator VIII. O objetivo deste relato é elucidar o manuseio pré-, peri- e pós-operatório de pacientes com tal doença. RELATO DO CASO: Paciente do sexo feminino, 42 anos, branca, 165 cm, 61 kg, ASA II, foi submetida à avaliação pré-anestésica para realização de rinoplastia, com diagnóstico prévio de doença de von Willebrand do tipo 1, sendo liberada para a intervenção cirúrgica após avaliação hematológica, com teste de DDAVP IN26 responsivo. No dia da operação, após medicação pré-anestésica e monitoração adequada, foi ofertado oxigênio por cateter nasal e infundida a solução de desmopressina (0,4 µg.kg-1 em 100 mL de NaCl a 0,9% por via venosa 30 minutos antes da operação. Em seguida, iniciou-se a indução anestésica com sufentanil (1 µg.kg-1, propofol (4 mg.kg-1 e rocurônio (0,6 mg.kg-1 por via venosa. Em seqüência, realizou-se intubação traqueal seguida de ventilação controlada mecânica em sistema com absorção de CO2, mantida com O2, N2O e sevoflurano. O ato cirúrgico durou 90 minutos. No intra-operatório a paciente manteve-se hemodinamicamente estável, apresentando sangramento desprezível. Ao final da operação foi extubada e encaminhada à sala de recuperação pós-anestésica, onde permaneceu por 120 minutos. No pós-operatório foi prescrito ácido aminocapróico (500 mg por via oral a cada oito horas, por 48 horas, com alta hospitalar após 24 horas, sem apresentar nenhuma complicação pós-operatória. CONCLUSÕES: A infusão de crioprecipitado ou plasma, utilizado na profilaxia e no tratamento das complicações hemorrágicas, produz um pico de concentração máxima de fator VIII após 48 horas, e é sustentado por 72 horas; entretanto, mesmo

  2. von Willebrand Disease

    Science.gov (United States)

    ... for type 1 von Willebrand disease is called desmopressin. It causes a temporary increase in the von ... injection or by being sniffed into the nose. Desmopressin may also help some people with type 2 ...

  3. von Willebrand Disease

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  4. Cesariana em paciente com doença de von Willebrand associada à infecção pelo HIV: relato de caso Cesárea en paciente con enfermedad de von Willebrand asociada a la infección por el HIV: relato de caso Anesthesia for cesarean section in patient with von Willebrand's disease and HIV infection: case report

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    Vanessa Rezende Balle

    2004-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand é a alteração inata da coagulação mais freqüente em mulheres jovens. A infecção por HIV tem mostrado incidência progressivamente maior em mulheres, constatando-se transmissão vertical em até 25% dos casos. O objetivo deste relato é mostrar o caso de uma paciente com doença de von Willebrand e HIV positivo submetida à cesariana. RELATO DO CASO: Paciente de 24 anos, portadora de anemia microcítica, doença de von Willebrand e HIV, chegou à emergência obstétrica em início de trabalho de parto. Não realizou pré-natal. Foi indicada cesariana a fim de diminuir os riscos de transmissão vertical em paciente com carga viral de HIV desconhecida. Apresentava hematomas pelo corpo e história de hematoma de parede abdominal em cesariana anterior. Os testes de coagulação eram pouco alterados. Após infusão de concentrado de fator VIII foi realizada anestesia geral. Mãe e recém-nascido apresentaram evolução satisfatória. CONCLUSÕES: A avaliação de manifestações clínicas em pacientes com coagulopatia é fundamental na decisão do tipo de anestesia a ser indicada para cada paciente. A avaliação deve ser individualizada, considerando os riscos e benefícios da técnica escolhida. Nestas pacientes, deve-se sempre restringir ao máximo a indicação de interrupção da gestação por via alta, optando-se sempre pelos métodos menos invasivos. A terapia com concentrado de fator VIII é atualmente a melhor opção de tratamento, corrigindo a deficiência específica e diminuindo os riscos de transmissão viral.JUSTIFICATIVA Y OBJETIVOS: La enfermedad de von Willebrand es la alteración innata de la coagulación más frecuente en mujeres jóvenes. La infección por HIV ha mostrado incidencia progresivamente mayor en mujeres, constatandose transmisión vertical en hasta 25% de los casos. El objetivo de este relato es mostrar el caso de una paciente con Enfermedad de von

  5. Anestesia para septoplastia e turbinectomia em paciente portador de doença de von Willebrand: relato de caso Anestesia para septoplastia y turbinectomia en paciente portador de enfermedad de von Willebrand: relato de caso Anesthesia for septoplasty and turbinectomy in von Willebrand disease patient: case report

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    Múcio Paranhos de Abreu

    2003-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Embora a doença de von Willebrand seja o mais comum dos distúrbios hemorrágicos hereditários, as publicações nacionais, relacionando esta doença e a prática anestésica, são escassas. O objetivo deste relato é apresentar um caso de anestesia geral para septoplastia e turbinectomia em paciente portador de doença de von Willebrand - Tipo I, tratado profilaticamente com desmopressina (1-deamino-8-D-arginina vasopressina, DDAVP nos períodos pré e pós-operatório. RELATO DO CASO: Paciente com 19 anos, sexo feminino, 58 kg, portadora de hipotiroidismo, controlado com L-tiroxina (75 mg, e de doença de von Willebrand, que se manifestou há três anos, após extração dentária dos sisos, com sangramento persistente no período pós-operatório. Com o objetivo de se evitar novos episódios hemorrágicos nos períodos per e pós-operatório da cirurgia de septoplastia e turbinectomia a que foi submetida, a paciente foi tratada profilaticamente com desmopressina (0,3 µg.kg-1. A indução anestésica foi realizada com midazolam (2,5 mg, fentanil (150 µg, droperidol (2,5 mg, lidocaína (60 mg, atracúrio (30 mg e metoprolol (4 mg, seguida de intubação traqueal e ventilação sob pressão positiva intermitente. A manutenção da anestesia foi realizada com mistura de oxigênio e óxido nitroso a 50% e sevoflurano a 2%. Esta técnica proporcionou um bom controle da freqüência cardíaca e dos níveis pressóricos durante a cirurgia. A paciente permaneceu com tampão nasal por 24 horas e, quando este foi retirado, não houve sangramento. A paciente recebeu alta hospitalar no dia seguinte ao da cirurgia, sem intercorrências. Não houve episódio hemorrágico no período pós-operatório imediato ou tardio. CONCLUSÕES: O tratamento profilático com DDAVP associado à técnica anestésica utilizada nesse caso, mostrou-se eficaz no controle do sangramento per e pós-operatório.JUSTIFICATIVA Y OBJETIVOS: Aun cuando

  6. Living with von Willebrand Disease

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  7. Von Willebrand factor and aging.

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    Konkle, Barbara A

    2014-09-01

    von Willebrand factor (VWF) plays critical roles in initiating primary hemostasis and extending the half-life of coagulation factor VIII in circulation. VWF levels increase with age and elevated levels are associated with an increased risk of venous thromboembolism and cardiovascular disease (CVD). Patients with von Willebrand disease (VWD) due to a deficiency or dysfunction of VWF may have symptoms that ameliorate with aging or may have exacerbation of their disease. Bleeding sites of particular challenge in the aging patient include gastrointestinal bleeding and hematuria. Some medications used to treat VWD should be used with special precaution in older patients, including desmopressin and VWF-containing factor concentrates. Patients with VWD may have some protection from CVD, but in those patients who develop CVD, management is very challenging, given the role of antiplatelet therapy as the mainstay of treatment. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Sangramento uterino anormal pós operatório em paciente portadora de doença de Von Willebrand: relato de caso

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    Eduardo Borges Coscia

    2016-10-01

    Full Text Available Introdução: O sangramento uterino anormal (S.U.A pode ser uma queixa presente em até 1/3 das consultas ginecológicas. A Doença de von Willebrand é a coagulopatia hereditária mais comum, cujo diagnóstico muitas vezes só é obtido à menarca, com constatação de sangramento abundante (menorragia, anemia e prejuízo na qualidade de vida. Relato de caso: S.G.M, 36 anos, parda, casada, nuligesta. Possui diagnóstico de Doença de von Willebrand (vWD há aproximadamnte 20 anos. Em uso de ácido tranexâmico e contraceptivo oral combinado com boa resposta terapêutica. Foi encaminhada ao ambulatório de patologia Trato genital inferior com diagnóstico de biópsia do colo uterino compatível com NIC III. O tratamento indicado foi a realização de excisão da zona de transformação do colo uterino através de cirurgia de alta frequência (CAF, com confirmação de NIC III e margens livres. Evoluiu com sangramento pós operatório abundante por 3 dias e necessitou infusão de fator VIII para controle hemostático. Discussão: A menorragia pode ser o único sintoma nas mulheres com DvW. O diagnóstico baseia-se na história pessoal e familiar de sangramento e nos exames laboratoriais que demonstrem defeito qualitativo e/ou quantitativo do fator de von Willebrad (FvW. Recomenda-se monitorar o fator VIII a cada 12 horas, no dia da cirurgia e diariamente a partir do primeiro dia pós-operatório.O tratamento inicial objetiva a elevação do FvW para níveis acima de 50% e da atividade do fator VIII à nível clinicamente aceitável.

  9. von Willebrand disease phenotype and von Willebrand factor marker genotype in Doberman Pinschers.

    Science.gov (United States)

    Brooks, M B; Erb, H N; Foureman, P A; Ray, K

    2001-03-01

    To define the relationship between clinical expression of a type-1 von Willebrand disease phenotype and genotype at 2 von Willebrand factor marker loci in Doberman Pinschers. 102 client-owned Doberman Pinschers. Dogs were recruited on the basis of plasma von Willebrand factor concentration, clinical history, and pedigree. Blood samples and response to a history questionnaire were obtained for each dog. Plasma von Willebrand factor concentration was measured by use of an ELISA, and genotyping was performed via polymerase chain reaction for 1 intragenic and 1 extragenic von Willebrand factor marker. Amplification product size was determined by use of polyacrylamide gel electrophoresis (intragenic marker) or automated sequence analysis (extragenic marker). Western blots were prepared from a subset of dogs with low plasma von Willebrand factor concentration to evaluate multimer distribution. Strong associations were detected between plasma von Willebrand factor concentration and von Willebrand factor marker genotype. Twenty-five dogs had substantial reduction in plasma von Willebrand factor concentration and multiple hemorrhagic events. All were homozygous for a 157-base-pair intragenic marker allele and homozygous or compound heterozygous for 1 of 4 extragenic marker alleles. These marker genotypes were exclusively detected in dogs with low plasma von Willebrand factor concentration, although some dogs with these genotypes did not have abnormal bleeding. Type-1 von Willebrand disease in Doberman Pinschers is associated with the von Willebrand factor gene locus; however, the expression pattern in this breed appears more complex than that of a simple recessive trait.

  10. How Is von Willebrand Disease Treated?

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  11. How Is von Willebrand Disease Diagnosed?

    Science.gov (United States)

    ... the condition. For example, the school nurse, teacher, daycare provider, coach, or any leader of afterschool activities ... MedlinePlus) Von Willebrand Disease (MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn more about getting ...

  12. Genetics Home Reference: von Willebrand disease

    Science.gov (United States)

    ... Jun;5(6):1165-9. Citation on PubMed Kessler CM. Diagnosis and treatment of von Willebrand disease: ... consult with a qualified healthcare professional . About Selection Criteria for Links Data Files & API Site Map Customer ...

  13. Doença de von Willebrand e anestesia Enfermedad de von Willebrand y anestesia Von Willebrand's disease and anesthesia

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    Fabiano Timbó Barbosa

    2007-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A doença de von Willebrand ocorre devido à mutação no cromossomo 12 e é caracterizada por deficiência qualitativa ou quantitativa do fator de von Willebrand. A diversidade de mutações leva ao aparecimento das mais variadas manifestações clínicas possibilitando a divisão dos pacientes em vários tipos e subtipos clínicos. A coagulopatia se manifesta basicamente através da disfunção plaquetária associada à diminuição dos níveis séricos do fator VIII coagulante. O objetivo dessa revisão foi mostrar os cuidados relacionados aos pacientes portadores da doença de von Willebrand durante o período perioperatório. CONTEÚDO: Foram definidas as características da doença de von Willebrand quanto à fisiopatologia, à classificação, ao diagnóstico laboratorial, ao tratamento atual e aos cuidados com o manuseio do paciente no período perioperatório. CONCLUSÕES: A doença de von Willebrand é o distúrbio hemorrágico hereditário mais comum, porém ela é subdiagnosticada pela complexidade da própria doença. A correta classificação do paciente, o uso apropriado da desmopressina e a transfusão do fator de von Willebrand são medidas fundamentais para a realização do procedimento anestésico bem-sucedido.JUSTIFICATIVA Y OBJETIVOS: La enfermedad de von Willebrand ocurre debido a la mutación en el cromosoma 12 y se caracteriza por la deficiencia cualitativa o cuantitativa del factor de von Willebrand. La diversidad de mutaciones conlleva al aparecimiento de las más variadas manifestaciones clínicas posibilitando la división de los pacientes en varios tipos y subtipos clínicos. La coagulopatía se manifiesta básicamente a través de la disfunción plaquetaria asociada con la disminución de los niveles séricos del factor VIII coagulante. El objetivo de esa revisión fue mostrar los cuidados relacionados con las pacientes portadoras de la enfermedad de von Willebrand durante el per

  14. Active Von Willebrand Factor, thrombocytopenia and thrombosis

    NARCIS (Netherlands)

    Hulstein, J.J.J.

    2006-01-01

    Platelets and von Willebrand factor (VWF) are unable to interact in circulation. To induce an interaction, a conversion of VWF to a platelet-binding conformation is required. At higher shear stresses, the first step in thrombus formation is binding of VWF to the subendothelium. This results in

  15. Molecular mechanisms of von Willebrand Factor mechanoregulation

    NARCIS (Netherlands)

    Jakobi, A.J.|info:eu-repo/dai/nl/311489621

    2012-01-01

    Von Willebrand factor (VWF) multimers mediate primary adhesion and aggregation of platelets. The potency to recruit platelets critically depends on the size of VWF multimers, which is regulated by a feedback mechanism involving shear-induced unfolding of the A2 domain in VWF and cleavage by the

  16. Joint bleeding in von Willebrand disease

    NARCIS (Netherlands)

    Galen, K.P.M. van

    2017-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder occurring in approximately 1/100 people. Until now, joint bleeds did not get much attention in clinical research on VWD, since mucocutaneous bleeding is predominant. However, recurrent joint bleeds lead to arthropathy, the

  17. Laboratory Testing for Von Willebrand Factor Multimers.

    Science.gov (United States)

    Oliver, Susan; Lau, Kun Kan Edwin; Chapman, Kent; Favaloro, Emmanuel J

    2017-01-01

    Von Willebrand disease (VWD) is reportedly the most common inherited bleeding disorder and can also arise as an acquired syndrome (AVWS). These disorders develop due to defects and/or deficiency of the plasma protein von Willebrand factor (VWF). Laboratory testing for the VWF-related disorders requires assessment of both VWF level and VWF activity, the latter requiring multiple assays because of the many functions carried out by VWF to help prevent bleeding. As an additional step, an evaluation of VWF structural features by multimer analysis is useful in selective investigations. The current paper therefore describes a protocol for assessment of VWF multimers by gel electrophoresis, thus enabling identification of protein bands that represent differently sized multimers. The sample protocol described in this chapter is the methodology developed by Sebia.

  18. Treatment of patients with von Willebrand disease

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    Tuohy E

    2011-04-01

    Full Text Available Emma Tuohy1, Emma Litt1, Raza Alikhan1,21Department of Haematology, University Hospital of Wales, Cardiff, UK; 2Haemophilia and Thrombosis Centre, University Hospital of Wales, Cardiff, UKAbstract: Von Willebrand disease (vWD is the most common hereditary bleeding disorder. The aim of therapy is to correct the dual hemostatic defect, due to defective platelet adhesion-aggregation and abnormal coagulation due to Factor VIII (FVIII deficiency. The choice of treatment depends on a number of factors, including the severity of the bleed, the procedure planned, the subtype and severity of the disease and the age and morbidity of the patient. Desmopressin (DDAVP is the treatment of choice for type 1 vWD as it increases endogenous release of FVIII and von Willebrand factor (vWF and is also used in some subtypes of type 2 vWD. In those patients in whom DDAVP is ineffective or contraindicated, levels can be restored by infusing vWF:FVIII concentrates. The role of antifibrinolytic treatment is an important adjunct to replacement therapy during minor or major surgery involving mucosal surfaces. The dosing and timing of vWF:FVIII concentrates is important depending on the nature of the surgical procedure. The role of secondary prophylaxis needs to be further defined.Keywords: von Willebrand disease, treatment, DDAVP 

  19. Comparison of automated von Willebrand factor activity assays

    DEFF Research Database (Denmark)

    Timm, Annette; Hillarp, Andreas; Philips, Malou

    2015-01-01

    INTRODUCTION: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. Measurement of von Willebrand factor (VWF) activity in plasma is often based on platelet agglutination stimulated by the ristocetin cofactor activity. Novel assays, based on latex beads with recombinant...

  20. von Willebrand disease and aging : an evolving phenotype

    NARCIS (Netherlands)

    Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.

    Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related

  1. Translational medicine advances in von Willebrand disease.

    Science.gov (United States)

    Lillicrap, D

    2013-06-01

    Following the recognition of von Willebrand disease (VWD) in 1926 and the cloning of the gene for von Willebrand factor (VWF) in 1985, significant advances have been made in our fundamental knowledge of both the disease and the protein. Some of this new knowledge has also begun to impact the clinical management of VWD. First, the progressive increase in our understanding of the molecular genetic basis of VWD has resulted in rational applications of molecular testing to complement the current range of phenotypic tests for VWD. These molecular genetic strategies are most effectively directed at the prenatal diagnosis of type 3 VWD and confirmatory testing for types 2B and 2N disease. In contrast, the use of molecular testing to clarify the diagnosis of type 1 VWD is of marginal benefit, at best. In terms of VWD therapies, a new recombinant VWF concentrate has recently completed successful clinical trials and is now awaiting more widespread application. There have even been some preclinical successes with VWF gene transfer although the clinical rationale for this therapeutic strategy needs careful consideration. Much more remains to be learnt about the biology of VWF and further translational advances for the enhancement of VWD care will inevitably be realized. © 2013 International Society on Thrombosis and Haemostasis.

  2. VON WILLEBRAND DISEASE: DIAGNOSIS AND TREATMENT

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    Majda Benedik Dolničar

    2004-12-01

    Full Text Available Background. Von Willebrand disease (VWD is a most frequently inborn bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor (VWF. VWF promotes platelet-vessel wall (adhesion and plateletplatelet interaction (aggregation. It is also the carrier for factor VIII (F VIII in plasma. A deficiency of VWF may results in impairment of both, primary and secondary haemostasis. Therefore, patients with VWD can have bleeding symptoms typical fot the defect in primary haemostasis (mucocutaneous haemorrhages. In severe deficiency of VWF there are also haemarthroses and haematomas typical for patients with coagulation defects. Several types and subtypes of VWD have been described. The diagnosis is based on measurements of VWF concentration and activity and F VIII activity in plasma. The tests identifying VWD subtypes are ristocetin induced platelet agglutination (RIPA, multimeric analysis of VWF and measurement of the binding of VWF to F VIII.Conclusions. Due to heterogeneity of VWF defects, the correct diagnosis of types and subtypes is sometimes difficult but is important for appropriate treatment. There are two main therapeutic options for patients with VWD: desmopressin and blood derived concentrates of F VIII/VWF. In certain cases antifibrinolytics and hormones can be suitable treatment. Desmopressin is the treatment of choice in patients with type 1 VWD. It raises endogenous F VIII and VWF and thereby corrects the intrinsic coagulation defect as well as the prolonged bleeding time (BT or closure time (CT-PFA100 in most type 1 VWD patients. In type 3 and in the majority of type 2 patients desmopressin is not effective and it is necessary to use concentrates containing F VIII and VWF. These are always effective in raising of F VIII activity, whereas the BT/CT may not be completely corrected, but the normalisation of the BT/CT is not always necessary.

  3. Revascularization Operation for Moyamoya Disease with Concurrent von Willebrand Disease.

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    Miki, Kenji; Arimura, Koichi; Nishimura, Ataru; Yoshimoto, Koji; Sayama, Tetsuro; Iihara, Koji

    2017-12-01

    Although extracranial-intracranial (EC-IC) bypass is an effective treatment strategy for symptomatic moyamoya disease, surgeons need to be cautious regarding the possibility of postoperative hemorrhagic complications in patients with a concurrent coagulation disorder. Here, we describe a case of EC-IC bypass for moyamoya disease concurrent with von Willebrand disease type 1. Following perioperative replacement of the von Willebrand factor, the patient showed an uneventful and uncomplicated clinical course. This is the first reported case of EC-IC bypass being performed for moyamoya disease in a patient with concurrent von Willebrand disease. We emphasize the importance of appropriate management with replacement of the von Willebrand factor during the perioperative period to avoid hemorrhagic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Prophylaxis escalation in severe von Willebrand disease: A prospective study from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    T.C. Abshire (Thomas Calvin); J. Cox-Gill; C.L. Kempton; F.W.G. Leebeek (Frank); M. Carcao (M.); P. Kouides (P.); S. Donfield (S.); E. Berntorp

    2015-01-01

    textabstractBackground: Treatment of mucosal bleeding (epistaxis, gastrointestinal bleeding, and menorrhagia) and joint bleeding remains problematic in clinically severe von Willebrand disease (VWD). Patients are often unresponsive to treatment (e.g. desmopressin or antifibrinolytic therapy) and may

  5. Polymorphism in the promoter region of von Willebrand factor gene and von Willebrand disease type 1

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    Daniel Simon

    2003-12-01

    Full Text Available The -1185A/G polymorphism in the 5'-regulatory region of the von Willebrand factor (VWF gene was associated with VWF plasma levels in a normal population. This study was undertaken to evaluate whether there is a relationship between this polymorphism and type 1 von Willebrand disease (VWD, a disorder characterized by a quantitative deficiency of VWF. The association between this polymorphism and plasma VWF levels in normal Brazilian individuals was also analyzed. Control subjects (n = 460 and type 1 VWD patients (n = 41 were studied. Polymerase chain reaction (PCR amplification of the 864-bp VWF promoter region followed by AccII restriction-digestion was used to identify the -1185A/G genotypes. The -1185G allele frequency was 57% in normal individuals and 63% in type 1 VWD patients, this difference was not significant (p = 0.29. No significant association was observed between -1185A/G genotypes and VWF plasma levels in normal individuals, although VWF levels were in the same direction as those reported by another study, with subjects carrying the G allele having the lower levels. These results suggest that -1185A/G polymorphism is not associated with the partial deficiency of VWF in type 1 VWD patients.

  6. Acquired von Willebrand syndrome: A rare disorder of heterogeneous etiology

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    P Kasatkar

    2013-01-01

    Full Text Available Context: Acquired von Willebrand syndrome (AVWS is a rare bleeding disorder that mimics the inherited form of von Willebrand disease (VWD in terms of laboratory findings and clinical presentation. Aims: To study the etiology of acquired VWD. Settings and Design: The patients referred from various hospitals in and out of Mumbai were included in the study. Materials and Methods: Six patients with AVWS diagnosed at this center over the last 10 years were analyzed against 171 patients with inherited VWD. The differential diagnosis of AVWS was made based on reduced levels of von Willebrand antigen and von Willebrand ristocetin cofactor, decrease in ristocetin induced platelet aggregation, absence of correction in mixing studies with no prior history of bleeding problems and a negative family history for bleeding disorders. Results: In three patients, the disease was associated with systematic lupus erythematosus, out of which one was also associated with Kikuchi lymphadenitis and second with autoimmune hemolytic anemia. Fourth case was associated with hypothyroidism and fifth was a case of dermatitis and vitiligo. The last patient was a case of hemophilia A with Burkitts lymphoma, who developed autoantibodies to von Willebrand factor. Except two patients, all other patients responded to immune suppressive therapy with corticosteroids, while the patient with hypothyroidism responded to oral thyroxine. Conclusion: AVWS is a rare condition and may often be missed or diagnosed as inherited disease associated with heterogeneous disease conditions.

  7. Diurnal variation of von Willebrand factor in plasma

    DEFF Research Database (Denmark)

    Timm, Annette; Fahrenkrug, Jan; Jørgensen, Henrik L

    2014-01-01

    BACKGROUND: Quantitation of von Willebrand factor (VWF) in plasma is a central element in assessing von Willebrand disease (VWD). VWF activity is known to vary, which has partly been ascribed to biological and preanalytical variation. However, a possible diurnal expression of VWF has not been...... of light and 9 h of darkness); the plasma concentration of melatonin was used as an internal control to confirm the normal 24-h rhythms of the individual participants. RESULTS: The data, analyzed by rhythmometric statistics, revealed a significant variation (P = 0.02) and total amplitude of 22.6% in VWF...... and VWF and (ii) VWF propeptide and VWF was determined. Taken together, the data suggest changes in release and not in clearance. CONCLUSIONS: Diurnal variation in von Willebrand antigen and activity in plasma represents an important aspect of the biological variation. Standardized time-of-day plasma...

  8. An ELISA for the quantitation of von Willebrand Factor

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Overgaard, Martin; Diederichsen, Axel Cosmus Pyndt

    2013-01-01

    BACKGROUND: Von Willebrand factor (VWF) is pivotal in arterial thrombosis, and osteoprotegerin (OPG) is besides being a bone protein also related to cardiovascular diseases. OPG can bind VWF, but the significance of this interaction is not known. OBJECTIVES: The aim was to develop an assay...... for measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human plasma. Furthermore, the significance of VWF:OPG complex as a marker of cardiovascular disease (CVD) was evaluated. PATIENTS/METHODS: A sandwich ELISA for quantification of VWF:OPG was developed using a polyclonal rabbit anti...

  9. CHANGES OF VON WILLEBRAND FACTOR DURING PREGNANCY IN WOMEN WITHOUT AND WITH VON WILLEBRAND DISEASE

    Directory of Open Access Journals (Sweden)

    Giancarlo Castaman

    2013-07-01

    Full Text Available Delivery in von Willebrand disease (VWD represents a significant hemostatic challenge because of the variable pattern of changes observed during pregnancy of von Willebrand factor (VWF  and factor VIII (FVIII, the protein carried by VWF. The wide heterogeneity of phenotypes and of the underlying pathophysiological mechanisms associated with this disorder prompt a careful evaluation of pregnant women with VWD to plan the most appropriate treatment at time of parturition. VWF and FVIII increase significantly during pregnancy in normal women, already within the first trimester, reaching levels by far > 100 U/dL by the time of parturition. In women with VWD, levels at baseline of VWF and FVIII > 30 U/dL are usually associated with a high likelihood to achieve normal levels at the end of pregnancy and specific anti-hemorrhagic prophylaxis is seldom required. Women with basal level < 20 U/dL usually have a poor increase since most of these women carry mutations associated with increased VWF clearance or are compound heterozygous for different VWF mutations which prevent the achievement of satisfactory hemostatic levels. While women with mutations associated with increased clearance show a full, albeit transitory correction of their hemostatic deficiency after desmopressin administration, compound heterozygous need replacement therapy because they do not respond well to this agent. Patients with abnormal VWF:RCo/VWF:Ag ratio at baseline (e.g. < 0.6, typically associated with type 2 VWD, maintain the abnormality throughout pregnancy and VWF:RCo usually does not attain safe levels ³ 50 U/dL. These women require replacement therapy with VWF-FVIII concentrates. Delayed post-partum bleeding may occur when replacement therapy is not continued for some days. Tranexamic acid may be useful at discharge to avoid excessive lochia.

  10. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    Background: Polymorphisms in von Willebrand factor (VWF) gene are an important contributor to the expression of VWF gene and differences in ethnic distribution of these single nucleotide polymorphisms (SNPs) exists. Aims: Our objective was to molecularly characterize the exon 28 of the VWF gene in the three major ...

  11. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    2016-05-12

    May 12, 2016 ... two probable cases among 95 patients with hemophilia A and 11 with hemophilia B between 1980 and 1986, but full investigation and family studies were not performed. In. Nigeria, we have been unable to find documented cases of. Molecular characterization of exon 28 of von Willebrand's factor gene in ...

  12. DEEP VEIN THROMBOSIS IN PATIENT WITH VON WILLEBRAND DISEASE

    Directory of Open Access Journals (Sweden)

    V. A. Elykomov

    2016-01-01

    Full Text Available Objective: to identify the possible factors of thrombogenic risk and ways of its prevention in patients with von Willebrand disease.Case description. Patient X., 42 years old, who suffers from von Willebrand disease type 3 with 5-years of age. Asked on reception to the traumatologist in the polyclinic of the Regional Hospital with pain in the left hip joint. Recommended planned operative treatment in the Altai Regional Clinical Hospital. Preoperative preparation included the infusion of concentrate of von Willebrand factor and coagulation factor VIII. Operation – cement total arthroplasty of the left hip joint. In the postoperative period analgesic treatment, elastic compression of the lower extremities, iron supplements, also conducted infusion of concentrate of von Willebrand factor and coagulation factor VIII for 20 days and thromboprophylactic with dabigatran. On the 3rd day after the operation the patient revealed deep vein thrombosis of the femoral segment (floating clot.Results. The patient was operated for emergency indications in the Department of endovascular surgery – installation of venous cava filter “Volan”. Dabigatran is cancelled, appointed clexane for 3 months. In our clinical example the patient lacked risk factors of pulmonary embolism as obesity, age, smoking, prolonged immobilization, estrogen therapy. Overdose of factor VIII were not observed – the level of factor did not exceed 135 % on transfusions. At the same time, the patient was found polymorphisms in the genes ITGA2, FGB, MTHFR, MTR – heterozygote, MTRR – mutant homozygote, which may indicate the genetic factors of thrombogenic risk. Also a significant risk factor was massive surgical intervention (total hip replacement. Despite preventive measures (elastic compression, thromboprophylactic dabigatran, early activation we cannot to avoid thrombotic complications.Conclusion. This article presents a case demonstrating a thrombotic complication in patients

  13. The effect of exercise on von Willebrand factor and ADAMTS-13 in individuals with type 1 and type 2B von Willebrand disease

    NARCIS (Netherlands)

    Stakiw, J.; Bowman, M.; Hegadorn, C.; Pruss, C.; Notley, C.; Groot, E.; Lenting, P. J.; Rapson, D.; Lillicrap, D.; James, P.

    Background: The effect of exercise on von Willebrand factor (VWF) and ADAMTS-13 levels in individuals with von Willebrand disease (VWD) has never been reported. Objectives: The aim was to quantify the effect of a standardized exercise protocol on individuals with type 1 and type 2B VWD.

  14. Idiopathic pulmonary hypertension causing acquired von Willebrand disease and menorrhagia.

    Science.gov (United States)

    Sokkary, Nancy A; Dietrich, Jennifer E; Venkateswaran, Lakshmi

    2011-10-01

    Von Willebrand disease (VWD) maybe inherited or acquired; both etiologies can be associated with heavy menstrual bleeding. Pulmonary arterial hypertension may result in acquired VWD due to the destruction of high molecular weight von Willebrand multimers. We report a case of menorrhagia due to acquired VWD in a patient with idiopathic pulmonary hypertension. An adolescent female with known idiopathic pulmonary hypertension developed acquired VWD. Her primary disease necessitates the use of platelet inhibitors and intermittent anticoagulation. At menarche she also developed menorrhagia due to acquired VWD. She is currently controlled with stimate and progesterone-only therapy. VWD in a patient with idiopathic pulmonary hypertension causing menorrhagia. Although VWD and menorrhagia are commonly linked, the treatment and disease process in a patient with idiopathic pulmonary arterial hypertension is incredibly complex. Published by Elsevier Inc.

  15. Von Willebrand factor for menorrhagia: a survey and literature review.

    Science.gov (United States)

    Ragni, M V; Machin, N; Malec, L M; James, A H; Kessler, C M; Konkle, B A; Kouides, P A; Neff, A T; Philipp, C S; Brambilla, D J

    2016-05-01

    von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia. We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms 'von Willebrand factor,' 'menorrhagia' and 'von Willebrand disease' to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics. Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011-2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33-100 IU kg(-1) on day 1-6 of menstrual cycle. This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings. © 2016 John Wiley & Sons Ltd.

  16. Screening of Von Willebrand Disease in Iranian Women With Menorrhagia

    Science.gov (United States)

    Rahbar, Nahid; Faranoush, Mohammad; Ghorbani, Raheb; Sadr Alsadat, Bahare

    2015-01-01

    Background: Menorrhagia is a common health problem in women, particularly those with bleeding disorders. Little is known about the course of menorrhagia or other bleeding symptoms in women with the most common congenital bleeding disorder, von Willebrand disease (vWD). Objectives: The aim of this study was to estimate the prevalence of vWD in women with diagnosed menorrhagia. Materials and Methods: In this cross-sectional study, a total of 460 consecutive patients, presenting menorrhagia, were analyzed. The initial screening and confirmation tests for the diagnosis of vWD included determination of prothrombin time (PT), partial thromboplastin time (PTT), bleeding time (BT), fibrinogen, factor VIII, vWF antigen, and vWF activity. A questionnaire was filled for every patient. The data were then analyzed using the SPSS software. Results: Mean age of our patients was 32.5 ± 10.6 years. The level of von Willebrand factor in 22.5% and von Willebrand activity in 19.6% of patients was abnormal. The prevalence of vWD among patients with menorrhagia was 24%. Conclusions: The high prevalence of vWD among our patients was the same as other previous reports, suggesting low awareness about this disease and under diagnosis of mild cases. PMID:25763275

  17. Nordic Haemophilia Council's practical guidelines on diagnosis and management of von Willebrand disease

    DEFF Research Database (Denmark)

    Lassila, Riitta; Holme, Pål André; Landorph, Andrea

    2011-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder characterized by spontaneous or tissue injury-related, mostly mucocutaneous, bleeding events. VWD affects both males and females and is caused by quantitative or qualitative deficiency of Von Willebrand factor. The diagno...

  18. Current and Emerging Options for the Management of Inherited von Willebrand Disease

    NARCIS (Netherlands)

    Heijdra, J.M. (Jessica M.); M.H. Cnossen (Marjon); F.W.G. Leebeek (Frank)

    2017-01-01

    textabstractVon Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in approximately 1:10,000 individuals. VWD is caused by a deficiency and/or defect of von Willebrand factor (VWF). The most common

  19. Myomectomy in a case of von Willebrand's disease in a low ...

    African Journals Online (AJOL)

    Von Willebrand's disease (vWD) is an inherited bleeding disorder with an estimated prevalence of 1% in the general population. It is caused by deficiency or dysfunction of von Willebrand's factor. Surgical procedure on patients with vWD is usually associated with increased haemorrhage. Keywords: Clotting Factors ...

  20. Von Willebrand Disease in the Netherlands : from genetic variation to phenotypic variability

    NARCIS (Netherlands)

    Y.V. Sanders (Yvonne)

    2015-01-01

    markdownabstractAbstract Von Willebrand Disease (VWD) is the most common inherited bleeding disorder resulting in mucocutaneous bleeding, like epistaxis, oral cavity bleeding and menorrhagia. VWD is caused by reduced or dysfunctional von Willebrand Factor (VWF). VWF levels are highly variable

  1. von Willebrand factor, Jedi knight of the bloodstream.

    Science.gov (United States)

    Springer, Timothy A

    2014-08-28

    When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. © 2014 by The American Society of Hematology.

  2. Clinical measurement of von Willebrand factor by fluorescence correlation spectroscopy.

    Science.gov (United States)

    Torres, Richard; Genzen, Jonathan R; Levene, Michael J

    2012-06-01

    Identification of von Willebrand factor (vWF) abnormalities in a variety of conditions is hampered by the limitations of currently available diagnostic tests. Although direct multimer visualization by immunoelectrophoresis is a commonly used method, it is impractical as a routine clinical test. In this study, we used a biophysical analysis tool, fluorescence correlation spectroscopy (FCS), to measure vWF distributions. The goals were to develop a method that is quicker and simpler than vWF gel electrophoresis and to evaluate the potential of FCS as a clinical diagnostic technique. We analyzed plasma from 12 patients with type 1 von Willebrand disease (vWD), 14 patients with type 2 vWD, and 10 healthy controls using a fluctuation-based immunoassay approach. FCS enabled identification and proper classification of type 1 and type 2 vWD, producing quantitative results that correspond to qualitative gel multimer patterns. FCS required minimal sample preparation and only a 5-min analysis time. This study represents the first implementation of FCS for clinical diagnostics directly on human plasma. The technique shows potential for further vWF studies and as a generally applicable laboratory test method.

  3. Is the activated partial thromboplastin time suitable to screen for von Willebrand factor deficiencies?

    Science.gov (United States)

    Lippi, Giuseppe; Franchini, Massimo; Poli, Giovanni; Salvagno, Gian Luca; Montagnana, Martina; Guidi, Gian Cesare

    2007-06-01

    The diagnostic approach to von Willebrand factor deficiencies is challenging and requires discretionary use of laboratory resources. Although extensive preoperative testing is not recommended, the activated partial thromboplastin time may be useful, especially in selected categories of patients. To establish the diagnostic sensitivity of this test to identify isolate von Willebrand factor deficiencies, 204 consecutive patients underwent a routine preoperative screening consisting of activated partial thromboplastin time, von Willebrand factor antigen, intrinsic pathway clotting factors activity, lupus anticoagulants and thrombin time. Thirty-seven patients were diagnosed with haemostasis disturbances other than von Willebrand factor deficiencies and were excluded from the evaluation. Isolated von Willebrand factor deficiency was diagnosed in 11 of the remaining 167 patients. A significant correlation was observed between von Willebrand factor antigen and activated partial thromboplastin time. Receiver operating characteristic curve analysis showed an area under the curve of 0.982 (95% confidence interval: 0.972-0.992; P thromboplastin time, sensitivity and specificity were 100 and 85%, respectively, with negative and positive predictive values of 100 and 31%, respectively. These results demonstrate that activated partial thromboplastin time has an excellent diagnostic sensitivity and a satisfactory specificity for identifying isolated von Willebrand factor deficiencies.

  4. [Structure and function of the factor VIII/von Willebrand factor complex].

    Science.gov (United States)

    Müller, G

    1990-03-01

    In the blood plasma factor VIII is bound to the von Willebrand factor. The primary structure of the two proteins were clarified by gene clonation. Factor VIII descends from a precursor protein with 2,351 amino acids by splitting of 19 amino acid residues and is activated by partial proteolysis. In the blood coagulation factor VIII acts as co-factor for the activation of factor X by factor IX in the presence of phospholipids and Ca++ within the intrinsic coagulation system. The formation of the von Willebrand factor takes place by splitting of 22 and 741 amino acid residues, respectively, from pre-pro-von Willebrand factor via pro-von Willebrand factor. The subunits of the von Willebrand factor consist od 2,050 amino acid residues. In the blood plasma the von Willebrand factor is existing as a mixture of multimeres. Receptors of the von Willebrand factor on the thrombocytic membrane are the glycoproteins GPIb and GPIIb/GPIIIa, by means of which the adhesion of thrombocytes at the subendoethelium of the vascular wall and the aggregation of thrombocytes are mediated.

  5. Value of Von Willebrand Factor as a Predictor for Osteoporosis Development in Women with Hypothyroidism

    Directory of Open Access Journals (Sweden)

    I.V. Pankiv

    2015-08-01

    Full Text Available The paper presents the study of the value of von Willebrand factor as a marker of endothelial dysfunction for osteoporosis development and for prediction of risk of its formation in women with hypothyroidism. Postmenopausal women with hypothyroidism have significant increase of von Willebrand factor at lumbar osteopenia. High concentrations of von Willebrand factor in women with hypothyroidism follows to consider it as a predictor for osteoporosis development. Increased level of С-reactive protein belongs to the unfavorable prognostic signs in relation to the decline of bone mineral density for patients with primary hypothyroidism.

  6. SNAP23 Regulates Endothelial Exocytosis of von Willebrand Factor.

    Science.gov (United States)

    Zhu, Qiuyu Martin; Zhu, Qiuyu; Yamakuchi, Munekazu; Lowenstein, Charles J

    2015-01-01

    Endothelial exocytosis regulates vascular thrombosis and inflammation. The trafficking and release of endothelial vesicles is mediated by SNARE (Soluble NSF Attachment protein REceptors) molecules, but the exact identity of endothelial SNAREs has been unclear. Three SNARE molecules form a ternary complex, including isoforms of the syntaxin (STX), vesicle-associated membrane protein (VAMP), and synaptosomal-associated protein (SNAP) families. We now identify SNAP23 as the predominant endothelial SNAP isoform that mediates endothelial exocytosis of von Willebrand Factor (VWF). SNAP23 was localized to the plasma membrane. Knockdown of SNAP23 decreased endothelial exocytosis, suggesting it is important for endothelial exocytosis. SNAP23 interacted with the endothelial exocytic machinery, and formed complexes with other known endothelial SNARE molecules. Taken together, these data suggest that SNAP23 is a key component of the endothelial SNARE machinery that mediates endothelial exocytosis.

  7. Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD)

    DEFF Research Database (Denmark)

    Budde, U.; Schneppenheim, R.; Eikenboom, J.

    2008-01-01

    BACKGROUND: Type 1 von Willebrand disease (VWD) is a congenital bleeding disorder characterized by a partial quantitative deficiency of plasma von Willebrand factor (VWF) in the absence of structural and/or functional VWF defects. Accurate assessment of the quantity and quality of plasma VWF...... is difficult but is a prerequisite for correct classification. OBJECTIVE: To evaluate the proportion of misclassification of patients historically diagnosed with type 1 VWD using detailed analysis of the VWF multimer structure. Patients and methods: Previously diagnosed type 1 VWD families and healthy controls...

  8. Towards improved diagnosis of von Willebrand disease: comparative evaluations of several automated von Willebrand factor antigen and activity assays.

    Science.gov (United States)

    Favaloro, Emmanuel J; Mohammed, Soma

    2014-12-01

    von Willebrand disease (VWD) is reportedly the most common bleeding disorder and arises from deficiency and/or defects of von Willebrand factor (VWF). Laboratory diagnosis and typing has important management implications and requires a wide range of tests, including VWF activity and antigen, and involves differential identification of qualitative vs quantitative defects. We have assessed several VWF antigen and activity assays (collagen binding [VWF:CB], ristocetin cofactor [VWF:RCo] and the new Siemens INNOVANCE assay [VWF:Ac], employing latex particles and gain of function recombinant glycoprotein Ib to facilitate VWF binding and agglutination without need for ristocetin) using different instrumentation, including the new Sysmex CS-5100, with a large sample test set (n=600). We included retrospective plus prospective study designs, and also evaluated desmopressin responsiveness plus differential sensitivity to high molecular weight VWF. VWF:Ag and VWF:RCo results from different methods were respectively largely comparable, although some notable differences were evident, including one high false normal VWF:Ag value (105 U/dL) on a type 3 VWD sample, possibly due to heterophile antibody interference in the latex-based CS-5100 methodology. VWF:Ac was largely comparable to VWF:RCo, but VWF:CB showed discrepant findings to both VWF:RCo and VWF:Ac with some patients, most notably patients with type 2M VWD. (a) VWF:Ag on different platforms are largely interchangeable, as are VWF:RCo on different platforms, except for occasional (some potentially important) differences, and manufacturer recommended methods may otherwise require some assay optimization; (b) VWF:RCo and VWF:Ac are largely interchangeable, except for occasional differences that may also relate to assay design (differing optimizations); (c) VWF:CB provides an additional activity to supplement VWF:RCo or VWF:Ac activity assays, and is not interchangeable with either. Crown Copyright © 2014. Published by

  9. Diagnostic Differentiation of von Willebrand Disease Types 1 and 2 by von Willebrand Factor Multimer Analysis and DDAVP Challenge Test.

    Science.gov (United States)

    Michiels, Jan Jacques; Smejkal, Petr; Penka, Miroslav; Batorova, Angelika; Pricangova, Tatiana; Budde, Ulrich; Vangenechten, Inge; Gadisseur, Alain

    2017-09-01

    The European Clinical Laboratory and Molecular (ECLM) classification of von Willebrand disease (vWD) is based on the splitting approach which uses sensitive and specific von Willebrand factor (vWF) assays with regard to the updated molecular data on structure and function of vWF gene and protein defects. A complete set of FVIII:C and vWF ristocetine cofactor, collagen binding, and antigen, vWF multimeric analysis in low- and medium-resolution gels, and responses to desmopressin (DDAVP) of FVIII:C and vWF parameters are mandatory. The ECLM classification distinguishes recessive types 1 and 3 vWD from recessive vWD 2C due to mutations in the D1 and D2 domains and vWD 2N due to mutations in the D'-FVIII-binding domain of vWF. The ECLM classification differentiates between mild vWD type 1 with variable penetrance of bleedings from symptomatic dominant type 1 vWD secretion defect and/or clearance defect with normal vWF multimers versus vWD 1M and 2M with normal or smeary vWF multimers in low- and medium-resolution gels. High-quality multimeric analysis of vWF in medium-resolution gels based on a DDAVP challenge test clearly delineates and distinguishes each of the dominant type 2 vWDs 1/2E, 2M, 2B, 2A, and 2D caused by vWF gene mutations in the D3 multimerization domain, loss or gain-of-function mutations in the glycoprotein Ib receptor A1 domain, gene mutations in the A2 proteolytic domain, and the C-terminal dimerization domain, respectively.

  10. Acquired von Willebrand's disease and hypothyroidism: report of a case presenting with menorrhagia.

    Science.gov (United States)

    Blesing, N. E.; Hambley, H.; McDonald, G. A.

    1990-01-01

    A 17 year old woman presented with severe anaemia due to menorrhagia. On investigation, she was shown to have abnormalities of her haemostatic mechanism consistent with von Willebrand's disease Type I, although there was no family history of this disorder. In addition, she was shown to have severe primary hypothyroidism. On correction of hypothyroidism with oral thyroxine, her coagulation defects returned to normal and menorrhagia ceased. This is consistent with acquired von Willebrand's disease secondary to hypothyroidism. PMID:2217000

  11. Flow-induced elongation of von Willebrand factor precedes tension-dependent activation.

    Science.gov (United States)

    Fu, Hongxia; Jiang, Yan; Yang, Darren; Scheiflinger, Friedrich; Wong, Wesley P; Springer, Timothy A

    2017-08-23

    Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα. High-affinity sites develop only in upstream regions of VWF where tension exceeds ~21 pN and depend upon electrostatic interactions. Re-compaction of Von Willebrand factor is accelerated by intramolecular interactions and increases GPIbα dissociation rate. This mechanism enables VWF to be locally activated by hydrodynamic force in hemorrhage and rapidly deactivated downstream, providing a paradigm for hierarchical mechano-regulation of receptor-ligand binding.Von Willebrand factor (VWF) is a blood protein involved in clotting and is proposed to be activated by flow, but the mechanism is unknown. Here the authors show that VWF is first converted from a compact to linear form by flow, and is subsequently activated to bind GPIbα in a tension-dependent manner.

  12. Changes in bleeding patterns in von Willebrand disease after institution of long-term replacement therapy : results from the von Willebrand Disease Prophylaxis Network

    NARCIS (Netherlands)

    Holm, Elena; Abshire, Thomas C; Bowen, Joel; Álvarez, M Teresa; Bolton-Maggs, Paula; Carcao, Manuel; Federici, Augusto B; Gill, Joan Cox; Halimeh, Susan; Kempton, Christine; Key, Nigel S; Kouides, Peter; Lail, Alice; Landorph, Andrea; Leebeek, Frank; Makris, Michael; Mannucci, Pier; Mauser-Bunschoten, Eveline P; Nugent, Diane; Valentino, Leonard A; Winikoff, Rochelle; Berntorp, Erik

    Clinically, the leading symptom in von Willebrand disease (VWD) is bleeding, chiefly of mucosal type, for example, epistaxis, gingival, or gastrointestinal bleeding, and menorrhagia. In severe forms of VWD with secondary deficiency of factor VIII, spontaneous joint bleeding, resembling that observed

  13. Modeling Shear Induced Von Willebrand Factor Binding to Collagen

    Science.gov (United States)

    Dong, Chuqiao; Wei, Wei; Morabito, Michael; Webb, Edmund; Oztekin, Alparslan; Zhang, Xiaohui; Cheng, Xuanhong

    2017-11-01

    Von Willebrand factor (vWF) is a blood glycoprotein that binds with platelets and collagen on injured vessel surfaces to form clots. VWF bioactivity is shear flow induced: at low shear, binding between VWF and other biological entities is suppressed; for high shear rate conditions - as are found near arterial injury sites - VWF elongates, activating its binding with platelets and collagen. Based on parameters derived from single molecule force spectroscopy experiments, we developed a coarse-grain molecular model to simulate bond formation probability as a function of shear rate. By introducing a binding criterion that depends on the conformation of a sub-monomer molecular feature of our model, the model predicts shear-induced binding, even for conditions where binding is highly energetically favorable. We further investigate the influence of various model parameters on the ability to predict shear-induced binding (vWF length, collagen site density and distribution, binding energy landscape, and slip/catch bond length) and demonstrate parameter ranges where the model provides good agreement with existing experimental data. Our results may be important for understanding vWF activity and also for achieving targeted drug therapy via biomimetic synthetic molecules. National Science Foundation (NSF),Division of Mathematical Sciences (DMS).

  14. Cooperation within von Willebrand factors enhances adsorption mechanism.

    Science.gov (United States)

    Heidari, Maziar; Mehrbod, Mehrdad; Ejtehadi, Mohammad Reza; Mofrad, Mohammad R K

    2015-08-06

    von Willebrand factor (VWF) is a naturally collapsed protein that participates in primary haemostasis and coagulation events. The clotting process is triggered by the adsorption and conformational changes of the plasma VWFs localized to the collagen fibres found near the site of injury. We develop coarse-grained models to simulate the adsorption dynamics of VWF flowing near the adhesive collagen fibres at different shear rates and investigate the effect of factors such as interaction and cooperativity of VWFs on the success of adsorption events. The adsorption probability of a flowing VWF confined to the receptor field is enhanced when it encounters an adhered VWF in proximity to the collagen receptors. This enhancement is observed within a wide range of shear rates and is mostly controlled by the attractive van der Waals interactions rather than the hydrodynamic interactions among VWF monomers. The cooperativity between the VWFs acts as an effective mechanism for enhancing VWF adsorption to the collagen fibres. Additionally, this implies that the adsorption of such molecules is nonlinearly dependent on the density of flowing VWFs. These findings are important for studies of primary haemostasis as well as general adsorption dynamics processes in polymer physics. © 2015 The Author(s).

  15. Differential localization of P-selectin and von Willebrand factor during megakaryocyte maturation

    DEFF Research Database (Denmark)

    Zingariello, M; Fabucci, M E; Bosco, D

    2010-01-01

    Willebrand factor are two proteins present in the alpha-granules that recognize P-selectin glycoprotein ligand on neutrophils and collagen in the subendothelial matrix. These proteins may play an important role in determining the differential release of the alpha-granule contents in response to external....... These observations support the hypothesis that P-selectin and von Willebrand factor may ensure differential release of the alpha-granule content in response to external stimuli....

  16. Von Willebrand Factor Gene Variants Associate with Herpes simplex Encephalitis.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a rare complication of Herpes simplex virus type-1 infection. It results in severe parenchymal damage in the brain. Although viral latency in neurons is very common in the population, it remains unclear why certain individuals develop HSE. Here we explore potential host genetic variants predisposing to HSE. In order to investigate this we used a rat HSE model comparing the HSE susceptible SHR (Spontaneously Hypertensive Rats with the asymptomatic infection of BN (Brown Norway. Notably, both strains have HSV-1 spread to the CNS at four days after infection. A genome wide linkage analysis of 29 infected HXB/BXH RILs (recombinant inbred lines-generated from the prior two strains, displayed variable susceptibility to HSE enabling the definition of a significant QTL (quantitative trait locus named Hse6 towards the end of chromosome 4 (160.89-174Mb containing the Vwf (von Willebrand factor gene. This was the only gene in the QTL with both cis-regulation in the brain and included several non-synonymous SNPs (single nucleotide polymorphism. Intriguingly, in human chromosome 12 several SNPs within the intronic region between exon 43 and 44 of the VWF gene were associated with human HSE pathogenesis. In particular, rs917859 is nominally associated with an odds ratio of 1.5 (95% CI 1.11-2.02; p-value = 0.008 after genotyping in 115 HSE cases and 428 controls. Although there are possibly several genetic and environmental factors involved in development of HSE, our study identifies variants of the VWF gene as candidates for susceptibility in experimental and human HSE.

  17. Organization of von Willebrand factor on surface-activated platelets.

    Science.gov (United States)

    Escolar, G; White, J G

    1993-12-01

    The distribution and organization of von Willebrand factor (vWF) multimers on platelets after surface activation have not been fully characterized. In the present study, washed human platelets were allowed to interact with Formvar-coated, electron microscope grids for 20 minutes at 37 degrees C and then fixed. After fixation, cells were washed and then incubated with buffer alone, human plasma, human plasma preincubated with ristocetin (1.2 mg/mL), purified human vWF plus ristocetin, or bovine plasma. Macromolecular complexes were revealed by ultrastructural immunocytochemistry employing a polyclonal antibody against vWF and protein A-gold (PAG) as the electron-dense probe. vWF multimers were not present in discoid platelets but appeared on the central zone of dendritic cells and over larger central areas of fully spread platelets. Exposure to human plasma alone did not affect the distribution of electron-dense probes for vWF in central regions of surface-activated cells. Incubation of spread platelets with ristocetin-activated human plasma or bovine plasma resulted in the appearance of randomly dispersed, mottled areas of increased density covering the surface from edge to edge. Exposure to vWF antibody and PAG resulted in specific labeling of the dense areas in a serpentine, linear array. The gold-probe distribution suggested that the vWF multimers were not superimposed and were distributed in a random, irregular manner from edge to edge with label-free, clear areas between them. The results extend previous observations demonstrating that glycoprotein Ib-IX receptors are not spontaneously cleared from the plasma membranes of surface-activated platelets by showing that the receptor function of glycoprotein Ib-IX complex remains unchanged.

  18. Clinical and laboratory diagnosis of von Willebrand disease : A synopsis of the 2008 NHLBI/NIH guidelines

    NARCIS (Netherlands)

    Nichols, William L.; Rick, Margaret E.; Ortel, Thomas L.; Montgomery, Robert R.; Sadler, J. Evan; Yawn, Barbara P.; James, Andra H.; Hultin, Mae B.; Manco-Johnson, Marilyn J.; Weinstein, Mark

    Von Willebrand factor (VWF) mediates blood platelet adhesion and accumulation at sites of blood vessel injury, and also carries coagulation factor VIII (FVIII) that is important for generating procoagulant activity. Von Willebrand disease (VWD), the most common inherited bleeding disorder, affects

  19. Small GTP-binding protein Ral modulates regulated exocytosis of von Willebrand factor by endothelial cells

    NARCIS (Netherlands)

    de Leeuw, H. P.; Fernandez-Borja, M.; Reits, E. A.; Romani de Wit, T.; Wijers-Koster, P. M.; Hordijk, P. L.; Neefjes, J.; van Mourik, J. A.; Voorberg, J.

    2001-01-01

    Weibel-Palade bodies are endothelial cell-specific organelles, which contain von Willebrand factor (vWF), P-selectin, and several other proteins. Recently, we found that the small GTP-binding protein Ral is present in a subcellular fraction containing Weibel-Palade bodies. In the present study, we

  20. Efficiency of von Willebrand factor-mediated targeting of interleukin-8 into Weibel-Palade bodies

    NARCIS (Netherlands)

    Bierings, R.; van den Biggelaar, M.; Kragt, A.; Mertens, K.; Voorberg, J.; van Mourik, J. A.

    2007-01-01

    Background: After de novo synthesis in endothelial cells, the chemokine interleukin-8 (IL-8) is targeted to endothelial cell-specific storage vesicles, the Weibel-Palade bodies (WPBs), where it colocalizes with von Willebrand factor (VWF). Objective: In this study we investigated a putative

  1. Binding of von Willebrand factor and plasma proteins to the eggshell of Schistosoma mansoni

    NARCIS (Netherlands)

    Dewalick, Saskia; Hensbergen, Paul J; Bexkens, Michiel L; Grosserichter-Wagener, Christina; Hokke, Cornelis H; Deelder, André M; de Groot, Philip G; Tielens, Aloysius G M; van Hellemond, Jaap J

    Schistosoma mansoni eggs have to cross the endothelium and intestinal wall to leave the host and continue the life cycle. Mechanisms involved in this essential step are largely unknown. Here we describe direct binding to the S. mansoni eggshell of von Willebrand factor and other plasma proteins

  2. A systematic review of the effects of hemophilia and von Willebrand disease on arterial trombosis

    NARCIS (Netherlands)

    Biere-Rafi, Sara; Zwiers, M.; Peters, Marjolein; Van Der Meer, Jan; Rosendaal, Frits R; Buller, Harry R; Kamphuisen, Pieter W

    Background: Patients with hemophilia and von Willebrand disease (VWD) may be protected against arterial thrombosis, through a hy-pocoagulable state or atherosclerosis. We performed a systematic review to assess the association between these clotting disorders, arterial thrombosis and the prevalence

  3. Inheritance of von Willebrand's disease in a colony of Doberman Pinschers.

    Science.gov (United States)

    Riehl, J; Okura, M; Mignot, E; Nishino, S

    2000-02-01

    To determine the mode of inheritance of von Willebrand's disease (vWD) and perform linkage analysis between vWD and coat color or narcolepsy in a colony of Doberman Pinschers. 159 Doberman Pinschers. von Willebrand factor antigen (vWF:Ag) concentration was measured by use of ELISA, and results were used to classify dogs as having low ( 65%) vWF:Ag concentration, compared with results of analysis of standard pooled plasma. Buccal bleeding time was measured, and mode of inheritance of vWD was assessed by pedigree analysis. von Willebrand's disease was transmitted as a single autosomal gene defect. Results suggested that 27.04% of dogs were homozygous for vWD, 62.26% were heterozygous, and 10.69% did not have the defect. Most homozygous and some heterozygous dogs had prolonged bleeding times. Dogs with diluted coat colors (blue and fawn) were significantly overrepresented in the homozygous group, compared with black and red dogs, but a significant link between vWD and coat color was not detected. von Willebrand's disease is transmitted as an autosomal dominant trait with variable penetrance; most dogs in this colony (89.3%) were carriers of vWD. Homozygosity for vWD is not likely to be lethal. Some heterozygous dogs have prolonged bleeding times. An association between diluted coat colors and vWD may exist.

  4. Health-related quality of life among adult patients with moderate and severe von Willebrand disease.

    NARCIS (Netherlands)

    Wee, E.M. de; Mauser-Bunschoten, E.P.; Bom, J.G. Van Der; Degenaar-Dujardin, M.E.; Eikenboom, H.C.; Fijnvandraat, K.; Goede-Bolder, A. de; Laros, B.A.P.; Meijer, K.; Raat, H.; Leebeek, F.W.

    2010-01-01

    SUMMARY BACKGROUND: von Willebrand Disease (VWD) is the most frequent inherited bleeding disorder. It is unknown how this disorder affects quality of life. OBJECTIVES: This nationwide multicenter cross-sectional study determined health-related quality of life (HR-QoL) in adult patients with moderate

  5. von Willebrand Factor and Prekallikrein in Plasma Are Associated With Thrombus Volume in Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Ghulam, Qasam M; Bredahl, Kim; Gram, Jørgen Brodersen

    2016-01-01

    was consecutively obtained from 38 patients with asymptomatic infrarenal abdominal aortic aneurysm. von Willebrand factor activity, thrombin generation time, factor XII, and prekallikrein concentration were measured in plasma on automated and in-house platforms. In total, 8 patients were excluded due to ongoing...

  6. The effect of haemophilia and von Willebrand disease on arterial thrombosis : A systematic review

    NARCIS (Netherlands)

    Biere-Rafi, S.; Zwiers, M.; Peters, M.; van der Meer, J.; Rosendaal, F. R.; Buller, H. R.; Kamphuisen, P. W.

    Background: Patients with haemophilia and von Willebrand disease (VWD) may have a reduced cardiovascular mortality, due to a hypocoagulable state or decreased atherogenesis. We performed a systematic review to assess the association between haemophilia and VWD, and fatal and nonfatal arterial

  7. Gynaecological and obstetric bleeding in moderate and severe von Willebrand disease

    NARCIS (Netherlands)

    de Wee, Eva M.; Knol, H. Marieke; Mauser-Bunschoten, Eveline P.; van der Bom, Johanna G.; Eikenboom, Jeroen C. J.; Fijnvandraat, Karin; de Goede-Bolder, Arja; Laros-van Gorkom, Britta; Ypma, Paula F.; Zweegman, Sonja; Meijer, Karina; Leebeek, Frank W. G.

    2011-01-01

    A nation-wide cross-sectional study was initiated to assess gynaecological and obstetrical symptoms in an unselected cohort of women with moderate and severe von Willebrand disease (VWD) in the Netherlands. A total of 423 women aged >= 16 years were included. Bleeding severity was measured using the

  8. Gynaecological and obstetric bleeding in moderate and severe von Willebrand disease.

    NARCIS (Netherlands)

    Wee, E.M. de; Knol, H.M.; Mauser-Bunschoten, E.P.; Bom, J.G. Van Der; Eikenboom, J.C.; Fijnvandraat, K.; Goede-Bolder, A. de; Laros-van Gorkom, B.A.P.; Ypma, P.F.; Zweegman, S.; Meijer, K.; Leebeek, F.W.

    2011-01-01

    A nation-wide cross-sectional study was initiated to assess gynaecological and obstetrical symptoms in an unselected cohort of women with moderate and severe von Willebrand disease (VWD) in the Netherlands. A total of 423 women aged >/=16 years were included. Bleeding severity was measured using the

  9. Altered glycosylation of platelet-derived von Willebrand factor confers resistance to ADAMTS13 proteolysis

    NARCIS (Netherlands)

    McGrath, Rachel T.; van den Biggelaar, Maartje; Byrne, Barry; O'Sullivan, Jamie M.; Rawley, Orla; O'Kennedy, Richard; Voorberg, Jan; Preston, Roger J. S.; O'Donnell, James S.

    2013-01-01

    Platelet-von Willebrand factor (VWF) is stored within α-granules and accounts for ∼20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct from plasma-VWF and is enriched in high molecular weight multimers (HMWM). Previous studies have described significant functional

  10. ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer

    NARCIS (Netherlands)

    Pepin, M.; Kleinjan, A.; Hajage, D.; Buller, H. R.; Di Nisio, M.; Kamphuisen, P. W.; Salomon, L.; Veyradier, A.; Stepanian, A.; Mahe, I.

    Essentials Cancer patients are at high risk of venous thromboembolism (VTE). In this study, cases and controls were cancer patients who did or did not develop VTE. von Willebrand factor (VWF) levels were higher if compared with controls and correlated with cancer stage. VWF and ADAMTS-13 are

  11. Pseudo (Platelet-type von Willebrand disease in pregnancy: a case report

    Directory of Open Access Journals (Sweden)

    Grover Neetu

    2013-01-01

    Full Text Available Abstract Background Pseudo (platelet-type-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD. Case presentation We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient’s platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration

  12. Pseudo (platelet-type) von Willebrand disease in pregnancy: a case report.

    Science.gov (United States)

    Grover, Neetu; Boama, Vincent; Chou, Munazzah Rifat

    2013-01-17

    Pseudo (platelet-type)-von Willebrand disease is a rare autosomal dominant bleeding disorder caused by an abnormal function of the glycoprotein lb protein; the receptor for von Willebrand factor. This leads to an increased removal of VWF multimers from the circulation as well as platelets and this results in a bleeding diathesis. Worldwide, less than 50 patients are reported with platelet type von Willebrand disease (PT-VWD). We describe the management of platelet type von Willebrand disease in pregnancy of a 26 year old Caucasian primigravida. The initial diagnosis was made earlier following a significant haemorrhage post tonsillectomy several years prior to pregnancy. The patient was managed under a multidisciplinary team which included obstetricians, haematologists, anaesthetists and neonatologists. Care plans were made for the ante- natal, intra-partum and post-partum periods in partnership with the patient. The patient's platelet count levels dropped significantly during the antenatal period. This necessitated the active exclusion of other causes of thrombocytopenia in pregnancy. A vaginal delivery was desired and plans were made for induction of labour at 38 weeks of gestation with platelet cover in view of the progressive fall of the platelet count. The patient however went into spontaneous labour on the day of induction. She was transfused two units of platelets before delivery. She had an unassisted vaginal delivery of a healthy baby. The successful antenatal counselling has encouraged the diagnosis of the same condition in her mother and sister. We found this to be a particularly interesting case as well as challenging to manage due to its rarity. Psuedo von Willebrand disease in pregnancy can be confused with a number of other differential diagnoses, such as gestational thrombocutopenia, idiopathatic thrombocytopenia, thrombotic thrombocytopenic purpura and pre-eclampsia; all need consideration during investigations even in a case such as this where the

  13. Homocisteína plasmática total e fator von Willebrand no diabete melito experimental Total plasmatic homocysteine and von Willebrand factor in experimental diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Renato Delascio Lopes

    2007-04-01

    Full Text Available OBJETIVOS: Determinar os valores plasmáticos de homocisteína e fator von Willebrand, como marcador de disfunção endotelial, em ratos com diabete melito induzido por estreptozotocina. MÉTODOS: Trinta e cinco ratos (rattus norvegicus albinus, machos, adultos (180-200 g, randomizados em três grupos: controle (n=10 não receberam agente ou veículo; sham (n=10 receberam solução veículo da estreptozotocina; e diabético (n=15 receberam estreptozotocina. Após oito semanas de indução do diabete melito, os animais foram pesados, anestesiados e tiveram sangue colhido da aorta abdominal para determinação dos valores de homocisteína plasmática total, fator von Willebrand e glicemia. RESULTADOS: O modelo experimental foi reprodutível em 100% dos animais. A média das concentrações plasmáticas de homocisteína foi: 7,9 µmol/l (controle; 8,6 µmol/l (sham e 6,1 µmol/l (diabético, com diferença entre os grupos (pOBJECTIVES: To determine the plasma homocysteine and von Willebrand factor levels as markers of endothelial dysfunction in rats with diabetes mellitus induced by streptozotocin. METHODS: Thirty-five adult male rats (Rattus norvegicus albinus (weight between 180-200g were randomized into three groups: control group (n=10, which received no drugs or vehicles; sham group (n=10, which received streptozotocin solution; and diabetic group (n=15, which received streptozotocin. Eight weeks after diabetes mellitus induction, the animals were weighed and anesthesized; blood samples were collected from abdominal aorta for plasma total homocysteine, von Willebrand factor and glucose levels. RESULTS: The experimental model was reproducible in 100% of animals. The mean plasma homocysteine levels were: 7.9 µmol/l (control, 8.6µmol/l (sham and 6.1µmol/l (diabetic, with difference among the groups (p<0.01. Multiple comparison analysis among the groups showed that values in the diabetic group were lower than in the sham group (p<0.01. The mean

  14. Homocisteína plasmática total e fator von Willebrand no diabete melito experimental Total plasmatic homocysteine and von Willebrand factor in experimental diabetes mellitus

    OpenAIRE

    Renato Delascio Lopes; Lindalva Batista Neves; Vânia D'Almeida; Gleice Margarete de Souza Conceição; Alexandre Gabriel Junior

    2007-01-01

    OBJETIVOS: Determinar os valores plasmáticos de homocisteína e fator von Willebrand, como marcador de disfunção endotelial, em ratos com diabete melito induzido por estreptozotocina. MÉTODOS: Trinta e cinco ratos (rattus norvegicus albinus), machos, adultos (180-200 g), randomizados em três grupos: controle (n=10) não receberam agente ou veículo; sham (n=10) receberam solução veículo da estreptozotocina; e diabético (n=15) receberam estreptozotocina. Após oito semanas de indução do diabete me...

  15. Management of type 2b von Willebrand disease in the neonatal period.

    Science.gov (United States)

    Proud, Lindsay; Ritchey, A Kim

    2017-01-01

    Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting one in 1,000 people. Type 2b VWD is a less common subtype caused by a gain-of-function mutation in von Willebrand factor (VWF) that leads to the formation of large, ineffective VWF-platelet multimers in circulation. This unique pathophysiology creates diagnostic and treatment dilemmas. There is limited information on the management of type 2b VWD in the neonatal period. This report describes the management of a neonate with type 2b VWD with an emphasis on the added benefit of concomitant platelet transfusion and factor replacement therapy over factor replacement therapy alone. © 2016 Wiley Periodicals, Inc.

  16. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P. (Univ. of Vermont, Burlington (USA))

    1989-09-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO{sub 4}/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated {sup 125}I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function.

  17. Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs

    DEFF Research Database (Denmark)

    Krogh, Anne Kirstine Havnsøe; Legind, Pernille; Kjelgaard-Hansen, Mads

    2014-01-01

    Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidi......, activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, von Willebrand factor (vWf), D-dimer, platelet number, thyroid hormones, hematocrit and C-reactive protein (CRP)....

  18. The impact of von Willebrand factor on factor VIII memory immune responses

    OpenAIRE

    Chen, Juan; Schroeder, Jocelyn A.; Luo, Xiaofeng; Shi, Qizhen

    2017-01-01

    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis...

  19. Assembly of multimeric von Willebrand factor directs sorting of P-selectin

    NARCIS (Netherlands)

    Hop, C.; Guilliatt, A.; Daly, M.; de Leeuw, H. P.; Brinkman, H. J.; Peake, I. R.; van Mourik, J. A.; Pannekoek, H.

    2000-01-01

    We designed a model system to study the role of von Willebrand factor (vWF) in the sorting of P-selectin and the biogenesis of Weibel-Palade body (WPB)-like organelles. For that purpose, a human epithelial cell line (T24) that synthesizes P-selectin mRNA, but which is devoid of vWF mRNA synthesis

  20. Heritability of plasma von Willebrand factor antigen concentration in German Wirehaired pointers.

    Science.gov (United States)

    Brooks, M B; Castillo-Juarez, H; Oltenacu, P

    2001-07-01

    We applied quantitative genetic analyses to a population of German Wirehaired pointer dogs affected with type 2 von Willebrand disease. Plasma von Willebrand factor (vWF) protein concentration measured as vWF antigen (vWF:Ag), clinical history, and pedigree data were compiled for 331 dogs over a 5-year test period. Eight dogs had histories of abnormal bleeding and had markedly decreased plasma vWF:Ag concentrations (dogs were inbred, with an average inbreeding of 2.52%. The estimated heritability of plasma vWF concentration was 0.52. We found a major gene effect on vWF concentration. Using a single gene locus model and two different prediction methods, the upper threshold value for the aa genotype was less than 1% vWF:Ag, and the optimal threshold value for discrimination between the AA and Aa genotypes was between 68% and 72% vWF:Ag. Our analyses indicate that phenotype, assigned on the basis of a single vWF:Ag determination, is heritable and can be applied for selective breeding in a von Willebrand disease test programme.

  1. Polyphosphate binds to human von Willebrand factor in vivo and modulates its interaction with glycoprotein Ib.

    Science.gov (United States)

    Montilla, M; Hernández-Ruiz, L; García-Cozar, F J; Alvarez-Laderas, I; Rodríguez-Martorell, J; Ruiz, F A

    2012-11-01

    Polyphosphate, a phosphate polymer released by activated platelets, has recently been described as a potent modulator of blood coagulation and fibrinolysis. In blood plasma, polyphosphate binds to and alters the biological functions of factor XII, fibrin(ogen), thrombin and factor VII activating protease. The aim of the present study is to investigate whether polyphosphate also binds to von Willebrand factor (VWF) and alters some of its activities. When studying patients with type 1 von Willebrand disease (VWD) and their healthy relatives, we discovered a significant correlation between von Willebrand factor (VWF) and platelet polyphosphate levels. We have also found polyphosphate in preparations of VWF isolated from normal platelets and plasma. Surface plasmon resonance and electrophoretic mobility assays indicated that polyphosphate interacts with VWF in a dose- and time-dependent manner. Treatment of normal plasma with active exopolyphosphatase decreased the VWF ristocetin cofactor (VWF:RCo) activity, a functional measure of VWF binding to platelet glycoprotein receptor Ib. VWF collagen binding and multimerization were unaltered after polyphosphate depletion. Moreover, addition of polyphosphate increased the deficient VWF:RCo activity presented by plasma from patients with type 1 VWD. Our results reveal that a new role is played by polyphosphate in hemostasis by its interaction with VWF, and suggest that this polymer may be effective in the treatment of some types of VWD. © 2012 International Society on Thrombosis and Haemostasis.

  2. Interference from lupus anticoagulant on von Willebrand factor measurement in splenic marginal zone lymphoma

    DEFF Research Database (Denmark)

    Vinholt, Pernille J; Nybo, Mads

    2015-01-01

    We present a case concerning a patient with splenic marginal zone lymphoma (SMZL) and isolated prolonged activated partial thromboplastin time (aPTT) caused by lupus anticoagulant. Von Willebrand factor (VWF) activity and antigen were immeasurable by latex particle immunoturbidimetric assays......, and several coagulation factor levels were decreased. However, VWF activity and antigen were normal when analyzed by other methods. Also, coagulation factor levels were normal if an aPTT reagent with low lupus anticoagulant sensitivity or a chromogenic method was applied. Altogether, the initial findings were...

  3. Levonorgestrel intrauterine system as a treatment option for severe menorrhagia in adolescent with type III von Willebrand disease.

    Science.gov (United States)

    Silva, Carla Donato; Geraldes, Fernanda; Silva, Isabel Santos

    2013-04-30

    The authors describe a case of an adolescent with type III von Willebrand disease and severe menorrhagia since menarche. Antifibrinolytic, hormonal (estroprogestative pill in high doses, etonogestrel implant and gonadotropin-releasing hormone agonist goserelin) and Von Willebrand Factor/Factor VIII replacement therapies were prescribed to the patient, but symptomatic control was only obtained with high doses of VWF/FVIII twice a week. In March 2012, a levonorgestrel intrauterine system was inserted in a 14-year-old. At present, the patient is asymptomatic without regular prophylaxis (VWF/FVIII replacement therapy) and has had a remarkable improvement in her quality of life.

  4. Conventional rapid latex agglutination in estimation of von Willebrand factor: method revisited and potential clinical applications.

    Science.gov (United States)

    Mahat, Marianor; Abdullah, Wan Zaidah; Hussin, Che Maraina Che

    2014-01-01

    Measurement of von Willebrand factor antigen (VWF : Ag) levels is usually performed in a specialised laboratory which limits its application in routine clinical practice. So far, no commercial rapid test kit is available for VWF : Ag estimation. This paper discusses the technical aspect of latex agglutination method which was established to suit the purpose of estimating von Willebrand factor (VWF) levels in the plasma sample. The latex agglutination test can be performed qualitatively and semiquantitatively. Reproducibility, stability, linearity, limit of detection, interference, and method comparison studies were conducted to evaluate the performance of this test. Semiquantitative latex agglutination test was strongly correlated with the reference immunoturbidimetric assay (Spearman's rho = 0.946, P agglutination test and the reference assay. Using the scoring system for the rapid latex test, no agglutination is with 0% VWF : Ag (control negative), 1+ reaction is equivalent to 150% VWF : Ag (when comparing with immunoturbidimetric assay). The findings from evaluation studies suggest that latex agglutination method is suitable to be used as a rapid test kit for the estimation of VWF : Ag levels in various clinical conditions associated with high levels and low levels of VWF : Ag.

  5. Molecular characterization of exon 28 of von Willebrand's factor gene in Nigerian population.

    Science.gov (United States)

    Ezigbo, E D; Ukaejiofo, E O; Nwagha, T U

    2017-02-01

    Polymorphisms in von Willebrand factor (VWF) gene are an important contributor to the expression of VWF gene and differences in ethnic distribution of these single nucleotide polymorphisms (SNPs) exists. Our objective was to molecularly characterize the exon 28 of the VWF gene in the three major ethnic groups of Nigeria. We recruited 90 subjects, 45 had a history of bleeding. Questions included those used in the Zimmerman Program for the Molecular and Clinical Biology of von Willebrand disease (VWD), and the bleeding scores were calculated using the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD scoring system. Full blood count, coagulation profile, VWF:antigen level and VWF:collagen-binding activities were carried out. Data were analyzed using GraphPad Prism (5.03). GraphPad Software, Inc USA. The BigDye terminator chemistry was used to determine the nucleotide sequences of VWF gene (exon 28). Eight SNPs were identified, rs 216310 (T1547), rs 1800385 (V1565L), rs1800384 (A1515), rs1800383 (D1472H), rs 1800386 (Y1584C), rs 216311 (T1381A), rs 216312 (intronic) and rs 1800381 (P1337). The SNPs rs 216311, rs 1800383 and rs 1800386 associated significantly with bleeding in study subjects. rs1800386 occurred in all with bleeding history, no ethnic variations were noted.

  6. Prevalence of von Willebrand disease in women with iron deficiency anaemia and menorrhagia in Taiwan.

    Science.gov (United States)

    Chen, Y-C; Chao, T-Y; Cheng, S-N; Hu, S-H; Liu, J-Y

    2008-07-01

    Iron deficiency anaemia (IDA) is a frequently encountered disease, which can be attributed to menorrhagia. Most female patients with von Willebrand disease (VWD) have menorrhagia. The aim of this study was to investigate the prevalence of VWD in women with both IDA and menorrhagia in Taiwan. From January to December 2005 and November 2006 to January 2007, 56 consecutive patients with both IDA and menorrhagia were enrolled in this study. Their median age was 41 years (range 18-53). IDA was diagnosed by anaemia plus either low ferritin or transferrin saturation. Menorrhagia was evaluated by patient's menses history. Both von Willebrand factor antigen (VWF:Ag) and ristocetin cofactor activity (VWF:RCo) were measured for each patient. Bleeding time (BT) and platelet function analyser (PFA)-100 assay were determined as ancillary tests. The VWD diagnosis was established if: (i) both VWF:Ag (menorrhagia might develop IDA at younger age (34.3 vs. 39.7, P = 0.09) and had more IDA recurrence (75% vs. 16%, P = 0.03) than those patients without VWD. Of the eight VWD patients with VWF multimer analyses, all were revealed to have type I VWD. Our study demonstrates that VWD was not uncommon in women with both IDA and menorrhagia in Taiwan.

  7. Diagnosis and Treatment of von Willebrand Disease and Rare Bleeding Disorders

    Directory of Open Access Journals (Sweden)

    Giancarlo Castaman

    2017-04-01

    Full Text Available Along with haemophilia A and B, von Willebrand disease (VWD and rare bleeding disorders (RBDs cover all inherited bleeding disorders of coagulation. Bleeding tendency, which can range from extremely severe to mild, is the common symptom. VWD, due to a deficiency and/or abnormality of von Willebrand factor (VWF, represents the most frequent bleeding disorder, mostly inherited as an autosomal dominant trait. The diagnosis may be difficult, based on a bleeding history and different diagnostic assays, which evaluate the pleiotropic functions of VWF. Different treatment options are available for optimal management of bleeding and their prevention, and long-term outcomes are generally good. RBDs are autosomal recessive disorders caused by a deficiency of any other clotting factor, apart from factor XII, and cover roughly 5% of all bleeding disorders. The prevalence of the severe forms can range from 1 case in 500,000 up to 1 in 2–3 million, according to the defect. Diagnosis is based on bleeding history, coagulation screening tests and specific factor assays. A crucial problem in RBDs diagnosis is represented by the non-linear relationship between clinical bleeding severity and residual clotting levels; genetic diagnosis may help in understanding the phenotype. Replacement therapies are differently available for patients with RBDs, allowing the successful treatment of the vast majority of bleeding symptoms.

  8. Characterization of Zebrafish von Willebrand Factor Reveals Conservation of Domain Structure, Multimerization, and Intracellular Storage

    Directory of Open Access Journals (Sweden)

    Arunima Ghosh

    2012-01-01

    Full Text Available von Willebrand disease (VWD is the most common inherited human bleeding disorder and is caused by quantitative or qualitative defects in von Willebrand factor (VWF. VWF is a secreted glycoprotein that circulates as large multimers. While reduced VWF is associated with bleeding, elevations in overall level or multimer size are implicated in thrombosis. The zebrafish is a powerful genetic model in which the hemostatic system is well conserved with mammals. The ability of this organism to generate thousands of offspring and its optical transparency make it unique and complementary to mammalian models of hemostasis. Previously, partial clones of zebrafish vwf have been identified, and some functional conservation has been demonstrated. In this paper we clone the complete zebrafish vwf cDNA and show that there is conservation of domain structure. Recombinant zebrafish Vwf forms large multimers and pseudo-Weibel-Palade bodies (WPBs in cell culture. Larval expression is in the pharyngeal arches, yolk sac, and intestinal epithelium. These results provide a foundation for continued study of zebrafish Vwf that may further our understanding of the mechanisms of VWD.

  9. Characterization of recessive severe type 1 and 3 von willebrand disease (vwd), asymptomatic heterozygous carriers versus bloodgroup o-related von willebrand factor deficiency, and dominant type 1 VWD

    NARCIS (Netherlands)

    J.J. Michiels (Jan); Z. Berneman (Zwi); A. Gadisseur (Alain); M. van der Planken (Marc); W. Schroyens (Wilfried); A. van de Velde (Ann); H.H.D.M. van Vliet (Huib)

    2006-01-01

    textabstractRecessive type 3 von Willebrand disease (VWD) is caused by homozygosity or double heterozygosity for two non-sense mutations (null alleles). Type 3 VWD is easy to diagnose by the combination of a strongly prolonged bleeding time (BT), absence of ristocetine-induced platelet aggregation

  10. Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels

    DEFF Research Database (Denmark)

    Nossent, Anne Yaël; Robben, J H; Deen, P M T

    2010-01-01

    SUMMARY OBJECTIVES: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of V...

  11. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, Maartje; Bouwens, Eveline A. M.; Voorberg, Jan; Mertens, Koen

    2011-01-01

    Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both

  12. Requirements for cellular co-trafficking of factor VIII and von Willebrand factor to Weibel-Palade bodies

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bierings, R.; Storm, G.; Voorberg, J.; Mertens, K.

    2007-01-01

    von Willebrand factor (VWF) serves a critical role as a carrier of factor (F)VIII in circulation. While it is generally believed that FVIII and VWF assemble in circulation after secretion from different cells, an alternative view is that cells should exist that co-express FVIII and VWF. In this

  13. Factor VIII alters tubular organization and functional properties of von Willebrand factor stored in Weibel-Palade bodies

    NARCIS (Netherlands)

    Bouwens, Eveline A. M.; Mourik, Marjon J.; van den Biggelaar, Maartje; Eikenboom, Jeroen C. J.; Voorberg, Jan; Valentijn, Karine M.; Mertens, Koen

    2011-01-01

    In endothelial cells, von Willebrand factor (VWF) multimers are packaged into tubules that direct biogenesis of elongated Weibel-Palade bodies (WPBs). WPB release results in unfurling of VWF tubules and assembly into strings that serve to recruit platelets. By confocal microscopy, we have previously

  14. Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study

    NARCIS (Netherlands)

    Galen, K.P. van; Kleijn, P. de; Foppen, W.; Eikenboom, J.; Meijer, K.; Schutgens, R.E.; Fischer, K.; Cnossen, M.H.; Meris, J. de; Fijnvandraat, K.; Bom, J.G. Van Der; Laros-van Gorkom, B.A.P.; Leebeek, F.W.; Mauser-Bunschoten, E.P.

    2017-01-01

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds

  15. Long-term impact of joint bleeds in von Willebrand disease : A nested case-control study

    NARCIS (Netherlands)

    van Galen, Karin P.M.; de Kleijn, Piet; Foppen, Wouter; Eikenboom, Jeroen H C; Meijer, Karina; Schutgens, Roger E.G.; Fischer, Kathelijn; Cnossen, Marjon H; de Meris, Joke; Fijnvandraat, Karin; van der Bom, Johanna G; Laros-van Gorkom, Britta A P; Leebeek, Frank W G; Mauser-Bunschoten, Eveline P.

    2017-01-01

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds

  16. Long-term impact of joint bleeds in von Willebrand disease : A nested case-control study

    NARCIS (Netherlands)

    van Galen, Karin P. M.; de Kleijn, Piet; Foppen, Wouter; Eikenboom, Jeroen; Meijer, Karina; Schutgens, Roger E. G.; Fischer, Kathelijn; Cnossen, Marjon H.; de Meris, Joke; Fijnvandraat, Karin; van der Bom, Johanna G.; Laros-van Gorkom, Britta A. P.; Leebeek, Frank W. G.; Mauser-Bunschoten, Eveline P.

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds

  17. Long-term impact of joint bleeds in von Willebrand disease: A nested case-control study

    NARCIS (Netherlands)

    K.P.M. van Galen; P. de Kleijn; W. Foppen (Wouter); J.C.J. Eikenboom (Jeroen); K. Meijer; R. Schutgens (Roger); K. Fischer (Kathelijn); M.H. Cnossen (Marjon); J. de Meris (J.); K. Fijnvandraat; J.G. van der Bom (Anske); B.A.P. Laros-Van Gorkom (Britta); F.W.G. Leebeek (Frank); E.P. Mauser-Bunschoten (Eveline)

    2017-01-01

    textabstractPatients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified

  18. Von Willebrand factor in patients on mechanical circulatory support - a double-edged sword between bleeding and thrombosis.

    Science.gov (United States)

    Hudzik, Bartosz; Kaczmarski, Jacek; Pacholewicz, Jerzy; Zakliczynski, Michal; Gasior, Mariusz; Zembala, Marian

    2015-09-01

    Mechanical circulatory support (MCS) is an umbrella term describing the various technologies used in both short- and long-term management of patients with either end-stage chronic heart failure (HF) or acute HF. Most often, MCS has emerged as a bridge to transplantation, but more recently it is also used as a destination therapy. Mechanical circulatory support includes left ventricular assist device (LVAD) or bi-ventricular assist device (Bi-VAD). Currently, 2- to 3-year survival in carefully selected patients is much better than with medical therapy. However, MCS therapy is hampered by sometimes life-threatening complications including bleeding and device thrombosis. Von Willebrand factor (vWF) has two major functions in haemostasis. First, it plays a crucial role in platelet-subendothelium adhesion and platelet-platelet interactions (aggregation). Second, it is the carrier of factor VIII (FVIII) in plasma. Von Willebrand factor prolongs FVIII half-time by protecting it from proteolytic degradation. It delivers FVIII to the site of vascular injury thus enhancing haemostatic process. On one hand, high plasma levels of vWF have been associated with an increased risk of thrombosis. On the other, defects or deficiencies of vWF underlie the inherited von Willebrand disease or acquired von Willebrand syndrome. Here we review the pathophysiology of thrombosis and bleeding associated with vWF.

  19. Pulmonary hypertension secondary to hyperviscosity in a patient with rheumatoid arthritis and acquired von Willebrand disease: a case report.

    Science.gov (United States)

    Hernández-Gilsoul, Thierry; Atisha-Fregoso, Yemil; Vargas-Ruíz, Angel G; Rivero-Sigarroa, Eduardo; Dominguez-Cherit, Guillermo; Namendys-Silva, Silvio A

    2013-10-02

    Acquired von Willebrand disease is initiated by autoantibodies and hyperviscosity syndrome caused by a massive polyclonal hypergammaglobulinemia. Acquired von Willebrand disease associated with autoimmune disease in addition to pulmonary hypertension during emergency room presentation is a rare condition. To the best of our knowledge, this is the second case reported in the literature treated with success; the first one was reported in 1987. A 28-year-old mestizo man with a 3-year history of inflammatory arthritis was admitted to our hospital. An overlap of rheumatoid arthritis with systemic lupus erythematosus was suspected; therefore methotrexate was initiated, and later changed to leflunomide because of liver toxicity. Prothrombin time, international normalized ratio and activated partial thromboplastin times were normal (11/10.4 seconds; 1.2; 31.1/26.9 seconds, respectively), von Willebrand factor activity was observed with low ristocetin cofactor at 33.6UI/dL, high von Willebrand factor antigen >200UI/dL, and a low von Willebrand factor: ristocetin cofactor to von Willebrand factor antigen ratio. He was admitted to the emergency room with a 24-hour evolution of progressive dyspnea, cough, thoracic pain, and palpitations, 104 beats/min, 60/40 mmHg, temperature of 38°C, pulse oximetric saturation 88% and 30 breaths/minute. Cold, pale and mottled skin was also observed. He was then transferred to the intensive care unit. The placement of a pulmonary artery catheter was made. The initial patterns showed a precapillary pulmonary hypertension; acute pulmonary embolism was the first choice for diagnosis. Pulmonary angiography was conducted, and when no clot was discovered, pulmonary artery hypertension associated with connective tissue disease was considered. Serum protein electrophoresis confirmed the presence of a massive polyclonal hypergammaglobulinemia, and no paraproteinemia or monoclonal cell population was found from the electrophoretic pattern of the

  20. Regulation of plasma von Willebrand factor [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Karl C Desch

    2018-01-01

    Full Text Available Von Willebrand factor (VWF is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

  1. Von Willebrand factor availability in platelet concentrates stored for 5 days.

    Science.gov (United States)

    Cesar, J M; García-Avello, A; Monteagudo, J; Espinosa, J I; Lodos, J C; Castillo, R; Navarro, J L

    1994-02-01

    Von Willebrand factor (vWF) availability was assessed in platelet concentrates (PCs). After 5 days of storage, 82 +/- 9% of basal levels of ristocetin cofactor activity (vWF:RCo) remained in PCs. vWF antigen (vWF:Ag) increased up to 166 +/- 38% (P < 0.05) in the same period. Autoradiograph pattern of vW:Ag showed an increase in low molecular weight multimers, and fast migrating multimeric forms were visualized by crossed immunoelectrophoresis on day 5. Studies carried out in platelet free plasma stored as PCs showed similar changes in vWF:RCo but increments in vWF:Ag were not detected. These data indicate that PCs maintain vWF:RCo levels of clinical value even after 5 days of storage and suggest that vWF comes out from platelets to plasma during storage.

  2. Novel antiplatelet agents: ALX-0081, a Nanobody directed towards von Willebrand factor.

    Science.gov (United States)

    Bartunek, Jozef; Barbato, Emanuele; Heyndrickx, Guy; Vanderheyden, Marc; Wijns, William; Holz, Josefin-Beate

    2013-06-01

    This manuscript reviews the studies performed with ALX-0081 (INN: caplacizumab), a Nanobody targeting von Willebrand factor, in the context of current antithrombotic therapy in coronary artery disease. ALX-0081 specifically inhibits platelet adhesion to the vessel wall, and may control platelet aggregation and subsequent clot formation without increasing bleeding risk. A substantial number of antithrombotics are aimed at this cascade; however, their generally indiscriminative mode of action can result in a narrow therapeutic window, defined by the risk for bleeding complications, and thrombotic events. Nonclinically, ALX-0081 compared favorably to several antithrombotics. In Phase I studies in healthy subjects and stable angina patients undergoing percutaneous coronary intervention (PCI), ALX-0081 was well tolerated, and effectively inhibited pharmacodynamic markers. Following these results, a phase II study was initiated in high-risk acute coronary syndrome patients undergoing PCI. Based on its mechanism of action, ALX-0081 is also being developed for acquired thrombotic thrombocytopenic purpura.

  3. A comparative evaluation of a new automated assay for von Willebrand factor activity.

    Science.gov (United States)

    Lawrie, A S; Stufano, F; Canciani, M T; Mackie, I J; Machin, S J; Peyvandi, F

    2013-03-01

    The ristocetin cofactor assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity in the diagnosis of von Willebrand's Disease (VWD). However, the assay suffers from poor reproducibility and sensitivity at low levels of VWF and is labour intensive. We have undertaken an evaluation of a new immunoturbidimetric VWF activity (VWF:Ac) assay (INNOVANCE(®) VWF Ac. Siemens Healthcare Diagnostics, Marburg, Germany) relative to an established platelet-based VWF:RCo method. Samples from 50 healthy normal subjects, 80 patients with VWD and 50 samples that exhibited 'HIL' (i.e. Haemolysis, Icterus or Lipaemia) were studied. VWF:Ac, VWF:RCo and VWF:Ag were performed on a CS-analyser (Sysmex UK Ltd, Milton Keynes, UK), all reagents were from Siemens Healthcare Diagnostics. The VWF:Ac assay, gave low intra- and inter-assay imprecision (over a 31-day period, n = 200 replicate readings) using commercial normal (Mean 96.2 IU dL(-1), CV < 3.0%) and pathological (Mean 36.1 IU dL(-1), CV < 3.5%) control plasmas. The normal and clinical samples exhibited good correlation between VWF:RCo (range 3-753 IU dL(-1)) and VWF:Ac (rs = 0.97, P < 0.0001), with a mean bias of 5.6 IU dL(-1). Ratios of VWF:Ac and VWF:RCo to VWF:Ag in the VWD samples were comparable, although VWF:Ac had a superior lower level of detection to that of VWF:RCo (3% and 5% respectively). A subset (n = 97) of VWD and HIL samples were analysed for VWF:Ac at two different dilutions to assess the effect on relative potency, no significant difference was observed (P = 0.111). The INNOVANCE(®) VWF Ac assay was shown to be reliable and precise. © 2012 Blackwell Publishing Ltd.

  4. Postpartum Hemorrhage in Women with Von Willebrand Disease - A Retrospective Observational Study.

    Directory of Open Access Journals (Sweden)

    Igor Govorov

    Full Text Available von Willebrand disease (VWD is a hereditary bleeding disorder, caused by a deficiency in the levels and/or function of von Willebrand factor (VWF. Women with VWD appear to be at increased risk of experiencing postpartum hemorrhage (PPH, though the levels of VWF increase during pregnancy. There is limited knowledge of how PPH is associated with the subtype of VWD, plasma levels of other coagulations factors than VWF and given hemostatic treatment.The aims were to investigate the incidence of PPH in women with VWD and to analyse the correlation between PPH and: (1 type of VWD, (2 laboratory monitoring of VWF and FVIII and (3 hemostatic drug treatment.This was a retrospective observational study. The study participants (n = 34 were recruited from the Coagulation Unit, Karolinska University hospital. Fifty-nine deliveries, which occurred in 14 different obstetrics units (years 1995-2012 were included in the study.The incidence of primary PPH was 44%, severe primary PPH 20% and secondary PPH 12%. VWD type 3 was associated with a higher risk of experiencing severe primary PPH compared to other subtypes. FVIII:C in pregnancy was inversely correlated to blood loss during delivery. There was a significantly higher incidence of secondary PPH when the VWD diagnosis was unknown at time of delivery.The women with VWD are at higher risk of PPH, especially those with type 3 VWD or when diagnosis is unknown prior to delivery. Identification of pregnant women with undiagnosed VWD may be of importance in order to prevent PPH.

  5. Acquired von Willebrand syndrome in children with aortic and pulmonary stenosis.

    Science.gov (United States)

    Binnetoğlu, Fatih Köksal; Babaoğlu, Kadir; Filiz, Şayegan Güven; Zengin, Emine; Altun, Gürkan; Kılıç, Suar Çakı; Sarper, Nazan

    This prospective study was planned to investigate the frequency and relationship of acquired von Willebrand syndrome (AVWS) with aortic and pulmonary stenosis in patients. A total of 84 children, ranging from two to 18 years of age, were enrolled in this study. Of these, 28 had isolated aortic stenosis, 32 had isolated pulmonary stenosis and 24 were healthy. Children with aortic and pulmonary stenosis associated with other congenital heart diseases were excluded. Children with hypothyroidism, renal or liver disease, malignancy or autoimmune disease were also excluded. Wholeblood count, blood group, factor VIII level, prothrombin time (PT), activated partial thromboplastin time (aPTT), von Willebrand factor antigen (VWF:Ag), ristocetin co-factor (VWF:RCo), and bleeding time using a platelet-function analyser (PFA-100) were performed in all patients. All of the children in the study underwent a detailed physical examination and echocardiographic evaluation. A history of bleeding was positive in 18% of the aortic stenosis group, 9% of the pulmonary stenosis group, and 4% of the control group. Seven of 60 (12%) patients had laboratory findings that implied a diagnosis of AVWS, and two of these (28%) had a history of bleeding. The frequency of AVWS was 14% in patients with aortic stenosis and 9% in those with pulmonary stenosis. AVWS is not rare in stenotic obstructive cardiac diseases. A detailed history of bleeding should be taken from patients with valvular disease. Even if the history is negative, whole blood count, PT and aPTT should be performed. If necessary, PFA-100 closure time and further tests should be planned for the diagnosis of AVWS.

  6. Genetic heterogeneity in a large cohort of Indian type 3 von Willebrand disease patients.

    Directory of Open Access Journals (Sweden)

    Priyanka Kasatkar

    Full Text Available Though von Willebrand disease (VWD is a common coagulation disorder, due to the complexity of the molecular analysis of von Willebrand factor gene (VWF, not many reports are available from this country. Large size of the gene, heterogeneous nature of mutations and presence of a highly homologous pseudogene region are the major impediments in the genetic diagnosis of VWD. The study is aimed at unravelling the molecular pathology in a large series of VWD patients from India using an effective strategy.We evaluated 85 unrelated Indian type 3 VWD families to identify the molecular defects using a combination of techniques i.e. PCR-RFLP, direct DNA sequencing and multiple ligation probe amplification (MLPA.Mutations could be characterized in 77 unrelated index cases (ICs. 59 different mutations i.e. nonsense 20 (33.9%, missense 13 (22%, splice site 4 (6.8%, gene conversions 6 (10.2%, insertions 2 (3.4%, duplication 1 (1.7%, small deletions 10 (17% and large deletions 3 (5.1% were identified, of which 34 were novel. Two common mutations i.e. p.R1779* and p.L970del were identified in our population with founder effect. Development of alloantibodies to VWF was seen in two patients, one with nonsense mutation (p.R2434* and the other had a large deletion spanning exons 16-52.The molecular pathology of a large cohort of Indian VWD patients could be identified using a combination of techniques. A wide heterogeneity was observed in the nature of mutations in Indian VWD patients.

  7. Technological advances in diagnostic testing for von Willebrand disease: new approaches and challenges.

    Science.gov (United States)

    Hayward, C P M; Moffat, K A; Graf, L

    2014-06-01

    Diagnostic tests for von Willebrand disease (VWD) are important for the assessment of VWD, which is a commonly encountered bleeding disorder worldwide. Technical innovations have been applied to improve the precision and lower limit of detection of von Willebrand factor (VWF) assays, including the ristocetin cofactor activity assay (VWF:RCo) that uses the antibiotic ristocetin to induce plasma VWF binding to glycoprotein (GP) IbIXV on target platelets. VWF-collagen-binding assays, depending on the type of collagen used, can improve the detection of forms of VWD with high molecular weight VWF multimer loss, although the best method is debatable. A number of innovations have been applied to VWF:RCo (which is commonly performed on an aggregometer), including replacing the target platelets with immobilized GPIbα, and quantification by an enzyme-linked immunosorbent assay (ELISA), immunoturbidimetric, or chemiluminescent end-point. Some common polymorphisms in the VWF gene that do not cause bleeding are associated with falsely low VWF activity by ristocetin-dependent methods. To overcome the need for ristocetin, some new VWF activity assays use gain-of-function GPIbα mutants that bind VWF without the need for ristocetin, with an improved precision and lower limit of detection than measuring VWF:RCo by aggregometry. ELISA of VWF binding to mutated GPIbα shows promise as a method to identify gain-of-function defects from type 2B VWD. The performance characteristics of many new VWF activity assays suggest that the detection of VWD, and monitoring of VWD therapy, by clinical laboratories could be improved through adopting newer generation VWF assays. © 2014 John Wiley & Sons Ltd.

  8. Diagnosing von Willebrand disease: a short history of laboratory milestones and innovations, plus current status, challenges, and solutions.

    Science.gov (United States)

    Favaloro, Emmanuel J

    2014-07-01

    von Willebrand disease (VWD) is a disorder characterized by deficiency of, or defects in, von Willebrand factor (VWF). VWD was originally identified by Erik Adolf von Willebrand, who in early 1924 investigated a large family suffering from a bleeding disorder that seemed to differ from hemophilia. Erik von Willebrand undertook some initial laboratory investigations to conclude the involvement of a plasma factor, the lack of which prolonged the bleeding time, but failed to impair coagulation times and clot retraction. By the end of the 1960s, VWD was accepted as a combined deficiency of factor VIII (FVIII) and another plasma factor responsible for normal platelet adhesion. Just how these two functions were related to each other was less clear and the diagnostic tests available at the time were poorly reproducible, cumbersome, and unreliable; thus, VWD was poorly delineated from other coagulation and platelet disorders. The early 1970s saw a revolution in diagnostics when ristocetin was identified to induce platelet aggregation, and this formed the basis of the first consistent and reliable VWF "activity" test, permitting quantification of the platelet adhesive function missing in VWD. Concurrently, immunoprecipitating techniques specific for VWF were defined, and the application of such technologies permitted a clearer understanding of both VWF and VWD heterogeneity. Continued exploration of the structure and function of VWF contributed greatly to the understanding of platelet physiology, ligand receptor interaction and pathways of cellular interaction and activation. Recently, additional assays evaluating other functions of VWF, including collagen binding, platelet glycoprotein Ib binding, and FVIII binding, have improved the diagnosis of VWD. The purpose of this narrative review is to explore the history of phenotypic VWD diagnostics, with a focus on laboratory milestones from the past as well highlighting recent and ongoing innovations, and ongoing challenges and

  9. Mutant botrocetin-2 inhibits von Willebrand factor-induced platelet agglutination.

    Science.gov (United States)

    Matsui, T; Hori, A; Hamako, J; Matsushita, F; Ozeki, Y; Sakurai, Y; Hayakawa, M; Matsumoto, M; Fujimura, Y

    2017-03-01

    Essentials Botrocetin-2 (Bot2) binds to von Willebrand factor (VWF) and induces platelet agglutination. We identified Bot2 residues that are required for binding to VWF and glycoprotein (GP) Ib. We produced a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Mutant Bot2 could be used as a potential anti-thrombotic reagent to block VWF-GPIb interaction. Background Botrocetin-2 (Bot2) is a botrocetin-like protein composed of α and β subunits that have been cloned from the snake Bothrops jararaca. Bot2 binds specifically to von Willebrand factor (VWF), and the complex induces glycoprotein (GP) Ib-dependent platelet agglutination. Objectives To exploit Bot2's VWF-binding capacity in order to attempt to create a mutant Bot2 that binds to VWF but inhibits platelet agglutination. Methods and Results Several point mutations were introduced into Bot2 cDNA, and the recombinant protein (recombinant Bot2 [rBot2]) was purified on an anti-botrocetin column. The mutant rBot2 with either Ala at Asp70 in the β subunit (Aspβ70Ala), or Argβ115Ala and Lysβ117Ala, showed reduced platelet agglutination-inducing activity. rBot2 with Aspβ70Ala showed little binding activity towards immobilized VWF on an ELISA plate, whereas rBot2 with Argβ115Ala/Lysβ117Ala showed reduced binding activity towards GPIb (glycocalicin) after forming a complex with VWF. rBot2 point-mutated to oppositely charged Glu at both Argβ115 and Lysβ117 showed normal binding activity towards VWF but no platelet-agglutinating activity. Furthermore, this doubly mutated protein inhibited ristocetin-induced or high shear stress-induced platelet aggregation, and restrained thrombus formation under flow conditions. Conclusions Asp70 in the β subunit of botrocetin is important for VWF binding, and Arg115 and Lys117 in the β subunit are essential for interaction with GPIb. Doubly mutated rBot2, with Argβ115Glu and Lysβ117Glu, repels GPIb and might have potential as an antithrombotic reagent that

  10. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms.

    Science.gov (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D

    2016-05-01

    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  11. Long-term impact of joint bleeds in von Willebrand disease: a nested case-control study.

    Science.gov (United States)

    van Galen, Karin P M; de Kleijn, Piet; Foppen, Wouter; Eikenboom, Jeroen; Meijer, Karina; Schutgens, Roger E G; Fischer, Kathelijn; Cnossen, Marjon H; de Meris, Joke; Fijnvandraat, Karin; van der Bom, Johanna G; Laros-van Gorkom, Britta A P; Leebeek, Frank W G; Mauser-Bunschoten, Eveline P

    2017-09-01

    Patients with severe von Willebrand disease (VWD) may develop arthropathy after joint bleeds. Information on its prevalence and severity is limited. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. VWD patients with and without verified joint bleeds were matched for age, sex and Factor VIII level or von Willebrand Factor activity in a nested case-control study within the Willebrand in the Netherlands study. Assessments included the Hemophilia Joint Health Score (0-124), Pettersson score (0-13 per joint X-ray), Hemophilia Activity List score (0-100), joint pain (Visual Analog Scale 0-10), and the Impact on Participation and Autonomy questionnaire (0-20). Arthropathy was defined as a Hemophilia Joint Health Score of 10 or higher, or a Pettersson score over 3 of at least one joint. We included 48 patients with verified joint bleeds (cases) and 48 controls: 60% males, mean age 46 years (range 18-80), median von Willebrand Factor activity 5 versus 8 IU/dL and Factor VIII 24 versus 36 IU/dL. Arthropathy occurred in 40% of the cases versus 10% of the controls (PList score: 88 vs. 100, P3: 13 of 19 vs. 3 of 28, P<0.01, and median score on the participation questionnaire 6.1 vs. 0.9, P<0.01). In conclusion, arthropathy occurs in 40% of VWD patients after joint bleeds and is associated with pain, radiological abnormalities, functional limitations, and less social participation (Dutch trial register: NTR4548). Copyright© 2017 Ferrata Storti Foundation.

  12. PROTEOLYTIC PROCESSING OF VON WILLEBRAND FACTOR BY ADAMTS13 AND LEUKOCYTE PROTEASES

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    Stefano Lancellotti

    2013-09-01

    Full Text Available ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.   This protease specifically hydrolyzes von Willebrand factor (VWF multimers, thus causing VWF size reduction. ADAMTS13 belongs to the A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS family, involved in proteolytic processing of many matrix proteins. ADAMTS13 consists of numerous domains including a metalloprotease domain, a disintegrin domain, several thrombospondin type 1 (TSP1 repeats, a cysteine-rich domain, a spacer domain and 2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone morphogenetic protein domains. ADAMTS13 cleaves a single peptide bond (Tyr1605-Met1606 in the central A2 domain of the VWF molecule. This proteolytic cleavage is essential to reduce the size of ultra-large VWF polymers, which, when exposed to high shear stress in the microcirculation, are prone to form with platelets clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs. In this review, we a discuss the current knowledge of structure-function aspects of ADAMTS13 and its involvement in the pathogenesis of TMAs, b address the recent findings concerning proteolytic processing of VWF multimers by different proteases, such as the leukocyte-derived serine and metallo-proteases and c indicate the direction of future investigations

  13. Characterization of conformation-sensitive antibodies to ADAMTS13, the von Willebrand cleavage protease.

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    Zuben E Sauna

    2009-08-01

    Full Text Available The zinc metalloprotease ADAMTS13 is a multidomain protein that cleaves von Willebrand Factor (VWF and is implicated in Thrombotic Thrombocytopenic Purpura (TTP pathogenesis. Understanding the mechanism of this protein is an important goal. Conformation sensitive antibodies have been used to monitor protein conformation and to decipher the molecular mechanism of proteins as well as to distinguish functional and non-functional mutants.We have characterized several antibodies against ADAMTS13, both monoclonal and polyclonal. We have used flow cytometry to estimate the binding of these antibodies to ADAMTS13 and demonstrate that antibodies raised against the TSP and disintegrin domains detect conformation changes in the ADAMTS13. Thus for example, increased binding of these antibodies was detected in the presence of the substrate (VWF, mainly at 37 degrees C and not at 4 degrees C. These antibodies could also detect differences between wild-type ADAMTS13 and the catalytically deficient mutant (P475S. The flow cytometry approach also allows us to estimate the reactivity of the antibody as well as its apparent affinity.Our results suggest that these antibodies may serve as useful reagents to distinguish functional and non-functional ADAMTS13 and analyze conformational transitions to understand the catalytic mechanism.

  14. Von Willebrand factor, a key protein in the exposure of CD62P on platelets.

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    Broberg, M; Nygren, H

    2001-09-01

    When a biomaterial is introduced into the body water, electrolytes, and proteins adsorb to the surface. Platelets are then the first cells to interact with the surface adsorbed protein layer. We have studied the role of von Willebrand factor (vWF) for platelet-protein interaction by measuring different platelet responses to protein- and plasma-coated hydrophobic glass surfaces. A high exposure of CD62P on the platelet surface was seen after 10 min of incubation on platelets interacting with vWF and normal plasma-coated surfaces (79 and 67%, respectively). On the surfaces coated with albumin and factor VIII deficient plasma, the exposure was low (11 and 27%, respectively). A higher formation of filipodial extensions on the platelets was seen on the surfaces coated with vWF and normal plasma than on the surfaces coated with albumin or factor VIII deficient plasma. No significant differences were seen between the surfaces regarding the platelet release of PF4, ATP, or phospholipids. As shown by these results, vWF is a specific regulator of the exposure of CD62P by platelets and hence important for the interaction between platelets and later arriving neutrophils at biomaterial surfaces.

  15. Heavy menstrual bleeding and health-associated quality of life in women with von Willebrand's disease.

    Science.gov (United States)

    Govorov, Igor; Ekelund, Lena; Chaireti, Roza; Elfvinge, Petra; Holmström, Margareta; Bremme, Katarina; Mints, Miriam

    2016-05-01

    Women with the inherited bleeding disorder von Willebrand's disease (VWD) face gender-specific hemostatic challenges during menstruation. Heavy menstrual bleeding (HMB) can negatively affect their overall life activities and the health-associated quality of life. The purpose of the present study was to investigate whether women with VWD experienced HMB and an impaired health-associated quality of life. The study subjects were recruited from the Coagulation Unit of Karolinska University Hospital. Information was retrieved from various self-administered forms and medical records. Of the 30 women (18-52 years) that were included in the present study, 50% suffered from HMB, although the majority received treatment for HMB. In addition, almost all the included women perceived limitations in the overall life activities due to menstruation. The health-associated quality of life for women with HMB was significantly lower (Pwomen of the general population. In conclusion, women with VWD experienced reduced health-associated quality of life as a result of HMB. Therefore, preventing limitations in overall life activities and improving their health-associated quality of life thorough counseling on menstrual bleeding is important for women with VWD.

  16. Cost-utility analysis of von Willebrand disease screening in adolescents with menorrhagia.

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    Sidonio, Robert Francis; Smith, Kenneth J; Ragni, Margaret V

    2010-09-01

    To construct a decision analysis model to evaluate the cost utility of von Willebrand disease (VWD) testing in adolescents with menorrhagia. A 20-year Markov decision analytic model was constructed to evaluate the cost utility of two strategies: testing or not testing for VWD. The model includes probabilities of remaining well, suffering an acute menorrhagia bleeding event, surgical complications, oral contraceptive pill complications, or dying. Probabilities, costs, and utilities were estimated from published literature. The prevalence of type 1 VWD in adolescent females with menorrhagia was estimated at 13%. The cost of testing adolescents with menorrhagia for VWD was $1790, versus $1251 for not testing for VWD. The effectiveness of not testing in quality-adjusted life-years (QALYs) gained (14.237 QALYs) was similar to the VWD testing strategy (14.246 QALYs). Compared with not testing for VWD, screening for VWD had an incremental cost-effectiveness ratio of $62,791 per QALY, a value typically considered economically reasonable. In adolescents with menorrhagia, testing for VWD before the initiation of oral contraceptives is cost-effective. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  17. von Willebrand Factor and Oxidative Stress Parameters in Acute Coronary Syndromes

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    Zoran Koprivica

    2011-01-01

    Full Text Available Considering the role of von Willebrand factor (vWf in hemostasis, and the role of oxidative stress in the development of endothelial dysfunction and atherosclerotic disease, the aim of our study was to investigate the relationship between vWf, parameters of oxidative stress and different types of acute coronary syndromes (ACS. Levels of vWf activity (vWfAct, vWf antigen (vWfAg, nitric oxide (estimated through nitrites–NO2 −, superoxide anion radical (O2 −, hydrogen peroxide (H2O2, index of lipid peroxidation (estimated through thiobarbituric acid reactive substances–TBARS, superoxide dismutase (SOD and catalase (CAT activity of 115 patients were compared with those of 40 healthy controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well as TBARS levels, while their levels of NO2 −, H2O2, SOD and CAT activities were lower than controls'. vWfAg showed high specificity and sensitivity as a test to reveal healthy or diseased subjects. Multivariant logistic regression marked only vWfAg and TBARS as parameters that were under independent effect of ACS type. The results of our study support the implementation of vWf in clinical rutine and into therapeutic targets, and suggest that ACS patients are in need of antioxidant supplementation to improve their impaired antioxidant defence.

  18. Variable bleeding phenotype in an Amish pedigree with von Willebrand disease.

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    Gupta, Sweta; Heiman, Meadow; Duncan, Natalie; Hinckley, Jesse; Di Paola, Jorge; Shapiro, Amy D

    2016-10-01

    Through a cross-sectional study design, the bleeding phenotype in the Amish in Indiana (IN) and Wisconsin (WI) was described using two different bleeding scores. von Willebrand factor (VWF) testing was performed and bleeding questionnaires from Centers for Disease Control and Prevention (CDC) and European MCMDM-1 (Tosetto bleeding score (BS)) were administered to the IN and WI cohort respectively. Seven hundred and seventy nine subjects were recruited, 17% were diagnosed with VWD based on Ristocetin cofactor, VWF:RCo  T. The WI AF were much younger at a mean age 15 years vs 26 years in IN AF cohort. The AF subjects had a median VWF:RCo of 13IU/dl with a statistically significant higher median BS 1 versus 0 in the WI AF vs WI Unaffected (UA), 2 vs 1 in the IN AF vs IN UA, P Amish with VWD, despite a unifying mutation. Am. J. Hematol. 91:E431-E435, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  20. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease.

    Science.gov (United States)

    Soares, R P S; Bydlowski, S P; Nascimento, N M; Thomaz, A M; Bastos, E N M; Lopes, A A

    2013-04-01

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  1. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

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    Pena, S.D.J.; De Souza, K.T. (Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte (Brazil)); De Andrade, M.; Chakraborty, R. (Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States))

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  2. Complex changes in von Willebrand factor-associated parameters are acquired during uncomplicated pregnancy.

    Directory of Open Access Journals (Sweden)

    Danielle N Drury-Stewart

    Full Text Available The coagulation protein von Willebrand Factor (VWF is known to be elevated in pregnancy. However, the timing and nature of changes in VWF and associated parameters throughout pregnancy are not well understood.To better understand the changes in VWF provoked by pregnancy, we studied VWF-associated parameters in samples collected over the course of healthy pregnancies.We measured VWF antigen (VWF:Ag, VWF propeptide (VWFpp, Factor VIII (FVIII, and ADAMTS13 activity in samples collected from 46 women during pregnancy and at non-pregnant baseline. We also characterized pregnant vs. non-pregnant VWF multimer structure in 21 pregnancies, and performed isoelectric focusing (IEF of VWF in two pregnancies which had samples from multiple trimesters.VWF:Ag and FVIII levels were significantly increased during pregnancy. ADAMTS13 activity was unchanged. VWFpp levels increased much later in pregnancy than VWF:Ag, resulting in a progressive decrease in VWFpp:Ag ratios. FVIII:VWF ratios also decreased in pregnancy. Most pregnancies exhibited a clear loss of larger VWF multimers and altered VWF triplet structure. Further evidence of acquired VWF qualitative changes in pregnancy was found in progressive, reversible shifts in VWF IEF patterns over gestation.These data support a new view of pregnancy in which VWF can acquire qualitative changes associated with advancing gestational age. Modeling supports a scenario in which both increased VWF production and doubling of the VWF half-life would account for the data observed. We propose that gestation induces a prolongation in VWF survival, which likely contributes to increased total VWF levels and altered VWF structure.

  3. Secretion of von Willebrand factor by endothelial cells links sodium to hypercoagulability and thrombosis.

    Science.gov (United States)

    Dmitrieva, Natalia I; Burg, Maurice B

    2014-04-29

    Hypercoagulability increases risk of thrombi that cause cardiovascular events. Here we identify plasma sodium concentration as a factor that modulates blood coagulability by affecting the production of von Willebrand factor (vWF), a key initiator of the clotting cascade. We find that elevation of salt over a range from the lower end of what is normal in blood to the level of severe hypernatremia reversibly increases vWF mRNA in endothelial cells in culture and the rate of vWF secretion from them. The high NaCl increases expression of tonicity-regulated transcription factor NFAT5 and its binding to promoter of vWF gene, suggesting involvement of hypertonic signaling in vWF up-regulation. To elevate NaCl in vivo, we modeled mild dehydration, subjecting mice to water restriction (WR) by feeding them with gel food containing 30% water. Such WR elevates blood sodium from 145.1 ± 0.5 to 150.2 ± 1.3 mmol/L and activates hypertonic signaling, evidenced from increased expression of NFAT5 in tissues. WR increases vWF mRNA in liver and lung and raises vWF protein in blood. Immunostaining of liver revealed increased production of vWF protein by endothelium and increased number of microthrombi inside capillaries. WR also increases blood level of D-dimer, indicative of ongoing coagulation and thrombolysis. Multivariate regression analysis of clinical data from the Atherosclerosis Risk in Communities Study demonstrated that serum sodium significantly contributes to prediction of plasma vWF and risk of stroke. The results indicate that elevation of extracellular sodium within the physiological range raises vWF sufficiently to increase coagulability and risk of thrombosis.

  4. von Willebrand factor deficiency leads to impaired blood flow recovery after ischaemia in mice.

    Science.gov (United States)

    de Vries, Margreet R; Peters, Erna A B; Quax, Paul H A; Nossent, A Yaël

    2017-06-28

    Neovascularisation, i. e. arteriogenesis and angiogenesis, is an inflammatory process. Therefore attraction and extravasation of leukocytes is essential for effective blood flow recovery after ischaemia. Previous studies have shown that von Willebrand factor (VWF) is a negative regulator of angiogenesis. However, it has also been shown that VWF facilitates leukocyte attraction and extravasation. We aimed to investigate the role of VWF in arteriogenesis and angiogenesis during post-ischaemic neovascularisation. Wild-type (WT) and VWF deficient (VWF -/- ) C57BL/6 mice were subjected to hindlimb ischaemia via double ligation of the left femoral artery, and blood flow recovery was followed over time, using Laser Doppler Perfusion Imaging. Blood flow recovery was impaired in VWF -/- mice. After 10 days, VWF -/- mice showed a 43 ± 5 % recovery versus 68 ± 5 % in WT. Immunohistochemistry revealed that both arteriogenesis in the adductor muscles and angiogenesis in the gastrocnemius muscles were reduced in VWF -/- mice. Furthermore, leukocyte infiltration in the affected adductor muscles was reduced in VWF -/- mice. Residual paw perfusion directly after artery ligation was also reduced in VWF -/- mice, indicating a decrease in pre-existing collateral arteriole density. When we quantified collateral arterioles, we observed a 31 % decrease in the average number of collateral arterioles in the pia mater compared to WT mice (57 ± 3 in WT vs 40 ± 4 pial collaterals in VWF -/- ). We conclude that VWF facilitates blood flow recovery in mice. VWF deficiency hampers both arteriogenesis and angiogenesis in a hindlimb ischaemia model. This is associated with impaired leukocytes recruitment and decreased pre-existing collateral density in the absence of VWF.

  5. Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network*

    Science.gov (United States)

    Miszta, Adam; Pelkmans, Leonie; Lindhout, Theo; Krishnamoorthy, Ganeshram; de Groot, Philip G.; Hemker, Coenraad H.; Heemskerk, Johan W. M.; Kelchtermans, Hilde; de Laat, Bas

    2014-01-01

    Attachment of platelets from the circulation onto a growing thrombus is a process involving multiple platelet receptors, endothelial matrix components, and coagulation factors. It has been indicated previously that during a transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits and activates platelets via interactions with the platelet receptor complex glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a domain deletion mutant we demonstrated the involvement of the C domains of VWF in this binding. Substantial binding of VWF to fibrin monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via factor XIII is not essential for this phenomenon and suggesting the identification of a second mechanism through which VWF multimers incorporate into a fibrin network. Under high shear conditions, platelets were shown to adhere to fibrin only if VWF had been incorporated. In conclusion, our experiments show that the C domains of VWF and the E domain of fibrin monomers are involved in the incorporation of VWF during the polymerization of fibrin and that this incorporation fosters binding and activation of platelets. Fibrin thus is not an inert end product but partakes in further thrombus growth. Our findings help to elucidate the mechanism of thrombus growth and platelet adhesion under conditions of arterial shear rate. PMID:25381443

  6. Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A.

    Science.gov (United States)

    Delignat, S; Repessé, Y; Navarrete, A-M; Meslier, Y; Gupta, N; Christophe, O D; Kaveri, S V; Lacroix-Desmazes, S

    2012-03-01

    The development of inhibitory anti-factor VIII (FVIII) antibodies in patients with haemophilia A following replacement therapy is associated with several types of risk factors. Among these, the purity of FVIII concentrates, and in particular the presence of von Willebrand factor (VWF), was controversially proposed to influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective effect of VWF towards FVIII was investigated in vivo, in a model of haemophilia A. We studied the endocytosis of FVIII by murine bone marrow-derived dendritic cells and evaluated the capacity of VWF to block the internalization of FVIII. We characterized the relevance of VWF for the accumulation of FVIII in the marginal zone of the spleen, a secondary lymphoid organ where the immune response to therapeutically administered FVIII initiates. Our results confirm that VWF reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF is important for the accumulation of FVIII in the marginal zone of the spleen. We propose that VWF exerts at least two non-mutually exclusive immunoprotective roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by professional antigen-presenting cells by blocking the interaction of FVIII with as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of increasing the half-life of FVIII in the circulation, may allow an increased contact time with tolerogenic marginal zone B cells in the spleen. © 2011 Blackwell Publishing Ltd.

  7. Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

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    Soares, R.P.S. [Fundação Pró-Sangue Hemocentro de São Paulo, São Paulo, SP (Brazil); Bydlowski, S.P.; Nascimento, N.M. [Laboratório de Investigação Médica-31, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Thomaz, A.M.; Bastos, E.N.M.; Lopes, A.A. [Faculdade de Medicina, Instituto do Coração, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-04-05

    Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

  8. Increased deposition of von Willebrand factor in the rat heart after local ionizing irradiation

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    Boerma, M.; Loenen, M.M. van; Klein, H.R.; Bart, C.I.; Wondergem, J. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Kruse, J.J.C.M. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Dept. of Experimental Therapy (H6), Netherlands Cancer Inst., Amsterdam (Netherlands); Zurcher, C. [Dept. of Clinical Oncology (K1-P), Leiden Univ. Medical Center (Netherlands); Dept. of Pathology, Faculty of Veterinary Medicine, Univ. of Utrecht (Netherlands)

    2004-02-01

    Background and purpose: von willebrand factor (vWf), a glycoprotein involved in blood coagulation, is synthesized by endothelial cells. Increased amounts of vWf in blood plasma or tissue samples are indicative of damaged endothelium. In the present study, mRNA expression and localization of vWf were determined in irradiated rat heart tissue. Material and methods: sprague-dawley rats received local heart irradiation with a single dose of 0, 15, or 20 Gy. Hearts were dissected at different time points (up to 16 months) after irradiation. In a second experiment, rats were injected with the radioprotector amifostine (160 mg/kg, i.p.) 15-20 min before irradiation and sacrificed after 6 months. Immunohistochemistry was performed using a polyclonal anti-vWf antibody. Serial sections were subjected to a general rat endothelial cell immunostaining (RECA-1) or a collagen staining (picrosirius red). mRNA expression was determined by using PCR. Results: in control tissue, all endothelial cells lining the lumen of the endocardium and coronary arteries, but not capillary endothelial cells, were stained for vWf. 1 month after irradiation with both 15 and 20 Gy, myocardial capillaries became immunoreactive. From 3 months onward, staining was observed also within the extracellular matrix (ECM) of fibrotic areas. At mRNA level, no changes in vWf could be observed at all time points after irradiation, suggesting that vWf deposition was not due to increased biosynthesis of the protein. In sections of amifostine-treated rat hearts, vWf staining was increased to a lesser extent. Conclusion: these dose- and time-dependent increases in deposition of vWf indicate the presence of damaged endothelium in the irradiated rat heart. These increases in vWf accumulation precede development of fibrosis in the subendocardial layer and myocardium of the left ventricles, right ventricles, and atria. (orig.)

  9. In vivo analysis of the role of O-glycosylations of von Willebrand factor.

    Directory of Open Access Journals (Sweden)

    Idinath Badirou

    Full Text Available The objective of this project was to study the function of O-glycosylations in von Willebrand factor (VWF life cycle. In total, 14 different murine Vwf cDNAs mutated on one or several O-glycosylations sites were generated: 9 individual mutants, 2 doublets, 2 clusters and 1 mutant with all 9 murine glycosylation sites mutated (Del-O-Gly. We expressed each mutated cDNA in VWF deficient-mice by hydrodynamic injection. An immunosorbent assay with Peanut Agglutinin (PNA was used to verify the O-glycosylation status. Wild-type (WT VWF expressed by hepatocytes after hydrodynamic injection was able to bind PNA with slightly higher affinity than endothelial-derived VWF. In contrast, the Del-O-Gly VWF mutant did not bind PNA, demonstrating removal of O-linked glycans. All mutants displayed a normal multimeric pattern. Two mutants, Del-O-Gly and T1255A/T1256A, led to expression levels 50% lower than those induced by WT VWF and their half-life in vivo was significantly reduced. When testing the capacity of each mutant to correct the bleeding time of VWF-deficient mice, we found that S1486A, T1255A, T1256A and the doublet T1255A/T1256A were unable to do so. In conclusion we have shown that O-glycosylations are dispensable for normal VWF multimerization and biosynthesis. It also appears that some O-glycosylation sites, particularly the T1255 and T1256 residues, are involved in the maintenance of VWF plasma levels and are essential for normal haemostasis. As for the S1486 residue, it seems to be important for platelet binding as demonstrated in vitro using perfusion experiments.

  10. Comparative analysis of von Willebrand factor profiles after implantation of left ventricular assist device and total artificial heart.

    Science.gov (United States)

    Reich, H J; Morgan, J; Arabia, F; Czer, L; Moriguchi, J; Ramzy, D; Esmailian, F; Lam, L; Dunhill, J; Volod, O

    2017-08-01

    Essentials Bleeding is a major source of morbidity during mechanical circulatory support. von Willebrand factor (VWF) multimer loss may contribute to bleeding. Different patterns of VWF multimer loss were seen with the two device types. This is the first report of total artificial heart associated VWF multimer loss. Background Bleeding remains a challenge during mechanical circulatory support and underlying mechanisms are incompletely understood. Functional von Willebrand factor (VWF) impairment because of loss of high-molecular-weight multimers (MWMs) produces acquired von Willebrand disease (VWD) after left ventricular assist device (LVAD). Little is known about VWF multimers with total artificial hearts (TAHs). Here, VWF profiles with LVADs and TAHs are compared using a VWD panel. Methods VWD evaluations for patients with LVAD or TAH (2013-14) were retrospectively analyzed and included: VWF activity (ristocetin cofactor, VWF:RCo), VWF antigen (VWF:Ag), ratio of VWF:RCo to VWF:Ag, and quantitative VWF multimeric analysis. Results Twelve patients with LVADs and 12 with TAHs underwent VWD evaluation. All had either normal (47.8%) or elevated (52.2%) VWF:RCo, normal (26.1%) or elevated (73.9%) VWF:Ag and 50.0% were disproportional (ratio ≤ 0.7). Multimeric analysis showed abnormal patterns in all patients with LVADs: seven with high MWM loss; five with highest MWM loss. With TAH, 10/12 patients had abnormal patterns: all with highest MWM loss. High MWM loss correlated with presence of LVAD and highest MWM loss with TAH. Increased low MWMs were detected in 22/24. Conclusion Using VWF multimeric analysis, abnormalities after LVAD or TAH were detected that would be missed with measurements of VWF level alone: loss of high MWM predominantly in LVAD, loss of highest MWM in TAH, and elevated levels of low MWM in both. This is the first study to describe TAH-associated highest MWM loss, which may contribute to bleeding. © 2017 International Society on Thrombosis and

  11. Pitfalls in Interventional Pain Medicine: Hyponatremia after DDAVP for a Patient with Von Willebrand Disease Undergoing an Epidural Steroid Injection

    Directory of Open Access Journals (Sweden)

    Talal W. Khan

    2017-01-01

    Full Text Available Desmopressin (DDAVP, a synthetic analog of vasopressin, has been used in patients with von Willebrand disease (VWD, mild hemophilia A, and platelet dysfunction to reduce the risk of bleeding associated with surgical and interventional procedures. We report the case of a patient with VWD presenting with a bulging disc and radicular pain that underwent transforaminal epidural steroid injections. Her course was complicated with the interval development of headaches and dizziness symptomatic of moderate hyponatremia, likely due to excessive fluid intake. This report highlights a relatively rare side effect of DDAVP when used for prophylaxis in patients with VWD and reinforces the need for vigilance in these patients.

  12. Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qing; Zhou, Yan-Feng; Zhang, Cheng-Zhong; Zhang, Xiaohui; Lu, Chafen; Springer, Timothy A.; Harvard-Med

    2009-06-30

    The lengths of von Willebrand factor (VWF) concatamers correlate with hemostatic potency. After secretion in plasma, length is regulated by hydrodynamic shear force-dependent unfolding of the A2 domain, which is then cleaved by a specific protease. The 1.9-{angstrom} crystal structure of the A2 domain demonstrates evolutionary adaptations to this shear sensor function. Unique among VWF A (VWA) domains, A2 contains a loop in place of the {alpha}4 helix, and a cis-proline. The central {beta}4-strand is poorly packed, with multiple side-chain rotamers. The Tyr-Met cleavage site is buried in the {beta}4-strand in the central hydrophobic core, and the Tyr structurally links to the C-terminal {alpha}6-helix. The {alpha}6-helix ends in 2 Cys residues that are linked by an unusual vicinal disulfide bond that is buried in a hydrophobic pocket. These features may narrow the force range over which unfolding occurs and may also slow refolding. Von Willebrand disease mutations, which presumably lower the force at which A2 unfolds, are illuminated by the structure.

  13. Utility of platelet function analyzer as a screening tool for the diagnosis of von Willebrand disease in adolescents with menorrhagia.

    Science.gov (United States)

    Naik, Swati; Teruya, Jun; Dietrich, Jennifer E; Jariwala, Purvi; Soundar, Esther; Venkateswaran, Lakshmi

    2013-07-01

    Von Willebrand disease (VWD), and in particular, VWD type 1 and low VW factor (defined as Von Willebrand Ristocetin cofactor activity (RCoF) menorrhagia and both groups benefit from similar management. Platelet function analyzer (PFA-100®) is often used as a screening test to detect VWD. We analyzed the utility of PFA-100® as a screening tool in the detection of VWD type 1 and low VW factor (VWF) in an exclusive adolescent population with menorrhagia. The study population consisted of adolescents with menorrhagia who had simultaneously drawn blood samples for VWD and PFA-100®. Abnormal PFA-100® was defined as values >183 seconds for collagen/epinephrine and/or >126 seconds for collagen/ADP. Of a total of 235 patients tested, 23 patients had RCoF menorrhagia. We conclude that in the setting of adolescent menorrhagia, PFA-100® does not have utility as an initial screening test for the diagnosis of VWD and in particular, low VWF and that clinicians need to be aware of this limitation of PFA-100® while evaluating adolescents with menorrhagia. Copyright © 2013 Wiley Periodicals, Inc.

  14. [Desmopressin testing in children with von Willebrand syndrome in haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia].

    Science.gov (United States)

    Huhn, B; Hofmann, A; Hofmann, K; Sirb, H; Aumann, V; Kentouche, K; Sauerbrey, A; Franke, D; Kuhlisch, E; Knöfler, R

    2009-10-01

    The influence of desmopressin on hemostasis is mediated by the release of von Willebrand factor and of coagulation factor VIII from vascular endothelium. The necessity of testing desmopressin effectiveness on hemostasis is a matter of controversy and the performance of the test is not yet standardized. For this reason the desmopressin tests in 114 children with von Willebrand syndrome (type 1, n=98; type 2A, n=12; type 2M, n=2; type 2N, n=2) carried out in 7 paediatric haemostaseologic centers were retrospectively analyzed. The effectiveness of desmopressin was assessed using defined response criteria. As expected, the test performance showed a wide variation among the centers. In 99 children desmopressin was given intravenously as a short infusion at a dosage ranging from 0.25 to 0.41 microg/kg and in 15 intranasally at an absolute dose of 40 to 300 microg. The points of time for blood taking after desmopressin application ranged from 0.5 to 12 h. The absent desmopressin response in 7 patients (6%) and the partial response in 15 indicate the necessity of testing desmopressin effectiveness before the first therapeutic use. The application of desmopressin was well tolerated by the patients.

  15. Genome-wide linkage analysis of von Willebrand factor plasma levels: results from the GAIT project.

    Science.gov (United States)

    Souto, Juan Carlos; Almasy, Laura; Soria, Jose Manuel; Buil, Alfonso; Stone, William; Lathrop, Mark; Blangero, John; Fontcuberta, Jordi

    2003-03-01

    High plasma levels of von Willebrand factor (vWF) have been associated with the risk of thromboembolic disease. As a complex trait, this phenotype must be influenced by genetic and environmental factors. Among the genetic factors, only the ABO gene located on chromosome 9q34 has been clearly linked to the plasma levels of vWF. This locus explains about 30-40% of the genetic variability. Therefore, the source of the majority of the genetic component remains to be identified. To search for these unknown loci, we conducted a genomewide linkage screen for genes affecting normal variation in vWF levels in 21 Spanish families as part of the GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project. The results showed that the strongest linkage signal (LOD =3.46, p = 0.00003) for vWF was found on chromosome 9q34 at the DNA marker D9S290, where the ABO gene is located. Additional suggestive linkage signals were found on chromosomes 2q23.2 (LOD = 1.65, p = 0.003) and 1p36.13 (LOD =1.32, p = 0.007). After refining the linkage analysis, conditional to the ABO genotype, three additional loci on chromosomes 5, 6 and 22 showed LOD scores higher than 1, suggesting the presence of other genes linked to vWF levels. Curiously, no linkage signals were detected in other chromosome regions previously associated with vWF levels (like the structural VWF gene on 12p13.2 or Lewis blood group gene on 19q13). These results indicate that these loci are not important genetic determinants of the normal variation of vWF levels. Our results indicate that the ABO locus is the major genetic determinant of the plasma levels of the vWF in Spanish population. It is possible that there are other potential regions on chromosomes 1, 2, 5, 6 and 22 that influence this thrombosis risk factor. However, the structural vWF gene itself has a very low influence (if any) on the plasma levels of vWF.

  16. Insights into the mechanism(s) of von Willebrand factor degradation during mechanical circulatory support.

    Science.gov (United States)

    Bartoli, Carlo R; Dassanayaka, Sujith; Brittian, Kenneth R; Luckett, Andrew; Sithu, Srinivas; Siess, Thorsten; Raess, Daniel H; Spence, Paul A; Koenig, Steven C; Dowling, Robert D; D'Souza, Stanley E

    2014-05-01

    Left ventricular assist device support produces a bleeding diathesis. Evidence suggests a major role for von Willebrand factor (vWF). We examined vWF metabolism in a preclinical model of short-term mechanical circulatory support. In 25 calves (weight, 80-110 kg), the inflow/outflow graft of the Symphony Heart Assist System was sewn end-to-side to the carotid artery. Support was initiated (acute, n = 4; 1 week, n = 16; 2 weeks, n = 5). Acutely, carotid artery pressure and flow were measured to evaluate the hemodynamic changes near the anastomosis. At baseline and after ≤2 weeks of support, platelet aggregometry with adenosine 5'-diphosphate, collagen, and ristocetin was performed. Gel electrophoresis and wet immunoblotting qualitatively evaluated vWF multimers and quantified plasma ADAMTS-13, the vWF-cleaving protease. Carotid arterial rings near the anastomosis were studied with immunohistochemical staining for ADAMTS-13 and were cultured to quantify endothelial ADAMTS-13 production. Fluorescent resonance energy transfer was used to evaluate the enzymatic activity of ADAMTS-13 in the plasma and in supernatant from cultured carotid arterial rings. Plasma interleukin-6, which inhibits ADAMTS-13 activity, was measured using an enzyme-linked immunosorbent assay. During support, statistically significant (P < .05) changes in the carotid endothelium arterial hemodynamics were observed. The highest molecular weight vWF multimers were absent, and the vWF-ristocetin platelet aggregation pathway was significantly impaired. A modest but significant increase in plasma ADAMTS-13 protein and activity was observed. ADAMTS-13 decreased significantly in the carotid near the anastomosis but increased significantly in supernatant from cultured carotid arterial rings. The plasma interleukin-6 levels did not change significantly. Hemodynamic activation of vWF and increased plasma ADAMTS-13 activity may have reduced high-molecular-weight vWF multimers and thereby impaired the

  17. Von Willebrand factor and fibrinolytic parameters during the desmopressin test in patients with Cushing's disease

    Science.gov (United States)

    Giraldi, Francesca Pecori; Ambrogio, Alberto G; Fatti, Letizia M; Rubini, Valentina; Cozzi, Giovanna; Scacchi, Massimo; Federici, Augusto B; Cavagnini, Francesco

    2011-01-01

    AIMS Desmopressin, a vasopressin analogue, is used for various clinical purposes, including haemostasis and, in recent times, the diagnostic work-up of patients with Cushing's syndrome, a condition associated with a known prothrombotic profile. We decided to evaluate whether and to what extent a diagnostic dose of desmopressin induces significant changes in endothelial parameters in patients with Cushing's disease (CD) and obese and normal weight controls. METHODS Twelve patients with CD, 10 obese and five normal weight controls were studied. Von Willebrand antigen (VWF : Ag), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were measured at baseline and up to 4 h after 10 µg desmopressin i.v. RESULTS Desmopressin 10 µg transiently increased VWF : Ag and t-PA and decreased PAI-1 in all subjects. The magnitude of the VWF : Ag and t-PA increases after desmopressin was comparable in the three groups (VWF : Ag peak-to-basal ratio 1.9 ± 0.17, 1.5 ± 0.11 and 1.8 ± 0.13 and t-PA peak-to-basal ratio 1.6 ± 0.18, 1.6 ± 0.20 and 1.8 ± 0.24 for CD, obese and controls, respectively, all NS). The PAI-1 decrease observed in patients with CD was comparable with obese (0.7 ± 0.07 and 0.6 ± 0.09, NS) and controls (0.7 ± 0.07 vs. 0.4 ± 0.09, P = 0.08). CONCLUSIONS Administration of desmopressin to patients with CD for diagnostic purposes induces a transitory increase in VWF : Ag counterbalanced by a decrease in PAI-1 and increase in t-PA. The magnitude of these changes is largely comparable with that observed in obese and normal weight controls. Our data show that testing with desmopressin does not induce disease-specific changes in endothelial markers in patients with CD. PMID:21143510

  18. ADAMTS13 deficiency with elevated levels of ultra-large and active von Willebrand factor in P. falciparum and P. vivax malaria.

    NARCIS (Netherlands)

    Mast, Q. de; Groot, E. de; Asih, P.B.; Syafruddin, D.; Oosting, M.; Sebastian, S.; Ferwerda, B.; Netea, M.G.; Groot, P.G. de; Ven, A.J.A.M. van der; Fijnheer, R.

    2009-01-01

    A deficiency in ADAMTS13 (a von Willebrand factor [VWF] cleaving protease) is associated with accumulation of prothrombogenic unusually large VWF multimers (UL-VWF) in plasma. We studied VWF release and proteolysis in patients with symptomatic Plasmodium falciparum or P. vivax malaria on the

  19. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions

    NARCIS (Netherlands)

    van Galen, Karin Pm|info:eu-repo/dai/nl/325853886; Engelen, Eveline T; Mauser-Bunschoten, Evelien P|info:eu-repo/dai/nl/074719718; van Es, Robert Jj|info:eu-repo/dai/nl/216460646; Schutgens, Roger Eg|info:eu-repo/dai/nl/258752084

    2015-01-01

    BACKGROUND: Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular

  20. Dogs with hearth diseases causing turbulent high-velocity blood flow have changes in patelet function and von Willebrand factor multimer distribution

    DEFF Research Database (Denmark)

    Tarnow, Inge; Kristensen, Annemarie Thuri; Olsen, Lisbeth Høier

    2005-01-01

    The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated d...

  1. Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.

    Science.gov (United States)

    Borràs, Nina; Batlle, Javier; Pérez-Rodríguez, Almudena; López-Fernández, María Fernanda; Rodríguez-Trillo, Ángela; Lourés, Esther; Cid, Ana Rosa; Bonanad, Santiago; Cabrera, Noelia; Moret, Andrés; Parra, Rafael; Mingot-Castellano, María Eva; Balda, Ignacia; Altisent, Carme; Pérez-Montes, Rocío; Fisac, Rosa María; Iruín, Gemma; Herrero, Sonia; Soto, Inmaculada; de Rueda, Beatriz; Jiménez-Yuste, Víctor; Alonso, Nieves; Vilariño, Dolores; Arija, Olga; Campos, Rosa; Paloma, María José; Bermejo, Nuria; Berrueco, Rubén; Mateo, José; Arribalzaga, Karmele; Marco, Pascual; Palomo, Ángeles; Sarmiento, Lizheidy; Iñigo, Belén; Nieto, María Del Mar; Vidal, Rosa; Martínez, María Paz; Aguinaco, Reyes; César, Jesús María; Ferreiro, María; García-Frade, Javier; Rodríguez-Huerta, Ana María; Cuesta, Jorge; Rodríguez-González, Ramón; García-Candel, Faustino; Cornudella, Rosa; Aguilar, Carlos; Vidal, Francisco; Corrales, Irene

    2017-12-01

    Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. Copyright© 2017 Ferrata Storti Foundation.

  2. Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Victor H Jimenez-Zepeda

    2017-05-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT. Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

  3. Assessing the clinical severity of type 1 von Willebrand disease patients with a microchip flow-chamber system.

    Science.gov (United States)

    Nogami, K; Ogiwara, K; Yada, K; Shida, Y; Takeyama, M; Yaoi, H; Minami, H; Furukawa, S; Hosokawa, K; Shima, M

    2016-04-01

    The clinical phenotype of von Willebrand disease (VWD) is heterogeneous, and von Willebrand factor ristocetin cofactor activity (VWF:RCo) does not always reflect clinical severity, especially in VWD type 1. We have reported the potential of a microchip flow-chamber system (Total-Thrombus Formation Analysis System [T-TAS®]) for assessing physiologic hemostasis in VWD. Aim To evaluate the relationship between T-TAS, bleeding score (BS) and laboratory test results in type 1 VWD patients. Microchips coated with collagen (platelet chip [PL-chip]) or collagen/thromboplastin (AR-chip) were used to assess platelet thrombus formation (PTF) at high shear rates or fibrin-rich PTF at low shear rates, respectively, in whole blood from 50 patients. The times needed for the flow pressure to increase by 10 kPa and 30 kPa (T10 and T30 ) from baseline were calculated from flow pressure curves. BS was determined by the use of a standardized questionnaire. PL-T10 values correlated with BS (R(2) ~ 0.45) better than VWF:RCo (R(2) ~ 0.36), irrespective of the flow rate, whereas AR-T10 showed only a weak correlation with BS (R(2) ~ 0.18). Patients with PL-T10 > 10 min or AR-T10 > 30 min had lower VWF levels and higher BS than those with PL-T10 ≤ 10 min or AR-T10 ≤ 30 min, and the greatest differences were observed with PL-T10. Clinical severity appeared to correlate best with PL-T10 > 8 min. BS was significantly higher in patients with VWF:RCo of 8 min than in those with PL-T10 ≤ 8 min. T-TAS could be a useful technique for discriminating and predicting BS in VWD type 1 patients. © 2016 International Society on Thrombosis and Haemostasis.

  4. A 12.3-kb Duplication Within the VWF Gene in Pigs Affected by Von Willebrand Disease Type 3

    Directory of Open Access Journals (Sweden)

    Stefanie Lehner

    2018-02-01

    Full Text Available Von Willebrand Disease (VWD type 3 is a serious and sometimes fatal hereditary bleeding disorder. In pigs, the disease has been known for decades, and affected animals are used as models for the human disease. Due to the recessive mode of inheritance of VWD type 3, severe bleeding is typically seen in homozygous individuals. We sequenced the complete porcine VWF (Von Willebrand Factor complementary DNA (cDNA and detected a tandem duplication of exons 17 and 18, causing a frameshift and a premature termination codon (p.Val814LeufsTer3 in the affected pig. Subsequent next generation sequencing on genomic DNA proved the existence of a 12.3-kb tandem duplication associated with VWD. This duplication putatively originates from porcine Short Interspersed Nuclear Elements (SINEs located within VWF introns 16 and 18 with high identity. The premature termination truncates the VWF open reading frame by a large part, resulting in an almost entire loss of the mature peptide. It is therefore supposed to account for the severe VWD type 3. Our results further indicate the presence of strong, nonsense-mediated decay in VWF messenger RNA (mRNA containing the duplication, which was supported by the almost complete absence of the complete VWF protein in immunohistochemistry analysis of the VWD-affected pig. In the past, differentiation of wild-type and heterozygous pigs in this VWD colony had to rely on clinical examinations and additional laboratory methods. The present study provides the basis to distinguish both genotypes by performing a rapid and simple genetic analysis.

  5. A rapid, automated VWF ristocetin cofactor activity assay improves reliability in the diagnosis of Von Willebrand disease.

    Science.gov (United States)

    Bowyer, Annette E; Shepherd, Fiona; Kitchen, Stephen; Makris, Michael

    2011-04-01

    The effective diagnosis and monitoring of Von Willebrand Disease (VWD) requires an accurate assessment of ristocetin co-factor activity (VWF:RCo). Current methodologies include automated platelet aggregometry and manual visual agglutination both of which are laborious to perform and notoriously subject to a high degree of inter and intra assay variation. We have evaluated an automated VWF:RCo assay (BC Von Willebrand Reagent, Siemens, Marberg, Germany) for use on the Sysmex CS2100i analyser (Milton Keynes, UK) and retrospectively compared the results with an in-house manual visual agglutination assay and VWF antigen (Siemens) in normal subjects and in 53 patients with various types of VWD and 23 patients following VWF therapeutic treatment. The intra and interassay CV was improved with the automated assay (2.3% and 3.8% respectively) compared to 7% with the manual VWF:RCo assay. Good correlation was found between the two assays (r=0.91) in 53 patients with VWD. The mean manual VWF:RCo was 0.25IU/ml and mean automated VWF:RCo was 0.27IU/ml. A comparable increase in VWF:RCo following treatment, mostly with Desmopressin, was found in 13 patients with type 1 VWD (mean 3.9 fold increase with manual VWF:RCo and 3.1 fold with the automated VWF:RCo). In 13 patients with type 2 or 3 VWD following treatment mostly with concentrate , a higher increase was found with the automated VWF:RCo assay than the manual assay (mean 11.9 fold manually and mean 20.3 automated). The automated VWF:RCo assay shows enhanced precision and analysis time in this difficult and time consuming laboratory test and its introduction should greatly improve the reliability of VWF testing. Copyright © 2010. Published by Elsevier Ltd.

  6. von Willebrand Factor-Rich Platelet Thrombi in the Liver Cause Sinusoidal Obstruction Syndrome following Oxaliplatin-Based Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Naoto Nishigori

    Full Text Available Oxaliplatin-based chemotherapy is widely used to treat advanced colorectal cancer (CRC. Sinusoidal obstruction syndrome (SOS due to oxaliplatin is a serious type of chemotherapy-associated liver injury (CALI in CRC patients. SOS is thought to be caused by the sinusoidal endothelial cell damage, which results in the release of unusually-large von Willebrand factor multimers (UL-VWFMs from endothelial cells. To investigate the pathophysiology of CALI after oxaliplatin-based chemotherapy, we analyzed plasma concentration of von Willebrand factor (VWF and the distribution of VWFMs in CRC patients. Twenty-three patients with advanced CRC who received oxaliplatin-based chemotherapy with (n = 6 and without (n = 17 bevacizumab were analyzed. CALI (n = 6 and splenomegaly (n = 9 were found only in patients who did not treated with bevacizumab. Plasma VWF antigen (VWF:Ag and serum aspartate aminotransferase (AST levels increased after chemotherapy only in patients without bevacizumab. VWFM analysis in patients who did not receive bevacizumab showed the presence of UL-VWFMs and absence of high molecular weight VWFMs during chemotherapy, especially in those with CALI. In addition, plasma VWF:Ag and AST levels increased after chemotherapy in patients with splenomegaly (n = 9, but not in patients without splenomegaly (n = 14. Histological findings in the liver tissue of patients who did not receive bevacizumab included sinusoidal dilatation and microthrombi in the sinusoids. Many microthrombi were positive for both anti-IIb/IIIa and anti-VWF antibodies. Plasma UL-VWFM levels might be increased by damage to endothelial cells as a result of oxaliplatin-based chemotherapy. Bevacizumab could prevent CALI and splenomegaly through inhibition of VWF-rich platelet thrombus formation.

  7. Evaluation of von Willebrand factor phenotypes and genotypes in Hemophilia A patients with and without identified F8 mutations.

    Science.gov (United States)

    Boylan, B; Rice, A S; De Staercke, C; Eyster, M E; Yaish, H M; Knoll, C M; Bean, C J; Miller, C H

    2015-06-01

    Hemophilia A (HA) is an X-linked bleeding disorder caused by a deficiency in factor VIII (FVIII). von Willebrand disease (VWD) is characterized by a quantitative or qualitative defect in von Willebrand factor (VWF). Patients with VWD with severely low VWF or VWD Type 2N (VWD2N), a VWD subtype distinguished by defective VWF binding to FVIII, may have reduced FVIII levels secondary to their VWD. These patients superficially resemble patients with HA and pose a potential for misdiagnosis. To investigate the unexplained cause of bleeding in HA patients without known FVIII mutations by assessing plasma VWF antigen (VWF:Ag), FVIII binding capacities and VWF genotypes. Thirty-seven of 1027 patients with HA studied as part of the Hemophilia Inhibitor Research Study lacked identifiable F8 mutations. These patients (cases) and 73 patients with identified F8 mutations (controls) were evaluated for VWF:Ag, a patient's VWF capacity to bind FVIII (VWF:FVIIIB) and VWF sequence. Four cases had VWF:Ag < 3 IU dL(-1) and VWF mutations consistent with Type 3 VWD. Six cases and one control were heterozygous for mutations previously reported to cause Type 1 VWD (VWD1) (n = five cases and one control) or predicted to be deleterious by Polyphen2 and SIFT prediction tools (n = 1 case). One control had VWF:Ag < 30 IU dL(-1) and seven patients (four cases and three controls), including two cases who were heterozygous for a known VWD2N mutation, had reduced VWF:FVIIIB. These data emphasize that some patients diagnosed with HA require VWF assessments in order to achieve a comprehensive diagnosis and an optimal treatment strategy. © 2015 International Society on Thrombosis and Haemostasis.

  8. Platelet function analyser (PFA-100) results and von Willebrand factor deficiency: a 16-year 'real-world' experience.

    Science.gov (United States)

    Ardillon, L; Ternisien, C; Fouassier, M; Sigaud, M; Lefrançois, A; Pacault, M; Ribeyrol, O; Fressinaud, E; Boisseau, P; Trossaërt, M

    2015-09-01

    The platelet function analyser (PFA-100) is a biological tool designed to explore primary haemostasis. This system has thus been widely demonstrated as reliable in detecting von Willebrand factor (VWF) deficiency. However, most studies were based on patients benefitting from regular medical care and accurate diagnosis, and it would seem probable that the results were somewhat optimistic, and do not reflect its performances in 'real-world' situations. We have chosen to study the reliability of PFA-100 for screening VWF ristocetin cofactor (VWF:RCo) deficiency. We retrospectively analysed the results (n = 6431) of 4027 patients referred to our centre between October 1997 and June 2013 and in whom PFA-Epi, PFA-ADP, and VWF:RCo activity had been evaluated. We studied the influence of blood group on the results and the performances of each method in a subgroup of 213 patients with genetically confirmed von Willebrand disease. We have shown that the PFA-100 system, in our experience, constitutes an excellent screening test for detecting VWF:RCo deficiency, whatever the clinical situation, in 'real-world' conditions. The negative predictive value (NPV), the positive predictive value, the sensitivity and the specificity were respectively: 0.98, 0.51, 0.98 and 0.40. When values adjusted for blood group are used, NPV and sensitivity are inferior to those using normal values which have not been adjusted for blood group. We have shown the PFA-100 method to be more efficient in screening for VWF deficiency than the VWF:RCo technique. © 2015 John Wiley & Sons Ltd.

  9. Distribution of von Willebrand factor levels in young women with and without bleeding symptoms: influence of ABO blood group and promoter haplotypes

    DEFF Research Database (Denmark)

    Lethagen, S.; Hillarp, A.; Ekholm, C.

    2008-01-01

    The normal distribution of von Willebrand factor (VWF) levels is wide. Low levels are associated with bleeding symptoms and von Willebrand disease (VWD). We have recently described a high prevalence of bleeding symptoms in a whole age group of young females (n = 1,019) from Malmo, Sweden....... It was the objective of the present study to evaluate the distribution of VWF levels in young females with or without bleeding symptoms in this population, and the influence of ABO blood group and promoter haplotypes on VWF levels and to identify a possible increased prevalence of VWD in females with bleeding symptoms....... A random selection of the female age group (n = 246), into a study group (n = 176) with, and a control group (n = 70) without bleeding symptoms, was evaluated. Eighteen girls had VWF:RCo below the reference range, of which 17 belonged to the study group (17/176, 9.7%), and one to the control group (1/70, 1...

  10. Alterations in hemostatic parameters during hemodialysis with dialyzers of different membrane composition and flow design. Platelet activation and factor VIII-related von Willebrand factor during hemodialysis.

    Science.gov (United States)

    Schmitt, G W; Moake, J L; Rudy, C K; Vicks, S L; Hamburger, R J

    1987-09-01

    The effect of dialyzer membrane and design on hemostatic parameters during hemodialysis were evaluated in a prospective controlled study. This study demonstrated that hemodialysis is associated with significant platelet activation and loss, which are influenced by both dialyzer configuration and membrane composition. In addition, use of the cuprophan membrane is associated with greater perturbations of the vascular endothelium, as reflected in changes in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha concentrations not seen with the polyacrylonitrile membrane. Of the dialyzers studied, the polyacrylonitrile membrane in a hollow-fiber configuration appears to minimize platelet loss and activation, and to minimize increases in factor VIII-related von Willebrand factor and 6-keto-prostaglandin F1 alpha.

  11. Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD

    DEFF Research Database (Denmark)

    Castaman, G.; Lethagen, S.; Federici, A.B.

    2008-01-01

    We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase...... of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD Udgivelsesdato: 2008/4/1...

  12. Associations Between Diabetic Retinopathy and Plasma Levels of High-sensitive C-reactive Protein or Von Willebrand Factor in Long-term Type 1 Diabetic Patients

    DEFF Research Database (Denmark)

    Laursen, Jonas Vejvad Nørskov; Hoffmann, Stine Skovbo; Green, Anders

    2013-01-01

    a population-based cohort from Fyn County, Denmark. Plasma levels of hs-CRP and von Willebrand factor antigen were measured and related to the level of diabetic retinopathy (DR) as evaluated by dilated nine-field 45 degree monoscopic fundus photos captured by Topcon TRC-NWS6 and graded according to the Early...... Treatment Diabetic Retinopathy Study (ETDRS) adaptation of the modified Airlie House classification of DR. Results: Median age and duration of diabetes were 58.7 and 43 years, respectively. Median levels (10th-90th percentile) of hs-CRP and von Willebrand factor antigen were 1.31 mg/l (0.37-13.3 mg/l) and 1......Purpose: To evaluate high-sensitive C-reactive protein (hs-CRP) and von Willebrand factor as possible plasma markers of diabetic retinopathy in a population-based cohort of type 1 diabetic patients. Materials and Methods: This was a cross-sectional study of 201 type 1 diabetic patients from...

  13. Syringomyelia following surgery for a spontaneous spinal subdural hematoma in a 13-year-old girl with congenital von Willebrand disease: case report and literature review.

    Science.gov (United States)

    Ben Nsir, A; Boubaker, A; Jemel, H

    2016-04-01

    Spontaneous spinal subdural hematomas are rare. Their occurrence in a child with congenital von Willebrand disease and the complication of their surgery by a large secondary syringomyelia have never been previously reported. A 13-year-old girl with congenital von Willebrand disease presented to our emergency department in January 2011 for sudden onset of severe back pain centered in her thoracic spine rapidly aggravated by signs of acute myelopathy without any precipitating factor. MRI scan revealed a thoracic subdural collection anterior to the spinal cord at the T7-T9 level, hyperintense on T1- and T2-weighted sequences consistent with an acute spinal subdural hemorrhage. Evacuation of the subdural hematoma was realized immediately after hemostasis parameter correction, and post-operative course was uneventful with full functional recovery. One year later, the patient presented once again but with progressive and more severe myelopathy caused by a large syringomyelia extending from the T5 level to the conus medullaris. A syringopleural shunting was performed and the patient was unrolled under an intensive care and rehabilitation program. Her condition remarkably improved and she became able to walk independently within 2 weeks post-operatively. von Willebrand disease should be included as a possible factor of spontaneous spinal subdural hemorrhage. Surgery is advised in emergency and can be associated with remarkable recovery especially in children. Delayed syringomyelia can complicate the post-operative course and can be successfully addressed by syringopleural shunting. Long-term clinical and radiological follow-up is advocated.

  14. Elevated preoperative von Willebrand factor is associated with perioperative thrombosis in infants and neonates with congenital heart disease.

    Science.gov (United States)

    Hunt, R; Hoffman, C M; Emani, S; Trenor, C C; Emani, S M; Faraoni, D; Kimchi-Sarfaty, C; Ibla, J C

    2017-12-01

    Essentials Perioperative thrombosis is a major cause of morbidity and mortality in congenital heart disease. Neonates and infants undergoing repair of congenital heart lesions were prospectively followed. Elevated von Willebrand factor (VWF) to ADAMTS-13 activity ratios typified the postoperative period. Thrombosis was associated with preoperative VWF activity and cryoprecipitate transfusion SUMMARY: Background The surgical repair of congenital heart malformations is frequently complicated by perioperative thrombosis of unclear etiology. An imbalance between von Willebrand factor (VWF) and ADAMTS-13 is an emerging variable in thrombosis. Objectives To describe perioperative changes to VWF, ADAMTS-13 and NETosis, and evaluate clinical and biochemical associations with postoperative thrombosis. Methods Neonates and infants undergoing palliation or definitive surgical repair of congenital heart malformations were recruited (n = 133). Preoperative and postoperative plasma levels of VWF, ADAMTS-13 and markers of NETosis were determined. Patients were followed for up to 30 days for the occurrence of thrombosis. Univariate and multivariate logistic regression analyses were conducted to identify variables associated with thrombosis. Results We identified significant postoperative increases in VWF activity, VWF level, DNA-histone complexes and cell-free DNA with an overall decrease in ADAMTS-13 activity. Patients experiencing postoperative thrombotic events (9%) were characterized by surgery performed at a lower intraoperative temperature, higher preoperative lactic acid levels, and higher preoperative VWF activity and level. A multivariate logistic regression model identified preoperative VWF activity (odds ratio (OR) 8.39 per IU mL-1 , 95% confidence interval [CI] 1.73-40.55) and transfusion of cryoprecipitate (OR 1.10 per mL kg-1 , 95% CI 1.03-1.17) as being associated with thrombosis. Conclusions Pediatric patients undergoing surgical repair of congenital

  15. Identification and Characterization of Novel Variations in Platelet G-Protein Coupled Receptor (GPCR Genes in Patients Historically Diagnosed with Type 1 von Willebrand Disease.

    Directory of Open Access Journals (Sweden)

    Jacqueline Stockley

    Full Text Available The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12 could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis. Seven heterozygous single nucleotide variations were identified in 8 index cases. Two single nucleotide variations were detected in F2R; a novel c.-67G>C transversion which reduced F2R transcriptional activity and a rare c.1063C>T transition predicting a p.L355F substitution which did not interfere with PAR1 expression or signalling. Two synonymous single nucleotide variations were identified in F2RL3 (c.402C>G, p.A134 =; c.1029 G>C p.V343 =, both of which introduced less commonly used codons and were predicted to be deleterious, though neither of them affected PAR4 receptor expression. A third single nucleotide variation in F2RL3 (c.65 C>A; p.T22N was co-inherited with a synonymous single nucleotide variation in TBXA2R (c.6680 C>T, p.S218 =. Expression and signalling of the p.T22N PAR4 variant was similar to wild-type, while the TBXA2R variation introduced a cryptic splice site that was predicted to cause premature termination of protein translation. The enrichment of single nucleotide variations in G protein-coupled receptor genes among type 1 von Willebrand disease patients supports the view of type 1 von Willebrand disease as a polygenic disorder.

  16. Von Willebrand Factor, ADAMTS13 and D-Dimer Are Correlated with Different Levels of Nephropathy in Type 1 Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Caroline Pereira Domingueti

    Full Text Available We have investigated whether von Willebrand factor, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13, and D-Dimer were associated with different levels of renal function in patients with type 1 diabetes. Patients were classified according to level of renal function through estimated glomerular filtration rate: ≥90 and <130mL/min/1,73m2, n=52 (control group, ≥60 and <90mL/min/1,73m2, n=29 (mild renal dysfunction group, <60mL/min/1,73m2, n=28 (severe renal dysfunction group; and through urinary albumin excretion: normoalbuminuria, microalbuminuria and macroalbuminuria. Von Willebrand factor, ADAMTS13, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay. ADAMTS13 activity was determined by fluorescence resonance energy transfer assay. Von Willebrand factor levels were increased in patients with mild (P=0.001 and severe (P<0.001 renal dysfunction as compared to the control group. ADAMTS13 levels were also increased in mild (P=0.029 and severe (P=0.002 renal dysfunction groups in comparison to the control group, while ADAMTS13 activity was increased only in the severe renal dysfunction group as compared to the control group (P=0.006. No significant differences were observed among the groups regarding von Willebrand factor/ADAMTS13 ratio. ADAMTS13 activity/ADAMTS13 levels ratio was reduced in patients with mild (P=0.013 and severe (P=0.015 renal dysfunction as compared to the control group. D-Dimer levels were increased in patients with mild (P=0.006 and severe (P<0.001 renal dysfunction as compared to the control group; it was also higher in patients with severe renal dysfunction as compared to the mild renal dysfunction group (P=0.019. Similar results were found for albuminuria classification. Increased von Willebrand factor, ADAMTS13, and D-Dimer levels and decreased ADAMTS13 activity/ADAMTS13 levels ratio are associated with renal dysfunction in patients with type 1 diabetes

  17. Mechanism and functional impact of CD40 ligand-induced von Willebrand factor release from endothelial cells.

    Science.gov (United States)

    Möller, Kerstin; Adolph, Oliver; Grünow, Jennifer; Elrod, Julia; Popa, Miruna; Ghosh, Subhajit; Schwarz, Manuel; Schwale, Chrysovalandis; Grässle, Sandra; Huck, Volker; Bruehl, Claus; Wieland, Thomas; Schneider, Stefan W; Nobiling, Rainer; Wagner, Andreas H; Hecker, Markus

    2015-05-01

    Co-stimulation via CD154 binding to CD40, pivotal for both innate and adaptive immunity, may also link haemostasis to vascular remodelling. Here we demonstrate that human platelet-bound or recombinant soluble CD154 (sCD154) elicit the release from and tethering of ultra-large (UL) von Willebrand factor (vWF) multimers to the surface of human cultured endothelial cells (ECs) exposed to shear stress. This CD40-mediated ULVWF multimer release from the Weibel-Palade bodies was triggered by consecutive activation of TRAF6, the tyrosine kinase c-Src and phospholipase Cγ1 followed by inositol-1,4,5 trisphosphate-mediated calcium mobilisation. Subsequent exposure to human washed platelets caused ULVWF multimer-platelet string formation on the EC surface in a shear stress-dependent manner. Platelets tethered to these ULVWF multimers exhibited P-selectin on their surface and captured labelled monocytes from the superfusate. When exposed to shear stress and sCD154, native ECs from wild-type but not CD40 or vWF-deficient mice revealed a comparable release of ULVWF multimers to which murine washed platelets rapidly adhered, turning P-selectin-positive and subsequently capturing monocytes from the perfusate. This novel CD154-provoked ULVWF multimer-platelet string formation at normal to fast flow may contribute to vascular remodelling processes requiring the perivascular or intravascular accumulation of pro-inflammatory macrophages such as arteriogenesis or atherosclerosis.

  18. The membrane-proximal intermolecular disulfide bonds in glycoprotein Ib influence receptor binding to von Willebrand factor.

    Science.gov (United States)

    Mo, X; Luo, S-Z; Munday, A D; Sun, W; Berndt, M C; López, J A; Dong, J-F; Li, R

    2008-10-01

    In the platelet glycoprotein (GP)Ib-IX complex, the binding site for its ligand von Willebrand factor (VWF) is restricted to the N-terminal domain of the GPIbalpha subunit. How the other subunits in the complex, GPIbbeta and GPIX, regulate the GPIbalpha-VWF interaction is not clear. As GPIbalpha connects with two GPIbbeta subunits via disulfide bonds, we tested whether these intersubunit covalent links were important to the proper VWF-binding activity of the GPIb-IX complex by characterizing the structure and VWF-binding activity of a mutant GPIb-IX complex that lacked the GPIbalpha-GPIbbeta disulfide bonds. Mutating both Cys484 and Cys485 of GPIbalpha to serine prevents GPIbalpha from forming covalent disulfide bonds with GPIbbeta, while maintaining the integrity of the complex in the membrane. The mutations cause two GPIbbeta subunits to form a disulfide bond between themselves. As compared to Chinese hamster ovary (CHO) cells stably expressing the wild-type GPIb-IX complex at a comparable level, CHO cells stably expressing the mutant GPIb-IX complex bind to significantly less soluble VWF in the presence of ristocetin and roll on the immobilized VWF under flow at a higher velocity. The disulfide bonds between GPIbalpha and GPIbbeta are necessary for optimal GPIbalpha binding to VWF. The structural plasticity around the disulfide bonds may also help to shed light on the inside-out mechanism underlying GPIbbeta modulation of VWF binding.

  19. Space and Time Resolved Detection of Platelet Activation and von Willebrand Factor Conformational Changes in Deep Suspensions.

    Science.gov (United States)

    Biasetti, Jacopo; Sampath, Kaushik; Cortez, Angel; Azhir, Alaleh; Gilad, Assaf A; Kickler, Thomas S; Obser, Tobias; Ruggeri, Zaverio M; Katz, Joseph

    2017-01-01

    Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.

  20. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity.

    Science.gov (United States)

    Ristić, Gorica G; Subota, Vesna; Lepić, Toplica; Stanisavljević, Dejana; Glišić, Branislava; Ristić, Arsen D; Petronijević, Milan; Stefanović, Dušan Z

    2015-01-01

    To evaluate association between von Willebrand factor (vWF) activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA) and low cardiovascular risk. Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years). Intima-media thickness (IMT) was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%), none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately. RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, psubclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP), modified Health Assessment Questionnaire (psubclinical atherosclerosis (130±68% vs. 97±38%, psubclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of early atherosclerosis in RA patients.

  1. Role of 14-3-3ζ in Platelet Glycoprotein Ibα-von Willebrand Factor Interaction-Induced Signaling

    Directory of Open Access Journals (Sweden)

    Kesheng Dai

    2012-05-01

    Full Text Available The interaction of platelet glycoprotein (GP Ib-IX with von Willebrand factor (VWF exposed at the injured vessel wall or atherosclerotic plaque rupture initiates platelet transient adhesion to the injured vessel wall, which triggers intracellular signaling cascades leading to platelet activation and thrombus formation. 14-3-3ζ has been verified to regulate the VWF binding function of GPIb-IX by interacting with the cytoplasmic domains of GPIb-IX. However, the data regarding the role of 14-3-3ζ in GPIb-IX-VWF interaction-induced signaling still remain controversial. In the present study, the data indicate that the S609A mutation replacing Ser609 of GPIbα with alanine (S609A significantly prevented the association of 14-3-3ζ with GPIbα before and after the VWF binding to GPIbα. GPIb-IX-VWF interaction-induced activations of Src family kinases and protein kinase C were clearly reduced in S609A mutation. Furthermore, S609A mutation significantly inhibited GPIb-IX-VWF interaction-induced elevation of cytoplasmic Ca2+ levels in flow cytometry analysis. Taken together, these data indicate that the association of 14-3-3ζ with the cytoplasmic domain of GPIbα plays an important role in GPIb-IX-VWF interaction-induced signaling.

  2. The Carmat Bioprosthetic Total Artificial Heart Is Associated With Early Hemostatic Recovery and no Acquired von Willebrand Syndrome in Calves.

    Science.gov (United States)

    Smadja, David M; Susen, Sophie; Rauch, Antoine; Cholley, Bernard; Latrémouille, Christian; Duveau, Daniel; Zilberstein, Luca; Méléard, Denis; Boughenou, Marie-Fazia; Belle, Eric Van; Gaussem, Pascale; Capel, Antoine; Jansen, Piet; Carpentier, Alain

    2017-10-01

    To determine hemostasis perturbations, including von Willebrand factor (VWF) multimers, after implantation of a new bioprosthetic and pulsatile total artificial heart (TAH). Preclinical study SETTING: Single-center biosurgical research laboratory. Female Charolais calves, 2-to-6 months old, weighing 102-to-122 kg. Surgical implantation of TAH through a mid-sternotomy approach. Four of 12 calves had a support duration of several days (4, 4, 8, and 10 days), allowing for the exploration of early steps of hemostasis parameters, including prothrombin time; coagulation factor levels (II, V, VII+X, and fibrinogen); and platelet count. Multimeric analysis of VWF was performed to detect a potential loss of high-molecular weight (HMW) multimers, as previously described for continuous flow rotary blood pumps. Despite the absence of anticoagulant treatment administered in the postoperative phase, no signs of coagulation activation were detected. Indeed, after an immediate postsurgery decrease of prothrombin time, platelet count, and coagulation factor levels, most parameters returned to baseline values. HMW multimers of VWF remained stable either after initiation or during days of support. Coagulation parameters and platelet count recovery in the postoperative phase of the Carmat TAH (Camat SA, Velizy Villacoublay Cedex, France) implantation in calves, in the absence of anticoagulant treatment and associated with the absence of decrease in HMW multimers of VWF, is in line with early hemocompatibility that is currently being validated in human clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Analysis of von Willebrand factor A domain-related protein (WARP polymorphism in temperate and tropical Plasmodium vivax field isolates

    Directory of Open Access Journals (Sweden)

    Zakeri Sedigheh

    2009-06-01

    Full Text Available Abstract Background The identification of key molecules is crucial for designing transmission-blocking vaccines (TBVs, among those ookinete micronemal proteins are candidate as a general class of malaria transmission-blocking targets. Here, the sequence analysis of an extra-cellular malaria protein expressed in ookinetes, named von Willebrand factor A domain-related protein (WARP, is reported in 91 Plasmodium vivax isolates circulating in different regions of Iran. Methods Clinical isolates were collected from north temperate and southern tropical regions in Iran. Primers have been designed based on P. vivax sequence (ctg_6991 which amplified a fragment of about 1044 bp with no size variation. Direct sequencing of PCR products was used to determine polymorphism and further bioinformatics analysis in P. vivax sexual stage antigen, pvwarp. Results Amplified pvwarp gene showed 886 bp in size, with no intron. BLAST analysis showed a similarity of 98–100% to P. vivax Sal-I strain; however, Iranian isolates had 2 bp mismatches in 247 and 531 positions that were non-synonymous substitution [T (ACT to A (GCT and R (AGA to S (AGT] in comparison with the Sal-I sequence. Conclusion This study presents the first large-scale survey on pvwarp polymorphism in the world, which provides baseline data for developing WARP-based TBV against both temperate and tropical P. vivax isolates.

  4. Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals

    Science.gov (United States)

    Harrison, Jacqueline M. E.; Quanstrom, Leah M.; Robinson, Alex R.; Wobeser, Bruce; Anderson, Stacy L.

    2017-01-01

    Sepsis causes significant mortality in neonatal foals; however, there is little data describing the cellular and molecular pathways of lung inflammation in septic foals. This study was conducted to characterize lung inflammation in septic foals. Lung tissue sections from control (n = 6) and septic (n = 17) foals were compared using histology and immunohistology. Blinded pathologic scoring of hematoxylin and eosin stained samples revealed increased features of lung inflammation such as thickened alveolar septa and sequestered inflammatory cells in septic foals. Septic foal lungs showed increased expression of von Willebrand factor in blood vessels, demonstrating vascular inflammation. Use of MAC387 antibody to detect calprotectin as a reflection of mononuclear cell infiltration revealed a significant increase in their numbers in alveolar septa of lungs from septic foals compared to those from control foals. The mononuclear cells appeared to be mature macrophages and were located in the septal capillaries, suggesting they were pulmonary intravascular macrophages (PIMs). Finally, lungs from septic foals showed increased expression of Toll-like receptor 4 and 9 in mononuclear cells relative to the control. Taken together, this study is the first to show the expression of inflammatory molecules and an increase in PIMs in lungs from foals that died from sepsis. PMID:27297419

  5. Time course of soluble P-selectin and von Willebrand factor levels in trauma patients: a prospective observational study.

    Science.gov (United States)

    Tang, Ning; Yin, Shiyu; Sun, Ziyong; Pan, Yingying

    2013-09-14

    Coagulopathy often develops in patients with serious trauma and is correlated with the clinical outcome. The contribution of platelet activity and endothelial dysfunction to trauma-induced coagulopathy remain to be defined. The purpose of this study was to investigate the time courses of soluble P-selectin (sPsel, an index of platelet activation) and von Willebrand factor (VWF, an index of endothelial dysfunction) in trauma patients and elucidate their relationship to coagulation parameter levels, the presence of coagulopathy, and patient outcome. This prospective observational study, which took place in a university hospital intensive care unit (ICU), included 82 severely injured trauma patients. The sPsel, VWF antigen, protein C, and factor VII levels were measured and routine coagulation tests were performed upon admission to ICU and daily within the first week. The 30-day mortality rate was also determined. Thirty-seven (45.1%) patients developed coagulopathy upon admission to the ICU, and the 30-day mortality rate was 20.7% (n = 17). Both the admission sPsel and VWF levels were lower in patients with coagulopathy than in those without (p trauma patients in the ICU, lower levels of sPsel and VWF on admission were associated with the presence of coagulopathy and might not predict a better outcome. An increase in the VWF level at the end of the first week after admission to ICU was associated with increased 30-day mortality.

  6. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells.

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    Maartje van den Biggelaar

    Full Text Available BACKGROUND: Point mutations resulting in reduced factor VIII (FVIII binding to von Willebrand factor (VWF are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both proteins. The source of these VWF/FVIII co-storage pools and the mechanism of granule biogenesis are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: We studied intracellular trafficking of FVIII variants implicated in mild/moderate hemophilia A together with VWF in HEK293 cells and primary endothelial cells. The role of VWF binding was addressed using FVIII variants displaying reduced VWF interaction. Binding studies using purified FVIII proteins revealed moderate (Arg2150His, Del2201, Pro2300Ser to severe (Tyr1680Phe, Ser2119Tyr VWF binding defects. Expression studies in HEK293 cells and primary endothelial cells revealed that all FVIII variants were present within VWF-containing organelles. Quantitative studies showed that the relative amount of FVIII storage was independent of various mutations. Substantial amounts of FVIII variants are co-stored in VWF-containing storage organelles, presumably by virtue of their ability to interact with VWF at low pH. CONCLUSIONS: Our data suggest that the potential of FVIII co-storage with VWF is not affected in mild/moderate hemophilia A caused by reduced FVIII/VWF interaction in the circulation. These data support the hypothesis that Weibel-Palade bodies comprise the desmopressin-releasable FVIII storage pool in vivo.

  7. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  8. Von Willebrand factor and alkaline phosphatase predict re-transplantation-free survival after the first liver transplantation.

    Science.gov (United States)

    Wannhoff, Andreas; Rauber, Conrad; Friedrich, Kilian; Rupp, Christian; Stremmel, Wolfgang; Weiss, Karl Heinz; Schemmer, Peter; Gotthardt, Daniel N

    2017-02-01

    After liver transplantation (LT), there are liver-related, infectious and cardiovascular complications that contribute to reduced graft survival. These conditions are associated with an increase in the Von Willebrand factor antigen (VWF-Ag), which was previously correlated with survival in cirrhotic patients. Evaluate VWF-Ag as a predictive marker of re-transplantation-free survival in patients after LT. We measured VWF-Ag in patients after first LT and then followed them prospectively with regard to the primary endpoint, namely re-transplantation-free survival. There were 6 out of 80 patients who died or received re-LT during follow-up. In these patients, the median VWF-Ag was 510.6%, which was significantly higher (p = 0.001) than in the patients who were alive at the end of follow-up (with a median VWF-Ag = 186.8%). At a cut-off of 286.8%, VWF-Ag was significantly correlated with re-transplantation-free survival (p alkaline phosphatase (ALP), but not the model of end-stage liver disease (MELD) score, donor age, nor cold ischemia time. A score combining VWF-Ag and ALP showed an impressive capability in the receiver operating characteristic (ROC) analysis (with area under the curve (AUC) = 0.958) to distinguish between patients with regard to the primary endpoint. VWF-Ag is a non-invasive marker that can predict outcome in patients after LT. Its diagnostic performance increased when combined with ALP in a newly developed scoring system.

  9. Cerebral venous thrombosis and plasma concentrations of factor VIII and von Willebrand factor: a case control study.

    Science.gov (United States)

    Bugnicourt, Jean-Marc; Roussel, Bertrand; Tramier, Blaise; Lamy, Chantal; Godefroy, Olivier

    2007-07-01

    High plasma concentrations of factor VIII (FVIII) and von Willebrand factor (VWF) have been recently associated with a moderately increased risk of venous thrombosis, but their roles in cerebral sinus and venous thrombosis (CSVT) have not been addressed. To determine whether elevation of FVIII and VWF is more frequent in CSVT, we analysed plasma levels of FVIII and VWF in a case control study. The study population consisted of 25 consecutive patients (of whom nine were excluded) admitted for CSVT to the Department of Neurology, Amiens University Hospital, France, from January 1997 to December 2002, for a general screening for thrombophilia. Sixty-four healthy subjects matched for age and sex formed the group control. Mean FVIII (CSVT: 167.3 (SD 48.8) IU/dl; control group: 117.9 (39.8) IU/dl; p = 0.001) and VWF levels (CSVT: 165.4 (76.5)%; control group: 108.5 (27.8)%; p = 0.01) were significantly higher in the CSVT group. Using the 95th percentile of the control group as the cut off value, elevated FVIII (>190 IU/dl) occurred in 25% (4/16) (p = 0.005) and elevated VWF (>168%) in 37.5% (6/16) of patients with CSVT (p150 IU/dl or >150%) showed the same results (FVIII: p = 0.005; VWF: p = 0.009). Our study suggests that elevation of plasma factor VIII levels is the most common prothrombotic risk factor for CSVT. Elevation of VWF is also associated with an increased risk of CSVT but its effect seems to be partly mediated through FVIII.

  10. A model for the conformational activation of the structurally quiescent metalloprotease ADAMTS13 by von willebrand factor

    Science.gov (United States)

    South, Kieron; Freitas, Marta O.; Lane, David A.

    2017-01-01

    Blood loss is prevented by the multidomain glycoprotein von Willebrand factor (VWF), which binds exposed collagen at damaged vessels and captures platelets. VWF is regulated by the metalloprotease ADAMTS13, which in turn is conformationally activated by VWF. To delineate the structural requirements for VWF-mediated conformational activation of ADAMTS13, we performed binding and functional studies with a panel of truncated ADAMTS13 variants. We demonstrate that both the isolated CUB1 and CUB2 domains in ADAMTS13 bind to the spacer domain exosite of a truncated ADAMTS13 variant, MDTCS (KD of 135 ± 1 0.1 nm and 86.9 ± 9.0 nm, respectively). However, only the CUB1 domain inhibited proteolytic activity of MDTCS. Moreover, ADAMTS13ΔCUB2, unlike ADAMTS13ΔCUB1-2, exhibited activity similar to wild-type ADAMTS13 and could be activated by VWF D4-CK. The CUB2 domain is, therefore, not essential for maintaining the inactive conformation of ADAMTS13. Both CUB domains could bind to the VWF D4-CK domain fragment (KD of 53.7 ± 2.1 nm and 84.3 ± 2.0 nm, respectively). However, deletion of both CUB domains did not prevent VWF D4-CK binding, suggesting that competition for CUB-domain binding to the spacer domain is not the dominant mechanism behind the conformational activation. ADAMTS13ΔTSP8-CUB2 could no longer bind to VWF D4-CK, and deletion of TSP8 abrogated ADAMTS13 conformational activation. These findings support an ADAMTS13 activation model in which VWF D4-CK engages the TSP8-CUB2 domains, inducing the conformational change that disrupts the CUB1-spacer domain interaction and thereby activates ADAMTS13. PMID:28209710

  11. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli - An Anti-thrombotic Mechanism in the Kidney.

    Science.gov (United States)

    Tati, Ramesh; Kristoffersson, Ann-Charlotte; Manea Hedström, Minola; Mörgelin, Matthias; Wieslander, Jörgen; van Kooten, Cees; Karpman, Diana

    2017-02-01

    Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3), cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  12. Contrast ultrasound imaging of the aorta alters vascular morphology and circulating von Willebrand factor in hypercholesterolemic rabbits.

    Science.gov (United States)

    Smith, Brendon W; Simpson, Douglas G; Sarwate, Sandhya; Miller, Rita J; Blue, James P; Haak, Alexander; O'Brien, William D; Erdman, John W

    2012-05-01

    Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol-fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta. Male New Zealand White rabbits (n = 41) were weaned onto an atherogenic diet containing 1% cholesterol, 10% fat, and 0.11% magnesium. At 21 days, rabbits were exposed to contrast US at 1 of 4 pressure levels using either the UCA Definity (Lantheus Medical Imaging, Inc, North Billerica, MA) or a saline control (n = 5 per group). Blood samples were collected and analyzed for lipids and von Willebrand factor (vWF), a marker of endothelial function. Animals were euthanized at 42 days, and tissues were collected for histologic analysis. After adjustment for pre-exposure vWF, high-level US (in situ [at the aorta] peak rarefactional pressure of 1.4 or 2.1 MPa) resulted in significantly lower vWF 1 hour post exposure (P = .0127; P(adj) < .0762). This difference disappeared within 24 hours. Atheroma thickness in the descending aorta was lower in animals receiving the UCA compared to animals receiving saline. Contrast US affected the descending aorta, as evidenced by two separate outcome measures. These results may be a first step in elucidating a previously unknown biological effect of UCAs. Further research is warranted to characterize the effects of this procedure.

  13. The study of the effect of splicing mutations in von Willebrand factor using RNA isolated from patients' platelets and leukocytes.

    Science.gov (United States)

    Corrales, I; Ramírez, L; Altisent, C; Parra, R; Vidal, F

    2011-04-01

    In von Willebrand factor (VWF) the effect of mutations potentially affecting mRNA processing or splicing is less predictable than that of other mutations (e.g. nonsense or missense substitutions). Bioinformatic tools can provide a valuable means to determine the consequences of potential splice site mutations (PSSM), but functional studies are mandatory to elucidate the true effect of the variation detected. After identification of PSSM in VWD patients, we began a systematic study of their in vivo effect in RNA extracted from the patients' platelets and leukocytes. Thirteen pairs of primers were designed for full amplification of VWF mRNA by RT-PCR that, after sequencing of aberrant products, enabled elucidation of the PSSM consequences for mRNA processing. This procedure was used to study seven different PSSM identified in four patients demonstrating diverse molecular mechanisms such as exon skipping (c.533-2A>G and c.8155+3G>C) and the activation of a cryptic splice site (c.7730-1G>C). No visible effect was evident for c.1533+15G>A and c.5170+10C>T and the consequence of c.[546G>A;7082-2A>G] was hidden by nonsense-mediated mRNA decay (NMD). Results were compared with in silico predictions of four splice-site analysis tools. We demonstrate selective degradation of VWF mRNA bearing PSSM by NMD for several mutations, which suggests that NMD represents a general mechanism for truncating mutations in VWF. Furthermore, because NMD efficiency varies between cell types, use of RNA from both platelets and leukocytes for in vivo study of VWF PSSM offers complementary results, particularly in cases in which NMD occurs in the allele carrying the mutation. © 2011 International Society on Thrombosis and Haemostasis.

  14. The spider hemolymph clot proteome reveals high concentrations of hemocyanin and von Willebrand factor-like proteins.

    Science.gov (United States)

    Sanggaard, Kristian W; Dyrlund, Thomas F; Bechsgaard, Jesper S; Scavenius, Carsten; Wang, Tobias; Bilde, Trine; Enghild, Jan J

    2016-02-01

    Arthropods include chelicerates, crustaceans, and insects that all have open circulation systems and thus require different properties of their coagulation system than vertebrates. Although the clotting reaction in the chelicerate horseshoe crab (Family: Limulidae) has been described in details, the overall protein composition of the resulting clot has not been analyzed for any of the chelicerates. The largest class among the chelicerates is the arachnids, which includes spiders, ticks, mites, and scorpions. Here, we use a mass spectrometry-based approach to characterize the spider hemolymph clot proteome from the Brazilian whiteknee tarantula, Acanthoscurria geniculata. We focused on the insoluble part of the clot and demonstrated high concentrations of proteins homologous to the hemostasis-related and multimerization-prone von Willebrand factor. These proteins, which include hemolectins and vitellogenin homologous, were previously identified as essential components of the hemolymph clot in crustaceans and insects. Their presence in the spider hemolymph clot suggests that the origin of these proteins' function in coagulation predates the split between chelicerates and mandibulata. The clot proteome reveals that the major proteinaceous component is the oxygen-transporting and phenoloxidase-displaying abundant hemolymph protein hemocyanin, suggesting that this protein also plays a role in clot biology. Furthermore, quantification of the peptidome after coagulation revealed the simultaneous activation of both the innate immune system and the coagulation system. In general, many of the identified clot-proteins are related to the innate immune system, and our results support the previously suggested crosstalk between immunity and coagulation in arthropods. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. The markers of platelet functions and Von Willebrand factor serum content from patients with type 2 diabetes mellitus and ishemic stroke

    Directory of Open Access Journals (Sweden)

    Tetiana Tsarenko

    2016-03-01

    Full Text Available Introduction: The est and #1110;mated number of people with diabetes worldwide in 2015 is 415 million persons, up to 91% of adults hadtype 2 diabetes and the crude incidence of stroke among patients with diabetes of the 2ndtype can be more than 3 times that in the general population. It is known platelet activation and aggregation are critical in the pathogenesis of acute ischemic cerebrovascular diseases. Thus to examine the evidence of platelet functioning such as platelet count,aggregation in response to ADP, coagulation von Willebrand factor and serotonin content, monoamine oxidase (MAO activity in the blood of patients with ischemic stroke and with ischemic stroke complicated with the 2ndtype diabetes are the aim of the present study. Methods: The platelet aggregation was assayed for photo-optical aggregometer, von Willebrand factor was determined by Elisa, serotonin determination included ion-exchange chromatography and fluorescence spectrophotometry. Determination of monoamine-oxidase serum activity was spectophotometry. Results: The investigation has shown an increase of serotonin and Von Willebrand factor blood content in both groups of patients with ischemic stroke andtype 2 diabetes and stroke alone compared with the values of the control group. The monoamine oxidase activity and platelet count were reduced in blood of patients with diabetes of the 2ndtype with ischemic stroke against to the values from the group of healthy donors. Platelet aggregation in response to ADP increased under the investigated pathologies. Conclusions: These obtained data suggested a significant imbalance in vascular platelet element of hemostasis under the ischemic stroke and amplification of negative changes under the stroke with the 2ndtype diabetes. [Biomed Res Ther 2016; 3(3.000: 542-547

  16. Elevated levels of plasma von Willebrand factor and the risk of macro- and microvascular disease in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    Gaede, P; Vedel, P; Parving, H H

    2001-01-01

    according to baseline plasma von Willebrand factor levels below or above the median. The main outcome was cardiovascular disease (cardiovascular mortality, non-fatal stroke, non-fatal myocardial infarction, coronary artery bypass graft and revascularization or amputation of legs), progression to diabetic...... nephropathy or progression in diabetic retinopathy. RESULTS: At baseline the two groups were comparable for HbA(1c), fasting levels of s-total-cholesterol, s-HDL-cholesterol and s-triglycerides, systolic and diastolic blood pressure, gender, known diabetes duration, smoking habits, previous cardiovascular...

  17. Insulin resistance is accompanied by increased von Willebrand factor levels in nondiabetic women: a study of offspring of type 2 diabetic subjects compared to offspring of nondiabetic subjects

    DEFF Research Database (Denmark)

    Foss, Anne-Catherine; Vestbo, Else; Frøland, Anders

    2002-01-01

    : We compared vWF, fibrinogen and fibronectin in 88 nondiabetic offspring of type 2 diabetic subjects (relatives) and 103 offspring of nondiabetic subjects (controls). Other measurements included urinary albumin excretion rate, blood pressure, lipid profile and insulin resistance using homeostasis......OBJECTIVES: To examine whether levels of von Willebrand factor (vWF), fibrinogen and fibronectin are related to a parental history of type 2 diabetes and to determine possible explanatory factors for high versus low vWF and fibrinogen. DESIGN: Cross-sectional study. SUBJECTS, MAIN OUTCOME MEASURES...

  18. An external quality assessment program for von Willebrand factor laboratory analysis: an overview from the European concerted action on thrombosis and disabilities foundation.

    Science.gov (United States)

    Meijer, Piet; Haverkate, Frits

    2006-07-01

    The laboratory diagnosis of von Willebrand disease (vWD) is complex and requires a panel of different laboratory tests. Because of this complexity, a proper quality control process is necessary. Since 2003, the European Concerted Action on Thrombosis and Disabilities Foundation has provided an external quality control program for several laboratory tests included in the diagnosis of vWD. Currently, ~180 different laboratories participate in this program, of which the vast majority perform both von Willebrand factor (vWF):antigen (Ag) and activity tests. The lowest between-laboratory variation was observed for the vWF antigen assay (10 to 24%), with a better performance for the latex immunoassay (8 to 24%) than the enzyme immunoassay (13 to 25%). Both the ristocetin cofactor activity assay (RCo) and the collagen-binding assay showed a higher between-laboratory variation (20 to 40% and 17 to 29%, respectively). We have observed that the within-laboratory repeatability for normal samples ranged from 0 to 40% for the antigen assay and from 0 to 86% for the ristocetin cofactor activity assay. Normal samples were interpreted correctly by the majority of the participants. However, type 1 vWD samples were wrongly interpreted by 20 to 40% of the participants, which was mainly caused by a discordance in the vWF:RCo/vWF:Ag ratio. It can be concluded that further improvement in the laboratory diagnosis of vWD is necessary.

  19. Haemostasis prophylaxis using single dose desmopressin acetate and extended use epsilon aminocaproic acid for adenotonsillectomy in patients with type 1 von Willebrand disease.

    Science.gov (United States)

    Santoro, C; Hsu, F; Dimichele, D M

    2012-03-01

    In patients with confirmed or suspected type 1 von Willebrand disease (VWD), adenotonsillectomy has been reported to be associated with a rate of peri-operative hemorrhage between 8 and 23%. Desmopressin acetate (DDAVP, 1-deamino 8-D arginine- vasopressin) is the treatment of choice for type 1 patients with baseline von Willebrand factor levels of 10 IU/dL or greater. DDAVP is generally well tolerated; however, severe hyponatremia and seizures have been reported in young children less than 2 years of age, limiting its use in this age group. Antifibrinolytic therapy plays an important adjunctive role in the effective treatment of mucocutaneous bleeding, particularly in the oropharynx where the salivary concentration of fibrinolytic enzymes is high. During the past 10 years, we treated 6 pediatric patients with mild/moderate type 1 VWD undergoing an adenotonsillar procedure at our institution with the same hemostatic regimen consisting of one single dose of DDAVP and an extended use of EACA. In this small case series, the above mentioned prophylactic treatment regimen was both well tolerated and efficacious in controlling hemorrhage. Furthermore, DDAVP-related complications were avoided in a pediatric population with a higher risk of developing them. © 2011 Blackwell Publishing Ltd.

  20. Cuidados nos pacientes com hemofilia e doença de von Willebrand na cirurgia eletiva otorrinolaringológica Otolaryngology surgery: management of elective surgery in patients with haemophilia and von Willebrand disease

    Directory of Open Access Journals (Sweden)

    Marise P. C. Marques

    2003-01-01

    Full Text Available FORMA DE ESTUDO Clínico prospectivo. MATERIAL E MÉTODO: Foi realizado um estudo prospectivo de 10 anos de 20 pacientes com hemofilias ou doença de von Willebrand (DvW com indicação de cirurgia otorrinolaringológica. Os pacientes foram submetidos a um total de 25 cirurgias otorrinolaringológicas eletivas. A idade média foi de 23,75 anos (2 a 62 anos. O grupo de estudo consistiu em 14 hemofílicos, 11 com hemofilia A grave (1 do sexo feminino, uma portadora com 30% de atividade de fator VIII (FVIII, um hemofílico B leve e uma com deficiência grave de fator X; 6 com DvW, 4 tinham o tipo 1 (3 mulheres, um o tipo 2A e um o tipo 3. Treze hemofílicos tinham síndrome de imunodeficiência adquirida. A duração média do procedimento foi de 1 hora e 37 minutos (15 minutos a 12 horas. O defeito da coagulação foi corrigido com desmopressina (DDAVP, com concentrado de FVIII de pureza intermediária 8Y, com criopreciptado ou com complexo protrombínico não ativado (PPSB, de acordo com os níveis plasmáticos do fator e da severidade da cirurgia. O ácido épsilon aminocapróico também foi usado em associação. Em 1 hemofílico A grave houve sangramento pós-operatório que se resolveu com a elevação do nível mínimo de FVIII para 80% e em 1 paciente com DvW do Tipo 3 houve sangramento pós-operatório pela dificuldade de identificação do melhor concentrado a ser reposto. Após o uso do concentrado de pureza intermediária 8Y, houve controle do sangramento. RESULTADO: Todos os outros pacientes apresentaram a hemostasia considerada normal ou excelente. CONCLUSÃO: Concluiu-se que pacientes com hemofilias ou DvW não apresentam um risco cirúrgico aumentado se for realizada uma terapia adequada.STUD DESIGN: Clinical prospective. MATERIAL AND METHOD: A 10-year prospective research was conducted in 20 patients with hemophilia or von Willebrand disease (vWD. They were submitted to a total of 25 elective otolaryngological surgical events. The

  1. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity.

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    Gorica G Ristić

    Full Text Available To evaluate association between von Willebrand factor (vWF activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA and low cardiovascular risk.Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years. Intima-media thickness (IMT was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%, none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately.RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05. Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP, modified Health Assessment Questionnaire (p<0.01 for all, duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all, and anti-CCP antibodies (p<0.01. In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05 or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05 than in those without. Duration of smoking was significantly associated with vWF activity (β 0.026, p = 0.039.We demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of

  2. Function of von Willebrand factor in children with diarrhea-associated hemolytic-uremic syndrome (D+ HUS).

    Science.gov (United States)

    Sutor, A H; Thomas, K B; Prüfer, F H; Grohmann, A; Brandis, M; Zimmerhackl, L B

    2001-06-01

    Reports on von Willebrand factor (vWF) in hemolytic-uremic syndrome (HUS) are not unequivocal. Because of potential pathogenic implications, we examined the ability of vWF to bind to collagen in vitro, which reflects its function. Plasma vWF antigen (vWF:Ag) and collagen-binding activity (vWF:CBA) were measured by enzyme-linked immunosorbent assay in children with (1) diarrhea-associated (D+) HUS (n = 27), (2) chronic renal insufficiency (CRI) (n = 8), (3) gastroenteritis (GE) not associated with HUS (n = 15), (4) immune thrombocytopenia (ITP) (n = 40) and from controls (n = 35). Structural vWF was evaluated by multimer analysis. Children with D+ HUS had vWF:Ag of 2.53 and vWF:CBA of 1.98 U/mL. The corresponding values for patients with ITP were 1.35 and 1.82 U/mL, with CRI 1.55 and 1.55 U/mL, and with GE 1.68 and 2.10 U/mL; all values were higher than in controls (1.04 and 1.16 U/mL). The mean ratio of vWF:CBA to vWF:Ag ratio in controls was 1.13; only children with HUS had a dysfunctional vWF, as indicated by a low ratio of 0.78; the ratio was elevated in children with ITP (1.36) and GE (1.27) and was normal in those with CRI (1.06). No ultralarge molecular multimers of vWF were detected in any group, including HUS. The very high concentration of plasma vWF:Ag in HUS probably reflects endothelial cell damage or irritation. In contrast to all other groups, only children with HUS had a dysfunctional vWF, caused either by a primary (due to enterohemorrhagic Escherichia coli) or secondary (due to consumption of functionally active vWF) process. This abnormality was not obvious as structural anomaly by multimer analysis.

  3. von Willebrand Disease

    Science.gov (United States)

    ... or increase the risk of bleeding. Examples include aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), clopidogrel, warfarin, or heparin. Any history of liver or kidney disease, blood or bone ...

  4. von Willebrand Factor Test

    Science.gov (United States)

    ... Hormone Binding Globulin (SHBG) Shiga toxin-producing Escherichia coli Sickle Cell Tests Sirolimus Smooth Muscle Antibody (SMA) ... Ratio Valproic Acid Vancomycin Vanillylmandelic Acid (VMA) VAP Vitamin A Vitamin B12 and Folate Vitamin D Tests ...

  5. GENÉTICA MOLECULAR DE LA HEMOFILIA A EN UNA FAMILIA COLOMBIANA CON DIAGNÓSTICO DE ENFERMEDAD DE VON WILLEBRAND Y DE HEMOFILIA A

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    Diana Carolina Polanía Villanueva

    2014-12-01

    Full Text Available El Factor von Willebrand circula en el plasma formando un complejo con el Factor VIII de coagulación por enlaces no covalentes. Esta interacción evita la degradación enzimática del Factor VIII y asegura su transporte al lugar de formación del coágulo de fibrina. Debido a su estrecha relación, la disminución de la actividad de un factor puede afectar la actividad del otro, lo que genera un diagnóstico clínico equivocado en cuanto a qué enfermedad se padece, si Hemofilia A o Enfermedad de von Willebrand. Este estudio reporta el caso de una familia colombiana que según diagnóstico clínico de su fenotipo, padecía las dos enfermedades. Sin embargo, dicha familia carecía de un estudio genético que permitiera verificar y contrastar el diagnóstico que hacen las entidades de salud. Por tal razón, se realizó un diagnóstico genético por pruebas moleculares que detectan mutaciones, como las inversiones en los intrones 1 y 22 por PCR de fragmentos largos y la secuenciación del gen del Factor VIII, esta última no aplicada y publicada en Colombia hasta el momento. Se encontraron dos mutaciones sinónimas en los exones 14 y 26 que no alteran la secuencia de aminoácidos en la proteína; por tanto, se descarta la presencia de Hemofilia A en la familia. Se plantea la posibilidad de un caso de Enfermedad de von Willebrand únicamente. El estudio demuestra la necesidad que hay en el país de ampliar las pruebas clínicas y de incluir el diagnóstico genético en casos de ambigüedad en el diagnóstico de estas coagulopatías.

  6. Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

    Science.gov (United States)

    Anthony, P P; Ramani, P

    1991-01-01

    A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver. Images PMID:1705261

  7. Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia.

    Science.gov (United States)

    Ragni, Margaret V; Jankowitz, Rachel C; Jaworski, Kristen; Merricks, Elizabeth P; Kloos, Mark T; Nichols, Timothy C

    2011-10-01

    Lack of effective treatment for menorrhagia is the greatest unmet healthcare need in women with von Willebrand disease (VWD). We conducted a single-centre phase II clinical trial to determine efficacy and safety of recombinant IL-11 (rhIL-11, Neumega®) given subcutaneously for up to seven days during six consecutive menstrual cycles each in seven women with mild VWD and menorrhagia refractory to haemostatic or hormonal agents. rhIL-11 reduced menstrual bleeding severity as measured by pictorial blood assessment chart (PBAC) ≥ 50% (to 0.05. Platelet VWF mRNA expression by quantitative PCR increased mean four-fold (1.0-13.5). rhIL-11 was well tolerated with grade 1 or less fluid retention, flushing, conjunctival erythema, and local bruising. In summary, rhIL-11 reduces menorrhagia safely and warrants further study.

  8. Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia*

    Science.gov (United States)

    Ragni, Margaret V.; Jankowitz, Rachel C.; Jaworski, Kristen; Merricks, Elizabeth P.; Kloos, Mark T.; Nichols, Timothy C.

    2014-01-01

    Summary Lack of effective treatment for menorrhagia is the greatest unmet healthcare need in women with von Willebrand disease (VWD). We conducted a single-centre phase II clinical trial to determine efficacy and safety of recombinant IL-11 (rhIL-11, Neumega®) given subcutaneously for up to seven days during six consecutive menstrual cycles each in seven women with mild VWD and menorrhagia refractory to haemostatic or hormonal agents. rhIL-11 reduced menstrual bleeding severity as measured by pictorial blood assessment chart (PBAC) ≥50% (to 0.05. Platelet VWF mRNA expression by quantitative PCR increased mean four-fold (1.0–13.5). rhIL-11 was well tolerated with grade 1 or less fluid retention, flushing, conjunctival erythema, and local bruising. In summary, rhIL-11 reduces menorrhagia safely and warrants further study. PMID:21833452

  9. von Willebrand disease type 1 in Doberman Pinscher dogs: genotyping and prevalence of the mutation in the Buenos Aires region, Argentina.

    Science.gov (United States)

    Crespi, Julian A; Barrientos, Laura S; Giovambattista, Guillermo

    2018-03-01

    von Willebrand disease (vWD) is the most common inherited coagulopathy in dogs, particularly in Doberman Pinschers. We developed a pyrosequencing-based assay to estimate the frequency of the c.7437G>A mutation associated with vWD type 1 in the Doberman Pinscher population of Buenos Aires, Argentina. We found a 0.41 frequency for the mutated allele, which varied significantly within families (family 1 = 0.43, family 2 = 0.58, unrelated animals = 0.35). The use of a popular founder male carrier of mutant allele A increased vWD incidence within a family and in the general population. The mode of inheritance was confirmed as autosomal dominant with incomplete penetrance. No differences were found between sexes and coat colors. Pyrosequencing was a good complement to clinical and coagulation tests for vWD type 1 diagnosis and a useful alternative for detecting the c.7437G>A mutation.

  10. Safety of a pasteurized plasma-derived Factor VIII and von Willebrand factor concentrate: analysis of 33 years of pharmacovigilance data.

    Science.gov (United States)

    Kouides, Peter; Wawra-Hehenberger, Kathrin; Sajan, Anna; Mead, Henry; Simon, Toby

    2017-10-01

    Haemate-P/Humate-P (Humate-P) is a pasteurized human plasma-derived concentrate containing both Factor VIII and von Willebrand factor for treatment of hemophilia A and von Willebrand disease (VWD). We analyzed the safety of Humate-P based on more than 33 years of postmarketing pharmacovigilance data, representing an estimated exposure of approximately 25,000 patient-years. The analysis comprises reports of potential adverse drug reactions (ADRs) from all sources, reported as part of routine pharmacovigilance at CSL Behring. ADRs considered clinically relevant or potential risks of Humate-P were identified based on defined and standardized Medical Dictionary for Regulatory Activities queries. Recognizing the limitations of spontaneous reporting, we also reviewed the literature, including clinical trials with mandatory reporting. From 1982 to 2015, a total of 670 postmarketing cases had been reported via pharmacovigilance, for an overall reporting rate of approximately one ADR per 3900 administered standard doses. Of these cases, 343 involved ADRs considered clinically relevant risks (33 thromboembolic complications, 97 inhibitor formation, 110 hypersensitivity or allergic reactions) or potential risks (103 suspected virus transmissions) for Humate-P. Most thromboembolic complications occurred in patients undergoing surgery or with other known risk factors. Inhibitor formation occurred mostly in patients with hemophilia A (24 cases were high titer). Most patients with hypersensitivity or allergic reactions had VWD. None of the reported suspected virus transmission cases were confirmed to be associated with Humate-P. Reported results of company-sponsored studies showed a low incidence of adverse events possibly or probably related to Humate-P. More than 33 years of pharmacovigilance data continue to support the safety of Humate-P. © 2017 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  11. Crystallization and preliminary X-ray analysis of the complex of the first von Willebrand type C domain bound to bone morphogenetic protein 2

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    Qiu, Li-yan; Zhang, Jin-li [Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany); Kotzsch, Alexander [Lehrstuhl für Molekulare Pflanzenphysiologie und Biophysik, Julius-von-Sachs Institut der Universität Würzburg, Julius-von-Sachs Platz 2, D-97082 Würzburg (Germany); Sebald, Walter [Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany); Rudolf-Virchow-Zentrum (DFG Forschungszentrum) der Universität Würzburg, Versbacher Strasse 9, D-97070 Würzburg (Germany); Mueller, Thomas D., E-mail: mueller@botanik.uni-wuerzburg.de [Lehrstuhl für Molekulare Pflanzenphysiologie und Biophysik, Julius-von-Sachs Institut der Universität Würzburg, Julius-von-Sachs Platz 2, D-97082 Würzburg (Germany); Rudolf-Virchow-Zentrum (DFG Forschungszentrum) der Universität Würzburg, Versbacher Strasse 9, D-97070 Würzburg (Germany); Lehrstuhl für Physiologische Chemie II, Theodor-Boveri-Institut (Biozentrum) der Universität Würzburg, Am Hubland, D-97074 Würzburg (Germany)

    2008-04-01

    Crystals of the complex of the first von Willebrand type C domain (VWC1) of crossveinless 2 (CV2) bound to bone morphogenetic protein 2 (BMP2) exist in two tetragonal crystal forms belonging to either space group P4{sub 1}2{sub 1}2 or I4{sub 1}, with one complete BMP2 dimer and two CV2 VWC1 domains per asymmetric unit, and diffract to 2.6 Å resolution. Crossveinless 2 (CV2) is a member of the chordin family, a protein superfamily that modulates the activity of bone morphogenetic proteins such as BMP2. The BMPs represent a large group of secreted proteins that control many steps during embryonal development and in tissue and organ homeostasis in the adult organism. The gene encoding the first von Willebrand type C domain (VWC1) of CV2 was cloned, expressed in Escherichia coli and purified to homogeneity. The binary complex of CV2 VWC1 and BMP2 was purified and subjected to crystallization. Crystals of SeMet-labelled proteins were obtained in two different forms belonging to the tetragonal space groups P4{sub 1}2{sub 1}2 and I4{sub 1}, with unit-cell parameters a = b = 86.7, c = 139.2 Å and a = b = 83.7, c = 139.6 Å, respectively. Initial analysis suggests that a complete binary complex consisting of one BMP2 dimer bound to two CV2 VWC1 domains is present in the asymmetric unit.

  12. Antifibrinolytic therapy for preventing oral bleeding in patients with haemophilia or Von Willebrand disease undergoing minor oral surgery or dental extractions.

    Science.gov (United States)

    van Galen, Karin P M; Engelen, Eveline T; Mauser-Bunschoten, Evelien P; van Es, Robert J J; Schutgens, Roger E G

    2015-12-24

    Minor oral surgery or dental extractions (oral or dental procedures) are widely performed and can be complicated by hazardous oral bleeding, especially in people with an inherited bleeding disorder such as haemophilia or Von Willebrand disease. The amount and severity of singular bleedings depend on disease-related factors, such as the severity of the haemophilia, both local and systemic patient factors (such as periodontal inflammation, vasculopathy or platelet dysfunction) and intervention-related factors (such as the type and number of teeth extracted or the dimension of the wound surface). Similar to local haemostatic measures and suturing, antifibrinolytic therapy is a cheap, safe and potentially effective treatment to prevent bleeding complications in individuals with bleeding disorders undergoing oral or dental procedures. However, a systematic review of trials reporting outcomes after oral surgery or a dental procedure in people with an inherited bleeding disorder, with or without, the use of antifibrinolytic agents has not been performed to date. The primary objective was to assess the efficacy of local or systemic use of antifibrinolytic agents to prevent bleeding complications in people with haemophilia or Von Willebrand disease undergoing oral or dental procedures. Secondary objectives were to assess if antifibrinolytic agents can replace or reduce the need for clotting factor concentrate therapy in people with haemophilia or Von Willebrand disease and to further establish the effects of these agents on bleeding in oral or dental procedures for each of these populations. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, compiled from electronic database searches of the Cochrane Central Register of Controlled Trials (CENTRAL), of MEDLINE and from handsearching of journals and conference abstract books. We additionally searched the reference lists of relevant articles and reviews. We searched Pub

  13. Gender and age peculiarities of content changes of protein C, von Willebrand factor, vascular cell adhesion molecules sVCAM-1 in patients with acute left ventricle Q-wave myocardial infarction

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    S. M. Kyselov

    2015-04-01

    Full Text Available Markers of hemostasis have an influence on the state of postinfarction remodeling processes. Aim. In order to study the gender and age peculiarities, to determine the predictive value of the protein C, von Willebrand factor and vascular cell adhesion molecules sVCAM-1 concentration, we examined 76 patients with acute Q-wave myocardial infarction. Methods and results. On the 1st day of the disease, higher concentrations of protein C were detected in young women, vascular cell adhesion molecules sVCAM-1 - in men of any age. On the 10th day of the disease, both in men and women increase in the content of protein C, reducing the concentration of von Willebrand factor and vascular cell adhesion molecules sVCAM-1 were detected. Conclusion. Protein C has the highest prognostic potential in relation to the formation of heart aneurysm after Q-wave myocardial infarction in women of young age, and von Willebrand factor and vascular cell adhesion molecules sVCAM-1 - in older men.

  14. Raquianestesia para cirurgia ortopédica de urgência em paciente portadora de doença de Von Recklinghausen: relato de caso Raquianestesia para cirugía ortopédica de urgencia en una paciente portadora de enfermedad de Von Recklinghausen: relato de caso Spinal block for urgency orthopedic surgery in Von Recklinghausen's disease patient: case report

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    Fabiano Timbó Barbosa

    2005-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A doença de Von Recklinghausen é uma doença neurogenética causada por uma anomalia no cromossomo 17. O objetivo deste relato foi descrever a conduta anestésica em paciente com doença de Von Recklinghausen submetida à cirurgia ortopédica de urgência. RELATO DO CASO: Paciente do sexo feminino, 28 anos, portadora da doença de Von Recklinghausen, submetida à cirurgia ortopédica em hospital de emergência sob raquianestesia. Não apresentou complicações no período intra-operatório, nem na sala de recuperação pós-anestésica. Teve alta hospitalar no 4º dia de pós-operatório. CONCLUSÕES: No caso relatado foi possível a realização da raquianestesia sem haver necessidade de manuseio da via aérea.JUSTIFICATIVA Y OBJETIVOS: La enfermedad de Von Recklinghausen es una enfermedad neurogenética causada por una anomalía en el cromosoma 17. Este relato tiene por objetivo describir la conducta anestésica en una paciente con enfermedad de Von Recklinghausen sometida a cirugía ortopédica de urgencia. RELATO DEL CASO: Paciente del sexo femenino, 28 años, portadora de la enfermedad de Von Recklinghausen, sometida a cirugía ortopédica en un hospital de emergencia con raquianestesia. No presentó complicaciones en el período intra-operatorio, tampoco en la sala de recuperación pos-anestésica. Tuvo alta hospitalar en el 4º día de pos-operatorio. CONCLUSIONES: En el caso relatado fue posible la realización de la raquianestesia sin haber necesidad de manejar de la vía aérea.BACKGROUND AND OBJECTIVES: Von Recklinghausen's disease is a neurogenetic disease due to chromosome 17 abnormality. This report aimed at describing the anesthetic approach for Von Recklinghausen's disease patient submitted to urgency orthopedic surgery. CASE REPORT: Female patient, 28 years old, with Von Recklinghausen's disease, submitted to emergency orthopedic surgery under spinal block. There have been no complications both in

  15. Von Willebrand factor antigen predicts response to double dose of aspirin and clopidogrel by PFA-100 in patients undergoing primary angioplasty for ST elevation myocardial infarction.

    Science.gov (United States)

    Gianetti, Jacopo; Parri, Maria Serena; Della Pina, Francesca; Marchi, Federica; Koni, Endrin; De Caterina, Alberto; Maffei, Stefano; Berti, Sergio

    2013-01-01

    Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

  16. Plasma fibrinolysis is related to the degree of organ dysfunction but not to the concentration of von Willebrand Factor in critically ill patients

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    Vincent Jean-Louis

    2009-06-01

    Full Text Available Abstract Background Endothelial cell dysfunction, by promoting fibrin deposition, has been implicated in the development of multiple organ failure. Altered fibrinolysis during inflammation may participate in microvascular alterations. We sought to determine whether plasma fibrinolysis was related to the severity of organ dysfunction and/or to the levels of von Willebrand factor (vWF antigen, as a marker of endothelium dysfunction, in critically ill patients. Methods Forty-nine consecutive patients admitted to an adult medico-surgical intensive care unit (ICU with (18 or without sepsis (31 were included. C-reactive protein and vWF levels were measured on ICU admission and plasma fibrinolysis was assessed by the Euglobulin Clot Lysis Time (ECLT. The sequential organ failure assessment (SOFA score and the simplified acute physiology score (SAPS II were calculated on admission. Results ECLT was significantly longer in septic than in non-septic patients [1033 min (871–1372 versus 665 min (551–862, p = 0.001]. There were significant correlations between ECLT and C-reactive protein (CRP concentrations (r = 0.78, p Conclusion ECLT measurement at admission could be a marker of organ dysfunction and a prognostic indicator in critically ill patients.

  17. Trends in clinical management of women with von Willebrand disease: a survey of 75 women enrolled in haemophilia treatment centres in the United States.

    Science.gov (United States)

    Kirtava, A; Crudder, S; Dilley, A; Lally, C; Evatt, B

    2004-03-01

    To assess the management of women with von Willebrand disease( vWD) in an Heamophilia Treatment Center (HTC) setting. A total of 75 women with vWd who were registered in HTCs in the United States participated in this study. A telephone interview elicited information about symptoms pertaining to bleeding disorders, diagnostic issues, referral patterns, treatment modalities before and after the enrollment in the HTC, HTC services provided, and satisfaction with care in the HTC. Menorrhagia was the most commonly reported symptom (84%). The average time from the first symptom until clinician recognition was 16 years (range 0-39). In HTC, DDAVP was the most commonly used drug (31%). Of the 75 women, 71 reported a strong positive opinion and satisfaction about their care in the HTCs. Women with VWD were typically diagnosed with the condition well into adulthood, in spite of the fact that majority of them experienced several bleeding symptoms beginning in early childhood. In general an HTC setting is appropriate for management of women with bleeding disorders. Diagnosis, treatment and education provided in the HTCs were viewed positively by those surveyed.

  18. Adhesive Forces between A1 Domain of von Willebrand Factor and N-terminus Domain of Glycoprotein Ibα Measured by Atomic Force Microscopy.

    Science.gov (United States)

    Tobimatsu, Hiroaki; Nishibuchi, Yuichiro; Sudo, Ryo; Goto, Shinya; Tanishita, Kazuo

    2015-01-01

    von Willebrand factor (VWF) plays an important role in the regulation of hemostasis and thrombosis formation, particularly under a high shear rate. However, the adhesive force due to the molecular interaction between VWF and glycoprotein Ibα (GPIbα) has not been fully explored. Thus, we employed atomic force microscopy to directly measure the adhesive force between VWF and GPIbα. We measured the adhesive force between VWF and GPIbα at the molecular level using an atomic force microscope (AFM). An AFM cantilever was coated with recombinant N-terminus VWF binding site of GPIbα, whereas a cover glass was coated with native VWF. The adhesive force at the molecular level was measured using an AFM. In the presence of 1 μg/mL VWF, the adhesion force was nearly 200 pN. As per the Gaussian fit analysis, the adhesive force of a single bond could have been 54 or 107 pN. Our consideration with the Gaussian fit analysis proposed that the adhesive force of a single bond could be 54 pN, which is very close to that obtained by optical tweezers (50 pN).

  19. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

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    Kubisz Peter

    2012-10-01

    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  20. The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow.

    Science.gov (United States)

    Zhang, Ping; Pan, Weilan; Rux, Ann H; Sachais, Bruce S; Zheng, X Long

    2007-09-15

    ADAMTS13 cleaves von Willebrand factor (VWF) between Tyr(1605) and Met(1606) residues at the central A2 subunit. The amino-terminus of ADAMTS13 protease appears to be sufficient to bind and cleave VWF under static and denatured condition. However, the role of the carboxyl-terminus of ADAMTS13 in substrate recognition remains controversial. Present study demonstrates that ADAMTS13 cleaves VWF in a rotation speed- and protease concentration-dependent manner on a mini vortexer. Removal of the CUB domains (delCUB) or truncation after the spacer domain (MDTCS) significantly impairs its ability to cleave VWF under the same condition. ADAMTS13 and delCUB (but not MDTCS) bind VWF under flow with dissociation constants (K(D)) of about 50 nM and about 274 nM, respectively. The isolated CUB domains are neither sufficient to bind VWF detectably nor capable of inhibiting proteolytic cleavage of VWF by ADAMTS13 under flow. Addition of the TSP1 5-8 (T5-8CUB) or TSP1 2-8 repeats (T2-8CUB) to the CUB domains restores the binding affinity toward VWF and the inhibitory effect on cleavage of VWF by ADAMTS13 under flow. These data demonstrate directly and quantitatively that the cooperative activity between the middle carboxyl-terminal TSP1 repeats and the distal carboxyl-terminal CUB domains may be crucial for recognition and cleavage of VWF under flow.

  1. A Novel Single-Domain Antibody Against von Willebrand Factor A1 Domain Resolves Leukocyte Recruitment and Vascular Leakage During Inflammation-Brief Report.

    Science.gov (United States)

    Aymé, Gabriel; Adam, Frédéric; Legendre, Paulette; Bazaa, Amine; Proulle, Valérie; Denis, Cécile V; Christophe, Olivier D; Lenting, Peter J

    2017-09-01

    von Willebrand factor (VWF) is crucial to hemostasis, but also plays a role in inflammatory processes. Unfortunately, no proper monoclonal antibodies to study VWF function in mice are currently available. We therefore aimed to generate single-domain antibodies (sdAbs) recognizing murine VWF and blocking its function in vivo. Llama-derived sdAbs recognizing both human and murine VWF were isolated via phage display technology. One of them (designated KB-VWF-006) recognized the VWF A1 domain with picomolar affinity. This sdAb avidity was strongly enhanced via dimerization using a triple Ala linker (KB-VWF-006bi). When administered in vivo to wild-type mice, KB-VWF-006bi dose dependently induced bleeding in a tail clip model. In 2 distinct models of inflammation, KB-VWF-006bi efficiently interfered with leukocyte recruitment and vascular leakage. KB-VWF-006bi is an sdAb recognizing the A1 domain of human VWF and murine VWF that interferes with VWF-platelet interactions in vivo. By using this sdAb, we now also show that the A1 domain is pertinent to the participation of VWF in the inflammatory response. © 2017 American Heart Association, Inc.

  2. Immunohistochemial study on the expression of von Willebrand factor (vWF) after onlay autogenous iliac grafts for lateral alveolar ridge augmentation

    Science.gov (United States)

    2013-01-01

    Introduction The main problems of autogenous bone transplants are their unpredictable atrophy and their loss of structure. One key factor lies in the poor revascularization of simple onlay grafts. The the aim of this study was to evaluate the revascularization processes in autogenous bone grafts from the iliac crest to the alveolar ridge. Methods In a sheep model, autogenous bone grafts were harvested from the iliac crest. A combination of a resorbable collagen membrane (CM) and deproteinized bovine bone material (DBBM) was used to modify the bone graft (experiment 2). This was compared with a simple onlay bone graft (control group, experiment 1). The amount of vessels in bone and connective tissue (CT), and the amount of CT were analyzed. The expression of von Willebrand factor (vWF) was compared between the two experimental groups using immunohistochemical analysis. Results The ratio of the amount of vessels in bone and CT changed over time, and more vessels could be detected in bone at 12–16 weeks of graft healing. The number of vessels were significantly higher in experiment 2 than in experiment 1. More CT was found in experiment 1, whereas the amount of CT in both experiments decreased over time. Conclusion This study shows a more intensive and extensive revascularization in experiment 2, as significantly more vessels were detected. The decreased amount of CT in experiment 2 clarifies its clinical superiority. PMID:24330606

  3. Characterization of an entomopathogenic fungi target integument protein, Bombyx mori single domain von Willebrand factor type C, in the silkworm, Bombyx mori.

    Science.gov (United States)

    Han, F; Lu, A; Yuan, Y; Huang, W; Beerntsen, B T; Huang, J; Ling, E

    2017-06-01

    The insect cuticle works as the first line of defence to protect insects from pathogenic infections and water evaporation. However, the old cuticle must be shed in order to enter the next developmental stage. During each ecdysis, moulting fluids are produced and secreted into the area among the old and new cuticles. In a previous study, the protein Bombyx mori single domain von Willebrand factor type C (BmSVWC; BGIBMGA011399) was identified in the moulting fluids of Bo. mori and demonstrated to regulate ecdysis. In this study we show that in Bo. mori larvae, BmSVWC primarily locates to the integument (epidermal cells and cuticle), wing discs and head. During the moulting stage, BmSVWC is released into the moulting fluids, and is then produced again by epidermal cells after ecdysis. Fungal infection was shown to decrease the amount of BmSVWC in the cuticle, which indicates that BmSVWC is a target protein of entomopathogenic fungi. Thus, BmSVWC is mainly involved in maintaining the integrity of the integument structure, which serves to protect insects from physical damage and pathogenic infection. © 2017 The Royal Entomological Society.

  4. Assembly and activation of alternative complement components on endothelial cell-anchored ultra-large von Willebrand factor links complement and hemostasis-thrombosis.

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    Nancy A Turner

    Full Text Available Vascular endothelial cells (ECs express and release protein components of the complement pathways, as well as secreting and anchoring ultra-large von Willebrand factor (ULVWF multimers in long string-like structures that initiate platelet adhesion during hemostasis and thrombosis. The alternative complement pathway (AP is an important non-antibody-requiring host defense system. Thrombotic microangiopathies can be associated with defective regulation of the AP (atypical hemolytic-uremic syndrome or with inadequate cleavage by ADAMTS-13 of ULVWF multimeric strings secreted by/anchored to ECs (thrombotic thrombocytopenic purpura. Our goal was to determine if EC-anchored ULVWF strings caused the assembly and activation of AP components, thereby linking two essential defense mechanisms.We quantified gene expression of these complement components in cultured human umbilical vein endothelial cells (HUVECs by real-time PCR: C3 and C5; complement factor (CF B, CFD, CFP, CFH and CFI of the AP; and C4 of the classical and lectin (but not alternative complement pathways. We used fluorescent microscopy, monospecific antibodies against complement components, fluorescent secondary antibodies, and the analysis of >150 images to quantify the attachment of HUVEC-released complement proteins to ULVWF strings secreted by, and anchored to, the HUVECs (under conditions of ADAMTS-13 inhibition. We found that HUVEC-released C4 did not attach to ULVWF strings, ruling out activation of the classical and lectin pathways by the strings. In contrast, C3, FB, FD, FP and C5, FH and FI attached to ULVWF strings in quantitative patterns consistent with assembly of the AP components into active complexes. This was verified when non-functional FB blocked the formation of AP C3 convertase complexes (C3bBb on ULVWF strings.AP components are assembled and activated on EC-secreted/anchored ULVWF multimeric strings. Our findings provide one possible molecular mechanism for clinical

  5. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    Science.gov (United States)

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-04

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism.

  6. Platelets, inflammatory cells, von Willebrand factor, syndecan-1, fibrin, fibronectin, and bacteria co-localize in the liver thrombi of Bacillus anthracis-infected mice.

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    Popova, Taissia G; Millis, Bryan; Bailey, Charles; Popov, Serguei G

    2012-01-01

    Vascular dysfunction and thrombosis have been described in association with anthrax infection in humans and animals but the mechanisms of these dysfunctions, as well as the components involved in thrombi formation are poorly understood. Immunofluorescent microscopy was used to define the composition of thrombi in the liver of mice challenged with the Bacillus anthracis Sterne spores. Lethal infection with the toxigenic Sterne strain, in contrast to the non-lethal, non-toxigenic delta-Sterne strain, demonstrated time-dependent increase in the number of vegetative bacteria inside the liver sinusoids and central vein. Massive appearance of thrombi typically occluding the lumen of the vessels coincided with the sudden death of infected animals. Bacterial chains in the thrombi were stained positive for syndecan-1 (SDC-1), fibronectin, and were surrounded by fibrin polymers, GPIIb-positive platelets, von Willebrand Factor (vWF), CD45-positive leukocytes, and massive amount of shed SDC-1. Experiments with human umbilical vein endothelial cells (HUVECs) demonstrated the active role of the host response to the secreted pathogenic factors of bacteria during the onset of the pro-thrombotic condition. The bacterial culture supernatants, as well as the isolated proteins (the pore-forming toxin anthrolysin O and phospholipase C) induced release of vWF, while anthrolysin O, sphingomyelinase and edema toxin induced release of thrombin from HUVECs and polymerization of fibrin in the presence of human plasma. Our findings suggest that activation of endothelium in response to infection can contribute to the formation of occlusive thrombi consisting of aggregated bacteria, vWF, shed SDC-1, fibrin, activated platelets, fibronectin and leukocytes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. The important role of von Willebrand factor in platelet-derived FVIII gene therapy for murine hemophilia A in the presence of inhibitory antibodies.

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    Shi, Q; Schroeder, J A; Kuether, E L; Montgomery, R R

    2015-07-01

    Our previous studies have demonstrated that targeting FVIII expression to platelets results in FVIII storage together with von Willebrand factor (VWF) in platelet α-granules and that platelet-derived FVIII (2bF8) corrects the murine hemophilia A phenotype even in the presence of high-titer anti-FVIII inhibitory antibodies (inhibitors). To explore how VWF has an impact on platelet gene therapy for hemophilia A with inhibitors. 2bF8 transgenic mice in the FVIII(-/-) background (2bF8(tg+/-) F8(-/-) ) with varying VWF phenotypes were used in this study. Animals were analyzed by VWF ELISA, FVIII activity assay, Bethesda assay and tail clip survival test. Only 18% of 2bF8(tg+/-) F8(-/-) VWF(-/-) animals, in which VWF was deficient, survived the tail clip challenge with inhibitor titers of 3-8000 BU mL(-1) . In contrast, 82% of 2bF8(tg+/-) F8(-/-) VWF(+/+) mice, which had normal VWF levels, survived tail clipping with inhibitor titers of 10-50,000 BU mL(-1) . All 2bF8(tg+/-) F8(-/-) VWF(-/-) mice without inhibitors survived tail clipping and no VWF(-/-) F8(-/-) mice survived this challenge. Because VWF is synthesized by endothelial cells and megakaryocytes and is distributed in both plasma and platelets in peripheral blood, we further investigated the effect of each compartment of VWF on platelet-FVIII gene therapy for hemophilia A with inhibitors. In the presence of inhibitors, 42% of animals survived tail clipping in the group with plasma-VWF and 50% survived in the platelet-VWF group. VWF is essential for platelet gene therapy for hemophilia A with inhibitors. Both platelet-VWF and plasma-VWF are required for optimal platelet-derived FVIII gene therapy for hemophilia A in the presence of inhibitors. © 2015 International Society on Thrombosis and Haemostasis.

  8. Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Jacopo Gianetti

    2013-01-01

    Full Text Available Von Willebrand factor (VWF is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100 with Collagen/Epinephrine (CEPI is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR. The objective of this study was to verify the effect of double dose (DD of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n=58 or DD of aspirin and clopidogrel (DD, n=58, maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2. At Times 1 and 2 we observed a significantly higher CEPI closure times (CT in DD as compared to SD (P<0.001. Delta of CEPI-CT (T1-T0 was significantly related to VWF (P<0.001 and inversely related to ADAMTS-13 (0.01. Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P=0.02. HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

  9. Protein replacement therapy and gene transfer in canine models of hemophilia A, hemophilia B, von willebrand disease, and factor VII deficiency.

    Science.gov (United States)

    Nichols, Timothy C; Dillow, Aaron M; Franck, Helen W G; Merricks, Elizabeth P; Raymer, Robin A; Bellinger, Dwight A; Arruda, Valder R; High, Katherine A

    2009-01-01

    Dogs with hemophilia A, hemophilia B, von Willebrand disease (VWD), and factor VII deficiency faithfully recapitulate the severe bleeding phenotype that occurs in humans with these disorders. The first rational approach to diagnosing these bleeding disorders became possible with the development of reliable assays in the 1940s through research that used these dogs. For the next 60 years, treatment consisted of replacement of the associated missing or dysfunctional protein, first with plasma-derived products and subsequently with recombinant products. Research has consistently shown that replacement products that are safe and efficacious in these dogs prove to be safe and efficacious in humans. But these highly effective products require repeated administration and are limited in supply and expensive; in addition, plasma-derived products have transmitted bloodborne pathogens. Recombinant proteins have all but eliminated inadvertent transmission of bloodborne pathogens, but the other limitations persist. Thus, gene therapy is an attractive alternative strategy in these monogenic disorders and has been actively pursued since the early 1990s. To date, several modalities of gene transfer in canine hemophilia have proven to be safe, produced easily detectable levels of transgene products in plasma that have persisted for years in association with reduced bleeding, and correctly predicted the vector dose required in a human hemophilia B liver-based trial. Very recently, however, researchers have identified an immune response to adeno-associated viral gene transfer vector capsid proteins in a human liver-based trial that was not present in preclinical testing in rodents, dogs, or nonhuman primates. This article provides a review of the strengths and limitations of canine hemophilia, VWD, and factor VII deficiency models and of their historical and current role in the development of improved therapy for humans with these inherited bleeding disorders.

  10. Influences of ABO blood group, age and gender on plasma coagulation factor VIII, fibrinogen, von Willebrand factor and ADAMTS13 levels in a Chinese population

    Directory of Open Access Journals (Sweden)

    Zongkui Wang

    2017-03-01

    Full Text Available Background ABO blood group is a hereditary factor of plasma levels of coagulation factor VIII (FVIII and von Willebrand factor (VWF. Age and gender have been shown to influence FVIII, VWF, fibrinogen (Fbg, and ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 motif, 13. We investigated the effects of ABO type, age, and gender on plasma levels of FVIII, Fbg, VWF, and ADAMTS13 in a Chinese population. Methods A total of 290 healthy volunteers were eligible for this study. ABO blood group was determined by indirect technique. FVIII:C and Fbg were measured by clotting assays. VWF antigen (VWF:Ag, collagen-binding activity (VWF:CBA, and ADAMTS13 antigen were assessed by ELISA, whereas VWF ristocetin cofactor activity (VWF:Rcof was performed by agglutination of platelets with ristocetin. Results Mean FVIII:C and VWF levels (VWF:Ag, VWF:CBA, and VWF:Rcof were significantly higher in non-O than in O type subjects (p < 0.05 for all comparison. ADAMTS13 antigen decreased with increasing age, whereas the other parameters increased. Other than ADAMTS13 (p < 0.01, no gender-related variations were observed in the other parameters. Moreover, FVIII:C, Fbg, VWF:Ag, VWF:CBA, and VWF:Rcof showed significant and positive relationships with age (r = 0.421, 0.445, 0.410, 0.401, and 0.589, resp.; all p < 0.001, whereas a negative relationship was observed for ADAMTS13 antigen (r = 0.306; p = 0.006. Furthermore, FVIII:C were strongly correlated with VWF:Ag, VWF:CBA, and VWF:Rcof (r = 0.746, r = 0.746, and r = 0.576, resp.; p < 0.0001. VWF parameters were also strongly correlated with each other (r = 0.0.847 for VWF:Ag and VWF:CBA; r = 0.722 for VWF:Ag and VWF:Rcof; p < 0.0001. Conclusions ABO blood group, age, and gender showed different effects on plasma levels of FVIII:C, Fbg, VWF:Ag, VWF:CBA, VWF:Rcof, and ADAMTS13 antigen. These new data on a Chinese population are quite helpful to compare with other ethnic groups.

  11. Inhibition of ADAMTS-13 by Doxycycline Reduces von Willebrand Factor Degradation During Supraphysiological Shear Stress: Therapeutic Implications for Left Ventricular Assist Device-Associated Bleeding.

    Science.gov (United States)

    Bartoli, Carlo R; Kang, Jooeun; Restle, David J; Zhang, David M; Shabahang, Cameron; Acker, Michael A; Atluri, Pavan

    2015-11-01

    The aim of this study was to investigate a potential therapy for left ventricular assist device (LVAD)-associated bleeding. Nonsurgical bleeding is the most frequent complication of LVAD support. Recent evidence has demonstrated that supraphysiological shear stress from continuous-flow LVADs accelerates von Willebrand factor (vWF) metabolism by the action of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS-13) (the vWF protease). An acquired vWF deficiency causes bleeding. This suggests that ADAMTS-13 is a clinical target to reduce vWF degradation. We tested the hypothesis that inhibition of ADAMTS-13 with doxycycline, an inexpensive, clinically approved drug, reduces vWF degradation during shear stress. Whole blood was collected from human donors (n = 15), and purified, recombinant ADAMTS-13 protein was obtained. An enzyme-linked immunosorbent assay (ELISA) was used to quantify the dose relationship between doxycycline and ADAMTS-13 activity prior to shear stress (n = 10). To determine the effect of shear stress, plasma and recombinant ADAMTS-13 were exposed to LVAD-like supraphysiological shear stress (approximately 175 dyne/cm(2)). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting (n = 10). Förster resonance energy transfer was used to quantify plasma ADAMTS-13 activity (n = 10). An ELISA was used to quantify vWF:collagen binding activity. Platelet aggregometry was performed with adenosine 5'-diphosphate, collagen, and ristocetin (vWF-platelet pathway) agonism (n = 10). Doxycycline significantly decreased plasma ADAMTS-13 activity (p = 0.01) and the activity of recombinant human ADAMTS-13 protein by 21%. After plasma was exposed to shear stress, the same pattern of vWF degradation was observed as previously reported for LVAD patients, and vWF:collagen binding activity decreased significantly (p = 0.002). Doxycycline significantly decreased ADAMTS-13 activity (p = 0.04) and

  12. Alexander von Humboldt y el relato de su viaje americano redactado en Filadelfia

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    Puig-Samper, Miguel Ángel

    2002-04-01

    Full Text Available This paper presents for the first time in Spanish language the autobiographical memoir that Alexander von Humboldt handed over to the American Philosophical Society in Philadelphia. This text was written in June 1804 during Alexander von Humboldt´s stay in the United States of America, when he was about to end his well-known American expedition. It constitutes the first —and until now the only— complete description of the expedition undertaken by the Prussian traveller. In order to present these series of autobiographical notes that Alexander von Humboldt wrote through his life, these memoirs will be mentioned briefly in the introduction of the paper in order to define the characteristics of the particular text introduced.

    En este artículo se da a conocer la memoria autobiográfica que Alexander von Humboldt entregó en la American Philosophical Society de Filadelfia, por primera vez en su traducción al español. Este texto fue redactado en junio de 1804 durante su estancia en los Estados Unidos, cuando estaba finalizando su famosa expedición americana y constituye la primera —y hasta ahora única— narración completa de esta expedición hecha por el viajero prusiano. Con objeto de encuadrar bien este texto en una serie de notas autobiográficas que escribió Humboldt a lo largo de su vida, en la introducción se mencionan brevemente estas memorias, para después definir las características del escrito presentado aquí.

  13. von Willebrand Disease (For Parents)

    Science.gov (United States)

    ... disorder. The most common treatment for vWD is desmopressin, a medication that causes a temporary increase in ... surgery, although they usually can be treated with desmopressin. Medication to inhibit the breakdown of blood clots ( ...

  14. Assessment of the olfactory function in Italian patients with type 3 von Willebrand disease caused by a homozygous 253 Kb deletion involving VWF and TMEM16B/ANO2.

    Directory of Open Access Journals (Sweden)

    Valentina Cenedese

    Full Text Available Type 3 Von Willebrand disease is an autosomal recessive disease caused by the virtual absence of the von Willebrand factor (VWF. A rare 253 kb gene deletion on chromosome 12, identified only in Italian and German families, involves both the VWF gene and the N-terminus of the neighbouring TMEM16B/ANO2 gene, a member of the family named transmembrane 16 (TMEM16 or anoctamin (ANO. TMEM16B is a calcium-activated chloride channel expressed in the olfactory epithelium. As a patient homozygous for the 253 kb deletion has been reported to have an olfactory impairment possibly related to the partial deletion of TMEM16B, we assessed the olfactory function in other patients using the University of Pennsylvania Smell Identification Test (UPSIT. The average UPSIT score of 4 homozygous patients was significantly lower than that of 5 healthy subjects with similar sex, age and education. However, 4 other members of the same family, 3 heterozygous for the deletion and 1 wild type, had a slightly reduced olfactory function indicating that socio-cultural or other factors were likely to be responsible for the observed difference. These results show that the ability to identify odorants of the homozygous patients for the deletion was not significantly different from that of the other members of the family, showing that the 253 kb deletion does not affect the olfactory performance. As other genes may compensate for the lack of TMEM16B, we identified some predicted functional partners from in silico studies of the protein-protein network of TMEM16B. Calculation of diversity for the corresponding genes for individuals of the 1000 Genomes Project showed that TMEM16B has the highest level of diversity among all genes of the network, indicating that TMEM16B may not be under purifying selection and suggesting that other genes in the network could compensate for its function for olfactory ability.

  15. Choroba von Willebranda – najczęstsza osoczowa skaza krwotoczna

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    Bożena Sokołowska

    2010-08-01

    Full Text Available Von Willebrand disease is the most common hereditary haemorrhagic disorder. A majority of patients (70%have classic mild or moderate (type I von Willebrand disease, and women are mostly affected. Clinical manifestationsinclude menorrhagia and post partum bleeding.

  16. Van Willebrand's disease in the Western Cape

    African Journals Online (AJOL)

    Von Willebrand's disease (VWD) is a mild-ta-moderately severe bleeding disorder characterised by mucosal bleeding such as epistaxis, gingival bleeding, gastro-intestinal bleeding and menorrhagia Haemarthroses, deep subcutaneous and intramuscular haematomas, typically seen in the severe haemophilias. are ...

  17. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Directory of Open Access Journals (Sweden)

    Jensen GS

    2016-10-01

    Full Text Available Gitte S Jensen,1 Miki Lenninger,1 Michael P Ero,2 Kathleen F Benson,1 1NIS Labs, Klamath Falls, OR, 2Machaon Diagnostics, Inc., Oakland, CA, USA Objective: The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations.Materials and methods: A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD, a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF, and platelet factor-4. Seventy-four people completed the study with good compliance.Results: Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05, and reached a high level of significance for males consuming nattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (P<0.006. A decrease in vWF was seen in the female population consuming nattokinase (P<0.1. In the subpopulation with low plasma renin activity levels at baseline (<0.29 ng/mL/h, an increase was seen for 66% of the people after 8-week consumption of nattokinase (P

  18. High-Affinity DNA Aptamer Generation Targeting von Willebrand Factor A1-Domain by Genetic Alphabet Expansion for Systematic Evolution of Ligands by Exponential Enrichment Using Two Types of Libraries Composed of Five Different Bases.

    Science.gov (United States)

    Matsunaga, Ken-Ichiro; Kimoto, Michiko; Hirao, Ichiro

    2017-01-11

    The novel evolutionary engineering method ExSELEX (genetic alphabet expansion for systematic evolution of ligands by exponential enrichment) provides high-affinity DNA aptamers that specifically bind to target molecules, by introducing an artificial hydrophobic base analogue as a fifth component into DNA aptamers. Here, we present a newer version of ExSELEX, using a library with completely randomized sequences consisting of five components: four natural bases and one unnatural hydrophobic base, 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). In contrast to the limited number of Ds-containing sequence combinations in our previous library, the increased complexity of the new randomized library could improve the success rates of high-affinity aptamer generation. To this end, we developed a sequencing method for each clone in the enriched library after several rounds of selection. Using the improved library, we generated a Ds-containing DNA aptamer targeting von Willebrand factor A1-domain (vWF) with significantly higher affinity (KD = 75 pM), relative to those generated by the initial version of ExSELEX, as well as that of the known DNA aptamer consisting of only the natural bases. In addition, the Ds-containing DNA aptamer was stabilized by introducing a mini-hairpin DNA resistant to nucleases, without any loss of affinity (KD = 61 pM). This new version is expected to consistently produce high-affinity DNA aptamers.

  19. Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel.

    Science.gov (United States)

    Favaloro, E J; Smith, J; Petinos, P; Hertzberg, M; Koutts, J

    1999-10-01

    We report an evaluation of current laboratory practice for the diagnosis of von Willebrand's disease (VWD) by means of a multilaboratory survey. This assessment was undertaken with the RCPA Quality Assurance Program (QAP) in Haematology, which covers a wide geographic area encompassing Australia, New Zealand and Asia. A total of 25 laboratories actively involved in testing for VWD were selected to participate in a sample testing assessment exercise. Samples comprised 10 plasmas: (i) a normal plasma pool (in duplicate), (ii) this pool diluted to 50% (in duplicate), (iii) a normal individual (X1), (iv) severe Type 1 VWD (X1), (v) Type 2B VWD (x2 unrelated donors), (vi) Type 3 VWD (x1), (vii) Type 2A VWD (x1). Laboratories were asked to perform all tests available to them in order to establish a laboratory diagnosis of VWD, and then to comment on the possibility or otherwise of VWD. Overall findings indicated a wide variation in test practice, in the effectiveness of various test procedures in detecting VWD, and in the ability of various composite test panels to identify type 2 VWD subtypes. Firstly, while all laboratories (n = 25) performed tests for FVIII:C activity, von Willebrand factor 'antigen' (VWF:Ag) and a functional VWF assay [using the ristocetin cofactor assay (VWF:RCo; n = 23) and/or the collagen binding assay (VWF:CBA; n = 12)], only three laboratories carried out VWF:Multimer analysis. Secondly, for the three quantitative VWF assays, 10/25 (40%) laboratories performed all three, whereas 15/25 (60%) performed only two [VWF:Ag and VWF:RCo (n = 13); VWF:Ag and VWF:CBA (n = 2)]. Thirdly, a variety of assay methodologies were evident for VWF:Ag [ELISA, electro-immuno diffusion (EID), latex immuno-assay (LIA), and VIDAS assay] and VWF:RCo (platelet agglutination/'aggregometry' and a 'functional VWF:RCo-alternative' ELISA assay). Between method analysis for the quantitative VWF assays showed that the VWF:RCo yielded the greatest degree of inter

  20. The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of α2δ subunits is key to trafficking voltage-gated Ca2+ channels

    Science.gov (United States)

    Cantí, C.; Nieto-Rostro, M.; Foucault, I.; Heblich, F.; Wratten, J.; Richards, M. W.; Hendrich, J.; Douglas, L.; Page, K. M.; Davies, A.; Dolphin, A. C.

    2005-01-01

    All auxiliary α2δ subunits of voltage-gated Ca2+ (CaV) channels contain an extracellular Von Willebrand factor-A (VWA) domain that, in α2δ-1 and -2, has a perfect metal-ion-dependent adhesion site (MIDAS). Modeling of the α2δ-2 VWA domain shows it to be highly likely to bind a divalent cation. Mutating the three key MIDAS residues responsible for divalent cation binding resulted in a MIDAS mutant α2δ-2 subunit that was still processed and trafficked normally when it was expressed alone. However, unlike WT α2δ-2, the MIDAS mutant α2δ-2 subunit did not enhance and, in some cases, further diminished CaV1.2, -2.1, and -2.2 currents coexpressed with β1b by using either Ba2+ or Na+ as a permeant ion. Furthermore, expression of the MIDAS mutant α2δ-2 reduced surface expression and strongly increased the perinuclear retention of CaVα1 subunits at the earliest time at which expression was observed in both Cos-7 and NG108–15 cells. Despite the presence of endogenous α2δ subunits, heterologous expression of α2δ-2 in differentiated NG108–15 cells further enhanced the endogenous high-threshold Ca2+ currents, whereas this enhancement was prevented by the MIDAS mutations. Our results indicate that α2δ subunits normally interact with the CaVα1 subunit early in their maturation, before the appearance of functional plasma membrane channels, and an intact MIDAS motif in the α2δ subunit is required to promote trafficking of the α1 subunit to the plasma membrane by an integrin-like switch. This finding provides evidence for a primary role of a VWA domain in intracellular trafficking of a multimeric complex, in contrast to the more usual roles in binding extracellular ligands in other exofacial VWA domains. PMID:16061813

  1. Expressão imunoistoquímica da endoglina (CD105 e do fator de von Willebrand em carcinoma epidermoide oral e sua relação com parâmetros clinicopatológicos

    Directory of Open Access Journals (Sweden)

    Rodrigo Porpino Mafra

    2016-03-01

    Full Text Available Resumo Contexto A angiogênese tem sido associada à progressão de neoplasias malignas e, embora haja estudos acerca de marcadores angiogênicos no carcinoma epidermoide oral (CEO, existem resultados conflitantes na literatura. Objetivos Avaliar a expressão imunoistoquímica do CD105 e do fator de von Willebrand (FvW em CEO e sua relação com parâmetros clínicos do tumor. Métodos A imunoexpressão dos referidos biomarcadores foi analisada em 30 casos de CEO e correlacionada a parâmetros clínicos do tumor (idade e sexo dos pacientes, localização anatômica e estadiamento clínico Tumor, Nodo e Metástase, TNM. Resultados A imunomarcação com o anticorpo anti-FvW foi mais efetiva que a do CD105 no CEO. No que concerne à localização anatômica, o assoalho bucal e a região retromolar apresentaram diferenças estatisticamente significativas quanto aos índices angiogênicos (p = 0,004, determinados pela técnica de contagem microvascular (MVC. Não houve relação estatisticamente significativa entre o estadiamento clínico TNM e os índices angiogênicos, com os dois biomarcadores. Conclusões Com base nos achados deste estudo, sugere-se um envolvimento da neoformação vascular na carcinogênese oral, embora não tenha sido evidenciada associação significativa com o estágio clínico da lesão.

  2. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Science.gov (United States)

    Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

    2016-01-01

    Objective The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. Materials and methods A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Results Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (Pnattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (Pnattokinase (Pnattokinase (Pnattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase’s effect on vWF and hypertension. PMID:27785095

  3. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial.

    Science.gov (United States)

    Jensen, Gitte S; Lenninger, Miki; Ero, Michael P; Benson, Kathleen F

    2016-01-01

    The objective of this study is to evaluate the effects of consumption of nattokinase on hypertension in a North American hypertensive population with associated genetic, dietary, and lifestyle factors. This is in extension of, and contrast to, previous studies on Asian populations. A randomized, double-blind, placebo-controlled, parallel-arm clinical study was performed to evaluate nattokinase (NSK-SD), a fermented soy extract nattō from which vitamin K2 has been removed. Based on the results from previous studies on Asian populations, 79 subjects were enrolled upon screening for elevated blood pressure (BP; systolic BP ≥130 or diastolic BP ≥90 mmHg) who consumed placebo or 100 mg nattokinase/d for the 8-week study duration. Blood collections were performed at baseline and 8 weeks for testing plasma renin activity, von Willebrand factor (vWF), and platelet factor-4. Seventy-four people completed the study with good compliance. Consumption of nattokinase was associated with a reduction in both systolic and diastolic BP. The reduction in systolic BP was seen for both sexes but was more robust in males consuming nattokinase. The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (Pnattokinase, where the average diastolic BP dropped from 86 mmHg to 81 mmHg (Pnattokinase (Pnattokinase (Pnattokinase consumption in a North American population is associated with beneficial changes to BP in a hypertensive population, indicating sex-specific mechanisms of action of nattokinase's effect on vWF and hypertension.

  4. Patient with von Willebrand Disease for Gynaecologic Surgery - Perianaesthetic Concerns

    Directory of Open Access Journals (Sweden)

    Rakesh Garg

    2008-01-01

    Patients with vWD do not carry an increased operative risk during elective procedures if appropriate prophylac-tic and corrective therapy is administered. Although the administration of cryoprecipitate and other blood products has traditionally been the cornerstone of treatment for vWD, the recent development of desmopressin(DDAVP for clinical use may provide an effective alternative to replacement therapy with blood products. Further laparaoscopic procedures, taking care during ryle′s tube and foley′s catheter insertion, in such patients are the safer alternative for all kind of gynecologic surgeries.

  5. Molecular cloning, expression and assembly of multimeric von Willebrand factor

    NARCIS (Netherlands)

    Pannekoek, H.; Voorberg, J.

    1989-01-01

    Recently, substantial progress has been made in our knowledge of the domains involved in correlating structure and function of vWF, as well as in the biosynthesis and assembly of multimeric vWF. These studies were greatly supported by the development of three new techniques. (1) In vitro culturing

  6. Molecular characterization of exon 28 of von Willebrand's factor ...

    African Journals Online (AJOL)

    2016-05-12

    May 12, 2016 ... two probable cases among 95 patients with hemophilia A and 11 with hemophilia B between 1980 and 1986, but full investigation and family studies were not performed. In. Nigeria, we ... bleeding symptoms are epistaxis, menorrhagia (in women), easy bruising, oral cavity bleeding, bleeding after dental.

  7. Von Willebrand's disease: case report and review of literature ...

    African Journals Online (AJOL)

    His birth histories, his familie's social history and developmental milestones were unremarkable. He was born at full term with no antenatal or perinatal complications. Prior to the symptoms, the child was on a normal diet and was thriving appropriately. The child presented one days before his admission trauma to the inner ...

  8. Characterization of a novel mutation in the von Willebrand factor propeptide in a distinct subtype of recessive von Willebrand disease

    DEFF Research Database (Denmark)

    Lanke, Elsa; Kristoffersson, Ann-Charlotte; Philips, Malou

    2008-01-01

    mutation in the VWFpp abolishes multimerization of VWF. The mutation probably disrupts the normal configuration of the VWFpp, which is essential for correct orientation of the protomers and ultimately multimerization. The mutant amino acid is located in a region that is highly conserved across several...

  9. Acquired Von Willebrand’s Syndrome in Systemic Lupus Erythematosus

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    Sara Taveras Alam

    2014-01-01

    Full Text Available Acquired von Willebrand syndrome (AVWS is an uncommon, underdiagnosed, and heterogeneous disease which is increasingly recognized as a cause of bleeding diatheses. Systemic lupus erythematosus (SLE is an infrequent cause of AVWS. Herein, we report a case of AVWS diagnosed during the initial presentation of SLE in a previously healthy young man with no family history of bleeding diathesis who presented with worsening epistaxis, gastrointestinal bleeding, and anasarca. He was found to have severe anemia and prolonged activated partial thromboplastin time (aPTT with severely decreased levels of von Willebrand factor (VWF measurements in addition to markedly decreased factor VIII levels. Further evaluation revealed nephrotic syndrome and interstitial lung disease due to SLE. He initially received combination therapy with intravenous immunoglobulin (IVIG and von Willebrand factor/factor VIII concentrates without significant improvement. Treatment with steroids, cyclophosphamide, and rituximab was followed by clinical improvement evidenced by cessation of bleeding. The short follow-up did not allow us to definitely prove the therapeutic effect of immunosuppressive treatment on AVWS in SLE patients. This case adds to the literature supporting the relationship between AVWS and SLE and highlights the importance of combination therapy in the treatment of severe AVWS as well as the role of IVIG, cyclophosphamide, and rituximab in AVWS associated with SLE.

  10. Memoria y relato

    Directory of Open Access Journals (Sweden)

    Igoa, José Manuel

    2004-01-01

    Full Text Available En este artículo se hacen algunas reflexiones acerca de las relaciones entre la memoria y el relato partiendo de un intento de aclarar la semántica de estos dos términos, sobre todo del primero. En su primera parte, se examinan diversas maneras de entender y abordar estas relaciones desde una óptica predominantemente psicológica. La segunda parte del artículo se dedica a explorar el papel que desempeñan los diversos sistemas y mecanismos de la memoria humana, tal y como se conciben y estudian actualmente en la Psicología Cognitiva, en las tareas de comprender y recordar relatos. También se subrayan en ella algunos problemas relevantes que han atraído la atención de los investigadores y expertos en la materia.…

  11. von Willebrand’s disease diagnosis and laboratory issues

    Science.gov (United States)

    CASTAMAN, G.; MONTGOMERY, R. R.; MESCHENGIESER, S. S.; HABERICHTER, S. L.; WOODS, A. I.; LAZZARI, M. A.

    2015-01-01

    Summary In this paper, the recent developments in the diagnosis and laboratory issues of von Willebrand’s disease (VWD) are presented. Dr. Castaman reviews the functional tests available for the diagnosis of VWD and their pathophysiological significance, focusing on which tests are best used in the diagnosis and classification of VWD. Dr Montgomery reviews an emerging issue that is accelerated clearance of von Willebrand factor (VWF) occurring in some variants of VWD. This phenotype can be suspected by the presence of an increased ratio between the VWF propeptide and the VWF antigen. These patients have typically a robust, but short-lived increase of FVIII and VWF after desmopressin. Dr Meschengieser reviews the determinants of bleeding after surgery in patients with VWD, emphasizing the role of bleeding history in predicting this risk. PMID:20590859

  12. Plasma level of von Willebrand factor: An indicator of severity in ...

    African Journals Online (AJOL)

    Background: Sickle cell anaemia is a congenital hemolytic disorder caused by mutation in the â-globin gene at position 6 with replacement of glutamic acid by valine. Patients who arehomozygous for this mutation suffer from hemolytic anaemia and other serious complications. The underlying pathology of much of these ...

  13. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin.

    OpenAIRE

    Hill-Eubanks, D C; Parker, C G; Lollar, P

    1989-01-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. We isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as ...

  14. Structural studies on B2-glycoprotein I and von Willebrand factor A3 domain

    NARCIS (Netherlands)

    Bouma, B.

    2000-01-01

    The integrity of blood circulation is a prerequisite for life; its malfunctioning is a leading cause of morbidity and mortality in developed countries. For that reason the haemostatic system is a critical component of homeostasis. In Chapter I an overview is given of the biophysical and biochemical

  15. Transient von Willebrand factor-mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

    NARCIS (Netherlands)

    Kirschbaum, Marc; Jenne, Craig N; Veldhuis, Zwanida J; Sjollema, Klaas A; Lenting, Peter J; Giepmans, Ben N G; Porte, Robert J; Kubes, Paul; Denis, Cécile V; Lisman, Ton

    2017-01-01

    Background & AimsIn addition to their function in thrombosis and haemostasis, platelets play an important role in the stimulation of liver regeneration. It has been suggested that platelets deliver mitogenic cargo to the regenerating liver, and accumulation of platelets in the regenerating liver has

  16. Nitric oxide level and von Willebrand factor (vWF) secretion are not ...

    African Journals Online (AJOL)

    Jane

    2011-08-15

    Aug 15, 2011 ... ACKNOWLEDEGMENTS. We are highly indebted to Dr. Haghjoo for help in NO and. vWF measurement, and Massah A. for his help in. Behjati et al. 8875 luminescence measurement. This study was funded by grant no. 287097 from Deputy of Research, Isfahan. University of Medical Sciences, Isfahan, Iran ...

  17. Leukocyte telomere length is inversely correlated with plasma Von Willebrand factor

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob V B; Nzietchueng, Rosine; Kimura, Masayuki

    2010-01-01

    attrition, ultimately resulting in shortened LTL. METHODS: We studied 3 cohorts: the ADELAHYDE study (age 60-87years), the ERA study (age 41-88years) and the Longitudinal Study of Aging Danish Twins (LSADT) (age 73-94years). RESULTS: Multiple regression analysis with LTL as the dependent variable, and age...... resistance, cigarette smoking and low socio-economic status. We examined the association between LTL and VWF plasma levels to test the hypothesis that high levels of VWF promote an increase in the turnover of blood cells, including leukocytes. Such a process would heighten the rate of age-dependent LTL...

  18. Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood

    NARCIS (Netherlands)

    Kas-Deelen, AM; Harmsen, MC; de Maar, EF; Oost-Kort, WW; Tervaert, JWC; van der Meer, J; van Son, WJ; The, TH

    2000-01-01

    Background. Human cytomegalovirus (HCMV) infections in transplantation patients are associated with vascular endothelial damage. This is reflected by the appearance of cytomegalic endothelial cells (CECs) and noninfected endothelial cells (ECs) in blood. To get more insight in the extent of vascular

  19. Platelet-independent adhesion of calcium-loaded erythrocytes to von Willebrand factor

    NARCIS (Netherlands)

    Smeets, M.W.J. (Michel W.J.); R. Bierings (Ruben); Meems, H. (Henriet); F.P.J. Mul (F. P J); D. Geerts (Dirk); A.P.J. Vlaar (Alexander); J. Voorberg (Jan); P.L. Hordijk (Peter )

    2017-01-01

    textabstractAdhesion of erythrocytes to endothelial cells lining the vascular wall can cause vaso-occlusive events that impair blood flow which in turn may result in ischemia and tissue damage. Adhesion of erythrocytes to vascular endothelial cells has been described in multiple hemolytic disorders,

  20. Transient von Willebrand factor-mediated platelet influx stimulates liver regeneration after partial hepatectomy in mice

    NARCIS (Netherlands)

    Kirschbaum, Marc; Jenne, Craig N; Veldhuis, Zwanida J; Sjollema, Klaas A; Lenting, Peter J; Giepmans, Ben N G; Porte, Robert J; Kubes, Paul; Denis, Cécile V; Lisman, Ton

    2017-01-01

    BACKGROUND & AIMS: In addition to their function in thrombosis and hemostasis, platelets play an important role in the stimulation of liver regeneration. It has been suggested that platelets deliver mitogenic cargo to the regenerating liver, and accumulation of platelets in the regenerating liver

  1. Plasma concentration of von Willebrand factor predicts mortality in patients on chronic renal replacement therapy

    NARCIS (Netherlands)

    Péquériaux, Nathalie C.; Fijnheer, Rob; Gemen, Eugenie F.; Barendrecht, Arjan D.; Dekker, Friedo W.; Krediet, Raymond T.; Beutler, Jaap J.; Boeschoten, Elisabeth W.; Roest, Mark

    2012-01-01

    Background. Traditional cardiovascular risk factors do not explain the high incidence of cardiovascular mortality and morbidity in patients with end-stage renal disease. A prothrombotic state could accelerate the process of vascular disease in these patients. Methods. In this study, four platelet

  2. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.

    2011-01-01

    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  3. Cellular fibronectin and von Willebrand factor concentrations in plasma of rats treated with monocrotaline pyrrole

    NARCIS (Netherlands)

    Schultze, A.E.; Emeis, J.J.; Roth, R.A.

    1996-01-01

    The monocrotaline pyrrole (MCTP)-treated rat is a useful model for the study of certain chronic pulmonary vascular diseases. A single, i.v. administration of a low dose of MCTP causes pneumotoxicity, pulmonary vascular remodeling, sustained increases in pulmonary arterial pressure, and right

  4. CRIPTOCOCOSE: RELATO DE CASO

    Directory of Open Access Journals (Sweden)

    Fernanda Alvarez GENTIL

    2016-12-01

    Full Text Available Criptococose, doença infecciosa fúngica, oportunista, potencialmente fatal, que acomete animais silvestres e domésticos, principalmente cachorro e gato e o homem. Causada pela levedura, Cryptococcus neoformans. Mais frequente em adultos, comumente diagnosticada em pacientes imunodeprimidos, como os soropositivos, fator predisponente mais frequente. Outros fatores são: uso prolongado de medicações imunossupressoras, doenças como diabetes, sarcoidose, doença de Hodgkin e outras neoplasias hematológicas, lúpus eritematoso, artrite reumatoide, doença de Behçet, e transplante de vísceras sólidas. Geralmente adquirida pela inalação do agente etiológico. Objetivo: este estudo objetiva relatar o caso de um paciente portador de criptococose, que esteve invernado no Hospital São José do Avaí (HSJA de Itaperuna, no mês de setembro de 2016, corroborando na literatura descrita sobre o tema, justifica-se o tema pela raridade do caso. Metodologia: inicialmente realizou-se pesquisa bibliográfica através da seleção de autores que asseguraram uma fundamentação teórico-metodológica que serviu de arcabouço para o desenvolvimento do estudo. A metodologia apresentada refere-se a um relato de caso, realizado a partir do prontuário do paciente e dos exames disponíveis. Resultados: a Radiografia de tórax evidenciou massa pulmonar em lobo inferior direito e a Tomografia de tórax também demonstrou esse acometimento; sendo realizada biópsia desse fragmento, que consolidou o diagnóstico de criptococose. A lâmina do paciente, corada com hematoxilina-eosina demonstrou aspectos característicos do acometimento por esse fungo. Conclusão: para o tratamento, pode-se utilizar antifúngicos como a anfotericina B associado com 5-flucitosina, em infecções disseminadas; ou fluconazol e itraconazol, para infecções cutâneas. 

  5. Interaktive Visualisierung von Strukturmechaniksimulationen

    OpenAIRE

    Sommer, Ove

    2003-01-01

    A) Motivation und Problemstellung Der Computer ist heute eines der wichtigsten Hilfsmittel beim Entwurf und der Entwicklung von Fahrzeugen. Zunächst wurde er von Konstrukteuren für das Computer Aided Design (CAD) von virtuellen Fahrzeugmodellen eingesetzt. Inzwischen ist er in vielen anderen Bereichen der Fahrzeugentwicklung unentbehrlich geworden: der Entwicklungszyklus von Automobilen ist durch die Computer-gestützte numerische Simulation substanziell verkürzt worden. An virtuellen Prot...

  6. Lernen von und bei Max von Laue

    Science.gov (United States)

    Thiessen, P. A.

    Erinnerungen an die Entstehungsgeschichte und die Frühzeiten der Röntgenstrukturanalyse.Translated AbstractLearning at Max von LaueRemembrances of the historical rise and the early times of X-ray structure analysis.

  7. Carl von Clausewitz

    DEFF Research Database (Denmark)

    Højrup, Thomas

    2009-01-01

    Forskningsbaseret præsentation af Carl von Clausewitz' krigsteori og dens betydning for statsbegrebet og udviklingen af teori om statsdannelse og statssystem. Krigsbegrebets betydning for politikbegrebet ekspliciteres, og de indre relationer imellem de to begreber demonstreres med konkrete eksemp...

  8. Ellis Von Creveld Syndrome

    Directory of Open Access Journals (Sweden)

    Afshar H

    1999-01-01

    Full Text Available One patient with Ellis Von Creveld syndrome contains: dwarfism, congenital heart"ndisease, ectodermal dysplasia, polyductyly, an abnormally wide labial frenum and maxillary"nmolars with single root.

  9. Ascensión al Teide de Alexander von Humboldt

    Directory of Open Access Journals (Sweden)

    Thomas Heyd

    2015-05-01

    Full Text Available Zusammenfassung In dieser kurzen Abhandlung wird dargelegt, dass Alexander von Humboldt durch die Besteigung des Teide eine integrierende Perspektive erwerben konnte, die ihm als Rahmen wissenschaftlicher Kommunikation dienen würde um die Vielzahl der Daten, welche er sich vorgenommen hatte auf der Insel zu sammeln, zu vereinen. Darüber hinaus wird ihm dieser Rahmen von hier an auch dazu dienen, um den unzähligen und verschiedenartigen Informationen, die er in den verbleibenden fünf Reisejahren sammeln würde, einen einheitlichen Sinn zu geben. Um die Blickrichtung von Humboldts Besuch auf Teneriffa darzulegen, untersuche ich seinen Bericht über die Besteigung des Teide unter der Annahme, dass er den Aufbau epischer Reisen und Pilgerfahrten hat. Summary In this brief essay I propose that, with the ascent of the Teide, Alexander von Humboldt was able to acquire an integrating perspective that served him as a framework for scientific communication to unify the multitude of data that he had set out to collect during his brief stay on the island. Moreover, thereafter this framework would also serve him to give a unified sense to the countless and diverse kinds of information that he could collect during the remaining five years of travel. To bring out the focus of Humboldt’s visit to Tenerife, I analyse his account of the ascent of the Teide by assuming that it is structured in the manner of the stories of epic journeys and pilgrimages. Resumen En este breve ensayo propongo que en la ascensión al Teide Alexander von Humboldt pudo adquirir una perspectiva integral, que le sirvió como marco de comunicación científica para aunar la multitud de datos que se había dispuesto a recoger en su breve estancia en la isla. Más aun, de ahí en adelante este marco además le serviría para darle sentido de conjunto a las incontables y diversas informaciones que recogería en los restantes cinco años de viaje. Para poner en evidencia el enfoque de la

  10. Relatos de pesquisas científicas

    Directory of Open Access Journals (Sweden)

    Congresso Internacional de Dislexia

    2011-05-01

    Full Text Available Relatos de pesquisas científicas apresentadas na terceira edição do Congresso Internacional de Dislexia (CID, realizado nas dependências do Centro Universitário Metodista Izabela Hendrix, em maio de 2011. Tratam-se de relatos de resultados de pesquisas científicas, descritivas ou experimentais das áreas da Psicologia, Fonoaudiologia, Piscopedagogia, Pedagogia e Neurociências realizadas no contexto nacional e internacional em torno da temática dislexia. 

  11. Amount of H Antigen Expressed on Circulating von Willebrand Factor Is Modified by ABO Blood Group Genotype and Is a Major Determinant of Plasma von Willebrand Factor Antigen Levels

    National Research Council Canada - National Science Library

    O’Donnell, James; Boulton, Frank E; Manning, Richard A; Laffan, Michael A

    2002-01-01

    .... AvWF was correlated strongly with plasma levels of A transferase activity. Thus, we have clearly demonstrated a direct relationship between ABO genotype, A transferase expression, and the amount of A antigen expressed on circulating vWF...

  12. Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD)

    DEFF Research Database (Denmark)

    Haberichter, S.L.; Castaman, G.; Budde, U.

    2008-01-01

    VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half...

  13. Raquitismo carencial: relato de caso

    Directory of Open Access Journals (Sweden)

    Porto, Juliana Antola et al.

    2005-01-01

    Full Text Available Introdução: O raquitismo é uma doença do tecido ósseo em formação, onde há falha na calcificação e conseguinte acúmulo de tecido osteóide. O raquitismo carencial é decorrente da deficiência dos precursores da vitamina D, sendo a causa de raquitismo mais facilmente evitável e tratável. Objetivo: Relatar um caso, revisar a etiopatogenia e o tratamento do raquitismo carencial. Relato de caso: Paciente masculino com 2 anos de idade, previamente hígido, consulta com dificuldade de deambular progressiva, até incapacidade total da marcha. A criança tinha exposição aos raios solares regularmente, recebeu aleitamento materno até os 8 meses, mas não fez uso de vitamina D profilática. Ao exame havia deformidade óssea evidente em membros superiores e inferiores, principalmente com alargamento das metáfises distais e encurvamento das epífises dos ossos longos. A investigação laboratorial e de imagem confirmaram raquitismo carencial. Discussão: Há uma grande variedade nas possíveis etiologias do raquitismo, sendo doenças renais, hepáticas, distúrbios primários ou deficiências no metabolismo do cálcio e fósforo algumas delas. A maioria dessas patologias exige um longo período de investigação e tratamento. O raquitismo carencial, entretanto, é uma condição de relativa facilidade para diagnóstico, manejo, e profilaxia, derivando daí, a importância do artigo.

  14. Von Willebrand disease and other bleeding disorders in women: consensus on diagnosis and management from an international expert panel

    NARCIS (Netherlands)

    James, Andra H.; Kouides, Peter A.; Abdul-Kadir, Rezan; Edlund, Mans; Federici, Augusto B.; Halimeh, Susan; Kamphuisen, Pieter W.; Konkle, Barbara A.; Martínez-Perez, Oscar; McLintock, Claire; Peyvandi, Flora; Winikoff, Rochelle

    2009-01-01

    Reproductive tract bleeding in women is a naturally occurring event during menstruation and childbirth. In women with menorrhagia, however, congenital bleeding disorders historically have been underdiagnosed. This consensus is intended to allow physicians to better recognize bleeding disorders as a

  15. Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: A retrospective survey

    NARCIS (Netherlands)

    S.C.M. Stoof (Carina); van Steenbergen, H.W. (H. W.); Zwagemaker, A. (A.); Y.V. Sanders (Yvonne); S.C. Cannegieter (Suzanne); Duvekot, J.J. (J. J.); F.W.G. Leebeek (Frank); M. Peters; M.J.H.A. Kruip (Marieke); J.C.J. Eikenboom (Jeroen)

    2015-01-01

    textabstractPregnant women with bleeding disorders require specialised peripartum care to prevent postpartum haemorrhage (PPH). If third trimester coagulation factor levels are <0.50 IU mL-1, prophylactic treatment is indicated and administered according to international guidelines.

  16. Primary postpartum haemorrhage in women with von Willebrand disease or carriership of haemophilia despite specialised care: a retrospective survey

    NARCIS (Netherlands)

    Stoof, S. C. M.; van Steenbergen, H. W.; Zwagemaker, A.; Sanders, Y. V.; Cannegieter, S. C.; Duvekot, J. J.; Leebeek, F. W. G.; Peters, M.; Kruip, M. J. H. A.; Eikenboom, J.

    2015-01-01

    Pregnant women with bleeding disorders require specialised peripartum care to prevent postpartum haemorrhage (PPH). If third trimester coagulation factor levels are <0.50 IU mL(-1) , prophylactic treatment is indicated and administered according to international guidelines. However, optimal dose and

  17. Von Braun Fountain

    Science.gov (United States)

    1999-01-01

    A fountain representing a rocket launch was dedicated in the Von Braun courtyard outside of Building 4200 at Marshall Space Flight Center during the weekend celebrating the 30th arniversary of the Apollo 11 lunar landing. On hand for the festivities were many of the Saturn and Apollo astronauts.

  18. Rhizostomeen von Manila

    NARCIS (Netherlands)

    Stiasny, G.

    1924-01-01

    Die hier beschriebene kleine Scyphomedusen-Sammlung wurde von Herrn Director P. B. Sivickis, Dept. of Zoology, University of Philippines, Manila, dem Rijksmuseum van Natuurlijke Historie in Leiden überwiesen. Das Material wurde im December 1922 in Manila-bay gefischt und befindet sich in bestem

  19. Karman, Prof. Theodore von

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1961 Honorary. Karman, Prof. Theodore von. Date of birth: 11 May 1881. Date of death: 6 May 1963. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. Theory Of Evolution. Posted on 23 January 2018. Joint Statement by the Three Science Academies of India on the ...

  20. Schmetterlinge von Madeira

    NARCIS (Netherlands)

    Martin, K.

    1941-01-01

    Wer auf einer ozeanischen Insel Schmetterlinge sammeln will, darf seine Erwartungen nicht zu hoch spannen; aber dennoch waren meine Frau und ich sehr enttäuscht, als uns auf einer Reise nach Madeira von einer dort angesessenen, gebildeten Dame gesagt wurde, sie habe auf der Insel niemals einen

  1. Relato de caso: esclerose tuberosa

    Directory of Open Access Journals (Sweden)

    Samuel Simis

    2016-10-01

    Full Text Available Introdução: O Complexo de Esclerose Tuberosa (CET é uma síndrome neurocutânea transmitida hereditariamente, de traço autossômico dominante e que se manifesta por uma tríade clássica: deficiência mental, convulsões e adenoma sebáceo. A mutação responsável pela síndrome está presente em até 85% dos portadores de CET e.ocorre nos genes supressores tumorais TSC1 e TSC2, que produzem hamartina e tuberina, respectivamente.A prevalência do CET é de 1:10.000 a 1:170.000, atinge mais indivíduos do sexo masculina e é rara em negros. Relato de Caso: R.C.S.B., paciente do sexo feminino, 16 anos, vem encaminhada ao ambulatório de neurologia devido a quadro de convulsões tônico-clônicas generalizadas e crises de ausência diárias há 1 ano, mas com história de convulsões aos 2 anos que cessaram espontaneamente. Está em tratamento com fenitoína 200mg/dia e carbamazepina 800mg/dia, mas ainda apresenta crises de ausência. A paciente apresenta as lesões cutâneas típicas do CET: adenomas sebáceos (angiofibroma em face distribuídos simetricamente entre nariz e bochechas, envolvendo ainda fronte e queixo. Não há sinais de retardo mental. A ressonância nuclear magnética revelou imagens com padrão compatível com áreas de desmielinização. O eletroencefalograma encontrava-se normal. Conclusão: O tratamento do CET ainda é um desafio para muitos neurologistas, uma vez que não há tratamento específico para doença. A paciente deve contar com equipe multidisciplinar, por vezes é necessário acompanhamento com neurologista, dermatologista, geneticista, psicólogos e outros, dependendo das manifestações do CET. A finalidade terapêutica é a qualidade de vida da paciente, que pode ser prejudicada pelas várias convulsões ou alterações estéticas da doença.

  2. Ascite meconial - relato de caso

    Directory of Open Access Journals (Sweden)

    Celeste Gomez Sardinha Oshiro

    2016-10-01

    Full Text Available INTRODUÇÃO: A ascite meconial resultante da perfuração intestinal fetal tem baixa incidência (1:30.000 nascimentos e elevada mortalidade (50%. Os achados ecográficos fetais incluem ascite e calcificações intra-abdominais. OBJETIVO: Relatar um caso de ascite meconial neonatal no Conjunto Hospitalar de Sorocaba. METODOLOGIA: Descrição do referido caso e revisão de literatura. RELATO DE CASO: Recém-nascido de J.A.P., masculino, de parto cesáreo por iteratividade em 12/05/2016, cuja mãe com 44 anos, sem intercorrências no pré-natal, negou consanguinidade, vícios e infecções; ultrassonografia obstétrica evidenciou ascite moderada, circunferência abdominal >p95, hepatomegalia e hidrocele. Ao nascimento, idade gestacional 3 8 2 /7 semanas, peso=3630g, comprimento=49 cm, Apgar 8/9. Apresentava abdome globoso, fígado a 4 cm do rebordo costal direito e hidrocele volumosa. Realizada paracentese com saída de 310 ml de líquido esverdeado (meconial. No 5o dia de vida, durante laparotomia, observou-se aderência de alças intestinais, perfuração de íleo terminal a 8 cm da vávula íleo-cecal, sendo realizada ileostomia. O anátomo-patológico de apêndice cecal evidenciou processo inflamatório crônico, neovascularização e fibrose. Paciente recebeu nutrição parenteral por 14 dias; houve progressão da dieta do 6o ao 36o dia de vida, recebendo alta em aleitamento materno e boa recuperação clínica. CONCLUSÃO: A ascite meconial por perfuração intestinal deve ser considerada no diagnóstico diferencial de ascite fetal. O diagnóstico ecográfico pré-natal é fundamental para o prognóstico pós-natal.

  3. Kommunikative Konstitution von Organisationen

    DEFF Research Database (Denmark)

    Schoeneborn, Dennis; Wehmeier, Stefan

    2014-01-01

    Beiträge zur Unternehmenskommunikation behandeln in der Regel (strategisch) geplante interne oder externe Kommunikation. Der vorliegende Beitrag stellt einen alternativen Theorieansatz vor, der aktuell im nordamerikanischen Forschungsgebiet „Organizational Communication“ vorherrschend ist....... zunehmende Aufmerksamkeit erhält Der sogenannten „CCO-Perspektive“ („Communicative Constitution of Organizations“) zufolge bestehen Unternehmen aus einer Vielzahl von internen und externen Kommunikationspraktiken, die nur in bedingtem Maße strategisch steuerbar sind. Zugleich sind es eben diese...

  4. Diphyllobothrium latum: relato de caso no Brasil

    Directory of Open Access Journals (Sweden)

    Emmel Vanessa Erichsen

    2006-01-01

    Full Text Available Difilobotriose é causada em humanos pela infecção com vermes adultos do gênero Diphyllobothrium adquiridos pelo consumo de peixe cru ou mal cozido. Diphyllobothrium latum foi confirmado pelo exame dos proglotes grávidos e típicos ovos operculados nas fezes. O paciente havia comido crustáceos e peixes. É o relato do primeiro brasileiro infectado.

  5. Kulturelle Aspekte von Textsorten

    Directory of Open Access Journals (Sweden)

    Siegfried Heusinger

    1998-12-01

    Full Text Available Ich fasse meine Überlegungen zu kulturellen Aspekten von Textsorten zusammen: 1. Mit unseren Kulturverständnis ist die terminologisierte Wortgruppe "interkulturelle Kommunikation" nicht zu begreifen als Kommunikation zwischen Menschen verschiedener kultureller Bindungen, sondern sie ist nicht zu begreifen als Kommunikation zwischen Menschen verschiedener kultureller Bindungen, sondern sie ist ethnisch wie auch ethisch angepasstes sprachlichkommunikatives Verhalten an kulturelle Traditionen der jeweils für den Kommunkations- akt vereinbarten Sprache. 2. Das Adjektiv "interkulturell" referiert auf idiomatisierte Wendungen im zwischenmenschlichen Kontakt wie auch auf kulturell gebundene Unterschiede in der Benennungsmotivation (z.B. anloben/österr./, vereidigen /dt./ 3. Das Adjektiv "interkulturell" ist ebenfalls zu beziehen auf den Austausch von Erfahrungen und Ideen, auf den Dialog von Kulturen. 4. Textsorten existieren in ihrer kulturellen in ihrer kulturellen Tradition, wobei das Kulturspezifische vornehmlich in traditionellen (aber entwicklungsoffenen Formulierungs- und Gestaltungsmustern zu suchen iost. Andere Textsortencharakteristika wie die situative Einbettung, die kommunikative Zwecksetzung, die thematische Bindung und die Komposition haben offenbar kaum eine kulturspezifische Prägung. 5. Im Trend zur Internationalisierung der Textsorten erweisen sich die kulturell geprägten Textmustervor allem zwischen angrenzenden Nationen häufig als affin.

  6. La presencia del narratario en el relato audiovisual

    OpenAIRE

    Prósper Ribes, Josep

    2015-01-01

    El narratario es un elemento básico en el relato audiovisual estrechamente relacionado con el narrador. Siempre hay una instancia narrataria y puede haber en un relato narratarios delegados. El narratario es fundamental para configurar la narración. La

  7. Nutzerorientiertes Management von materiellen und immateriellen Informationsobjekten

    OpenAIRE

    Hübsch, Chris

    2001-01-01

    Schaffung einer stabilen, erweiterbaren und skalierbaren Infrastruktur für die Bereitstellung von Diensten im Umfeld von Bibliotheken und ähnlichen wissensanbietenden Einrichtungen unter Verwendung von XML-RPC und Python.

  8. Hemangioma de úvula: relato de um caso

    Directory of Open Access Journals (Sweden)

    G. Sobrinho Fernando P.

    2003-01-01

    Full Text Available O hemangioma é o mais comum tumor de origem vascular, benigno, freqüentemente diagnosticado em crianças, e com predileção pela cabeça e pescoço, mas que raramente tem origem na úvula. Neste órgão, apresenta risco de traumatismo local e sangramento. Este artigo relato um caso de hemangioma de úvula num adulto jovem com disfagia orofaríngea progressiva e sensação de corpo estranho na garganta, tratado com sucesso por ressecção cirúrgica do tumor com bisturi de radiofreqüência.

  9. Pielite enfisematosa unilateral: relato de caso

    Directory of Open Access Journals (Sweden)

    Eduardo Gonçalves

    2013-02-01

    Full Text Available Relata-se um caso de paciente de 22 anos de idade, gênero feminino, que foi admitida no pronto-socorro com lombalgia aguda, disúria, vômitos e febre (38,5ºC. Os achados de exames de urina e tomografia computadorizada demonstraram infecção no trato urinário associada a gás no sistema coletor, configurando pielite enfisematosa unilateral por Gram-negativo. O presente relato enfatiza a ocorrência deste agravo como complicação de infecção no trato urinário.

  10. Diphyllobothrium latum: relato de caso no Brasil

    OpenAIRE

    Emmel,Vanessa Erichsen; Inamine,Everton; Secchi,Carina; Brodt, Tereza C.Z.; Amaro, Maria Cristina O.; Cantarelli, Vlademir Vicente; Spalding,Sílvia

    2006-01-01

    Difilobotriose é causada em humanos pela infecção com vermes adultos do gênero Diphyllobothrium adquiridos pelo consumo de peixe cru ou mal cozido. Diphyllobothrium latum foi confirmado pelo exame dos proglotes grávidos e típicos ovos operculados nas fezes. O paciente havia comido crustáceos e peixes. É o relato do primeiro brasileiro infectado. Diphyllobothriasis is caused in humans by infection with adult tapeworms of the genus Diphyllobothrium acquired by consuming raw or undercooked fr...

  11. Relatos de vivências educacionais

    Directory of Open Access Journals (Sweden)

    Congresso Internacional de Dislexia

    2011-05-01

    Full Text Available Relatos de experiências em educação, abrangendo a descrição de projeto ou vivência específica em sala de aula ou outro ambiente educacional, que envolva o trabalho com escolares com dislexia e outros transtornos da aprendizagem da leitura e escrita.Os trabalhos foram apresentados na terceira edição do Congresso Internacional de Dislexia (CID, realizado nas dependências do Centro Universitário Metodista Izabela Hendrix, em maio de 2011. 

  12. Relatos de mercado en la literatura mundial

    OpenAIRE

    Molina, Cristian

    2009-01-01

    Desde finales de los 80, aparece una proliferación de relatos de mercado en la literatura mundial correlacionados con el contexto de la globalización que se esgrime como proyecto político planetario. Ese proyecto construido por las dirigencias de Occidente estuvo caracterizado por la imposición de un patrón económico como regulador de las sociedades a través del Mercado; de modo tal que algunos han leído la emergencia de una "sociedad de mercado" o de "vidas de consumo" o de "c...

  13. Estética del relato posmoderno

    OpenAIRE

    Fernández Porta, Eloy, 1974-

    2014-01-01

    El presente trabajo de investigación se propone ofrecer una definición conceptual y tipológica del paradigma del relato breve literario a lo largo de la época posmoderna. Partiendo de una perspectiva comparatista, la base de esta investigación consiste en un conjunto de oposiciones en relación con el modelo moderno. A partir de ellas tesis toma como caso central el movimiento posmoderno norteamericano y traza una serie de vínculos teóricos y conceptuales, principalmente con las literaturas de...

  14. John von Neumann Birthday Centennial

    Energy Technology Data Exchange (ETDEWEB)

    Grcar, Joseph F.

    2004-11-12

    In celebration of John von Neumann's 100th birthday, a series of four lectures were presented on the evening of February 10, 2003 during the SIAM Conference on Computational Science and Engineering in San Diego. The venue was appropriate because von Neumann spent much of the later part of his life, in the 1950's, as an unofficial ambassador for computational science. He was then the only senior American scientist who had experience with the new computers (digital, electronic, and programmable) and a vision of their future importance. No doubt he would have relished the chance to attend a meeting such as this. The first speaker, William Aspray, described the ''interesting times'' during which computers were invented. His remarks were based on his history [1] of this period in von Neumann's life. We were honored to have John von Neumann's daughter, Marina von Neumann-Whitman, as our second speaker. Other accounts of von Neumann's life can be found in books by two of his colleagues [2] and [3]. Our third speaker, Peter Lax, provided both mathematical and international perspectives on John von Neumann's career. Finally, Pete Stewart spoke about von Neumann's numerical error analysis [4] in the context of later work; this talk did not lend itself to transcription, but readers may consult the historical notes in [5]. Our thanks to all the speakers for a remarkable evening. We are grateful to the DOE Applied Mathematical Sciences (AMS) program for partially supporting these lectures. Thanks are also due to SIAM and William Kolata, to our emcee, Gene Golub, to Paul Saylor for recording and editing, and to Barbara Lytle for the transcriptions. More about von Neumann's work can be learned from the recent American Mathematical Society proceedings [6].

  15. Alejandro Von Humboldt

    Directory of Open Access Journals (Sweden)

    Gerardo Paz Otero

    1965-09-01

    Full Text Available Diverso fue y sigue siéndolo, el destino de los dos hermanos Humboldt, Guillermo y Alejandro. Sino que se inicia con el nacimiento: Guillermo, el mayor, nace el 22 de junio de 1767 en Potsdam, residencia de los emperadores prusianos, la ciudad de los palacios imperiales, el imperio del militarismo germano; su cuna se meció cerca al palacete de Sans-Soussi, donde Federico el Grande forja ba el poderío de Prusia, cultivaba las ciencias y las artes, anfitrionaba a los intelectuales de Europa, y era "vasallo espiritual de Volta ire", según la aguda frase de Goethe. Alejandro viene al mundo dos años después (14 de septiembre de 1769 en Berlín, en la casa burguesa de la Jagerstrasse (calle del cazador que su madre Elizabeth von Humboldt heredara de su primer esposo.

  16. Der Einfluss von Phlorizin auf den programmierten Zelltod von Erythrozyten

    OpenAIRE

    Meier, Anja Doris

    2013-01-01

    Erythrozyten sind in der Lage, suizidalen Zelltod zu betreiben. Von einigen Substanzen ist bereits bekannt, dass sie die sogenannte Eryptose beeinflussen. Beispiele dafür sind Quecksilber, Monensin, Benzethonium und Oridonin, welche zu den Stimulatoren der Eryptose gehören. Blebbistatin, Koffein und Endothelin, gehören zu den Inhibitoren. In dieser Studie sollte untersucht werden, welchen Einfluss Phlorizin auf den Ablauf des suizidalen Zelltodes von Erythrozyten hat. Es wurde belegt, dass si...

  17. Einsatz von Nickel-Katalysatoren zum Cracken von Teerprodukten aus der Niederdruckaufkohlung von Stahl mit Ethin

    OpenAIRE

    Mbadinga Mouanda, Gelase

    2009-01-01

    Die Niederdruckaufkohlung von Stahl ist ein modernes Verfahren, das zur Einsatzhärtung von Stahlbauteilen dient. Bei Temperaturen zwischen 900 und 1050 °C und Drücken unter 50 mbar werden Bauteile durch heterogene Pyrolyse von Ethin in einem Ofen einsatzgehärtet. Das während der Pyrolyse erzeugte Abgas enthält aromatische Kohlenwasserstoffe und kann katalytisch behandelt werden. Der Katalysator wird durch Rußablagerung desaktiviert und muss zyklisch durch Verbrennung mit Luft regeneriert werd...

  18. Ueber einige Coelenterata von Australien

    NARCIS (Netherlands)

    Stiasny, G.

    1931-01-01

    I. Hydromedusen. *Olindias singularis Browne. II. Scyphomedusen. *Atolla wyvillei Haeckel. *Linuche unguiculata O. Swartz. Pelagia noctiluca Péron u. Lesueur. Cyanea capillata var. annaskala von Lendenfeld. Netrostoma coerulescens Maas. *Versura anadyomene (Maas) Mayer. Catostylus mosaicus L.

  19. Kleben von Kunststoff mit Metall

    CERN Document Server

    Brockmann, W; Käufer, H

    1989-01-01

    Das Buch behandelt das Kleben von Kunststoffen mit Metallen in einer fur den Praktiker verstandlichen und umsetzbaren Form. Es leitet zu Klebeverfahren an, die optimale Ergebnisse hinsichtlich Qualitat, Dauerhaftigkeit und Wirtschaftlichkeit liefern.

  20. Fluorido-Komplexe von Technetium

    OpenAIRE

    Mariappan Balasekaran, Samundeeswari

    2013-01-01

    Zusammenfassung Diese Dissertationsschrift befasst sich mit der Synthese und Charakterisierung neuer Technetiumfluoride mit dem Metall in den Oxidationsstufen “+1”, “+2”, “+4” und “+6”. Im ersten Kapitel wird über die Isolierung von unterschiedlichen Salzen von Fluoridonitridotechnetaten(VI) entweder aus Nitridotechnetium(VI)-säure oder aus Pertechnetat durch den Einsatz geeigneter Reduktionsmittel berichtet. Das Cäsiumsalz dieser Verbindung bildet einen oxido-verbrückten, dimeren Kompl...

  1. Effiziente chemoenzymatische Synthese von dhydroartemisinaldehyd

    OpenAIRE

    Demiray, Melodi; Tang, Xiaoping; Wirth, Thomas; Faraldos, Juan A.; Allemann, Rudolf K.

    2017-01-01

    Artemisinin aus der Pflanze Artemisia annua ist das wirkungsvollste Arzneimittel zur Behandlung von Malaria. Die Sesquiterpen-Cyclase Amorphadien-Synthase, ein Cytochrom-abhängiges CYP450 und eine Aldehyd-Reduktase wandeln in der Pflanze Farnesyl-Diphosphat (FDP) in Dihydroartemisinaldehyd (DHAAl) um, welches ein Schlüsselzwischenprodukt in der Biosynthese von Artemisinin und eine halbsynthetische Vorstufe in der chemischen Synthese des Arzneimittels ist. Hier berichten wir über einen chemoen...

  2. Relato literario, relato periodístico: el caso Elián González

    Directory of Open Access Journals (Sweden)

    Lic. María Inés Loyola

    2000-01-01

    Full Text Available Nos proponemos estudiar las relaciones entre relato literario y relato periodístico a partir del caso del niño balsero cubano, Elián González, que estuvo retenido en Estados Unidos durante siete meses. En este análisis, el principal objetivo es describir las diferencias y similitudes respecto a la construcción discursiva de la historia narrada, sus personajes y escenarios. La finalidad de la comparación es demostrar cómo los relatos "no ficcionales" que los medios imponen como verdaderos y actuales descansan en recursos retóricos y estrategias de construcción afines a los relatos ficcionales literarios. Las conclusiones a que llegamos pueden contribuir a la reflexión acerca de la manera en que los medios de comunicación social construyen la realidad.

  3. Tricoepitelioma palpebral: relato de 2 casos

    OpenAIRE

    Sugano,Débora Mayumi; Lucci,Lúcia Miriam Dumont; Ávila,Mariana Pereira de; Rehder,José Ricardo Carvalho Lima; Pettinati,Juliana

    2005-01-01

    O tricoepitelioma é tumor cutâneo benigno derivado dos folículos pilosos. É comum na face, porém há poucos relatos sobre a ocorrência na pálpebra. não é freqüentemente reconhecido devido à sua raridade, controvérsias na sua classificação, origem e potencial biológico. O objetivo deste artigo é apresentar 2 casos de tricoepitelioma solitário na pálpebra, o exame histopatológico e seu tratamento. Esta lesão deve ser considerada quando for encontrado um nódulo solitário na região facial e difere...

  4. Osteocondromatose em gato: relato de caso

    Directory of Open Access Journals (Sweden)

    S. Winter

    Full Text Available RESUMO A osteocondromatose é caracterizada por nódulos únicos ou múltiplos decorrentes de um crescimento ósseo excessivo benigno. É encontrada em cães, gatos, equinos e humanos. Em felinos, tem maior incidência dos dois aos quatro anos de idade. A etiologia em gatos está relacionada ao vírus da leucemia felina, e também já foi encontrada relação com o fibrossarcoma. A manifestação clínica depende do local acometido e do tamanho da lesão. O diagnóstico definitivo é por meio de histopatologia e o prognóstico é desfavorável, pois ocorrem muitas recidivas. Este relato de caso objetiva descrever a apresentação dessa enfermidade em um felino jovem.

  5. Hipomelanose de Ito - relato de um caso

    Directory of Open Access Journals (Sweden)

    Adriana S. de Almeida

    2001-02-01

    Full Text Available Objetivo: Os autores têm como objetivo relatar um caso de hipomelanose de Ito (HI, uma síndrome neurocutânea rara, com alterações neurológicas e cromossômicas associadas ao comprometimento cutâneo e pneumonias de repetição. Relato do caso: Este relato é referente a um paciente masculino, 1 ano e 11 meses, internado no Hospital Universitário São Vicente de Paulo por broncopneumonia bilateral. Ao exame foram observadas máculas hipocrômicas na pele compatíveis com HI, além de atraso do desenvolvimento neuropsicomotor. O paciente foi submetido à biópsia incisional de pele das lesões do abdômen, eletroencefalograma, ressonância magnética e estudo citogenético. Resultados: Os exames histológico e imunoistoquímico evidenciaram ausência de melanina e diminuição de melanócitos em áreas focais da epiderme, respectivamente. O eletroencefalograma apresentou disfunção córtico-subcortical difusa. A ressonância magnética do encéfalo foi compatível com cisto aracnoídeo em região temporal. O cariótipo evidenciou mosaicismo cromossômico com uma linhagem normal (46,XY e uma linhagem celular que apresentava deleção intersticial nas bandas 22.2 - 24.2 do braço longo do cromossomo 10 (25%. Conclusões: Os autores, com o presente estudo, destacam a importância das lesões de pele na definição etiológica das desordens neuropediátricas.

  6. Die Wertigkeit von Bildinformationskategorien und ihre Rolle bei der Beurteilung von Bildern als Medien

    OpenAIRE

    Wieczorek, Ulrich

    1997-01-01

    Die Wertigkeit von Bildinformationskategorien und ihre Rolle bei der Beurteilung von Bildern als Medien. - In: Die Geographiedidaktik ist tot, es lebe die Geographiedidaktik : Festschr. zur Emeritierung von Josef Birkenhauer / hrsg. von Friedhelm Frank ... - München, 1997. - S. 253-271. - (Münchner Studien zur Didaktik der Geographie ; 8)

  7. Ethnographische Filme und die Darstellung von Frauen

    Directory of Open Access Journals (Sweden)

    Judith Keilbach

    2002-03-01

    Full Text Available In dieser Filmographie werden ethnographische und koloniale Filme aus dem Bestand des Nederlands Filmmuseum kommentiert, die für die Frage nach der Darstellung von Frauen und Geschlechterverhältnissen von Interesse sind.

  8. John von Neumann selected letters

    CERN Document Server

    2005-01-01

    John von Neuman was perhaps the most influential mathematician of the twentieth century, especially if his broad influence outside mathematics is included. Not only did he contribute to almost all branches of mathematics and created new fields, but he also changed post-World War II history with his work on the design of computers and with being a sought-after technical advisor to many figures in the U.S. military-political establishment in the 1940s and 1950s. The present volume is the first substantial collection of (previously mainly unpublished) letters written by von Neumann to colleagues, friends, government officials, and others. The letters give us a glimpse of the thinking of John von Neumann about mathematics, physics, computer science, science management, education, consulting, politics, and war. Readers of quite diverse backgrounds will find much of interest in this fascinating first-hand look at one of the towering figures of twentieth century science.

  9. An Invitation from Lars von Trier

    DEFF Research Database (Denmark)

    Skadhauge, Troels; Tønder, Lars

    2015-01-01

    Translation of Martin Krasnik interview with Lars von Trier broadcast on DR2, January 12, 2015. The following is an interview of Lars von Trier (LvT) by the Danish journalist Martin Krasnik (MK). The interview took place in Lars von Trier’s home in Brede, a small town just outside Copenhagen...

  10. Management von Anforderungsdokumenten mittels semantischer Wikis

    OpenAIRE

    Decker, B.

    2005-01-01

    Im Projekt RISE wird untersucht, wie durch den Einsatz von Wikis das Anforderungsmanagement von Software Projekten agil unterstützt werden kann. Um das oftmals chaotische Wachstum von Inhalten in den Griff zu bekommen, werden maschinelle Lernverfahren genutzt, um Inhalte zu strukturieren und dem Benutzer zugänglich zum machen.

  11. Multivariat-statistische Auswertung von energiedispersiven Röntgenfluoreszenzspektren zur Identifizierung von Substanzen

    OpenAIRE

    Kessler, Thorsten

    2001-01-01

    Es wurde der Einsatz von multivariater Auswertung von energiedispersiven Röntgenfluoreszenzanalyse (EDRFA) -Spektren für die Zuordnung von Substanzen getestet. Hierbei erfolgten u. a. Untersuchungen zur Zuordnungsanalytik von Chemikalien ohne und mit Verpackungen. Zur Untersuchung von Chemikalien mit Verpackung wurden ausschließlich anorganische, feste Chemikalien in z.T. unterschiedlicher Verpackung herangezogen. Zusätzlich sollte ein Vergleich zwischen Messungen durch gleiche Verpackungen u...

  12. Homopteren von Java, gesammelt von Herrn Edw. Jacobson

    NARCIS (Netherlands)

    Melichar, L.

    1914-01-01

    Herr Edw. Jacobson hat auf Java in den Jahren 1908— 1910 Homopteren gesammelt und mir die Bearbeitung des gesammelten Materiales übertragen. Die Jacobson’sche Ausbeute ist insoferne bemerkenswert, als dieselbe viele Mikrohomopteren enthält, welche von nichtfachkundigen Sammlern gewöhnlich nicht

  13. Sinusopatia fúngica - relato de caso

    Directory of Open Access Journals (Sweden)

    Augusto Riedel Abrahão

    2014-10-01

    Full Text Available Introdução: O relato visa à discussão das sinusopatias exclusivamente esfenoidais, sobretudo fúngicas, entidades raras com sintomatologia inespecífica, que constituem um  desafio diagnóstico na prática clínica. Relato do Caso: Paciente masculino, 80 anos, cefaléia em peso à esquerda e obstrução nasal há 3 meses. Diabetes não-insulino dependente controlada. Laboratoriais sem evidência de eosinofilia.Tomografia: esclerose e espessamento das paredes do seio esfenoidal e calcificações no seu interior à direita. Obliteração do recesso esfenoetmoidal direito. Realizada cirurgia endoscópica com acesso esfenoidal via transetmoidal. Retirada grande quantidade de material esverdeado compatível com fungo. Anatomopatológico: edema e infiltrado linfomononuclear de lamina própria. Pesquisa de fungos negativa. Paciente evolui com resolução da cefaléia no trigéssimo pós-operatório.Discussão: A rinossinusite   esfenoidal isolada é em sua maioria resultado de processo inflamatório crônico, sendo a bola fúngica a terceira etiologia mais frequente. A cefaléia é percebida em até 85% dos casos seguida por obstrução e gotejamento pós-nasal. Os achados tomográficos são inespecíficos, sendo   esclerose,  calcificação e opacificação completa dos seios achados sugestivos de bola fúngica. Conclusão: A perspicácia do otorrinolaringologista em suspeitar de rinossinusite esfenoidal isolada associada a sinais radiológicos e/ou endoscópicos são essenciais para o diagnostico precoce e, consequentemento, para o sucesso terapêutico da doença.

  14. Replikation von µ-Peptidarrays

    OpenAIRE

    Striffler, Jakob

    2014-01-01

    In der vorliegen Arbeit wurde ein Verfahren erarbeitet und mit Photometrie, XPS und ToF-SIMS charakterisiert, mit dem durch mikropartikelbasierte Verfahren hergestellte µ-Peptidarrays von Syntheseoberflächen abgespalten und auf beliebige Zieloberflächen transferiert werden können.

  15. Von Krahl ON! / Terje Metsavas

    Index Scriptorium Estoniae

    Metsavas, Terje

    2008-01-01

    Madli Pesti ja Terje Metsavas kohtusid Von Krahli teatri tehnilise meeskonnaga teatri black-box-saalis. Teatri tehniline meeskond on tehnikadirektor Enar Tarmo, video- ja multimeediaga tegelev Lauri Sepp, tehnikud Janno "John" Jaanus, Oliver Kulpsoo ja Allan Räim. Selles, kuidas sünnivad "tehnikaimed" ja kuidas lahendatakse lavastuslikke projekte

  16. Integration von Produktion und Instandhaltung

    OpenAIRE

    Hans-Böckler-Stiftung

    2003-01-01

    Die Faktoren Produktqualität und Kosten-Nutzen-Verhältnis sind entscheidend im Wettbewerb. Um diese Faktoren zu optimieren, suchen die Unternehmen nach innovativen Modellen der Integration von Produktion und Instandhaltung. Über Konzeption und Erprobung solcher Modelle berichtet eine Arbeitsgruppe der Engeren Mitarbeiter der Arbeitsdirektoren Stahl Fachausschuss 1/00.

  17. figuras y recursos de relatos cotidianos

    Directory of Open Access Journals (Sweden)

    Marisela Hernández-H.

    2005-01-01

    Full Text Available Este texto forma parte de un estudio más amplio que busca explorar formas y sentidos de la belleza en la vida cotidiana. Entre las preguntas que se hace el estudio se destacan aquí las siguientes: ¿en cuáles términos y maneras se relata la belleza cotidiana?, ¿qué podrían significar esas maneras de decir la belleza? Tratando de responder esas preguntas interpretamos 15 relatos, y encontramos figuras y recursos. Las figuras sugeridas son: el derecho a la ilusión, de lo sublime a lo trivial, los diminutivos del cariño, la alegría de los sentidos, por todas partes el color, tormentos y dolores, manías y demás enfermedades, totalidad y vida, buenitas acciones, bonitas (y feas maneras, la perfección, lo feo, lo cursi y la belleza hace la felicidad... Los recursos identificados son: señalar dificultades, hablar desde mí, e indiferenciar.

  18. [Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images] / Ulrike Plath

    Index Scriptorium Estoniae

    Plath, Ulrike, 1972-

    2014-01-01

    Arvustus: Friedrich Ludwig von Maydelli pildid Baltimaade ajaloost = Friedrich Ludwig von Maydells Baltische Geschichte in Bildern = Friedrich Ludwig von Maydell ́s Baltic history in images. Eesti kunstimuuseum, Kadrioru kunstimuuseum. Tallinn 2013

  19. Von den Veranschaulichungsmethoden in den Rundfunkpredigten von der Heiligkreuz- Kirche

    Directory of Open Access Journals (Sweden)

    Witold Ostafiński

    2004-12-01

    Full Text Available In der gegenwärtigen Verkündigung des Wortes Gottes spielt die Veranschaulichung der Überlieferung eine nicht zu überschätzende Rolle. Vor diesem Hintergrund wird es sehr wichtig, dass man den Predigern nicht nur auf die Funktion des Bildes in der Verkündigung, sondern auch auf die Art und Weise seines Entstehens auf der narrativen Ebene aufmerksam macht. Während die Kenner der Homiletik die Notwendigkeit des Auftretens der Bildeigenschaften in den Predigten betonen, erinnern sie gleichzeitig daran, dass der moderne, von der „Bild-Zivilisation“ gestaltete Mensch, „immer mehr sehen als hören“ möchte. Der vorliegende, die Rundfunkpredigten von der Heiligkreuz-Kirche analysierende Aufsatz, nimmt auf und bringt zugleich nahe die Problematik der Notwendigkeit des Bildes in der Wort-Gottes-Verkündigung. Der Artikel stellt die Erzählungsform als eine wichtige Möglichkeit der Glaubensüberlieferung dar, behandelt das Problem der Aktualisierung evangelischen Werte, bringt das von den Predigten gestaltete synästhetische Weltbild nahe und analysiert die Rolle des Zitats und Beispiels (exemplum bei der Gestaltung der Bildhaftigkeit einer Predigt. Darüber hinaus überprüft der Aufsatz in seinem letzten Teil die in den gegenwärtigen Rundfunkpredigten meist verwendeten Redefiguren

  20. Analyse von Schnittstellenkompatibilität von Steuergeräten auf Basis von MSC-Beschreibungen

    OpenAIRE

    Ma, Zheng

    2008-01-01

    In modernen Fahrzeugen befindet sich eine Vielzahl von Steuergeräten, die verschiedenste Funktionen, wie z.B. das Antiblockiersystem (ABS) realisieren. Die Funktionalitäten von Steuergeräten werden heute mit unterschiedlichen Methoden beschrieben. Eine dieser Methoden sind Message Sequence Charts (MSCs). Aufgrund der Freiheitsgrade von MSCs gibt es verschiedene Möglichkeiten gleiche Funktionalität unterschiedlich zu beschreiben. In dieser Arbeit wird eine Methode definiert, wie...

  1. Männlichkeiten von rechts

    Directory of Open Access Journals (Sweden)

    Marc Gärtner

    2004-11-01

    Full Text Available Oliver Geden, Doktorand am Institut für europäische Ethnologie der Humboldt Universität Berlin untersucht Männlichkeitskonzepte im zeitgenössischen Rechtspopulismus – ein Thema, zu dem überraschend lange keine einschlägigen Studien vorlagen. Anhand von Parteimedien und Interviews rekonstruiert er strategische Positionen zu Männlichkeit und Geschlechterverhältnissen auf unterschiedlichen Organisationsebenen der Österreichischen „Haider-Partei“ FPÖ. Statt eines monolithischen „Neo-Macho-Projektes“ findet er im Kern zwar ähnliche Traditionalisierungsbemühungen auf allen Ebenen, je nach Kontext aber differenzierbare pragmatische, verunsicherte und neo-naturalistische Perspektiven auf die Geschlechterthematik. Durch die Einbeziehung von Gruppeninterviews im Nachwuchsverband der Partei erhält die Publikation eine besondere Brisanz. Geden analysiert die methodischen und forschungsethischen Implikationen ebenso hervorragend wie das Kernthema selbst.

  2. von Hippel-Lindau disease

    DEFF Research Database (Denmark)

    Binderup, Marie Louise Mølgaard; Gimsing, Steen; Kosteljanetz, Michael

    2013-01-01

    Endolymphatic sac tumours (ELSTs) of the inner ear occur in 16% of patients with the hereditary tumor syndrome von Hippel-Lindau disease (vHL). ELSTs of all sizes can cause irreversible hearing loss which can, however, be prevented through early diagnosis and treatment. We aim to emphasize the ch...... the challenges of prophylactic ELST screening and to explore the role of audiometry in pre-symptomatic ELST screening....

  3. Methode zur Entwicklung von Prozessportalen

    OpenAIRE

    Alt, Rainer; Caesar, Marc; Leser, Florian; Österle, Hubert; Puschmann, Thomas; Reichmayr, Christian; Zurmuehlen, Rudolf

    2004-01-01

    Die in Kapitel 2 dargestellte Architektur zeigt Gestaltungselemente auf den drei Ebenen Strategie, Prozess und System. Zahlreiche Beispiele in den darauf folgenden Kapiteln haben die Anwendung dieser Architektur gezeigt. Um ein intuitives Vorgehen bei Entwurf und der Umsetzung von Echtzeit-Portalen zu vermeiden, sollen die bei den Fallbeispielen erzielten Erkenntnisse und Erfahrungen in ein systematisches Vorgehen einfliessen. Obgleich sich der Entwurf einer Architektur für das Echtzeit-Unter...

  4. Einfluss von Hypoxie auf das Transkriptom und das mitochondriale Proteom von Arabidopsis thaliana

    OpenAIRE

    Willeke, Claudia

    2011-01-01

    Hypoxie beeinflusst Wachstum und Entwicklung von Pflanzen. Da Sauerstoff als finaler Elektronenakzeptor der Atmungskette dient, sind Mitochondrien möglicherweise an der Wahrnehmung von Hypoxie und der Weiterleitung des Signals durch retrograde Regulierung beteiligt. In dieser Arbeit wurden daher die Auswirkungen von Hypoxie auf das Transkriptom und das mitochondriale Proteom von Arabidopsis thaliana untersucht. Zu diesem Zweck wurden Inkubationssysteme für Zellkulturen, Keimlinge und Pflanzen...

  5. Dr. von Braun Briefing Walt Disney

    Science.gov (United States)

    1965-01-01

    Dr. von Braun began his association with Walt Disney in the 1950s when the rocket scientist appeared in three Disney television productions related to the exploration of space. Years later, Dr. von Braun invited Disney and his associates to tour the Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This photograph is dated April 13, 1965. From left are R.J. Schwinghamer from the MSFC, Disney, B.J. Bernight, and Dr. von Braun.

  6. Offenes Baukastensystem zur effizienten Dimensionierung von Materialflusssystemen

    OpenAIRE

    Meinhardt, Ingolf; Marquardt, Hans-Georg

    2007-01-01

    Die optimale Gestaltung logistischer Systeme und Prozesse bekommt eine immer größere Bedeutung für die Wirtschaftlichkeit und Wettbewerbsfähigkeit von Unternehmen. Für Einzelkomponenten von Materi-alflusssystemen sind neben exakten analytischen Verfahren auch Näherungslösungen und Ersatzmodelle in Form von Polynomen, neuronalen Netzen oder zeitdiskreten Verfahren vorhanden, mit denen eine gute Nachbildung des Verhaltens dieser Komponenten möglich ist. Ziel des Baukastensystems ist es, für...

  7. Modellierung von Anwenderverhalten im Social Semantic Web

    Science.gov (United States)

    Ulbrich, Armin; Höfler, Patrick; Lindstaedt, Stefanie

    Ziel dieses Kapitels ist es, gemeinsame Verwendungsszenarien des Semantic Web und des Social Web zu identifizieren und zu benennen. Dabei wird ein Teilaspekt des Themengebiets im Detail betrachtet: die Nutzung von Services, die Beobachtungen des Verhaltens von Anwendern analysieren, um daraus maschinell interpretierbare Informationen zu erhalten und diese als Modelle zu organisieren. Es werden zunächst einige Eigenschaften und Unterscheidungsmerkmale von Anwenderverhalten und organisierten Modellen dargestellt. Anschließend wird der mögliche wechselseitige Nutzen von Anwenderverhalten und Modellen diskutiert. Den Abschluss bildet eine Betrachtung einiger exemplarischer Software-Services, die heute schon verwendet werden, um Anwenderverhalten in Modelle überzuführen.

  8. The Social Science of Carl von Clausewitz

    Science.gov (United States)

    2006-01-01

    The Social Science of Carl von Clausewitz JANEEN KLINGER C arl von Clausewitz’s great, unfinished book On War is well-known as be- ing prone to...COVERED 00-00-2006 to 00-00-2006 4. TITLE AND SUBTITLE The Social Science of Carl von Clausewitz 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...Raymond Aron, Clausewitz: Philos- opher of War (New York: Simon and Schuster, 1983), p. 206. 88 Parameters 2. Carl Von Clausewitz , On War, ed. and trans

  9. Die naturräumliche Gliederung von Schwaben

    OpenAIRE

    Fischer, Klaus

    1985-01-01

    Die naturräumliche Gliederung von Schwaben. - In: Historischer Atlas von Bayerisch-Schwaben / hrsg. von Hans Frei ... - 2., neu bearb. u. erg. Aufl. - Augsburg : Schwäb. Forschungsgem. - Lifg. 2. (1985). - Kt. II, 7.

  10. Mucopolissacaridose tipo VI: relato de caso

    Directory of Open Access Journals (Sweden)

    Lais Orosco Bialon Santana

    2014-10-01

    Full Text Available Introdução: As mucopolissacaridoses são erros inatos do metabolismo de depósito lisossomal subclassificadas segundo a enzima deficiente. A arilsulfatase B (ARSB, responsável por degradar os glicosaminoglicanos (GAGs, que atuam no tecido conjuntivo, é deficiente na mucopolissacaridose tipo VI (MP VI. A MP VI tem clínica variável, sem anormalidades ao nascimento, evidenciando-se progressivamente ao acúmulo de GAGs. O diagnóstico se faz pela redução da atividade da ARSB ou da mutação genética. A principal causa de óbito é insuficiência cardíaca, ocorrendo na segunda ou terceira década de vida. Relato de Caso: Masculino, 4 anos, portador de MP VI, há 3 dias com febre e sinais flogísticos em sítio de acesso central, colocado para reposição enzimática, com flutuação e saída de material purulento. Ultrassom evidenciou coleção laminar e borramento de planos gordurosos. Ecocardiograma demonstra hipertensão pulmonar discreta decorrente de prolapso valvar mitral com refluxo discreto, além de endocardite da valva mitral. Optou-se por retirada cirúrgica do dispositivo e administração de vancomicina e amicacina. Durante internação, evoluiu bem, sem complicações pós operatórias. Conclusão: A MP VI têm inteligência preservada, baixa estatura e alterações osteomusculares, como no caso relatado. Não há correlação entre a gravidade clínica e a atividade residual enzimática. Dificuldade respiratória pode levar a hipóxia crônica, hipertensão pulmonar e insuficiência cardíaca congestiva. Das alterações cardíacas, encontramos valvulopatias, insuficiência cardíaca e hipertensão pulmonar, observadas no caso. O tratamento se faz com transplante de células-tronco hematopoiéticas e terapia de reposição enzimática.

  11. Eritema polimorfo farmacoinduzido: relato de caso

    Directory of Open Access Journals (Sweden)

    Lais Orosco Bialon Santana

    2014-10-01

    Full Text Available Introdução: Farmacodermias são queixas comuns devendo ser diferenciadas para o tratamento e a investigação precoce de complicações. O eritema polimorfo é uma doença inflamatória caracterizada por lesões em alvo que permanecem fixas por mais de 6 dias. As etiologias são medicamentosa (anticonvulsivantes, antibióticos e anti- inflamatórios e infecções, sendo o vírus herpes o mais relacionado. Classificado na forma minor, associado a infecções, sem sintomas sistêmicos ou lesões mucosas, e major, com padrão inflamatório e mucoso, considerado forma leve da síndrome de Stevens-Johnson. O diagnóstico é clínico e histopatológico. Relato de Caso: Paciente epilética, com diagnóstico de infecção de via aérea há 12 dias tratada com amoxicilina, ibuprofeno, ácido acetil salicílico e loratadina. Após 10 dias, apresentou edema, prurido, eritema, e bolhas por todo corpo, acompanhadas de febre, dispnéia e odinofagia, além de uma convulsão tônico clônica com perda da consciência. Devido à epilepsia, fazia uso de fenobarbital, o qual foi ajustado há 3 dias (50mg para 100mg/dia. Feito diagnóstico, feito hidrocortisona IV, dipirona e cuidados de suporte. Evoluiu com leucocitose e aumento de PCR, introduziu-se ceftriaxona e aciclovir. Houve em uma semana, melhora das lesões cutâneas e estado geral da paciente. Conclusão: As principais causas de farmacodermias são anticonvulsivantes e anti- inflamatórios, usados pela paciente. Alguns medicamentos estão mais associados à certos padrões de lesão, colaborando para o diagnóstico, confirmado através da biopsia cutânea. Frente aos quadros de eritema, as farmacodermias devem ser aventadas como importante diagnóstico diferencial. O fator causal deve ser identificado a fim do tratamento adequado e diminuição da morbidade.

  12. Rinoscleroma: relato de caso Rhinoscleroma: case report

    Directory of Open Access Journals (Sweden)

    Mônica Elisabeth Simons

    2006-08-01

    Full Text Available Rinoscleroma é uma doença crônica granulomatosa, comprometendo principalmente a mucosa do trato respiratório, especialmente a cavidade nasal podendo eventualmente se estender através das vias aéreas inferiores. Esta doença é endêmica em alguns países da América Central (El Salvador e Guatemala, Indonésia, Índia, Polônia, Hungria, Rússia e alguns países da África, porém é rara na América do Sul. Trata-se de um paciente do sexo masculino de 51 anos de idade residente de uma instituição psiquiátrica em São Paulo (capital. Apresentou queixa de obstrução nasal progressiva, cefaléia frontal, rinorréia amarelada e massa exteriorizando-se pelo vestíbulo da fossa nasal direita. Este relato de caso descreve um rinoscleroma, onde o exame anatomopatológico teve papel decisivo no diagnóstico. O paciente foi, portanto, submetido a procedimento cirúrgico, seguido de tratamento clínico com ciprofloxacina. O paciente evoluiu bem e manteve assintomático sem evidência clínica de recidiva até sua última visita em nosso departamento seis meses após o tratamento inicial.Rhinoscleroma is a chronic, granulomatous infection that most frequently affects the respiratory mucosa, especially the nasal cavity and eventually extending through the lower respiratory tract. The disease is endemic in some countries of Central America (El Salvador and Guatemala, Indonesia, India, Poland, Hungary, Russia and some African countries as well. It is a rare disease in South America. We report a 51-year-old male resident of a psychiatric institution in São Paulo presenting with progressive nasal obstruction, frontal headache, yellowish nasal discharge and a mass extruding through the right nasal vestibule. The present case report describes a Rhino-Sinus scleroma where histopathology was vital in the diagnosis. The patient was treated by surgical excision of the nasal mass followed by a course of ciprofloxacin. He has remained asymptomatic up to the

  13. Relato de caso: mediastinite necrotizante descendente

    Directory of Open Access Journals (Sweden)

    José Mauro da Silva Rodrigues

    2016-10-01

    Full Text Available Introdução: Mediastinite é um processo inflamatório raro do tecido conectivo do mediastino e pode ter como base infecções bacterianas da orofaringe (denominada, mediastinite necrotizante descendente (MND. Cerca de 70% tem como origem infecções odontogênicas. Possui alta mortalidade e o diagnóstico precoce, a intervenção cirúrgica e o uso de antibióticos são essenciais à resolução do quadro. Objetivo: relatar um caso de MND acompanhado no Conjunto Hospitalar de Sorocaba (CHS em abril de 2016. Metodologia: acompanhamento das cirurgias, revisão do prontuário e da literatura. Relato de caso: M.D.B, masculino, 27 anos, entrou na emergência do CHS com quadro de abcesso em região cervical, dor em tórax e dispneia há 3 dias. Negou comorbidades. Ao exame encontrava-se em mau estado geral, febril (39ºC, com diminuição global do murmúrio vesicular do hemitórax D; FR=30 ipm, sat 90%,FC=110 bpm e PA= 160 x 100 mmHg. O raio-x de tórax demonstrou: opacificação em hemitórax D, aumento de mediastino e silhueta cardíaca. A tomografia evidenciou derrame pleural difuso em hemitórax D, ar e líquido no mediastino e derrame pericárdico. A hipótese de Mediastinite e empiema de origem odontogênica foi considerada, sendo indicada a cirurgia. Foi efetuada a Toracotomia anterolateral D com retirada de grande quantidade de fibrina e secreção purulenta por toda a cavidade torácica, além de pus em mediastino e pericárdio. O paciente foi encaminhado para a UTI e após 11 dias passou por nova cirurgia, pelo mesmo acesso cirúrgico, devido à nova coleção em loja superior do mediastino. Houve boa evolução e o paciente recebeu alta após 23 dias. Conclusão: MND é uma doença rara e possui alta mortalidade. O diagnóstico precoce e tratamento adequado fazem-se necessários para resolução do quadro.

  14. Trombocitemia essencial familiar: um relato de caso

    Directory of Open Access Journals (Sweden)

    Marcelo Gil Cliquet

    2015-10-01

    Full Text Available A Trombocitemia Essencial (TE é classificada como pertencente ao grupo de distúrbios mieloproliferativos clássicos BCR/ABL negativos. Está associada à mutação JAK2V617F em aproximadamente 50% dos casos, também descrita em outros distúrbios mieloproliferativos, assim como mutações nos genes CALR e MPL. Estudos indicam incidência sete vezes maior em familiares de indivíduos afetados, com transmissibilidade compatível com modelo de herança recessiva. Objetivo e Metodologia: Relatar o caso de duas irmãs com diagnóstico de TE, portadoras da mutação JAK2 (V617F; as informações foram obtidas por meio de revisão de prontuário. Relato dos casos: Paciente 01, idade 75 anos, sexo feminino. Com diagnóstico de TE, portadora da mutação JAK2, BCR/ABL negativo, tratada com Hydroxiurea e AAS, evoluiu com neutropenia secundária ao uso de HU. Paciente 2, idade 72 anos, sexo feminino. Encaminhada ao Ambulatório de Hematologia do CHS por plaquetose em agosto de 2014. Tem hemograma prévio (2007 com plaquetose acima de 1.000.000/mm³. Na investigação, presença da mutação da JAK2 V617F, BCR/ABL negativo, e hemograma com contagem de plaquetas 1.745.000/mm³, leucócitos 17.200/mm³, neutrófilos 13.244/mm³ e 1.032/mm³ bastonetes. Feito o diagnóstico de TE e tratamento com HU e AAS. Evoluiu também com toxicidade à HU apresentando hemograma realizado em maio de 2015, com contagem de plaquetas em 203.000/mm³, 1.280 neutrófilos e Hb 9,2 g/dl. Conclusão: Relatamos os casos de duas irmãs com diagnósticos confirmados de TE, ambas com mutação da JAK2 V617F. Lembrando a possível hereditariedade dessa doença e sabendo que o diagnóstico precoce pode prevenir eventos trombóticos, consideramos interessante a investigação dos parentes, com a realização de um simples hemograma.

  15. Los mochileros y sus relatos : Desde una mirada etnográfica

    OpenAIRE

    Belloli Orrijola, Luciana

    2014-01-01

    La presente tesis propone indagar como se reconfigura los relatos de Mochileros como viajero y generador de relatos/escritos gracias a sus vivencias durante el viaje, desde una mirada etnográfica. Se desarrolla partiendo del marco teórico explicativo, con conceptos a describir e interpretar como el viaje, el viajero y el turista, los mochileros, y los relatos. Se aplica una metodología cualitativa, utilizando como técnica la etnografía, recurriendo a insumos como el relato de viajes tanto per...

  16. Influence of atrial fibrillation on plasma von Willebrand factor, soluble E-selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart failure

    DEFF Research Database (Denmark)

    Freestone, B.; Gustasson, F.; Chong, A.Y.

    2008-01-01

    with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. Results: One hundred ninety patients (73% men; mean age, 69......Background: Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. it is unknown whether AF influences the degree of endothelial dysfunction...

  17. Planung von CLIL-Unterricht

    Directory of Open Access Journals (Sweden)

    Josef Leisen

    2015-10-01

    Full Text Available Der Beitrag formuliert die Sprachlernbedingungen und die Leitlinien des Sprachlernens im Fach und nennt Merkmale des guten integrierten Fach- und Sprachlehrens. Ausgehend von den Sprachproblemen, die sich im CLIL-Unterricht auftun, wird der sprachsensible CLIL-Unterricht definiert, und es werden Anregungen zur Gestaltung gegeben. Sprachliche Standardsituationen umfassen die kommunikativen Situationen im CLIL-Unterricht, die beim fachlichen Lernen auftreten und von der CLIL-Lehrkraft professionell bewältigt werden müssen. Im Beitrag wird ein Lehr-Lern-Modell ausführlich beschrieben und erläutert. Die Steuerungen von Sprachlernprozessen im CLIL durch Aufgabenstellungen, Methoden-Werkzeuge, Moderation und Diagnose/Rückmeldung werden ausführlich beschrieben. Die Planung einer Lernlinie in sechs Schritten wird dargestellt und erläutert. Planungsraster für CLIL-Lernlinien schließen den Beitrag ab. The article sets out the conditions for language learning in general as well as guiding principles of language learning in the subject and puts forward criteria for successfully integrated content and language learning. Based on typical language problems arising in CLIL-classrooms, the language-sensitive CLIL-classroom is defined and organisational suggestions are given. Linguistic standard situations comprise the communicative situations in the CLIL-classroom which are encountered in subject-related learning and have to be professionally mastered by the CLIL-teacher. The article extensively describes and explains a model of teaching and learning that can be used for the CLIL-classroom. It gives detailed information on managing language learning processes in CLIL by means of tasks, resources and methods as well as discourse facilitation, evaluation and feedback. In addition, a six-step lesson unit is outlined and explained. The article concludes by giving a planning matrix for CLIL lesson units.

  18. Homoepitaxie von ZnO

    OpenAIRE

    Neumann, Christian

    2006-01-01

    Die Arbeit beschäftigt sich mit der homoepitaktischen Darstellung von ZnO-Dünnschichten. Die Arbeit beginnt mit einer theoretischen Betrachtung des Materialsystems und den daraus für eine erfolgreiche Epitaxie zu ziehenden Schlüssen. Es wurde eine Temperbehandlung zur Oberflächenmodifikation kommerziell erhältlicher ZnO-Einkristallsubstrate erarbeitet, die für eine erfolgreiche Epitaxie erforderlich ist. Im Anschluß daran wird die Entwicklung eines CVD-Prozesses mit metallischer Zin...

  19. Riidaja mõis / Elma von Stryk

    Index Scriptorium Estoniae

    Stryk, Elma von

    2006-01-01

    renoveerimise ootel barokne puithäärber (1762), kompleksi ümbritsev kivimüür, maakividest hobusetall, pargivaade, punastest tellistest neogooti stiilis kabel (1864), mis taastati von Strykkide perekonna toel. 11 ill.; fotod: Raivo Tasso; kabelis on Elma von Stryki loodud Kristust kujutav altarimaal

  20. Sorten- und Nachbaueignung von Hafer und Weizen

    OpenAIRE

    Spieß, Hartmut

    2000-01-01

    Der Beitrag gibt anhand alter und neuer Sortenvergleiche von Hafer und Weizen Einblick in die Problematik ökologischer Züchtung und Sortenwahl. Dabei geht es neben spezifischen Sorteneigenschaften um die Ausgewogenheit von Ertrags- und Qualitätsbildung im Verhältnis zur Pflanzengesundheit.

  1. Alteraciones del relato: los niños con TDAH

    Directory of Open Access Journals (Sweden)

    Ygual Fernández, Amparo

    2004-01-01

    Full Text Available Los niños con TDAH tienen dificultades para la elaboración y comprensión de relatos relacionadas con las características cognitivas propias del trastorno. Las alteraciones que experimentan en el control inhibitorio, en la memoria de trabajo y, en suma, en el funcionamiento ejecutivo son responsables de los problemas en el relato. Estos se pueden producir en varios estadios del procesamiento: las dificultades atencionales pueden influir interfiriendo en la entrada de la información; las dificultades en la memoria operativa los hace menos eficaces en el reparto y control de recursos durante la realización de la tarea, lo cual se traduce en dificultades en la evocación de sucesos,…

  2. Psoríase pustulosa da infância: relato de caso Childhood pustular psoriasis: case report

    Directory of Open Access Journals (Sweden)

    Yuri Nogueira Chaves

    2010-12-01

    Full Text Available A psoríase pustulosa generalizada é tipo raro de psoríase descrita pela primeira vez, em 1910, por Von Zumbusch. A psoríase pustulosa generalizada na criança tende a ter um curso mais benigno que no adulto, entretanto, em sua forma grave, pode por em risco a vida do paciente. Talvez, pela raridade da doença, nenhuma opção terapêutica se mostrou consistentemente eficaz e segura até o momento. Relatos isolados sugerem ser o retinoide a droga de escolha nesses casos, porém trata-se de fármaco que, na primeira infância, traz mais dificuldades no manejo. Relata-se exemplo dessa rara doença em lactente, quadro extenso e grave, com resposta satisfatória ao uso de dapsona, com boa tolerabilidade.Generalized pustulous psoriasis is a rare type of psoriasis first described in 1910 by Von Zumbusch. This disease tends to have a more benign development in children when compared to its development in adults. However, in its serious form it may represent a risk to the patient's life. Maybe, due to being such a rare disease no therapeutic option has so far consistently proved to be both effective and safe. Isolated reports suggest that retinoid is the best choice of drug in these cases. However, it is difficult to manage this drug in early infancy. The present report describes a serious case of this rare disease in an infant with a satisfactory response and good tolerance to the use of dapsone.

  3. RELATOS DE PROFESSORAS, ANDANÇAS DE SENTIDOS

    Directory of Open Access Journals (Sweden)

    Mitsi Pinheiro de Lacerda

    2016-03-01

    Full Text Available O artigo trata da natureza inaugural dos relatos de professoras, os quais contêm séculos de conversações. Compreendidos enquanto transportes que conduzem os sentidos postos por elas, alguns relatos são desdobrados para, em seu interior, serem encontradas algumas influências que se prendem ao pensamento. Com isso, a escuta também é afetada, implicando a reflexão epistemológica de quem ouve. O artigo sinaliza que, em sua superfície, a racionalidade técnica predomina em muitas narrativas docentes, e que costuma lhes ser imputada. O texto denuncia a existência não deliberada de concepções mecanicistas nas narrativas docentes. Junto às orientações certeaunianas, abandona os resquícios de um discurso formatado para, talvez, adentrar o espaço habitado pela professora. Palavras-chave: Relatos. Racionalidade Técnica. Formação de Professoras.

  4. Jacob Stael von Holstein ja palladionism eesti arhitektuuris / Ants Hein

    Index Scriptorium Estoniae

    Hein, Ants, 1952-

    2005-01-01

    Sõjaväeinsenerist ja arhitektist Jacob Stael von Holsteinist (1628, Pärnu-1679), tema kavandatud hoonetest ja rollist 17. sajandi II poole arhitektuuris. Fabian von Ferseni Toompeal Lossiplatsil asunud elamust (lammutati 1894) ja Maardu mõisahoonest, Hans von Ferseni Mäo mõisahoonest Järvamaal, Otto Wilhelm von Ferseni majast Toompeal, Axel von Roseni majast Tallinnas Pikk t. 28 (1670-74), Otto Reinhold von Taube majast Tartus (hävinud), J. S. von Holsteini enda hoonetest: majast Tallinnas Toompea 1, Anija mõisahoonest, elamust Riias jm. Bibliograafia lk. 452

  5. Neues über das Tertiär von Java und die mesozoischen Schichten von West-Borneo

    NARCIS (Netherlands)

    Martin, K.

    1888-01-01

    Die Monographie, welche unter dem Titel Die Fossilien von Java herausgegeben wird ¹), ist so weit fortgeschritten, dass sich aus den in ihr beschriebenen Gastropoden bereits eine Anzahl von Schlussfolgerungen ableiten lässt, welche für die in Bearbeitung begriffene, geologische Karte von Java von

  6. Indikatorenbasierte Bewertung von Entwurfsentscheidungen auf Systemebene

    Science.gov (United States)

    Freier, M.; Wenzler, A.; Mayer, T.; Gerlach, J.; Rosenstiel, W.

    2013-07-01

    Bei dem Entwurf von anwendungsspezifischen integrierten Schaltungen muss ein Entwickler zusätzliche Funktionen integrieren und die zunehmende Komplexität bewältigen. Für die Reduzierung der Kosten bleibt weiterhin die Verkürzung der benötigten Entwicklungszeit ein Ziel. Ein entscheidender Faktor dabei ist die zuverlässige Absicherung von Entwurfsentscheidungen in einer frühen Entwurfsphase. In der vorliegenden Arbeit wird eine Methode vorgestellt, die eine Bewertung von Entwurfsentscheidungen bei Systemmodellen mittels automatisch ermittelter Indikatoren ermöglichen soll. Die Systemmodelle können mit der Entwurfsumgebung MATLAB/Simulink oder in SystemC beschrieben sein.

  7. The Digital Von Fahrenheid Pyramid

    Science.gov (United States)

    Bura, M.; Janowski, J.; Wężyk, P.; Zięba, K.

    2017-08-01

    3D Scanners Lab from Digital Humanities Laboratory at the University of Warsaw initiated the scientific project, the purpose of which was to call attention to systematically penetrated and devastated pyramid-shaped tomb from the XVIII/XIX century, of family von Fahrenheid in Rapa in Banie Mazurskie commune (NE Poland). By conducting a series of non-invasive studies, such as 3D inventory using terrestrial laser scanning (TLS), thermal imaging, georadar measurements (around and inside the tomb) and anthropological research of mummified remains as well - the complete dataset was collected. Through the integration of terrestrial (TLS) and airborne laser scanning (ALS) authors managed to analyse the surroundings of Fahrenheid pyriamid and influence of some objects (like trees) on the condition and visibility of the Pyramids in the landscape.

  8. Khazanah: Friedrich Karl von Savigny

    Directory of Open Access Journals (Sweden)

    Atip Latipulhayat

    2015-04-01

    Full Text Available Friedrich Karl von Savigny (1779-1861 adalah ahli hukum Jerman yang juga dianggap sebagai salah satu Bapak hukum Jerman. Savigny adalah tokoh mazhab sejarah (historical school jurisprudence yang dikembangkannya pada paruh pertama abad ke 19. Dia juga dianggap sebagai pelopor kajian mengenai relasi antara perkembangan hukum dan sosial. Sebagai seorang pemikir hukum yang senantiasa kreatif dalam membuat terobosan-terobosan (trail-blazing legal scientist, Savigny memberikan kontribusi penting dalam perkembangan ilmu hukum dan bahkan terhadap ilmu sosial. Dari sekian banyak kontribusinya antara lain teorinya mengenai kontinuitas antara institusi hukum saat ini dengan institusi hukum masa lalu, meletakkan fondasi bagi kajian sosiologi hukum, dan menegaskan mengenai urgensi metode historis dalam kajian hukum.

  9. Evaluierung und Entwicklung von Methoden zur automatisierten Erfassung von Waldstrukturen aus Daten flugzeuggetragener Fernerkundungssensoren

    OpenAIRE

    Heurich, Marco

    2006-01-01

    Auf Grund der rasanten technologischen Entwicklung im Bereich der Sensorik sowie der Computerhard- und -software haben sich in den letzten Jahren neue Perspektiven zur Erforschung von Wäldern ergeben. Im Rahmen dieser durch die High-Tech-Offensive Bayern geförderten Arbeit wurde deshalb untersucht, inwieweit sich der Einsatz neuer Technologien zur automatisierten Erfassung von Waldstrukturen eignet. Als Voraussetzung dafür wurde zunächst ein Referenzgebiet zum Testen von Fernerkundungssensore...

  10. Spezifische Bindung von Aluminium und Eisen an den kationenselektiven Kanal MppA von Microthrix parvicella

    OpenAIRE

    Knaf, Tobias

    2013-01-01

    Schwermetallsalze wie beispielsweise Aluminium- oder Eisensalze werden in der Abwasserbehandlung zur Prävention und Bekämpfung von Blähschlamm, Schwimmschlamm und Schaumbildung verwendet. Dadurch kann eine Verbesserung der Schlammabsetzeigenschaften im Nachklärbecken erreicht werden. Übermäßiges Wachstum des grampositiven Bakteriums Microthrix parvicella gilt dabei als Hauptursache von Schlammabsetzproblemen und kann ebenfalls durch die Dosierung von schwermetallhaltigen Flockungs- und Fällun...

  11. Das Tumorsuppressorprotein p53 - Rolle bei der Induktion von Apoptose und bei der Replikation von Adenoviren

    OpenAIRE

    Koch, Philipp

    2003-01-01

    Das Tumorsuppressorgen p53 gehört zu den zentralen Steuereinheiten von Proliferation und Wachstum in der Zelle. Mutationen und funktioneller Verlust bei diesem Protein ist eng mit der Entstehung maligner Tumoren assoziiert. So kann man in über 50% aller soliden Tumoren Mutationen von p53 nachweisen. Es vermittelt seine Funktion hauptsächlich durch transkriptionelle Aktivierung p53-responsiver Gene. Folge der Aktivierung von p53 is...

  12. Johann Friedrich Wilhelm Adolf von Baeyer

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 6. Johann Friedrich Wilhelm Adolf von Baeyer: A Pioneer of Synthetic Organic Chemistry. Gopalpur Nagendrappa. General Article Volume 19 Issue 6 June 2014 pp 489-522 ...

  13. Von Onlineplattformen und mittelalterlichen Märkten

    Directory of Open Access Journals (Sweden)

    Claudius Gräbner

    2017-12-01

    Full Text Available Mit der zunehmenden Digitalisierung und Vernetzung ökonomischer Systeme haben plattformbasierte Interaktionsbeziehungen stark an Bedeutung gewonnen. Hier werden zwei oder mehr Nutzungsgruppen durch eine dritte Seite, die Plattform, zusammengebracht. Die Interaktion wird in solchen zweiseitigen Märkten von den Plattformbetreibern kontrolliert. Kreditkartensysteme, Softwaremärkte oder werbefinanzierte Online-Communities stellen typische Beispiele dar. Da die Analyse von zweiseitigen Märkten mit Gleichgewichtsmodellen aufgrund der algebraischen Struktur des Problems in der Regel nicht praktikabel ist, präsentieren wir im vorliegenden Beitrag ein agentenbasiertes Modell, welches in einem kürzlich erschienenen Artikel ausführlicher diskutiert wird. Anhand von illustrativen Beispielen verdeutlichen wir die Implikationen eines agentenbasierten Ansatzes für die Innovationsökonomik im Allgemeinen und das Studium von Technologieentwicklung im Besonderen.

  14. Ist Pop die Volksmusik von heute?

    OpenAIRE

    Arbeitskreis Studium Populärer Musik

    1986-01-01

    Zugegeben, die Frage, ob Pop die Volksmusik von heute sei, ist provokant. Genau das war beabsichtigt. Sehr schnell erhielten wir auf unser Vorhaben, ein Seminar zu diesem Thema zu veranstalten, eine Vielzahl von Rückmeldungen. Pop-, Rock- und Jazzspezialisten, Musikwissenschaftler und Musikotiunologen fühlten sich animiert, Stellung zu beziehen und ein Referat zu halten. Intensive Diskussionen schlossen sich an, beflügelt auch durch die ansprechende Atmosphdre in der stil...

  15. Begehrte Körper jenseits von Geschlecht?

    Directory of Open Access Journals (Sweden)

    Corinna Tomberger

    2001-03-01

    Full Text Available Obwohl die visuelle Konstruktion des männlichen Körpers im Mittelpunkt von Daniel Wildmanns Studie steht, gelingt es ihm paradoxerweise, die Kategorie Geschlecht weitgehend zu ignorieren. In seiner Analyse des Films Olympia von Leni Riefenstahl zeigt der Autor auf, wie der ‚arische‘ Körper als Objekt des Begehrens für das Publikum entworfen wird.

  16. Dr. von Braun With German Rocket Experimenters

    Science.gov (United States)

    1930-01-01

    Dr. von Braun was among a famous group of rocket experimenters in Germany in the 1930s. This photograph is believed to be made on the occasion of Herman Oberth's Kegelduese liquid rocket engine being certified as to performance during firing. From left to right are R. Nebel, Dr. Ritter, Mr. Baermueller, Kurt Heinish, Herman Oberth, Klaus Riedel, Wernher von Braun, and an unidentified person.

  17. 50th birthday of Christian von Ferber

    Directory of Open Access Journals (Sweden)

    2011-06-01

    Full Text Available On May 15, 2011 Christian von Ferber - member of the Editorial Board of "Condensed Matter Physics" and renowned expert in the fields of soft matter physics and complex systems - celebrated his 50th birthday. The Editorial board of CMP, colleagues and friends warmy congratulate Christian von Ferber and wish him and his family continuing good health and to enjoy many adventures and discoveries in his future scientific travels!

  18. Dr. von Braun With Management Team

    Science.gov (United States)

    1961-01-01

    Dr. von Braun is shown in this photograph, which was probably taken in the early 1960s, with members of his management team. Pictured from left to right are, Werner Kuers, Director of the Manufacturing Engineering Division; Dr. Walter Haeussermarn, Director of the Astrionics Division; Dr. William Mrazek, Propulsion and Vehicle Engineering Division; Dr. von Braun; Dieter Grau, Director of the Quality Assurance Division; Dr. Oswald Lange, Director of the Saturn Systems Office; and Erich Neubert , Associate Deputy Director for Research and Development.

  19. Hullud päevad von Krahlis

    Index Scriptorium Estoniae

    2006-01-01

    Von Krahli Teatris mängitakse neil päevi neli korda Peeter Jalaka lavastuses Tõnu Kõrvitsa kammeroopereid "Tuliaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libreto autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  20. Visualisierung von typisierten Links in Linked Data

    Directory of Open Access Journals (Sweden)

    Georg Neubauer

    2017-09-01

    Full Text Available Das Themengebiet der Arbeit behandelt Visualisierungen von typisierten Links in Linked Data. Die wissenschaftlichen Gebiete, die im Allgemeinen den Inhalt des Beitrags abgrenzen, sind das Semantic Web, das Web of Data und Informationsvisualisierung. Das Semantic Web, das von Tim Berners Lee 2001 erfunden wurde, stellt eine Erweiterung zum World Wide Web (Web 2.0 dar. Aktuelle Forschungen beziehen sich auf die Verknüpfbarkeit von Informationen im World Wide Web. Um es zu ermöglichen, solche Verbindungen wahrnehmen und verarbeiten zu können sind Visualisierungen die wichtigsten Anforderungen als Hauptteil der Datenverarbeitung. Im Zusammenhang mit dem Sematic Web werden Repräsentationen von zuhammenhängenden Informationen anhand von Graphen gehandhabt. Der Grund des Entstehens dieser Arbeit ist in erster Linie die Beschreibung der Gestaltung von Linked Data-Visualisierungskonzepten, deren Prinzipien im Rahmen einer theoretischen Annäherung eingeführt werden. Anhand des Kontexts führt eine schrittweise Erweiterung der Informationen mit dem Ziel, praktische Richtlinien anzubieten, zur Vernetzung dieser ausgearbeiteten Gestaltungsrichtlinien. Indem die Entwürfe zweier alternativer Visualisierungen einer standardisierten Webapplikation beschrieben werden, die Linked Data als Netzwerk visualisiert, konnte ein Test durchgeführt werden, der deren Kompatibilität zum Inhalt hatte. Der praktische Teil behandelt daher die Designphase, die Resultate, und zukünftige Anforderungen des Projektes, die durch die Testung ausgearbeitet wurden.

  1. Relato autobiográfico e identidad personal: Un modelo de análisis narrativo

    Directory of Open Access Journals (Sweden)

    Dante Duero

    2007-05-01

    Full Text Available En el siguiente trabajo analizamos cómo las estrategias narrativas que las personas emplean para construir relatos autobiográficos condiciona sus formas de pensar acerca de sí mismas, el mundo y sus propias acciones. Hemos partido del supuesto de que la organización y la coherencia de esta clase de relatos constituyen un aspecto clave para entender el problema de la identidad personal. Analizamos los relatos autobiográficos de dos muestras de estudiantes universitarios, pertenecientes a la Universidad Nacional de Córdoba (Argentina a la Universidad Autónoma de México (México. Nos hemos propuesto, en primer lugar, describir y analizar los diferentes relatos autobiográficos que obtuvimos en ambas muestras a través de entrevistas en profundidad. A través de dicho análisis, hemos procurado caracterizar el proceso de construcción narrativa, estableciendo la estructura y las funciones que los elementos del relato cumplen en su organización, contribuyendo a su coherencia y composición. Teniendo en cuenta esto, y teniendo en cuenta los datos de ambos grupos, intentamos, por una parte, identificar diferentes tipos de relatos. Simultáneamente, analizamos cómo las características de las historias condicionaba el modo en que las personas construyen su propia identidad, en tanto personajes de tales relatos.

  2. Prolapso uterino em felinos: relato de um caso

    OpenAIRE

    Soares, Jefferson Aparecido Guillen; Universidade Estadual de Londrina; Suzuki, Luci Mitiko; Universidade Estadual de Londrina,

    1992-01-01

    Relato de um caso de prolapso uterino pós-parto em uma gata, S.R.D., primípara, com 12 meses de idade, atendida pela área de Reprodução e Obstetrícia Animal do Hospital Veterinário da Universidade Estadual de Londrina. O prolapso ocorreu em ambos os comos e corpo uterinos, caracterizando um prolapso uterino completo, que perdurou por 4 dias.     A case of pos-partum uterine prolapse in a 12-month-old crossbred cat, assisted in the Veterinary Hospital-State University of Londrina. The ut...

  3. Estado confusional e enxaqueca infantil: relato de um caso

    Directory of Open Access Journals (Sweden)

    Deusvenir de Souza Carvalho

    1986-03-01

    Full Text Available Relato do caso de um paciente masculino, que teve episódios de confusão e déficits motores aos 5, 9 e 11 anos de idade e que foi internado nessas três ocasiões. Toda investigação resultou normal exceto o EEG. A chave para o diagnóstico clínico de estado confusional devido a enxaqueca foi dada pelo fato de ter o paciente apresentado várias crises de enxaqueca dos 9 aos 11 anos. Considerações sobre a fisiopatologia, baseadas na literatura, são apresentadas.

  4. Privatiserung von Geschichte. Probleme einer differenzierten Aufarbeitung

    Directory of Open Access Journals (Sweden)

    Birthe Kundrus

    2000-11-01

    Full Text Available Ausgangspunkt der Untersuchung von Vera Neumann ist die These, daß im Krieg Erlebtes und Erlittenes in den Wiederaufbau- und Wirtschaftswunderjahren Westdeutschlands einem Thematisierungstabu unterlegen sei. Anhand von 50 Interviews, die in den 80er Jahren im Rahmen des von Lutz Niethammer geleiteten Projekts „Lebensgeschichte und Sozialgeschichte im Ruhrgebiet 1930–1960“ (LUSIR entstanden sind und die sie jetzt anhand der Tonbandprotokolle und Abschriften ein zweites Mal auswertet, möchte die Historikerin diese Verschüttungen aufspüren. Im Anschluß an Niethammers These der „Privatisierung von Geschichte“ will sie zeigen, daß seelische und körperliche Kriegsfolgen wie Deprivations- und Überlastungsgefühle, der Verlust von Angehörigen und Kriegsbeschädigungen „privatisiert“, d.h. an die Familien übertragen wurden. Dort seien dann in erster Linie die weiblichen Familienmitglieder mit der Versorgungs- und Pflegearbeit konfrontiert worden. An vier Fallbeispiele schließt sich eine detaillierte Auswertung des gesamten Interviewmaterials an. Diesen Teilen folgt ein Abschnitt zur staatlichen Kriegsopferversorgung in der frühen Bundesrepublik.

  5. An MRI Von Economo - Koskinas atlas.

    Science.gov (United States)

    Scholtens, Lianne H; de Reus, Marcel A; de Lange, Siemon C; Schmidt, Ruben; van den Heuvel, Martijn P

    2016-12-28

    The cerebral cortex displays substantial variation in cellular architecture, a regional patterning that has been of great interest to anatomists for centuries. In 1925, Constantin von Economo and George Koskinas published a detailed atlas of the human cerebral cortex, describing a cytoarchitectonic division of the cortical mantle into over 40 distinct areas. Von Economo and Koskinas accompanied their seminal work with large photomicrographic plates of their histological slides, together with tables containing for each described region detailed morphological layer-specific information on neuronal count, neuron size and thickness of the cortical mantle. Here, we aimed to make this legacy data accessible and relatable to in vivo neuroimaging data by constructing a digital Von Economo - Koskinas atlas compatible with the widely used FreeSurfer software suite. In this technical note we describe the procedures used for manual segmentation of the Von Economo - Koskinas atlas onto individual T1 scans and the subsequent construction of the digital atlas. We provide the files needed to run the atlas on new FreeSurfer data, together with some simple code of how to apply the atlas to T1 scans within the FreeSurfer software suite. The digital Von Economo - Koskinas atlas is easily applicable to modern day anatomical MRI data and is made publicly available online. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Von der Universitätsbibliothek Regensburg zum Bayerischen Bibliotheksverbund

    OpenAIRE

    Frankenberger, Rudolf

    1989-01-01

    Von der Universitätsbibliothek Regensburg zum Bayerischen Bibliotheksverbund : d. Entwicklung d. Bayer. Bibliotheksverbundes. - In: Bibliothekslandschaft Bayern : Festschr. für Max Pauer zum 65. Geburtstag / hrsg. von Paul Niewalda. - Wiesbaden : Harrassowitz, 1989. - S. 84-96

  7. Kerttu Wagner. Die historischen romane von Jaan Kross / Wolfgang Drechsler

    Index Scriptorium Estoniae

    Drechsler, Wolfgang, 1963-

    2001-01-01

    Arvustus: Wagner, Kerttu. Die historischen Romane von Jaan Kross : am Beispiel einer Untersuchung der deutschen und englischen Übersetzungen von "Professor Martensi ärasõit" (1984). Frankfurt am Main [etc.] : P. Lang, 2001.

  8. Gemeinsam hilfreich oder einsam lästig? Beurteilung von praktikumsbegleitenden Weblogs von angehenden Lehrpersonen

    Directory of Open Access Journals (Sweden)

    Nives Egger

    2017-02-01

    Full Text Available Weblogs werden an Hochschulen vermehrt zur Unterstützung von Lern- und Reflexionsprozessen eingesetzt, in der Lehrer/innenbildung auch zunehmend während der berufspraktischen Ausbildung. Die Studierenden beurteilen den Einsatz von Weblogs jedoch unterschiedlich. Dabei ist wenig bekannt, welchen Einfluss die Vergabe und das Erhalten von Peerfeedback auf den Beurteilungsprozess von praktikumsbegleitenden Weblogs sowie auf den Umfang von Blogpostings haben. Im folgenden Beitrag wird dieser Frage mittels einer Befragung von 74 angehenden Lehrpersonen nachgegangen, die praktikumsbegleitende Weblogs mit oder ohne Peerfeedback nutzten, um über herausfordernde Ereignisse im Praktikum zu reflektieren. Die Ergebnisse zeigen, dass Studierende, die Peerfeedback erhielten und andere Blogbeiträge kommentierten, den Weblogeinsatz nützlicher einschätzen sowie eine höhere Motivation und positivere Einstellung gegenüber den Einsatz von Weblogs aufweisen als Studierende, die ohne Peerfeedback bloggen. Keinen Einfluss hat Peerfeedback auf den Umfang der Blogbeiträge und auf die dafür aufgewendete Zeit.

  9. Polylaktidbeschichtung zur antithrombogenen Ausrüstung von Biomaterialien

    OpenAIRE

    Mebus, Siegrun

    2007-01-01

    In der Klinik etablierte Biomaterialien wurden mit einer Polylaktidbeschichtung und eingearbeiteten Antikoagulanzien ausgerüstet. Die mit einem in-vitro-Modell erarbeiteten Daten zeigen, daß der Arzneistoffträger innerhalb von 90 Tagen nicht abgebaut wurde. Die Freisetzung der Arzneistoffe erfolgte abhängig von deren Konzentration und dem Mischungsverhältnis von Iloprost und Hirudin. Iloprost beeinflußt die Freisetzungsrate von PEG-Hirudin bzw. r-Hirudin. Es konnte mit mikrobiologischen Metho...

  10. Nutzung der Eisenkorrosion zur Entfernung von Arsen aus Trinkwasser

    OpenAIRE

    Karschunke, Karsten

    2005-01-01

    In dieser Arbeit werden experimentelle Untersuchungen zur Nutzung von Eisenkorrosionsprozessen zur Entfernung von Arsen aus Trinkwasser vorgestellt. Auch in geringen Konzentrationen stellt diese Verunreinigung auf Grund der krebserregenden Wirkung von Arsen langfristig eine Gefahr für die menschliche Gesundheit dar. Verschiedene Entfernungsmethoden sind bekannt und in der Praxis der Trinkwasseraufbereitung bewährt, beispielsweise Flockungsverfahren unter Einsatz von Eisensalzen oder die Adsor...

  11. Liouville-von Neumann molecular dynamics.

    Science.gov (United States)

    Jakowski, Jacek; Morokuma, Keiji

    2009-06-14

    We present a novel first principles molecular dynamics scheme, called Liouville-von Neumann molecular dynamics, based on Liouville-von Neumann equation for density matrices propagation and Magnus expansion of the time-evolution operator. The scheme combines formally accurate quantum propagation of electrons represented via density matrices and a classical propagation of nuclei. The method requires a few iterations per each time step where the Fock operator is formed and von Neumann equation is integrated. The algorithm (a) is free of constraint and fictitious parameters, (b) avoids diagonalization of the Fock operator, and (c) can be used in the case of fractional occupation as in metallic systems. The algorithm is very stable, and has a very good conservation of energy even in cases when a good quality conventional Born-Oppenheimer molecular dynamics trajectories is difficult to obtain. Test simulations include initial phase of fullerene formation from gaseous C(2) and retinal system.

  12. Gasification of liquid manure; Vergasung von Guelle

    Energy Technology Data Exchange (ETDEWEB)

    Gudenau, H.W.; Hoberg, H.; Hirsch, U. [Technische Hochschule Aachen (Germany). Inst. fuer Eisenhuettenkunde

    1996-12-31

    The potential of thermal use of liquid manure is investigated. It is recommended to separate the liquid and solid fraction. While the liquid fraction can be used as fertilizer, the solid fraction can be used for generating a fuel gas for combined heat and power generation. (orig) [Deutsch] Die Untersuchungen haben ergeben, dass in der thermischen Verwertung von Guelle ein bisher nur wenig genutztes Potential vorliegt. Die zum Anbau von Getreide notwendige Duengung kann durch Separation von Guelle in Fest- und Duennfraktion effektiver und kostenguenstiger durchgefuehrt werden. Der Naehrstoffgehalt des Guellefeststoffs sollte durch thermische Aufbereitung aufkonzentriert werden, so dass eine Vermarktung auch mit laengeren Transpoertwegen darstellbar ist. Die bei der thermischen Behandlung gewonnene Waerme kann prozessintern genutzt und ueberschuessige Waerme an Abnehmer in der naeheren Umgebung geliefert werden. Genauso besteht die Moeglichkeit, ein Brenngas zu erzeugen und die Energie mit Kraft-Waerme-Kopplung zu nutzen. (orig)

  13. [Anja Wilhelmi. Lebensweltlen von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien] / Alexander Ewig

    Index Scriptorium Estoniae

    Ewig, Alexander, 1980-

    2011-01-01

    Arvustus: Wilhelmi, Anja. Lebenswelten von Frauen der deutschen Oberschicht im Baltikum (1800-1939). Eine Untersuchung anhand von Autobiographien. (Veröffentlichungen des Nordost-Instituts, 10.) (Wiesbaden : HArrassowitz 2008)

  14. Wachstum und Aufbau von Spongomorpha aeruginosa (Chlorophyta, Acrosiphoniales)

    NARCIS (Netherlands)

    Kornmann, Peter

    1967-01-01

    In zahlreichen Arbeiten dienten Algen als Objekte für das Studium von Regenerationsvorgängen und Erscheinungen der Polarität. Dagegen ist — von Chara abgesehen — über das normale Wachstum, den zeitlichen Ablauf von Teilung und Streckung der Zellen und die Entstehungsgeschichte des typischen Thallus

  15. Modellierung von Dienstleistungen mittels Business Service Blueprinting Modeling

    OpenAIRE

    Meis, Jochen; Menschner, Philipp; Leimeister, Jan Marco

    2010-01-01

    Der Beitrag stellt mit Business Service Blueprint Modeling (BSBM) einen konzeptionellen Ansatz zur Modellierung von Dienstleistungen vor, der ein systematisches und standardisiertes Vorgehen zur Modellierung von Dienstleistungen mit Kundeninteraktion anstrebt. BSBM verwendet hierzu die Business Process Modeling Notation (BPMN) in einem Service Blueprint (SB). Somit wird ein Modellierungskonzept geschaffen, das sowohl Kundeninteraktionspunkte berücksichtigt als auch von aktuellen Werkzeugen un...

  16. Spectral theory and quotients in Von Neumann algebras | West ...

    African Journals Online (AJOL)

    In this note we consider to what extent the functional calculus and the spectral theory in von Neumann algebras are preserved by the taking of quotients relative to two-sided ideals of the von Neumann algebra. Keywords:von Neumann algebra, functional calculus, spectral theory, quotient algebras. Quaestiones ...

  17. Market Timing und Finanzierungsentscheidungen: Unterscheidet sich Europa von den USA?

    NARCIS (Netherlands)

    Sautner, Z.; Spranger, J..

    2009-01-01

    Seit der Arbeit von Baker/Wurgler (2002) hat sich die Market-Timing-Theorie als alternative Kapitalstrukturtheorie etabliert. Sie impliziert, dass die Kapitalstruktur von Unternehmen das kumulierte Ergebnis von Versuchen des Equity Market Timing ist. Im Rahmen dieser Studie wird untersucht,

  18. Bewertung von Fahrzeuggeräuschen

    Science.gov (United States)

    Genuit, Klaus; Schulte-Fortkamp, Brigitte; Fiebig, André; Haverkamp, Michael

    Bei der Wahrnehmung und Beurteilung eines Automobils sind unzählige Merkmale und Eigenschaften von Bedeutung. Dabei können Merkmale objektiv-technisch beschrieben werden, wie Angaben zur Motorisierung, Höchstgeschwindigkeit, Drehmoment, zulässige Zuladung, Verbrauch usw. Daneben sind weitere Eigenschaften von Bedeutung, die sich einer einfachen objektiv-technischen Beschreibung entziehen. Hier sind Begriffe zu nennen, wie Sicherheit, allgemeine Qualitätsanmutung, Design, Ergonomie, Komfort, Haptik, Fahrdynamik, Zuverlässigkeit, die deutlich schwieriger objektiv erfassbar und beschreibbar sind (Abb. 4.1).

  19. [Von Recklinghausen disease and hepatic neurofibromatosis].

    Science.gov (United States)

    Guzman Toro, F; Hinestroza, D; Colmenares, D

    1995-01-01

    Von Recklinghausen's neurofibromatosis is one of the most common autosomal dominant disease with an estimated frecuency of 1:3000 live births. Characteristic lesions include cafe-au-lait spots and neurofibromas following the path of peripheral nerves. Liver involvement by neurofibromatosis is rare and very few cases have been reported. We present a case of a young man with Von Recklinhausen's disease and hepatic neurofibromatosis with multiple caf-au-lait spots, cutaneous neurofibromas, short stature and osseous lesions and compare the clinical, radiological, surgical and anatomopathological findings with others describe previously in the literature.

  20. Zur Aktivierung des Verbundtragverhaltens von Glaslaminaten

    OpenAIRE

    Sastré-Terrasa, Johannes (Hanno)

    2007-01-01

    Für jedes konstruktiv planerische Handeln ist ein fundiertes Wissen über die Baustoffe primäre Voraussetzung. Das trifft für Glas, auf Grund der Komplexität des Materialverhaltens, im besonderen Maße zu. Diese Arbeit beschäftigt sich deshalb zunächst mit dem Werkstoff Glas, den Grundlagen zum schadensfreien Fügen von Glas sowie dem Verhalten seiner Fügepartner. Die wichtigste Methode, das Kleben von Glas, wird im Wesentlichen durch die viskoelastischen und temperaturabhängig...

  1. Erwachsenenbildung im Spannungsfeld von Wissenschaft, Politik und Praxis: Heide von Felden, Christiane Hof und Sabine Schmidt-Lauff (Hrsg.). [Rezension

    OpenAIRE

    Filla, Wilhelm

    2016-01-01

    Rezension von: Felden, Heide von/Hof, Christiane/Schmidt-Lauff, Sabine (Hrsg.) (2013): Erwachsenenbildung im Spannungsfeld von Wissenschaft, Politik und Praxis. Dokumentation der Jahrestagung der Sektion Erwachsenenbildung der Deutschen Gesellschaft für Erziehungswissenschaften vom 27. bis 29. September 2012. Baltmannsweiler: Schneider Verlag Hohengehren.

  2. Die Verteilung und Eigenschaften von Bodenformen in der Deutschen Bucht, eine Rekonstruktion der Karten von Ulrich (1973)

    DEFF Research Database (Denmark)

    Winter, Christian; Lefebvre, Alice; Benninghoff, Markus

    2015-01-01

    Entstehung, Gestalt und Dynamik von Bodenformen in vergleichsweise kleinen Untersuchungsgebieten ist die Arbeit von ULRICH (1973) über die Verteilung von Bodenformen in der Deutschen Bucht bis heute die einzige verfügbare zusammenhängende Darstellung für die deutsche Nordseeküste. Die analogen Karten und die...

  3. Der Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer

    Directory of Open Access Journals (Sweden)

    Thomas Schmuck

    2012-10-01

    Full Text Available Zusammenfassung Der kurze, nicht vollständig erhaltene Briefwechsel zwischen Alexander von Humboldt und Karl Ernst von Baer behandelt sehr verschiedene Themen: Politik, Kriegsgefahr, den Wissenschaftsbetrieb, Auszeichnungen und Tagungen, Embryologie und Cholera. Gemeinsam mit Briefen und Reden ergibt sich dabei ein differenziertes Bild der Beurteilung der beiden Wissenschaftler durch den jeweils anderen. Während Baer sich als Bewunderer Humboldts erweist, erscheint umgekehrt Humboldts Einschätzung Baers als ambivalent. Abstract The short, not completely preserved correspondence between Alexander von Humboldt and Karl Ernst von Baer deals with a wide range of subjects: politics and the danger of war, academic activities, scientific awards and conferences, aspects of embryology and the cholera. Letters to third persons and speeches, together with the correspondence between Humboldt and Baer show a differentiated pattern of mutual appraisal: While Baer always remained an admirer of the elder naturalist, Humboldt’s estimation was characterized by ambivalence.

  4. Diabetes insipidus traumático: relato de caso

    Directory of Open Access Journals (Sweden)

    M. A. Oliveira

    1993-11-01

    Full Text Available Trata-se do relato do caso de paciente do sexo feminino, com 39 anos, politrau-matizada, que desenvolveu quadro de diabetes insipidus. A paciente faleceu onze dias após sua internação, período em que foram realizadas tomografia computadorizada e ressonância magnética, evidenciando lesões hipotalâmicas características. Estes fatos nos estimularam revisar a literatura e chamar a atenção para prevenção e prognóstico de síndromes endocrinas que podem acometer secundária e tardiamente pacientes vítimas de traumatismo crânio-encefálico e que, se diagnosticadas e tratadas de maneira precoce, podem ter sua morbidade diminuída.

  5. Úlcera de Marjolin: relato de 12 casos

    OpenAIRE

    Bauk,Vanessa O. Zagne; Assunção,Aline Mesquita; Domingues, Renata Ferreira; Nurimar C. Fernandes; Maya,Tullia Cuzzi; MACEIRA, Juan Piñeiro

    2006-01-01

    Relato de 12 casos de úlcera de Marjolin observados de 1990 a 2003 no HUCFF-UFRJ. Cinco pacientes do sexo feminino e sete do masculino, com idade variando de 38 a 86 anos. Tempo de evolução de 10 a 50 anos, da cicatriz até surgimento do carcinoma espinocelular. Ressecção da lesão em dois casos e amputação terapêutica em oito. Em um caso realizada exérese paliativa da lesão por apresentar metástase para coluna sacrococcígea. Um caso de impossibilidade terapêutica. Concluiu-se que a biópsia é e...

  6. Contar el exilio: Relatos sobre fronteras en la frontera

    Directory of Open Access Journals (Sweden)

    Nora Ricaud

    2009-07-01

    Ambos libros piden ser leídos no como textos cerrados, sino como un continuum, en tanto la escritura los presenta enlazados en un devenir de un texto en el otro, y del contenido en la forma. Cada una de estas historias es una estación del exilio. Una, subsumida en la otra; una, parida por la otra. El relato en primera persona cuenta tanto el exilio propio como el ajeno, transitando bordes en donde el juego de espejos oblitera la posibilidad de distinguir lo propio y lo ajeno, el sí mismo y el Otro. Es por ello que lo apropiado parece ser un abordaje que eluda la estabilización del sentido y que sea capaz de hacerse cargo del carácter insaturable de la escritura de Tununa Mercado.

  7. Paracoccidioidomicose palpebral: relato de três casos

    Directory of Open Access Journals (Sweden)

    Rocha Guilherme José Nunes Marques

    2002-01-01

    Full Text Available Objetivo: Relato clínico-patológico de três casos de paracoccidioidomicose multifocal comprometendo pálpebra e secundariamente a conjuntiva em dois deles. Métodos: Revisão dos prontuários e preparações histopatológicas obtidas das biópsias. Resultado: O estudo histopatológico realizado nos três casos, evidenciou reação inflamatória de tipo granulomatoso. A coloração pelo método de Grocott demonstrou a presença do Paracoccidioides brasiliensis. Conclusão: É importante a inclusão da paracoccidioidomicose no diagnóstico diferencial de lesões tumorais acometendo as pálpebras.

  8. SÍNDROME DE LERICHE – RELATO DE CASO

    OpenAIRE

    Fagundes da Costa Jr., Antônio; Alves da Silva, Silvio; Oliveira Mendes, Gabriella; Veiga Garbelini, Diogo; Martins Freitas Albuquerque, Wania; Nimrichter Valle, Carolina; Beltran Gondo, Fernando Hirohito; Barros Prehl, Vinícius

    2016-01-01

    O relato a seguir traz o caso de um paciente de 49 anos que apresentava a tríade: claudicação de coxas, diminuição ou ausência de pulsos femorais e disfunção erétil. Paciente foi diagnosticado com síndrome de Leriche, sendo que além do acometimento aorto-ilíaco, também apresentava lesão multissegmentar de artérias de membros inferiores, incluindo o acometimento difuso da artéria femoral profunda, em um paciente relativamente jovem. Para a realização do diagnóstico foi utilizado somente um exa...

  9. Anestesia em paciente com saturnismo: relato de caso

    OpenAIRE

    Lima,Luís Mauro Alvim de; Resende, Flávio Castro; Santos, Ana Carolina Janiques dos; Terra, Patricia Pimentel Duarte Rodrigues; Pantoja, Alberto Vieira; de Resende, Marco Antonio Cardoso

    2012-01-01

    JUSTICATIVA E OBJETIVOS: O saturnismo decorre da intoxicação crônica pelo chumbo, comum após exposição ocupacional. Projéteis retidos no corpo podem resultar em elevados níveis plasmáticos de chumbo com inúmeras repercussões clínicas, principalmente neurológicas. Apresentamos um caso de paciente sintomático, sem diagnóstico, que foi detectado durante visita pré-anestésica. RELATO DO CASO: Paciente apresentado para retirada de projétil alojado em joelho esquerdo há 14 anos, com polineuropatia ...

  10. Síndrome de Asperger: relato de um caso

    Directory of Open Access Journals (Sweden)

    Letícia Viana Pereira

    2012-04-01

    Full Text Available Objetivo: O presente estudo tem como real objetivo o relato de um caso de Síndrome de Asperger comprado às características descritas na literatura. Metodologia: A partir de um relato de um caso atendido na Clínica Escola de Fonoaudiologia do Centro Universitário Metodista Izabela Hendrix, determinadas características foram comparadas com o descrito na literatura pertinente. Os trabalhos foram lidos, fichados e agrupados, segundos algumas características de abordagem, para posterior análise e comparação com o caso clínico relatado. Discussão e resultados: As crianças com Síndrome de Asperger são, em geral, diferentes entre si. Freqüentemente procedimentos realizados que podem ser indicados para uma criança seriam inadequados para outra. Assim, sugestões apresentadas pela literatura devem ser consideradas para melhorar a assistência à criança, como a compreensão mais abrangente e a reflexão aprofundada em relação a cada caso em específico. Conclusão: O acompanhamento e tratamento fonoaudiológico nesses casos, é de suma importância para o desenvolvimento o mais próximo possível do considerado formal na linguagem e na comunicação destes indivíduos. Vivências clínicas mostram as estratégias que podem ser sugeridas para estas crianças, lembrando que casa criança possui suas particularidades, que devem sempre ser levadas em consideração.

  11. Interpenetration bei Parsons und Luhmann : Von der Integration zur Produktion von Unordnung

    OpenAIRE

    Künzler, Jan

    2010-01-01

    Talcott Parsons hatte den Interpenetrationsbegriff eingeführt, um strukturelle Beziehungen zwischen verschiedenen System arten erfassen zu können. Niklas Luhmann übernimmt den Begriff von Parsons und benutzt ihn nach weitreichenden Revisionen v. a. dazu, das Verhältnis von psychischen und sozialen Systemen auf den Begriff zu bringen. In dieser Intersystembeziehung spielt Sprache eine entscheidende Rolle. Ein systemtheoretisches Sprachkonzept, das dieser Vermittlungsleistung Rechnung trägt, st...

  12. Dentinhaftung von Zementen. Der Haftverbund von Zementen mit Dentin in Kombination mit verschiedenen indirekten Restaurationsmaterialien

    OpenAIRE

    Peutzfeldt, Anne; Sahafi, Alireza; Flury, Simon

    2011-01-01

    Einleitung: Die Anzahl zahnärztlicher Zemente sowie Restaurationsmaterialien steigt stetig. Die richtige Zementwahl für einen zuverlässigen Haftverbund zwischen Restaurationsmaterial und Zahnsubstanz ist von Interesse für den Kliniker. Ziel der vorliegenden in vitro-Studie war es daher, den Dentinhaftverbund von verschiedenen Zementen in Kombination mit verschiedenen indirekten Restaurationsmaterialien zu untersuchen. Material und Methoden: Zylindrische Probekörper aus sechs Restaurations...

  13. Identifizierung von Mikrodomän-Proteinen und funktionelle Charakterisierung von Cholesterin im Golgi-Apparat

    OpenAIRE

    Stüven, Ernstpeter

    2002-01-01

    Mittels Detergenzextraktion von Golgimembranen bei 0°C mit anschließender Dichtegradientenzentrifugation wurden sphingolipid- und cholesterinreiche Mikrodomänen isoliert, die zehn Proteine entsprechend der Coomassiefärbung in der SDS-PAGE enthalten. Im Rahmen dieser Arbeit wurden die zwei bisher nicht charakterisierten Proteine mit Molekulargewichten von 72 und 56 kDa als Untereinheiten A und B der vakuolären ATPase identifiziert. Daneben konnte mit NAP-22 eine elfte Komponente identifiziert ...

  14. Der "Bindungsfragebogen" von Grau und der "Bielefelder Fragebogen zu Partnerschaftserwartungen" von Hoger und Buschkamper im Vergleich

    National Research Council Canada - National Science Library

    Ina Grau; Ulrich Clashausen; Diether Hoger

    2003-01-01

    ...". Das Bindungsmuster ergibt sich aus der speziellen anhand von Clusteranalysen ermittelten Konfiguration der Skalen. In Clusteranalysen mit dem BinFB wurden vier Cluster aufgefunden, mit dem BFPE funf Cluster. Wahrend vier der BFPE-Cluster recht gut mit den vier BinFB-Clustern ubereinstimmen, wird eine funfte Personengruppe vom BFPE als "vermeidend-offnungsbereit" und von BinFB als "sicher" klassifiziert. Beide Interprctationsmoglichkeiten werden unter besonderer Berucksichtigung der Skala "Zuwendungsbedurfn...

  15. Authentizität von Milch und Fisch – Erkennung von Bioprodukten im Labor

    OpenAIRE

    Molkentin, Joachim

    2008-01-01

    Die Nachfrage nach Bio-Lebensmitteln ist in Deutschland in den letzten Jahren stetig gestiegen. So erhöhte sich der Absatz von Bio-Trinkmilch in 2007 im Vergleich zum Vorjahr erneut um 34 %. Aufgrund sporadisch resultierender Lieferengpässe bei Bio-Milch aber auch der erheblichen Handelspreisdifferenz – wie z. B. insbesondere bei Bio-Lachs – besteht ein potenzielles Risiko der Falschdeklaration konventioneller Produkte als Bio-Ware. Zum Schutz von Verbrauchern wie auch Erzeugern werden dah...

  16. Die Rezeptionsgeschichte von Ulrich Schmidels Wahrhaftige Beschreibung von 1567 bis heute

    OpenAIRE

    Obermeier, Franz

    2001-01-01

    Schmidels Werk hat bisher nur in Ansätzen die ihm zustehende Würdigung als eines der wichtigsten Quellenwerke der frühen Kolonialzeit Südamerikas erfahren. Es stand lange Zeit im Schatten des bekannteren und auch literarisch ansprechenderen Reisebuchs von Hans Staden (Wahrhaftige Historia, Marburg 1557), dessen persönliche Schilderung seiner Gefangenschaft dem modernen Leser durch den geschickten Einsatz von narrativen Elementen entsprechend der heutigen Genretradition des persönlich gefasste...

  17. Analyse von Arbeitsplätzen auf halbautomatischen Pflanzmaschinen mit Hilfe von MTM (Methods Time Measurement)

    OpenAIRE

    Remmele, Edgar

    2017-01-01

    Mit Hilfe von MTM (Methods Time Measurement), einem System vorbestimmter Zeiten, werden Bewegungsstudien an drei verschiedenen halbautomatischen Pflanzmaschinen durchgeführt. Hauptunterscheidungsmerkmal der untersuchten Pflanzmaschinen ist die Methode der Übergabe der Pflanze von der Pflanzperson an die Pflanzmaschine. Analysiert wird der Arbeitsplatz der Pflanzmaschine ACCORD-Standard mit der Methode Klemmscheibe, PES-Beetpflanzer 1500/1900 mit der Methode Pflanzfinger und Lännen RT-2 mit de...

  18. Zur Entwicklung von Containerschiffsflotten : eine Paneldatenanalyse

    OpenAIRE

    Prinz, Alexander; Schulze, Peter M.

    2004-01-01

    Diese Arbeit untersucht die regional aggregierten Containerschiffsflotten der wichtigsten Wirtschaftsräume entlang der Hauptverkehrsrouten der Seeschifffahrt. Anhand einer Paneldatenanalyse mit festen Effekten werden die positive Abhängigkeit der Containerschifffahrt von Weltwirtschaft und Welthandel quantifiziert und erklärende Variablen für die Entwicklung der Containerschifffahrt identifiziert.

  19. Von Kalifornien nach Taxham / Katri Soe

    Index Scriptorium Estoniae

    Soe, Katri, 1971-

    2005-01-01

    Neljas osa magistritööst "Von Kalifornien nach Taxham: Formen und Strukturen der Kommunikation in Peter Handkes Romanen "Der kurze Brief zum langen Abschied" und "In einer dunklen Nacht ging ich aus meinem stillen Haus"" (Tartu, 2000. Juhendaja: Claus Sommerhage)

  20. Euler-Chelpin, Prof. Hans von

    Indian Academy of Sciences (India)

    Euler-Chelpin, Prof. Hans von. Nobel Laureate (Chemistry) - 1929. Date of birth: 15 February 1873. Date of death: 6 November 1964 ... Posted on 21 December 2017. ASTROPHYSICS: An Observational View of the Universe. Math Art and Design: MAD about Math, Math Education and Outreach. Math and Finance ...

  1. Ueberreste vorweltlicher Proboscidier von Java und Banka

    NARCIS (Netherlands)

    Martin, K.

    1884-01-01

    Junghuhn führte in seinem Werke über Java nur einen einzigen Wirbelthierrest, Carcharias megalodon, an (7, IV, pag. 97); es war ihm nicht gelungen bei seinem ersten Aufenthalte auf der Insel Reste von Säugethieren zu finden, so eifrig er auch darnach in den Höhlen des Tertiaergebirges suchte (7, IV,

  2. Alte und neue Scyphomedusen von Australien

    NARCIS (Netherlands)

    Stiasny, G.

    1926-01-01

    In einer Collection Coelenterata, von verschiedenen australischen Fundorten herrührend, die mir vom Direktor des Australian Museum in Sydney, Dr. Ch. Anderson, zur Untersuchung übersendet wurden, fanden sich auch einige Scyphomedusen, die in den australischen Gewässern bisher noch nicht nachgewiesen

  3. Eigenschaften von Gott. Eine quantitative Analyse

    Directory of Open Access Journals (Sweden)

    Thomas Benesch

    2016-12-01

    Full Text Available ENGLISH: A quantitative research on 32 pupils of an elementary school (third and fourth class was performed. The questions regarded to socio-demographic issues as well as so called opposition pairs for God. These opposition pairs include the semantic differential of the loving God combined with the selection of 27 opposition pairs which were derived from literature. The image of God has been developed due to a factor analysis with respect to human and divine properties. These characteristics are depending on the religious education of children as well as their habits of reading in the Holy Bible. DEUTSCH: Eine quantitative Erhebung von 32 Volksschulkindern einer 3. und 4. Klasse wurde einerseits mit erweiterten sozio-demographischen Fragen und gleichzeitig mit Gegensatzpaaren für Gott beschrieben. Die Gegensatzpaare beinhalteten das semantische Differential des liebenden Gottes zusammen mit einer Auswahl von 27 Gegensatzpaaren, die deduktiv aus der Literatur abgeleitet wurden. Das Gottesbild hat sich anhand einer Faktorenanalyse darin entwickelt, dass Gott einerseits mit menschlichen Attributen versehen wird und andererseits mit Eigenschaften von Gott. Diese Eigenschaften von Gott sind abhängig davon, ob die Kinder religiös erzogen werden und ob sie gerne die Heilige Schrift lesen.

  4. Measurements and von Neumann projection/collapse

    Indian Academy of Sciences (India)

    unwanted superpositions of (system + apparatus)-states can be shown to be suppressed, leading eventually to the projection/collapse rule postulated in von Neumann's treatment of measurements [3]. In the next section, the measurement problem in quantum mechanics (QM) is recalled. In §3, some proposed improvements ...

  5. Guido von Pirquet: Austrian pioneer of astronautics

    Science.gov (United States)

    Sykora, F.

    1977-01-01

    The works of Guido von Pirquet, Austrian pioneer of rocketry, were assessed. Major emphasis was given to Pirquet's calculation of the route to Venus which in fact was followed by the first Russian rocket to Venus. Of interest also is Pirquet's valuable construction of a space station and his analysis of interstellar space flight.

  6. Soolopartiid Von Krahli katuse all / Kristi Eberhart

    Index Scriptorium Estoniae

    Eberhart, Kristi

    2007-01-01

    Von Krahli Teatri kolmest lavastusest: "Erki ja Tiina" (lavastaja Mart Kangro, tantsivad Erki Laur ja Tiina Tauraite), "Faust" (J. W. Goethe ainetel tekst ja lavastus Taavi Eelmaa, muusika ja laulud Chalice, osades Jarek Kasar ja Rein Pakk), "Hamletid" (William Shakespeare'i ainetel kontseptsiooni, lavastuse, koreograafia, kujunduse, valguse autor Sasha Pepeljajev, video- ja helikunstnik Taavet Jansen. Esitaja Juhan Ulfsak)

  7. De ziekte van Von Hippel-Lindau

    NARCIS (Netherlands)

    Los, M.; Links, T.P.; Lenders, J.W.M.; Voest, E.E.

    2000-01-01

    Von Hippel-Lindau disease (VHL) is an autosomal dominant inherited cancer syndrome. The disease was diagnosed in three patients: a 22-year-old woman who presented with decreased vision due to retinal angiomatosis and in whom a renal carcinoma was diagnosed five years later at a routine VHL analysis,

  8. Ueber eine Anomalie von Acromitus flagellatus (Stiasny)

    NARCIS (Netherlands)

    Stiasny, G.

    1934-01-01

    Bei erneuter Durchsicht des reichhaltigen Materiales von Acromitus flagellatus (Stiasny) in der Scyphomedusen-Sammlung des Rijksmuseum van Natuurlijke Historie in Leiden (vergl. meine Mitteilungen daruber, 1920, Uebersichtstabelle III und 1921, p. 131/136) fand ich ein Exemplar, das eine

  9. Laue, Prof. Max Theodor Felix von

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1954 Honorary. Laue, Prof. Max Theodor Felix von. Nobel Laureate (Physics) - 1914. Date of birth: 9 October 1897. Date of death: 24 April 1960. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. Theory Of Evolution. Posted on 23 January 2018. Joint Statement by the ...

  10. Ueber zwei neue Vogelarten von Java

    NARCIS (Netherlands)

    Finsch, O.

    1902-01-01

    Die beiden nachstehend beschriebenen Vögel wurden mir von Herrn Max Bartels als muthmasslich neu zugesandt. Die genaue Untersuchung hat dies bestätigt. Ich freue mich daher eine der Arten zu Ehren des Entdeckers benennen zu können. Seit einigen Jahren als Leiter der Plantage Pangerango bei Pasir

  11. Classical diagnostic radiological features of Von Recklinghausen's ...

    African Journals Online (AJOL)

    Neurofibromatosis type 1(NF-1, Von Recklinghausen disease or peripheral NF) is a rare autosomal dominant disorder with varied clinical manifestations involving the skin, nerves and bones. It is the most common of the neurocutaneous syndromes, with variable pathological and clinical expression. Approximately half of all ...

  12. Das Druckprofil von Sportkompressionsstrümpfen.

    Science.gov (United States)

    Reich-Schupke, Stefanie; Surhoff, Stefan; Stücker, Markus

    2016-05-01

    Zunehmend werden Sportkompressionsstrümpfe (SKS) eingesetzt, doch fehlt eine Norm in Analogie zu medizinischen Kompressionsstrümpfen (MKS). Ziel dieser Pilotstudie war der Vergleich der Druckprofile von fünf SKS ex vivo und in vivo miteinander sowie mit MKS-Normen. CEP Running-Progressive-Socks, Falke Running--Energizing, Sigvaris Performance, X-Socks Speed-Metal-Energizer und 2XU Compression--Race-Socks wurden an zehn Leistungssportlern (standardisiert in vivo, Kikuhime--Sensor) sowie im Hohenstein Institut (ex vivo) hinsichtlich ihres Druckprofils getestet. Die Ex-vivo-Messungen im Fesselbereich von CEP (25,6 mmHg) und 2XU (23,2 mmHg) entsprachen der deutschen MKS-Klasse 2, von Sigvaris-SKS (20,8 mmHg) der deutschen MKS-Klasse 1. Die übrigen SKS lagen darunter. Die ermittelten Druckprofile differierten stark und entsprachen nicht der MKS-Norm. Die In-vivo-Messungen zeigten für drei SKS (2XU, CEP, Sigvaris) durchschnittlich einen höheren Anpressdruck als die SKS von Falke und X-Socks. Alle SKS lagen in vivo jedoch unter der deutschen MKS-Klasse 1. Kein SKS bot den für MKS geforderten Druckabfall vom Messpunkt B nach D. Die in vivo und ex vivo ermittelten SKS-Druckprofile zeigten heterogene Ergebnisse und folgten kaum den MKS-Anforderungen. Entsprechend sind auch die klinisch-praktischen Effekte von SKS nicht vergleichbar. Wünschenswert wäre eine SKS-Klassifikation, die erlaubt, Produkte einzuordnen, zu vergleichen und nach konkreten Vorlieben und Bedürfnissen (hoher vs. geringer Druck, progressiver vs. degressiver Gradient) auszuwählen. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

  13. Integrales Lernen in und von Organisationen

    Directory of Open Access Journals (Sweden)

    Wendelin Kupers

    2006-06-01

    Full Text Available Bezogen auf das integrale Models von Ken Wilber untersucht der Beitrag die Bedeutung des Lernens in und von Organisationen. Nach einer Darstellung der Relevanz und des Grundverständnisses des Lernens im Organisationskontext, werden integrale Dimensionen des Lernens dargestellt. Im Einzelnen werden die verschiedenen Sphären eines inneren-subjektiven und äusseren-„objektiven“ Lernens des Einzelnen als auch ein gemeinschaftliches Lernen und Lernen im System auf der kollektiven Ebene dargestellt sowie deren interrelationaler Zusammenhang diskutiert. Schließlich beschreibt der Beitrag noch integrale Lernprozesse sowie integrale Gestaltungsfelder zur Förderung des Lernens in den verschiedenen Bereichen. Abschließend spricht der Artikel noch Schwierigkeiten und Probleme an sowie nimmt im Fazit ein perspektivischen Ausblick vor.

  14. Wir zeigen andere Bilder von Frauen ...

    Directory of Open Access Journals (Sweden)

    Bettina Rulofs

    2010-03-01

    Full Text Available Der vorliegende Beitrag beleuchtet die Bedeutung der Geschlechterordnung im Prozess der sportmedialen Kommunikation. Im Kern geht es um die Frage, inwiefern im Prozess der medialen Vermittlung von Sport traditionelle Geschlechterstereotype aufrechterhalten werden oder Möglichkeiten der Irritation solcher Stereotype bestehen. Dazu werden verschiedene Ebenen des massenmedialen Kommunikationsprozesses in den Blick genommen: die Medienprodukte, die Öffentlichkeitsarbeit und Selbst-Präsentation der Sportler/innen, die Medienrezeption und die Herstellungsprozesse von Medien in den Sportredaktionen. This article illustrates the relevance of gender in processes of sports media communication. The question in focus is in what way traditional gender stereotypes are perpetuated in the process of media communication in sport and how such stereotypes can be irritated. Therefore different levels of mass media communication are considered: the media products, the public relations of athletes and the presentation of themselves as athletes, the media-reception and the production processes in sport departments of media institutions.

  15. Virchow's triad: Kussmaul, Quincke and von Recklinghausen.

    Science.gov (United States)

    Stanifer, John W

    2016-02-01

    For most of the 19th century, Germany was the centre of the medical world. From there the most innovating research came and many of the physicians of that era are known to nearly every medical student and physician of today. Virchow, Kussmaul, Quincke, von Recklinghausen, Müller and Schönlein are familiar names in today's medicine but insofar as they are merely eponyms associated with signs, symptoms, disease and anatomy. The story of their lives, their research and their influence on each other has been little examined. This is an essay about Virchow's relationship with his mentors Müller and Schönlein and how these relationships shaped the development of Kussmaul, Quincke and von Recklinghausen as students of Virchow and their work in medicine and clinical observation after leaving Virchow's laboratory. © The Author(s) 2014.

  16. Evolution equations of von Karman type

    CERN Document Server

    Cherrier, Pascal

    2015-01-01

    In these notes we consider two kinds of nonlinear evolution problems of von Karman type on Euclidean spaces of arbitrary even dimension. Each of these problems consists of a system that results from the coupling of two highly nonlinear partial differential equations, one hyperbolic or parabolic and the other elliptic. These systems take their name from a formal analogy with the von Karman equations in the theory of elasticity in two dimensional space. We establish local (respectively global) results for strong (resp., weak) solutions of these problems and corresponding well-posedness results in the Hadamard sense. Results are found by obtaining regularity estimates on solutions which are limits of a suitable Galerkin approximation scheme. The book is intended as a pedagogical introduction to a number of meaningful application of classical methods in nonlinear Partial Differential Equations of Evolution. The material is self-contained and most proofs are given in full detail. The interested reader will gain a ...

  17. Abdome agudo obstrutivo pela veia porta - relato de caso

    Directory of Open Access Journals (Sweden)

    Celeste Gomes Sardinha Oshiro

    2016-10-01

    Full Text Available Introdução: A veia porta pré-duodenal é uma anomalia congênita rara, sintomática em apenas 50% dos casos, sendo que seu diagnóstico é feito por laparotomia exploradora. O tratamento de escolha é cirúrgico, com bom prognóstico. Objetivo: Relatar um caso de Abdome Agudo Obstrutivo por Veia Porta Pré Doudenal (VPPD no período neonatal no Conjunto Hospitalar de Sorocaba. Metodologia: Descrição do referido caso e revisão de literatura. Relato de Caso: Recém-nascido de F.S.S., feminino, de parto normal em 30/05/2016, cuja mãe com 21 anos, apresentou durante pré-natal Diabetes Mellitus Gestacional e polihidrâmnio; negou consanguinidade, vícios e infecções. Ao nascimento, idade gestacional 38 1/7 semanas, peso 2865g, comprimento 47 cm, Apgar 9/9. Durante rotinas de sala de parto, à aspiração gástrica, saída de 55 ml de líquido claro com grumos (LCCG. No 4o dia de vida, episódios de vômito com sangue e distensão abdominal. No 11° dia de vida, realizada Laparotomia Exploradora que identificou dilatação gástrica e duodenal, principalmente na 3° porção, onde passa anteriormente a Veia Porta, comprimindo parcialmente a borda antimesentérica duodenal, o que comprometia seu esvaziamento. Realizada anastomose duodeno-jejunal. Recebeu alimentação parenteral por 15 dias. RN apresentou infecções fúngica e bacteriana, tratadas durante internação. Recebe alta com 46 dias de vida em aleitamento materno e boa recuperação clínica. Conclusão: Existem poucos relatos sobre a formação anômala da veia porta e suas consequências. O diagnóstico pré-natal ou pré-operatório de VPPD raramente é feito. Boa evolução pós correção cirúrgica.

  18. RELATO POLICIAL Y EL CRIMEN QUE LO HABITA

    Directory of Open Access Journals (Sweden)

    Francisco de Undurraga

    2011-04-01

    Full Text Available La aparición de publicidad y de novelas en serie en las portadas de periódicos franceses, a partir de 1836, marca la relación entre el género policial y los nuevos modos de visibilidad de la información en las sociedades industrializadas. Algunos ejemplos, tomados de un periódico de la época, la “Gazette des Tribunaux”, permiten demostrar que la prensa estuvo desde sus comienzos vinculada a la literatura, si acaso no es una derivación de ella. E.A. Poe, creador del relato policial, conduce la retórica del morbo trabajada por Dante, Swift, Lautréamont y Baudelaire, de una apelación al lector, al orden del argumento y del procedimiento que lo estructura. En el relato policial conviven el discurso de lo que se cuenta, característico de la literatura, y el de la ciencia, pero solo en apariencia éste viene a suplantar a aquél, configurando de este modo su retórica.The emergence of publicity and of serialized novels in the covers of French newspapers, since 1836, characterizes the relation between crime story and new modes of visibility for information in industrialized societies. A few examples, coming from a journal of that time, the “Gazette des Tribunaux”, allow us to demonstrate that journalism was from the beginning related to literature, if it is not a derivation from it. Edgar Allan Poe, creator of crime story, leads the rhetoric of morbid fascination developed by Dante, Swift, Lautréamont and Baudelaire, from an appeal to the reader, toward the order of argument and the procedure that provides its structure. In crime story the discourse of what is told, that characterizes literature, and the discourse of science, live together, but the latter takes the place of the former only apparently, shaping in this way its rhetoric.

  19. La Medea de Lars von Trier

    Directory of Open Access Journals (Sweden)

    Iratxe Fresneda Delgado

    2013-04-01

    Full Text Available El presente artículo analiza el modo en el que Lars von Trier recrea para el cine el estereotipo de Medea. Mediante el análisis fílmico de la película y apoyándose en los estudios culturales, el texto se interroga acerca de la importancia y el poder potencial del cine a la hora recuperar el antiguo mito y demostrar su vigencia. El análisis amplía horizontes para la compresión de los mecanismos que articulan el entramado de significados de la película, donde Von Trier aporta una nueva visión del arquetipo de Medea uniéndola, a la tradición pictórica del Romanticismo. Una influencia que habita en las posteriores obras del director danés, donde el paisaje, la naturaleza, se erige en elemento catalizador de las pulsiones humanas, en su cómplice y testigo.This paper explores the way that Lars von Trier’s film recreates the stereotype of Medea. Using film analysis and based on cultural studies the article asks about the importance and potential power of cinema to recover the ancient myth and show their effects. The analysis expands horizons for the understanding of the mechanisms that link the network of meanings of the film, where the author offers a new vision of Medea's archetype attaching it to the pictorial tradition tied to the Romanticism. An influence that can be seen in the later works of Lars von Trier, where the landscape, the nature, stands as a catalyst of human drives, as his accomplice and witness.

  20. Von Medien, Übertragungen und Automaten

    Directory of Open Access Journals (Sweden)

    Alessandro Barberi

    2013-12-01

    Full Text Available Im Zuge der Debatten zum Medialen Habitus wurde vielfach betont, dass die >Theorie der Praxispraxeologischen Medientheorie< des Medialen Habitus avant la lettre gesprochen werden kann. Dieser Artikel untersucht – ausgehend von den Debatten zur "Medienkompetenz" – wie Bourdieu Sprache, Sprechen und Diskurs, sowie Akteure, Felder und Habitus als Medien begreift und betont dabei die Nützlichkeit der Bourdieuschen Bildungssoziologie im Rahmen einer sozialwissenschaftlichen Grundlegung der Medienpädagogik.

  1. Untersuchungen von Nanostrukturen magnetischer Kolloide mit Kleinwinkelstreuung

    OpenAIRE

    Kammel, Martin

    2005-01-01

    Mit Hilfe der Neutronenkleinwinkelstreuung mit polarisieren Neutronen wird eine Analyse so genannter Ferrofluide durchgeführt. Ferrofluide sind Dispersionen magnetisierbarer Teilchen, welche durch in den meisten Fällen organische Hüllen gegen irreversibler Aggregation geschützt sind. Anhand von verdünnten Magnetit-Kolloidlösungen wurden als Stabilisierung Dextran, Tenside (Laurinsäure/Marlipal) und elektrostatisch stabilisierte Magnetitteilchen untersucht. Dabei fanden sich in jedem dieser Fl...

  2. Maschinelle Erkennung von Verkehrsteilnehmern mittels heterogener Sensorik

    OpenAIRE

    Walchshäusl, Leonhard

    2009-01-01

    In modernen Fahrzeugen halten verstärkt Fahrerassistenzsysteme zum Insassenschutz und zum Schutz anderer Verkehrsteilnehmer Einzug. Typische, bereits seit längerem verfügbare Systeme, wie Airbag und Antiblockiersystem, erreichen schon heute eine hohe Marktdurchdringung. Künftige aktive Sicherheitssysteme, die von der Kollisionswarnung bis hin zur autonomen Gefahrenbremsung reichen, sind Gegenstand aktueller Forschung. Insbesondere Systeme, die aktiv in das Fahrgeschehen eingreifen, erfordern ...

  3. Mikrobieller Befall von Elektrotauchlack in der Automobilindustrie

    OpenAIRE

    Gühring, Ina Katrin

    2000-01-01

    Nach Umstellung auf umweltverträglichere Lackmaterialien (Reduzierung biozid wirkender Lösemittel, Schwermetalle) traten in Elektrotauchanlagen verschieder Werke der DaimlerChrysler AG vermehrt Beschichtungsstörungen bei Karossen auf. Dabei war ein pH-Anstieg des Lackmaterials, Schichtdickenanstieg, Abblättern des Lacks („Striptease“ Effekt), Oberflächenstörungen (Pusteln, Blasen, Krater), schlechter Umgriff, eine Bildung von Lackschlamm und geringerer Schichtwiderstand zu beobachten. Gleichz...

  4. Die Usability von Rich Internet Applications

    Science.gov (United States)

    Linder, Jörg

    Interaktiven Services, die dem Themenkreis Web 2.0 zugeordnet werden, haftet unter anderem das Attribut an, besonders leicht bedienbar zu sein. Flickr, Youtube und Wikipedia gelten als Erfolgsprojekte dieser neuen Art von interaktiven Websites. Wodurch zeichnet sich nun eine Usability 2.0 (so es sie überhaupt geben sollte) aus? Was ist zu beachten, wenn so genannte Rich Internet Applications gestaltet werden?

  5. Therapie von Vorhofflimmern: Rolle der Katheterablation

    OpenAIRE

    Hindricks G; Kircher S; Gaspar T.; Arya A

    2009-01-01

    Vorhofflimmern ist die häufigste Herzrhythmusstörung in der Gesamtbevölkerung und geht einher mit erhöhter Morbidität und Mortalität. Als prinzipielle Behandlungskonzepte stehen die "Frequenzkontrolle" und die "Rhythmuskontrolle" zur Verfügung. Während sich die medikamentöse Rhythmuskontrolle als insgesamt unzureichend erwiesen hat, stellt die Katheterablation von Vorhofflimmern einen etablierten, potenziell kurativen Therapieansatz mit beachtlichen Erfolgsraten dar. Obwohl hinsichtlich d...

  6. Modellierung von Preiserwartungen durch neuronale Netze

    OpenAIRE

    Heinemann, Maik; Lange, Carsten

    1997-01-01

    Das Papier untersucht, wie Erwartungsbildung mit Hilfe neuronaler Netze modelliert werden kann. Die Grundlage bildet ein Cobweb-Modell, in dem Firmen Preiserwartungen auf Basis eines Feedforward-Netzes bilden.Zunächst wird anhand von Simulationen gezeigt, daß Firmen durch neuronale Erwartungsbildung approximativ rationale Erwartungen bilden können. Im Gegensatz zur Hypothese rationaler Erwartungen ist dafür die Kenntnis des relevanten Modells nicht mehr erforderlich, lediglich Beobachtungen d...

  7. Expression von Blutgruppenantigenen durch humane mesenchymale Stammzellen

    OpenAIRE

    Schüle, Michael Christian

    2013-01-01

    Die vorliegende experimentelle Arbeit befasst sich mit der Untersuchung der Expression von Blutgruppenantigenen durch humane mesenchymale Stammzellen (MSC) aus dem Knochenmark. Der Fokus lag hierbei auf den klinisch bedeutsamen Antigenen A, B, H, Rhesus-D, -C, -c, -E, -e, RhAG, K, k, Jka, Jkb und DARC. Die Expression wurde systematisch auf Genom-, Transkriptom- und Proteinebene evaluiert. Alle untersuchten MSC Populationen exprimierten FUT1, RHCE, KEL und Kidd (HUT11) mRNA. mRNA der AB0-Gl...

  8. Weitere Vorkommen von Impatiens capensis in Hessen

    OpenAIRE

    Nawrath, Stefan

    1996-01-01

    Neue hessische Fundorte von Impatiens capensis aus dem Taunus und dessen Vorland sowie aus der Rheinebene werden berichtet. Die insbesondere im Schwarzbach-System zahlreichen Fundorte werden beschrieben und in einer Verbreitungskarte dargestellt. New Hessian stations of Impatiens capensis in the Taunus mountains as well as their foothills and in the Rhine valley are reported on. The stations which are particularly numerous in the Schwarzbach system, are described and demonstrated on a dist...

  9. [Orthopaedic manifestations of Von Recklinghausen's neurofibromatosis].

    Science.gov (United States)

    Trigui, Moez; Ayadi, Kamel; Sakka, Mourad; Zribi, Wassim; Frikha, Faten; Gdoura, Fakher; Sallemi, Sami; Zribi, Mohamed; Keskes, Hassib

    2011-03-01

    Von Recklinghausen's neurofibromatosis is a dominant autosomic genetic disease characterized by different clinical manifestations. The goal of this work was to study its orthopaedic manifestations and to show the characteristics of their management. A retrospective study was carried out on 15 patients having a Von Recklinghausen's neurofibromatosis. For each patient, different orthopaedic manifestations and their evolution after treatment were analyzed. These manifestations were classified in spinal deformities, pseudarthrosis of long bones and tumours of the peripheral nerves. The spinal deformities were observed in 9 cases. A dystrophic scoliosis was observed in 6 patients with an average angle of 50° and was associated to a kyphosis in 5 patients. The treatment was surgical by posterior arthrodesis in 2 cases and circumferential arthrodesis in 2 cases. The congenital curves and pseudarthroses of leg were observed in 5 cases, localized at the lower third of the leg in all cases. An Ilizarov external fixator with segmental osseous transport was carried out in 2 patients. The duration of the external fixator was 23 months ½ with 5 interventions in each case. Four plexiform neurofibromas and 3 nodular neurofibromas were observed. A transformation into neurofibrosarcoma was found in 2 patients. In one case, a resection without functional sacrifice was carried out and in the other case the patient was dead before the resection. The orthopaedic manifestations of Von Recklinghausen's neurofibromatosis are frequent, varied and have a difficult management. The functional and sometimes vital prognoses are challenging. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  10. Gestalt und Funktion von Animal Design : Versuch einer semiotischen Analyse

    OpenAIRE

    Schlüter, Wolfgang

    2009-01-01

    Dissertation zur Gestalt und Funktion von Animal Design (tieranaloges Design). Untersucht wird eine Auswahl an Produkten, die in ihrem Äußeren an Tiere erinnern. Hierbei stehen Aspekte wie die Emotionalisierung von Produkten, demonstrativer Konsum und die soziale Funktion im Fokus der Analyse. Anhand von Abbildungen und Zeichnungen wird u.a. dargestellt, welche Bedeutung die Tiergestalt für das jeweilige Produktdesign hat. Die Objekte werden jeweils unter phänomenologischen, hermeneutischen u...

  11. Bioethik in der Ukraine: Von Medizinischer zur Integrativen Bioethik

    OpenAIRE

    Gubenko, Anna

    2014-01-01

    Im Artikel wird die Chronologie der Entstehung und Entwicklung der Bioethik in der Ukraine analysiert. Dabei werden drei Hauptetappen der Herausbildung von Bioethik als a) einer gesellschaftlichen Organisation, b) einer Lerndisziplin und c) einer integrativen Wissenschaft unterschieden. Der Autor hat den Vektor von medizinischer zur integrativen Bioethik durch Ausbildung und soziale sowie pädagogische Praktiken bezeichnet. In diesem Sinne wird der Begriff von “pädagogischer Bioethik“ einge...

  12. Portrait of Dr. Von Braun with Walt Disney, 1954.

    Science.gov (United States)

    1954-01-01

    Marshall Center Director Dr. Wernher Von Braun is pictured with Walt Disney during a visit to the Marshall Space Flight Center in 1954. In the 1950s, Dr. Von Braun while working in California on the Saturn project, also worked with Disney studios as a technical director in making three films about Space Exploration for television. Disney's tour of Marshall in 1965 was Von Braun's hope for a renewed public interest in the future of the Space Program at NASA.

  13. Risiko und Akzeptanz von Industrieansiedlungen: Eine empirische Studie

    OpenAIRE

    Burgemeister, Jörg; Weber, Martin

    1992-01-01

    In der Bundesrepublik Deutschland stoßen Industrieansiedlungen oft auf den Widerstand der Bevölkerung. Bei der Akzeptanz einer Ansiedlung sind von den Bürgern subjektiv wahrgenommene Risiken und Nutzen der Ansiedlung von erheblicher Bedeutung. In einer Fragebogenstudie haben wir untersucht, wie Personen die Nutzen und Risiken von Industrieansiedlungen einschätzen, inwieweit sie Absiedlungen akzeptieren, welche Bestimmungsfaktoren ihren Risiko- und Akzeptanzurteilen zugrundeliegen, und wie sic...

  14. Erfolgsfaktoren von Internet-Auktionen: Eine empirische Analyse in PLS

    OpenAIRE

    Fritz, Wolfgang; Möllenberg, Antje; Dees, Heiko

    2004-01-01

    Internet-Auktionen haben sich zu einem der erfolgreichsten Geschäftsmodelle im E-Commerce entwickelt. Die stetig steigende Anzahl von Auktionen beim Marktführer eBay zeugen von einer zunehmenden Beliebtheit solcher Auktionen. Doch welche Determinanten beeinflussen den Erfolg einer Internet-Auktion? Im vorliegenden Beitrag wird dieses Thema aus dem Blickwinkel des Verkäufers am Beispiel von Ticket-Auktionen empirisch untersucht. Im Mittelpunkt steht dabei eine Kausalanalyse, die den Einfluss v...

  15. Saage tuttavaks : Elisabeth ja Karl von Hoerschelmann / Mai Levin

    Index Scriptorium Estoniae

    Levin, Mai, 1942-

    2004-01-01

    Kuraator M. Levin kuni 10. X 2004 Adamson-Ericu muuseumis avatud näitusest "Tuntud ja tundmatud Elisabeth von Rosendorff-Hoerschelmann ja Karl von Hoerschelmann". Enamik töid on kunstnike laste Konstantin Hoerschelmanni ja Anna Röder-Hoerschelmanni omand. Elisabeth Rosendorff (1898-1984) sündis Virumaal Maidlas eesti perekonnas, Karl von Hoerschelmann (1899-1951) Sevastoopolis saksa perekonnas

  16. Abbaukinetiken - und mechanismen von Lignin und Vanillin unter hydrothermalen Bedingungen

    OpenAIRE

    Curtze, Jan Henning

    2017-01-01

    Eine Methode zur energetischen Aufkonzentrierung von feuchten Abfallbiomassen ist die Hydrothermale Carbonisierung (HTC). Um technische HTC-Reaktoren rational auslegen zu können, sollte die Formalkinetik der vier Hauptkomponenten von Biomasse - Kohlenhydrate, Lignin, Fette/Öle und Proteine – bekannt sein. Des Weiteren spielt die Änderungskinetik des Feststoffes während der HTC eine wichtige Rolle. Der Fokus dieser Arbeit liegt auf der Untersuchung der HTC von Lignin, was ein hochkomplexes, ch...

  17. Studien zur Kinetik der Fehlfaltung un Aggregation von Proteinen

    OpenAIRE

    Modler, Andreas Johannes

    2003-01-01

    Diese Arbeit befasst sich mit der Kinetik der Fehlfaltung und Aggregation von Proteinen. Anhand dreier Beispiele, der Phosphoglyceratkinase (PGK) aus Hefe, einer Variante von Barstar und des Prion-Proteins des Syrischen Hamsters (SHaPrP(90-232)) wurde insbesondere die Kinetik der Bildung von Amyloidfibrillen und deren kinetischer Vorläuferstrukturen mittels dynamischer und statischer Lichtstreuung, Circulardichroismus, Infrarotspektroskopie, Elektronenmikroskopie und teilweise analytischer Ch...

  18. Brucelose canina: relato de caso Canine brucellosis: a case report

    Directory of Open Access Journals (Sweden)

    Agueda Castagna de Varga

    1996-08-01

    Full Text Available Relata-se a ocorrência de casos de brucelose em animais de um canil da cidade de Uruguaiana, Rio Grande do Sul. Devido a registros de aborto nesta criação, suspeitou-se desta enfermidade. O isolamento da Brucella canis foi realizado através da cultura de materiais obtidos dos fetos abortados, placenta e neonatos. O teste sorológico de imunodifusão em gel de ágar demonstrou que 72,7% (8/11 dos animais deste canil haviam se infectado com esta bactéria. Neste relato são descritos e discutidos os dados clínicos e sorológicos, assim como o isolamento da Brucella canis.The ocurrence of canine brucellosis is described in a kennel from Uruguaiana city. Due to abortion registered at the kennel the suspected disease was brucellosis. The isolation of Bucella canis was realized by culturing the material collected from aborted fetuses, placenta and neonatos. The agar gel immunodiffusion test was used for sorological evaluation and showed that 72.7% (8/11 of the dogs were infected wifh the bactéria. The authors describe also the clinical signs, serological findings and also the isolation of the Brucella canis.

  19. Maison de verre / Zonestraal. Relato de dos edificios

    Directory of Open Access Journals (Sweden)

    Jan Molema

    2014-01-01

    Full Text Available Desde los años sesenta del siglo XX el sanatorio Zonnestraal de Hilversum y la Maison de Verre en París han sido descritos extensamente en la literatura de la arquitectura moderna. Sin embargo, no se ha hecho ningún esfuerzo por colocarlos juntos en un mismo relato. Este ensayo es un esfuerzo para enmendar ese vacío. Ambos están relacionados íntimamente por sus autores: Bernard Bijvoet, como codiseñador de los planos de la Maison, y Johannes Duiker, quien trabajó con el anterior en los preliminares de Zonnestraal, aunque lo finalizó en solitario, al mismo tiempo que se terminó el diseño de la casa. En el trabajo se cuestiona además, ofreciendo fundadas conjeturas, la creencia establecida de que se precisó una nueva estructura metálica para sustentar la inalterada vivienda situada encima de la Maison de Verre.

  20. Contar el exilio: Relatos sobre fronteras en la frontera

    Directory of Open Access Journals (Sweden)

    Nora Ricaud

    2009-06-01

    Full Text Available Este escrito aborda el tema de los modos de la escritura autobiográfica y además habla sobre las formas del exilio. Más particularmente, se refiere a los modos en que ambos tópicos se concretan en dos textos de la escritora argentina Tununa Mercado: En estado de memoria y Yo nunca te prometí la eternidad. Ambos libros piden ser leídos no como textos cerrados, sino como un continuum, en tanto la escritura los presenta enlazados en un devenir de un texto en el otro, y del contenido en la forma. Cada una de estas historias es una estación del exilio. Una, subsumida en la otra; una, parida por la otra. El relato en primera persona cuenta tanto el exilio propio como el ajeno, transitando bordes en donde el juego de espejos oblitera la posibilidad de distinguir lo propio y lo ajeno, el sí mismo y el Otro. Es por ello que lo apropiado parece ser un abordaje que eluda la estabilización del sentido y que sea capaz de hacerse cargo del carácter insaturable de la escritura de Tununa Mercado.

  1. no cotidiano da enfermagem: um relato de experiência

    Directory of Open Access Journals (Sweden)

    Maria Cristina Soares Figueiredo Trezza

    2007-01-01

    Full Text Available Este trabajo trata sobre el relato de la experiencia de la realización del I Festival: Enfermería en el arte de educar en Salud, realizado por la Escuela de Enfermería y Farmacia de la Universidad Federal de Alagoas. En este evento se presentaron creaciones artísticas realizadas en el cotidiano de la Enfermería, las cuales surgieron como un instrumento para desarrollar procesos de Educación en salud. El evento fue realizado en tres fases: el Festival con la presentación de las creaciones para los jueces de las comisiones; la exposición de las creaciones ganadoras; y la publicación de un libro con las producciones presentadas. De las 77 creaciones presentadas, 15 fueron vencedoras, las cuales fueron hechas por enfermeros, auxiliares y estudiantes de enfermería, revelando así la creatividad de los profesionales de la enfermería en la difícil tarea de educar en salud. El Festival así como el libro que de él resultó, mostraron cómo los autores desarrollaron estrategias pedagógicas a través de las cuales los sujetos del aprendizaje alcanzaron el lugar que por derecho les pertenecía. La experiencia demostró que cuando se actúa innovadoramente, los resultados pueden sorprender.

  2. Síndrome de Isaacs: relato de um caso

    Directory of Open Access Journals (Sweden)

    Hélio Ghizoni Teive

    1988-06-01

    Full Text Available Relato do caso de paciente do sexo feminino com 40 anos de idade, com quadro progressivo de diminuição de força, disfonia, disfagia, dispnéia e hiperidrose. O exame físico revelava contratura em flexão das mãos, déficit de força muscular, fasciculações, mioquimia facial e pseudomiotonia nas mãos, A eletromiografia mostrou atividade elétrica contínua em repouso. O estudo histoquímico muscular revelou atrofia de fibras do tipo II, enquanto a microscopia eletrônica mostrou dilatação importante das cisternas do retículo sarcoplasmático. O diagnóstico de síndrome de Isaacs foi firmado. Excelente resposta clínica ao emprego de carbamazepina foi observada. São discutidos e revistos vários aspectos relacionados a essa rara síndrome.

  3. ANDARILHOS DE ESTRADA SEGUNDO OS RELATOS DE TRABALHADORES ASSISTENCIAIS

    Directory of Open Access Journals (Sweden)

    Eurípedes Costa Nascimento

    2015-04-01

    Full Text Available Os andarilhos de estrada são indivíduos que percorrem longas distâncias a pé pelas rodovias do país com um saco às costas onde carregam todos os seus pertences e em situações de extrema dificuldade recorrem às instituições assistenciais na busca de auxílio. Esta pesquisa teve como objetivo verificar como os trabalhadores assistenciais compreendem o modo de vida dos andarilhos pelas rodovias do país. A pesquisa foi realizada em quatro instituições assistenciais no Estado de São Paulo, sendo duas públicas e duas filantrópicas. Os relatos foram analisados pela técnica de análise de conteúdo. Os resultados indicaram que a compreensão desses trabalhadores em relação aos andarilhos está associada à vagabundagem, doença mental e desestrutura familiar. Esses dados mostram a necessidade de uma ampliação do debate em torno das políticas assistenciais e seus impactos diretos na errância dos andarilhos de estrada.

  4. Dr. von Braun and Army Ballistics Missile Agency (ABMA) Group

    Science.gov (United States)

    1959-01-01

    This photograph of Dr. von Braun, shown here to the left of General Bruce Medaris, was taken in the fall of 1959, immediately prior to Medaris' retirement from the Army. At the time, von Braun and his associates worked for the Army Ballistics Missile Agency in Huntsville, Alabama. Those in the photograph have been identified as Ernst Stuhlinger, Frederick von Saurma, Fritz Mueller, Hermarn Weidner, E.W. Neubert (partially hidden), W.A. Mrazek, Karl Heimburg, Arthur Rudolph, Otto Hoberg, von Braun, Oswald Lange, Medaris, Helmut Hoelzer, Hans Maus, E.D. Geissler, Hans Heuter, and George Constan.

  5. Einfluss von rekombinantem Adiponektin auf die monozytäre Expression von Annexin A6

    OpenAIRE

    Stögbauer, Fabian

    2009-01-01

    In der vorliegenden Arbeit wurden zunächst die CD14 Micro Beads titriert und so die Menge an CD14 Micro Beads bestimmt, die nötig ist, um eine große Anzahl Monozyten mit einem hohen Reinheitsgrad, verbunden mit geringen Kosten, aus Vollblut isolieren zu können. In den folgenden in vitro Untersuchungen wurden dann periphere Monozyten von humanen Spendern isoliert, um die dosis- und zeitabhängige Veränderung der Annexin A6-Proteinexpression unter dem Einfluss von Adiponektin feststellen zu k...

  6. Relato de sustentabilidade – práticas no setor financeiro emportugal e espanha

    OpenAIRE

    Gomes, Sebastião Duarte

    2016-01-01

    A presente dissertação discute as práticas de relato de sustentabilidade no setor financeiro em Portugal e em Espanha nos anos 2012 a 2014. O objetivo geral do presente estudo é contribuir para a revisão da literatura, sobre o relato de Sustentabilidade aplicado ao setor financeiro. Para o efeito, o estudo foi aplicado a bancos portugueses e espanhóis nos anos de 2012 a 2014, procurando estudar as práticas de divulgação voluntária de responsabilidade social empresarial, incluíd...

  7. Anestesia em paciente com Distrofia Muscular de Duchenne: relato de caso

    OpenAIRE

    Tonelli,Deoclécio; Pinho,Iglair; Sacco,Paula de Camargo Neves; Vianna,Eduardo Piccinini; Vasconcellos,José Correia de; Souza,Raquel Vasconcelos de; Umakoshi,Sidney

    2003-01-01

    JUSTIFICATIVA E OBJETIVOS: A distrofia muscular de Duchenne é uma afecção recessiva ligada ao cromossomo X, geralmente diagnosticada na infância, acentuando-se progressivamente até agravar a função respiratória. O objetivo deste relato é apresentar um caso de um paciente com distrofia muscular de Duchenne diagnosticada há 2 anos, submetido à postectomia, sob anestesia geral com cetamina S. RELATO DO CASO: Paciente com 9 anos de idade com Distrofia Muscular de Duchenne diagnosticada há 2 anos,...

  8. Anestesia em paciente com síndrome de Rubinstein-Taybi: relato de caso

    OpenAIRE

    Oliveira,Carlos Rogério Degrandi; Elias,Luciana

    2005-01-01

    JUSTIFICATIVA E OBJETIVOS: A síndrome de Rubinstein-Taybi (SRT) é uma doença genética causada por uma mutação ou apagamento do cromossomo 16, caracterizada por retardo físico e mental, anormalidades craniofaciais e hálux e polegares largos. Há pouca informação sobre esta síndrome na literatura anestésica. O objetivo deste relato foi apresentar a conduta anestésica em paciente submetido à cirurgia odontológica e discutir as características de interesse para a anestesia nesses pacientes. RELATO...

  9. Einfluss von Eugenol und Silikonöl auf die Dentinhaftung von adhäsiven Befestigungsmaterialien

    OpenAIRE

    Bigdali, Puria

    2015-01-01

    Zielsetzung Eugenolhaltige Zemente und Silikone stehen in Verdacht den Verbund von Kompositzementen zu beeinflussen. Ziel dieser Arbeit war es den Einfluss eugenolhaltiger und eugenolfreier Zemente und von Additions- und Kondensationssilikonen auf konventionell adhäsive und selbstadhäsive Kompositzemente zu untersuchen. Material und Methode Aus 200 extrahierten Rinderzähnen wurden 200 Dentinscheiben mit einer Dicke von 1 mm hergestellt, in welche eine definierte Kavität mit einem ...

  10. Automatisierte Generierung von Postleitzahlgebieten aus OpenStreetMap-Daten unter Verwendung von Open Source GIS Software

    OpenAIRE

    Hauck, Christian

    2011-01-01

    Das Projekt OpenStreetMap als freie Wiki-Weltkarte gewinnt als Quelle von Geodaten für unter-schiedlichste Bedürfnisse innerhalb der Geowissenschaften, des Geomarketings und auch im Alltag immer mehr an Bedeutung. Die kostenlosen, von Freiwilligen einer Community gesammelten geo-graphischen Daten, sogenannte nutzergenerierte Daten, dienen heute vielen Anwendern als Daten-grundlage und stehen in der Konkurrenz zu proprietären Geodaten von kommerziellen Anbietern. Neben Straßendaten sind zahlre...

  11. Ööklubi Club von Überlingen = Club von Überlingen

    Index Scriptorium Estoniae

    2008-01-01

    Ööklubi Club von Überlingen (Madara 22A, Tallinn) sisekujundusest. Sisearhitekt: Taavi Aunre (Boom.ee OÜ). Taavi Aunrest, tema tähtsamad tööd. I-II korruse plaan, 11 värv. vaadet, foto T. Aunrest

  12. Von den Liven von Oesel / August Ludwig Schlözer

    Index Scriptorium Estoniae

    Schlözer, August Ludwig

    2008-01-01

    Avaldatud Eberhard Winkleri initsiatiivil A. L. Schlözeri teose põhjal: Gesammelte Nachrichten von den Ueberresten der Liven, in Livland und Kurland. (1770), mis moodustab osa teosest: Schlözer, August Ludwig. M. Johann Joseph Haigold's Beylagen zum Neuveränderten Russland. Zweiter Theil. Riga und Leipzig, 1770

  13. Aino Lepik von Wiren / Aino Lepik von Wiren ; interv. Kadi Alatalu

    Index Scriptorium Estoniae

    Lepik von Wirén, Aino, 1961-

    2007-01-01

    Heinrich Marga eksiilvalitsuse (20.06.1990-7.10.1992) kohtuminister Aino Lepik von Wiren pagulaslapse elust Rootsis, haridusest ja elukutse valikust, tööst eksiilvalitsuses, tööleasumisest Eestisse 1992. aastal, seadusandlikust tegevusest ning aluse panekust välismaalaste- ja kodakondsuspoliitikale, naiste võimalustest poliitilisse tippu tõusmiseks, kodu- ja väliseestlaste vastandamisest

  14. Rezension: Träume von Räumen von Georges Perec

    Directory of Open Access Journals (Sweden)

    Thomas Ballhausen

    2015-12-01

    Full Text Available Mit "Träume von Räumen" liegt ein zentraler Text aus dem umfangreichen Œuvre Geroges Perecs vor, der zuletzt 1990 als Übersetzung greifbar war. Der ursprünglich 1974 erschienene Band ist in mehrfacher Hinsicht wesentlich für das Verständnis Perecs und seiner literarisch-philosophische Wunderwelt ...

  15. Wege des Exports von Glutathion aus Astrocyten

    OpenAIRE

    Minich, Tobias Florian

    2008-01-01

    Vorliegender Arbeit lag die Aufgabe zugrunde herauszufinden, welche(s) Transportsystem(e) außer dem Multidrug-Transporter 1 (multidrug resistance protein 1, MRP1) zum Austritt des Tripeptides Glutathion aus Primärkulturen von Astrogliazellen in das extrazelluläre Milieu beitragen. Als Grundlage für die Untersuchungen wurde zunächst an zwei Wildtyp Mausstämmen (NMRI und FVB/N) sichergestellt, dass astrogliareiche Primärkulturen aus Mäusen sowohl reduziertes als auch oxidiertes Glutathion expor...

  16. Die Behandlung von Intersexuellen in der Diskussion

    Directory of Open Access Journals (Sweden)

    Heinz-Jürgen Voß

    2008-11-01

    Full Text Available Wissenschaftler/-innen aus unterschiedlichen Fachdisziplinen und mit unterschiedlichen Ansichten zum Umgang mit intersexuellen Menschen kommen zu Wort – in diesem Sinne ist der Sammelband sehr heterogen. Es werden Erfahrungen mit Geschlechtsanpassung dargestellt, Begrifflichkeiten analysiert und Probleme bei der Therapie und in der Forschung erörtert. Vorangestellt, aber erfreulicherweise nicht abgetrennt, äußern sich Betroffene. Bereits wegen der sich im Abschluss des Bandes befindlichen Handlungsempfehlungen zur Behandlung von Säuglingen und Kindern mit ‚abweichenden‘ bzw. ‚uneindeutigen‘ Geschlechtsmerkmalen, die sich insbesondere an Eltern, Mediziner/-innen und Sozialpädagog/-innen wenden, ist das Buch unbedingt empfehlenswert.

  17. Electronic Resource Management System. Vernetzung von Lizenzinformationen

    OpenAIRE

    Michaela Selbach; Daniel Armin Rupp

    2014-01-01

    In den letzten zehn Jahren spielen elektronische Ressourcen im Bereich der Erwerbung eine zunehmend wichtige Rolle: Eindeutig lässt sich hier ein Wandel in den Bibliotheken (fort) vom reinen Printbestand zu immer größeren E-Only-Beständen feststellen. Die stetig wachsende Menge an E-Ressourcen und deren Heterogenität stellt Bibliotheken vor die Herausforderung, die E-Ressourcen effizient zu verwalten. Nicht nur Bibliotheken, sondern auch verhandlungsführende Institutionen von Konsortial- und ...

  18. Authentifizierung von Bio-Milch im Labor

    OpenAIRE

    Molkentin, Joachim

    2008-01-01

    In Deutschland ist die Nachfrage nach Bio-Lebensmitteln in den letzten Jahren stetig gestiegen. So erhöhte sich der Absatz von Bio-Trinkmilch in 2007 im Vergleich zum Vorjahr erneut kräftig um 34 Prozent (ZMP, Bonn) und der Bio-Anteil beträgt inzwischen bei Frischmilch knapp elf Prozent. Aufgrund sporadisch resultierender Lieferengpässe bei Bio-Milch sowie der vorhandenen Handelspreisdifferenz besteht zunehmend ein potenzielles Risiko der Falschdeklaration konventionell erzeugter Milch als Bi...

  19. Der Denkmalwert von Illegalität

    OpenAIRE

    Beyer, Dennis

    2012-01-01

    Kunst oder Schmiererei - Graffiti spalten die Gesellschaft. Für die einen sind sie illegale Schmierereien und Ausdruck von Vandalismus, für die anderen gelten sie als Kunst am Bau einer verkannten Avantgarde. Das Spektrum an Motivationen und Produkten innerhalb der Sprayer-Gemeinschaft ist tatsächlich derart vielfältig, dass eine sachliche Debatte ohne Polarisation kaum möglich scheint. Dennoch stellt sich die Frage, welche Bedeutung diese flüchtigen und illegalen Zeugnisse einer Minderheit i...

  20. Relato de caso – Displasia Tanatofórica

    Directory of Open Access Journals (Sweden)

    Izilda das Eiras Tamega

    2014-10-01

    Full Text Available Introdução: A Displasia Tanatofórica ocorre devido a mudanças no gene FGFR3, sendo a herança autossômica dominante. Apresenta incidência entre 1:33 mil a 1:50 mil nascidos vivos, não havendo predomínio por sexo. As características incluem a macrocefalia, dismorfismos faciais, membros extremamente curtos e tórax estreito com pulmões subdesenvolvidos. A maior parte dos nascidos vivos vem a óbito precocemente devido à insuficiência respiratória; Objetivos: Relatar caso de Displasia Tanatofórica em Sorocaba- SP; Metodologia: Acompanhamento de paciente no Conjunto Hospitalar de Sorocaba; Relato de Caso: RN do sexo feminino, terceira gestação de uma paciente de 29 anos, cujas ultrassonografias do pré-natal evidenciaram rizomelia, hipoplasia torácica, displasia musculoesquelética e polidrâmnio, apontando para a hipótese diagnóstica de Displasia Tanatofórica. Realizado parto cesáreo, recém-nascido a termo, pequeno para a idade gestacional, Apgar 2 e 6, e características morfológicas de nanismo, baixa implantação de orelha e pescoço curto. Apresentou hipoglicemia e permaneceu na UTI neonatal com ventilação mecânica, indo a óbito com 9 dias de vida; Conclusões: O diagnóstico intra-útero permite uma conduta perinatal mais adequada e possibilita a indicação de apoio psicológico para os pais ainda durante a gestação, uma vez que a mortalidade é alta.

  1. MODELAGEM MATEMÁTICA: RELATO DE UMA EXPERIÊNCIA

    Directory of Open Access Journals (Sweden)

    Aparecida Gasquez Sousa

    2012-12-01

    Full Text Available O presente relato trata de uma situação de Modelagem Matemática que se desenvolveu de forma interdisciplinar, envolvendo conteúdos de matemática e de geografia, com uma turma de terceiro ano do curso Técnico em Agropecuária Integrado ao Ensino Médio, do Instituto Federal de Rondônia, Campus Colorado do Oeste. Esse estudo ocorreu nos meses de dezembro de 2011 e janeiro de 2012 e teve como objetivo promover a aprendizagem de estatística, bem como de questões referentes à fome no Brasil, de modo significativo e pautado em situações reais.  Foi proposto e desenvolvido um trabalho de coleta e análise de dados dos custos e da origem (local de produção dos itens que integram a cesta básica nas cidades de Colorado do Oeste, Buritis, Cerejeiras, Costa Marques e Porto Velho. Colorado do Oeste apresentou o maior valor médio da cesta básica, R$ 231,49, enquanto que Buritis apresentou o menor valor, R$196,16. Também foi possível obter o custo médio da cesta básica do estado de Rondônia, sendo que esse ficou entre os seis mais baixos quando comparado às localidades em que o DIEESE realiza pesquisa. Além dos resultados apresentados, esse trabalho contemplou os princípios de interdisciplinaridade e a contextualização dos conteúdos de matemática e de geografia, que são defendidos por estudiosos da educação como mecanismos que contribuem para o envolvimento e o interesse dos alunos nas atividades escolares.   

  2. Hidrocefalia após meningite - relato de caso

    Directory of Open Access Journals (Sweden)

    Tássia Sabbadin Mancilha

    2015-10-01

    Full Text Available A malformação do sistema nervoso central é um dos fatores de risco para meningite no período neonatal, a qual se caracteriza pela ocorrência de um processo infeccioso nas meninges, ocorrendo entre o nascimento e o 28º dia de vida. As complicações mais frequentemente associadas á meningite neonatal são a ventriculite, síndrome convulsiva, síndrome da secreção impropria do hormônio antidiurético, hidrocefalia, abcesso cerebral, hemorragia intracraniana, leucomalácia e coleção subdural. O objetivo do presente relato é descrever um caso de um paciente portador de uma má formação do sistema nervoso central, que apresentou aos 28 dias de vida quadro de meningite bacteriana que evoluiu para uma hidrocefalia. Após abordagem cirúrgica para colocação de DVE, seguida de complicações e troca de DVP, paciente apresenta suspeita de hipertensão intracraniana, quadro de crises convulsivas e atraso no desenvolvimento neuropsicomotor. A meningite no período neonatal é considerada uma patologia grave, cuja mortalidade varia de 15 a 50%. Sua incidência varia de 0,3 a 1 caso por 1000 nascidos vivos. Dentre os sobreviventes cerca de 50 a 75% evoluem com deficiência auditiva, deficiência visual, atraso no desenvolvimento neuropsicomotor, retardo mental, convulsões e hidrocefalia. Desta forma fica evidente, devido ao diagnóstico clinico ser difícil, a necessidade de manejo e tratamento precoce a fim de minimizar o prognóstico e as dificuldades que poderá apresentar o paciente no futuro.

  3. Piometra em uma leoa (Panthera leo: relato de caso

    Directory of Open Access Journals (Sweden)

    L. Murer

    2015-06-01

    Full Text Available A piometra é uma infecção aguda ou crônica do útero que ocorre frequentemente em cadelas não castradas, podendo também ocorrer em gatas domésticas e selvagens, sendo poucos os estudos relacionados à piometra em grandes felídeos. O objetivo deste relato foi descrever um caso de piometra em uma leoa (Panthera leo de cativeiro, as lesões de necropsia e histológicas, bem como os resultados da análise microbiológica. Uma leoa com aproximadamente 23 anos, pertencente a um criadouro conservacionista de Santa Maria-RS, foi encontrada morta pela manhã em seu recinto. Após coleta de dados, procedeu-se à necropsia e à coleta de material para análise histopatológica e bacteriológica. A análise microbiológica revelou predomínio das bactérias Streptococcus sp. e Escherichia coli no conteúdo purulento do útero, caracterizando como piometra, e a bactéria predominante em plasma, fígado e medula óssea foi E. coli. De acordo com o laudo histopatológico, as alterações observadas nessa leoa sugerem um quadro de septicemia grave, sendo a origem do foco infeccioso bacteriano, provavelmente, a piometra. Considera-se importante chamar a atenção dos médicos veterinários de animais selvagens para um diagnóstico precoce dessa doença, que é comum em cadelas, mas que pode acometer também felídeos selvagens e levá-los à morte.

  4. Illustrierte Bestimmungshilfe zur Unterscheidung von Candelaria concolor und Candelaria pacifica

    OpenAIRE

    Stapper, Norbert J.

    2012-01-01

    Unterscheidungsmerkmale von Candelaria concolor und C. pacifica werden anhand von Makro- und Mikrofotos dargestellt. Im Gelände kann C. pacifica anhand der fehlenden Unterrinde erkannt werden. Characteristic features separating Candelaria concolor from C. pacifica are presented on macro and micro photographs. The lack of a lower cortex can be used to identify C. pacifica in the field.

  5. On two matrix derivatives by Kollo and von Rosen

    OpenAIRE

    Neudecker, Heinz

    2003-01-01

    The article establishes relationships between the matrix derivatives of Fwith respect to Xas introduced by von Rosen (1988), Kollo and von Rosen (2000) and the Magnus-Neudecker (1999) matrix derivative. The usual transformations apply and the Moore-Penrose inverse of the duplication matrix is used. Both Xand F have the same dimension. Peer Reviewed

  6. A New Generalization of von Neumann Relative Entropy

    Science.gov (United States)

    Li, Jing; Cao, Huaixin

    2017-11-01

    In quantum information, von Neumann relative entropy has a great applications and operational interpretations in diverse fields, and von Neumann entropy is an important tool for describing the uncertainty of a quantum state. In this paper, we generalize the classical von Neumann relative entropy S( ρ|| σ) and von Neumann entropy S( ρ) to f-von Neumann relative entropy \\widetilde {S}f(ρ ||σ ) and f-von Neumann entropy \\widetilde {S}f(ρ ) induced by a logarithm-like function f, respectively, and explore their properties. We prove that \\widetilde {S}f(ρ ||σ ) is nonnegative and then prove that \\widetilde {S}f(ρ ) has nonnegativity, boundedness, concavity, subadditivity and so on. Later, we show the stability and continuity of the \\widetilde {S}f(ρ ) with respect to the trace distance. In the case that f( x) = -log x, the resulted entropies reduce the classical von Neumann relative entropy and von Neumann entropy, respectively. This means that our results extend the usual results to a more general setting and then have some potential applications in quantum information.

  7. An accurate von Neumann's law for three-dimensional foams

    NARCIS (Netherlands)

    Hilgenfeldt, Sascha; Kraynik, Andrew M.; Koehler, Stephan A.; Stone, Howard A.

    2001-01-01

    The diffusive coarsening of 2D soap froths is governed by von Neumann's law. A statistical version of this law for dry 3D foams has long been conjectured. A new derivation, based on a theorem by Minkowski, yields an explicit analytical von Neumann's law in 3D which is in very good agreement with

  8. Minimum Moduli in Von Neumann Algebras | Gopalraj | Quaestiones ...

    African Journals Online (AJOL)

    Minimum Moduli in Von Neumann Algebras. Perumal Gopalraj, Anton Ströh. Abstract. In this paper we answer a question raised in [12] in the affirmative, namely that the essential minimum modulus of an element in a von. Neumann algebra, relative to any norm closed two-sided ideal, is equal to the minimum modulus of the ...

  9. Spin–momenta entanglement in moving frames: Properties of von ...

    Indian Academy of Sciences (India)

    well as locality, of information [9–11]. Expressed differently, the von Neumann entropy measures the stored qubits of information per states of the combined system while the reduced one quantifies the qubits per states that may be stored in one of the subsystems. [1]. It is then obvious that a deeper understanding of von ...

  10. Victor or Villain? Wernher von Braun and the Space Race

    Science.gov (United States)

    O'Brien, Jason L.; Sears, Christine E.

    2011-01-01

    Set during the Cold War and space race, this historical role-play focuses on Wernher von Braun's involvement in and culpability for the use of slave laborers to produce V-2 rockets for Nazi Germany. Students will grapple with two central questions. Should von Braun have been allowed to emigrate to the United States given his affiliation with the…

  11. Von Krahli teatris etenduvad Tõnu Kõrvitsa kammerooperid / Esme Kassak

    Index Scriptorium Estoniae

    Kassak, Esme

    2006-01-01

    20. apr. esietenduvad Von Krahli Teatris Peeter Jalaka lavastuses Tõnu Kõrvitsa uued kammerooperid "Tuleaed" ja "Mu luiged, mu mõtted", mille aluseks on luuletaja Marie Heibergi saatus. Libretode autor on Maarja Kangro. Kammerooperid tulevad lavale Von Krahli Teatri ja Nargen Opera koostöös. Esitavad Kädy Plaas, Helen Lokuta, Nargen Opera koor ja Tallinna Kammerorkester, dirigent Tõnu Kaljuste

  12. Condromatose sinovial de joelho: relato de caso Synovial chondromatosis of the knee: case report

    Directory of Open Access Journals (Sweden)

    Jorge Sayum Filho

    2011-10-01

    Full Text Available Os autores apresentam o relato de caso de um paciente ex-atleta de futebol com osteocondromatose sinovial em joelho.The authors report the case of a patient with synovial osteochondromatosis of the knee, who had previously been a soccer player.

  13. Condroma em socó-boi (Tigrisoma leneatum): relato de caso

    OpenAIRE

    Alexandre Aparecido Mattos da Silva Rego; Eliana Reiko Matushima; Maria Cândida Miguel

    1999-01-01

    Relata-se a ocorrência de neoplasia em Tigrisoma lineatum (socó-boi), localizada na região metacarpiana esquerda, caracterizada histologicamente como condroma. Este é um dos primeiros relatos desta patologia em indivíduos desta espécie.

  14. Condroma em socó-boi (Tigrisoma leneatum: relato de caso

    Directory of Open Access Journals (Sweden)

    Alexandre Aparecido Mattos da Silva Rego

    1999-01-01

    Full Text Available Relata-se a ocorrência de neoplasia em Tigrisoma lineatum (socó-boi, localizada na região metacarpiana esquerda, caracterizada histologicamente como condroma. Este é um dos primeiros relatos desta patologia em indivíduos desta espécie.

  15. Exposição ao vivo no tratamento de agorafobia: relato de caso

    Directory of Open Access Journals (Sweden)

    Gustavo J. Fonseca D'El Rey

    Full Text Available Relato de caso, em que a Exposição ao Vivo foi utilizada no tratamento de paciente com diagnóstico de agorafobia. O tratamento foi realizado em doze sessões, apresentando êxito no uso dessa técnica comportamental.

  16. [Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918] / Paul Kaegbein

    Index Scriptorium Estoniae

    Kaegbein, Paul

    2007-01-01

    Arvustus: Heinz von zur Mühlen. Das Bürgertum Fordert Blut. Ein Bolschewistiches Flugblatt von 1918. In : Ostseeprovinzen, baltische Staaten und das Nationale. Münster : LIT, 2005, lk. 403-414. 1918. aastast pärit lendlehest, mille käekirja järgi otsustades on kirjutanud Viktor Kingissepp

  17. Relatos audiovisuales de ficción sobre la identidad adolescente en contextos escolares

    Directory of Open Access Journals (Sweden)

    Laia Falcón Díaz-Aguado

    2014-01-01

    Full Text Available Los relatos audiovisuales que tienen a los adolescentes como audiencia y protagonistas son utilizados por éstos para buscar referencias con las que construir su identidad. Esta investigación busca comprender cómo es la identidad de los estudiantes adolescentes en distintos tipos de relatos audiovisuales de ficción, como punto de partida para la elaboración de materiales de alfabetización mediática que les ayude en dicho proceso. Para ello se seleccionaron tres narraciones europeas recientes sobre la vida escolar de adolescentes, con las que poder contrastar entre géneros, códigos y valores: la serie televisiva «Física o Química» y las películas «Harry Potter y la Orden del Fénix» y «La clase». El método ha sido el análisis textual de tipo cualitativo, utilizando como categorías las de la morfología del relato clásico. Los resultados reflejan que dicho esquema, familiar para el profesorado de Literatura, permite detectar importantes coincidencias entre relatos (como la importancia de las relaciones de pareja y amistad…, que hacen más significativas las diferencias del contraste (como la orientación hacia el futuro o el valor del pensamiento y del profesorado en dicho proceso. Se concluye que la comparación entre los tres tipos de relatos representa un óptimo recurso para la alfabetización mediática así como para ayudarles a tomar conciencia de cuáles son los valores con los que quieren identificarse y los problemas que pueden obstaculizarlos.

  18. Kontextualisierung von Queer Theory Contextualizing Queer Theory

    Directory of Open Access Journals (Sweden)

    Anna Voigt

    2008-03-01

    Full Text Available Christine M. Klapeer legt in diesem Einführungsband dar, aus welchen politischen und theoretischen Kontexten heraus sich ‚queer‘ zu einem Begriff mit besonderem politischem und theoretischem Gehalt entwickelt hat. Wesentlich zielt sie dabei auf eine kritische Kontextualisierung von „queer theory”. Die Autorin geht zunächst auf das Gay Liberation Movement ein, grenzt die Queer Theory vom Poststrukturalismus, von feministischen Theorien und den Lesbian and Gay Studies ab, beleuchtet Eckpunkte queeren Denkens und zeichnet schließlich die Entwicklungen in Österreich sowohl politisch-rechtlich als auch bewegungsgeschichtlich und in der Wissenschaftslandschaft nach.Christine M. Klapeer’s introductory volume demonstrates the manner in which ‘queer’ grew out of various political and theoretical contexts to become a term with special political and theoretical content. She focuses primarily on a critical contextualization of “queer theory.” The author begins by approaching the Gay Liberation Movement and then distinguishes Queer Theory from poststructuralism, from feminist theories, and from Lesbian and Gay Studies. She continues on to illuminate the key aspects of queer thought and concludes by sketching the development in Austria in terms of politics and the law, the history of movements, and within the landscape of knowledge.

  19. Guy von Dardel 1919-2009

    CERN Multimedia

    2009-01-01

    Guy von Dardel, a well-known figure at CERN and in the international particle physics community, passed away on 28 August. Guy von Dardel came to CERN when it was founded in 1954 and was a full-time staff member until 1964, performing several experiments and working on technical developments. These included the first measurement of the neutral pion’s life-time. Called to Lund University in 1964, he became professor there in 1965 and director of the 1.2 GeV electron accelerator. In the late 1960s, he performed an experiment at CERN’s PS that measured the decays of the Λ. Then, in the early 1970s, he involved the Lund group in a series of experiments at the Intersecting Storage Rings (ISR), where he measured the production of various types of particles. In particular, he participated in a series of experiments that observed the production of a high abundance of particles with large transverse momenta. This required an explanation...

  20. Suitability of tracers; Eignung von Tracern

    Energy Technology Data Exchange (ETDEWEB)

    Klotz, D. [GSF - Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg (Germany). Inst. fuer Hydrologie

    1999-02-01

    Hydrological tracer techniques are a means of making statements on the direction and speed of underground water. One of the simpler tasks is to find out whether there is hydrological communication between two given points. This requires a determination of the direction of flow, which places less exacting demands on the properties of the tracer than does the task of determining the flow velocity of underground water. Tracer methods can serve to infer from flow velocity the distance (flow) velocity, which is defined as the ratio between the distance between two points located in flow direction and the actual time it takes water to flow from one to the other. [Deutsch] Mit Hilfe der hydrologischen Markierungstechniken koennen Aussagen ueber die Richtung und die Geschwindigkeit von Bewegungen des unterirdischen Wassers gemacht werden. Der einfachere Fall liegt vor, wenn festgestellt werden soll, ob zwischen zwei Punkten eine hydrologische Verbindung besteht. Bei dieser Fliessrichtungsbestimmung sind die Forderungen an die Eigenschaften der einzusetzenden Tracer geringer als bei der Bestimmung der Geschwindigkeit des unterirdischen Wassers. Von den Geschwindigkeiten des unterirdischen Wassers ist die Abstands-(Fliess)geschwindigkeit, die definiert ist durch das Verhaeltnis aus dem Abstand und der wahren Fliesszeit zwischen zwei in Bewegungsrichtung gelegenen Punkten, durch Tracermethoden zu bestimmen. (orig.)

  1. Die Krakauer Kirche von Karmeliten und Karmelitaninnen

    Directory of Open Access Journals (Sweden)

    Józef Szymon Wronski

    2004-12-01

    Full Text Available 1. Die Klosterkirche der unbeschuhten Karmelitinnen Zum Heiligen Josef. Ein glücklicher Auftakt und somit die charakteristische Einführung in das 20. Jh. für den Kirchenbau von Krakau war die Errichtung der Karmeliterinnen St. Josephs-Kirche an der Lobzowska-Straße 40, in der die Architekten (Tadeusz Stryjeński (1849-1943 - Projektant der Kirche und Franciszek Mączyński (1874-1947 - Ausführer des Bauprojektes mit eigenen Verbesserungen die historisch- eklektizistischen Formen d.h. die mittelalterlichen Formen vor allem des sog. Übergangsstils vereinfachten. Die Kirche, die in den Jahren 1903-1905 errichtet wurde, steht inmitten vom Baukomplex des Klosters, dessen Grundriss das Quadrat ist49. Der Kirchenbau ist ein dem Gesamtbau des Klosters eingefügter Längsraum. Hinter dem Chor liegt das Oratorium des Konvents. Das Material Backstein (mit Verwendung von Stein erinnert an die Baukunst eines der besten Architekten jener Zeit, nämlich Teodor Talowskis (1857-1910, der viele Kirchen in Südpolen, aber auch viele Bürgerhäuser nicht nur in Krakau im ausgehenden 19. Jh. baute. Die Architektur der Karmeliterinnen St. Josephs-Kirche ist immer noch im Malerischen begriffen. Aber die Vereinfachung der historischen Formen führt zu ihrer „Beruhigung” und dadurch zur Wuchtigkeit des Ausdrucks. Bemerkenswert ist die in dieser Zeit (in der Anlage noch seltene ausgewogene Proportionierung des Baukörpers. Das methodische Prinzip jener Zeit ist der Kontrast. Im Kontrast zu den gedrungenen und wuchtigen Formen des Baukörpers stehen z.B. die sich verjüngenden obeliskenförmigen und pylonenartigen Türmchen, die nicht nur die Eingangsfassade der Kirche flankieren, sondern auch an den Ecken des Querhauses der Kirche stehen. Die ingravierten weißen Steine an der Fassade in der Zahl von Zehn erinnern an das Gebot des Karmelterinnenordens: Bete täglich den Rosenkranz und sind zugleich ein Vanitativmotiv. 2. Die Klosterkirche der unbeschuhten

  2. Von Neumann's quantization of general relativity

    Science.gov (United States)

    Arbuzov, A. B.; Cherny, A. Yu.; Cirilo-Lombardo, D. J.; Nazmitdinov, R. G.; Han, Nguyen Suan; Pavlov, A. E.; Pervushin, V. N.; Zakharov, A. F.

    2017-05-01

    Von Neumann's procedure is applied to quantizing general relativity. Initial data for dynamical variables in the Planck epoch, where the Hubble parameter value coincided with the Planck mass are quantized. These initial data are defined in terms of the Fock orthogonal simplex in the tangent Minkowski spacetime and the Dirac conformal interval. The Einstein cosmological principle is used to average the logarithm of the determinant of the spatial metric over the spatial volume of the visible Universe. The splitting of general coordinate transformations into diffeomorphisms and transformations of the initial data is introduced. In accordance with von Neumann's procedure, the vacuum state is treated is a quantum ensemble that is degenerate in quantum numbers of nonvacuum states. The distribution of the vacuum state leads to the Casimir effect in gravidynamics in just the same way as in electrodynamics. The generating functional for perturbation theory in gravidynamics is found by solving the quantum energy constraint. The applicability range of gravidynamics is discussed along with the possibility of employing this theory to interpret modern observational data.

  3. Entwicklung von Nickel-Trägerkatalysatoren für die Methanisierung von Kohlenstoffdioxid unter Anwendung von Parallelpräparation und statistischer Versuchsplanung

    OpenAIRE

    Thomys, Oliver Dieter

    2017-01-01

    Die Methanisierung von Kohlenstoffdioxid (Sabatier-Reaktion) gilt als aussichtsreiche Technologie für die chemische Speicherung überschüssigen elektrischen Stroms aus erneuerbaren Energien. Diese Arbeit befasst sich mit der Präparation von Nickel-Trägerkatalysatoren mit hoher Niedrigtemperatur-Aktivität und Langzeitstabilität. Durch Parallelsynthese-Konzepte und Methoden der statistischen Versuchsplanung konnten entsprechende Katalysatoren mit niedriger Metallbeladung präpariert werden, deren...

  4. Alexander von Humboldt in Daniel Kehlmanns Welt

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    Ottmar Ette

    2012-12-01

    Full Text Available Zusammenfassung Wie stark sich im Verlauf des zurückliegenden Vierteljahrhunderts der Bekanntheitsgrad Alexander von Humboldts in der deutschsprachigen Öffentlichkeit verändert hat, zeigen nicht nur Fernsehumfragen zu den berühmtesten Deutschen, in denen Alexander von Humboldt mittlerweile figuriert, oder Fernsehserien, die über aktuelle Expeditionen berichten und auf Humboldts Namen zurückgreifen. Am deutlichsten vielleicht belegt dies der enorme Erfolg von Daniel Kehlmanns Roman Die Vermessung der Welt, der ohne die zuvor skizzierte Entwicklung nicht denkbar gewesen wäre. Es ist vor diesem Hintergrund nicht nur reizvoll, sondern aufschlußreich, sich mit dem großen Erfolg dieses kleinen Romans zu beschäftigen. Worum geht es in Die Vermessung der Welt? Und wie läßt sich das „Phänomen Kehlmann“ aus etwas größerer Distanz erklären? Abstract In the last 25 years, Alexander von Humboldt‘s popularity has radically changed in the german-speaking public opinion. Proof of this are not only television surveys about the most famous germans - in which Alexander von Humboldt now regularly figures - or television series about contemporary expeditions, which constantly refer to Humboldt‘s name; perhaps what most clearly verifies this change is the great success of Daniel Kehlmann‘s novel Die Vermessung der Welt. Without the recent developments outlined above, this novel‘s degree of impact would have been unimaginable. To study the great success of this text against this backdrop is not only attractive, but also revealing. What is Die Vermessung der Welt really about? And how can we explain the „Kehlmann phenomenon“ from a greater distance? Resumen La popularidad de Alejandro de Humboldt ha cambiado profundamente dentro del último cuarto de siglo en la opinión pública de habla alemana. Prueba de esto son no sólo las encuestas televisivas sobre los alemanes más famosos, dentro de las cuales figura en estos momentos Alejandro

  5. Relatos audiovisuales de ficción sobre la identidad adolescente en contextos escolares/ Adolescent Students as Media Fictional Characters

    National Research Council Canada - National Science Library

    Laia Falcón; Ma José Díaz-Aguado

    2014-01-01

    ... Potter y la Orden del Fénix» y «La clase». El método ha sido el análisis textual de tipo cualitativo, utilizando como categorías las de la morfología del relato clásico. Los resultados reflejan que dicho esquema, familiar para el profesorado de Literatura, permite detectar importantes coincidencias entre relatos (como la importa...

  6. Crise tireotóxica - um relato de caso

    Directory of Open Access Journals (Sweden)

    Mariana Fidelis Solla

    2015-10-01

    Full Text Available A crise tireotóxica (CT é a complicação mais grave dohipertireoidismo, caracterizada por um conjunto de sinais e sintomassecundários à hipersecreção aguda de hormônios tireoidianos. Contudo, adescompensação da tireoide até o estado de CT ainda não está bemestabelecida. Os fatores desencadeantes incluem: infecções, cirurgias,traumas, extrações dentárias, alterações glicêmicas, suspensão da medicaçãoanti-tireoidiana, parto e palpação vigorosa da tireóide . A CT é uma emergênciamédica que exige cuidados em unidade de tratamento intensivo (UTI. Odiagnóstico precoce é imprescindível para o êxito terapêutico e influidiretamente no prognóstico e sobrevida do paciente. Objetivos: Relatar o casoda paciente do Conjunto Hospitalar de Sorocaba (CHS que ficou sobrecuidados na UTI devido à CT que evolui para fibrilação atrial (FA etromboembolismo pulmonar (TEP, contribuindo para o meio acadêmico ecientífico. Metodologia: As informações contidas nesse trabalho foram obtidaspor meio de análise de prontuário e revisão de literatura. Relato de caso:Paciente de 25 anos, sexo feminino, deu entrada ao pronto atendimento doCHS com quadro de dispneia, palpitações intensas, ansiosa e com tremores deextremidades. A ectoscopia revelou paciente corada, hidratada, anictérica,acianótica, febril e anasarca evidente. O exame específico da tireóidedemonstrou glândula aumentada de tamanho, bócio difuso, sem nodulações àpalpação. Observou-se veias jugulares ingurgitadas e hepatomegalia. Àausculta verificou-se bulhas arrítimicas com hiperfonese de P2 e FC:214bpm.O ECG padrão de FA e sobrecarga de VE. Conclusão: O hipertiroidismo semtratamento clínico pode evoluir ,culminando com sinais e sintomas compatíveiscom crise tireotóxica. sendo necessários diagnóstico e tratamento precoces.

  7. Notalgia parestésica: relato de caso

    Directory of Open Access Journals (Sweden)

    José Otávio Alquezar Gozzano

    2016-10-01

    Full Text Available Introdução: Notalgia parestésica (NP é uma condição neurocutânea, caracterizada por crises pruriginosas, hiperpigmentação e neuropatia sensorial. Apesar de pouco descrita em literatura, a doença é mais frequente do que se imagina, sendo subdiagnosticada em muitos casos. NP pode afetar qualquer idade e sexo, mas acomete principalmente pessoas de média idade e mulheres. Sua etiologia inclui alterações degenerativas vertebrais, trauma vertebral e predisposição genética. NP envolve o trajeto anatômico dos nervos espinhais e está relacionada com o comprometimento de neuropeptídios, dando origem a marcapassos neurais ectópicos, responsáveis pela clínica da NP. O diagnóstico é clínico, a partir da identificação de máculas hiperpigmentadas unilaterais em zona escapular, sem eritema ou descamação, com piora ao estresse. Deve-se diferenciar de líquen simples, amiloidose macular e hanseníase. Na anatomopatologia observa-se acantose focal e queratinócitos necróticos; a derme papilar mostra depósito de substância amiloide. Com sintomas leves o tratamento medicamentoso nem sempre é necessário, se mais severa utiliza-se capsaicina tópica, gabapentina, oxicarba-mazepina, corticoides e toxina botulínica. Objetivo: Relatar caso de NP. Material e métodos: Paciente atendida ambulatorialmente com revisão de literatura. Relato de Caso: Feminina, 50 anos, com queixa de mancha em dorso há 2 anos; refere dor na coluna torácica. Ao exame: presença de mácula hipercrômica. Hipótese diagnóstica: NP. Foi prescrito corticoide tópico para alívio de sintomas. Conclusão: Por tratar-se de uma doença subdiagnosticada, o conhecimento médico da clínica de NP é fundamental para o diagnóstico precoce, permitindo a escolha do tratamento específico, o que melhora a evolução dos pacientes e evita o uso de fármacos ineficazes.

  8. Anestesia para craniotomia em paciente acordado: relato de caso

    Directory of Open Access Journals (Sweden)

    Nelson Davi Bolzani

    2013-12-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: Alguns procedimentos intracranianos são possíveis com pacientes acordados e os desafios vão da cooperação do paciente até a homeostasia. O objetivo é apresentar um caso de cirurgia intracraniana para exérese de tumor em lobo parietal esquerdo com o paciente em estado vígil. RELATO DE CASO: Após seleção do paciente e preparo psicológico, foi esclarecida e aceita a proposta de exérese de lesão parietal esquerda em estado vígil. Administraram-se propofol e remifentanil em perfusão contínua para manter o escore de Ramsay entre 2-3. Foi feito um bloqueio bilateral do escalpo com ropivacaína. Foi instalado o fixador de Mayfield e os campos cirúrgicos foram ajustados para manter vias aéreas e olhos acessíveis para o mapeamento com eletroestimulação e exérese da lesão. Para incisão da dura-máter foi aplicada uma compressa com lidocaína 2% por três minutos. A cirurgia transcorreu sem intercorrências. O paciente recebeu alta hospitalar no sétimo dia de internação sem apresentar complicação. CONCLUSÃO: Apesar de ser um desafio manter analgesia e estabilidade hemodinâmica com o paciente acordado, a infusão alvo-controlada do propofol estabeleceu o nível de consciência desejado; a do remifentanil titulou a analgesia e a sedação sem o acúmulo da droga e o bloqueio com a ropivacaína, uma analgesia satisfatória. Concluímos que a técnica anestésica foi satisfatória para nosso paciente.

  9. Cistoadenoma mucinoso do pâncreas: relato de caso

    Directory of Open Access Journals (Sweden)

    Marilia Helena de Campos Machado

    2014-10-01

    Full Text Available Introdução: As neoplasias císticas do pâncreas (CNP correspondem a menos do que 10% das neoplasias pancreáticas.Os tipos mais comuns são: cistoadenoma seroso, cistoadenoma (mais frequentes e cistoadenocarcinoma mucinoso, adenoma mucinoso papilar intraductal e tumor sólido pseudopapilar ou tumor Franz. As manifestações clínicas são inespecíficas, sendo mais freqüente a dor abdominal. Objetivo: Relatar o caso de paciente portador de cistoadenoma mucinoso pancreático submetida a um tratamento cirúrgico. Contribuir com o meio cientifico através da ilustração do caso e seu manejo. Metodologia: As informações presentes neste trabalho foram obtidas por meio da revisão da literatura e das informações registradas em prontuário e exames. Relato de Caso: Paciente, sexo feminino, 48 anos, não tabagista, não etilista. Refere que em outubro/2013 começou a sentir fortes dores em hipocôndrio e flanco esquerdos que irradiava para o dorso em cólica com piora progressiva. Identificou-se em um exame de imagem de abdômen, uma lesão cística em cauda pancreática. A paciente foi admitida em janeiro/14 no CHS para exérese da lesão a qual foi realizada em três dias após sob anestesia peridural e geral. Foram realizados pancreatectomia parcial caudal, esplenectomia e colecistectomia. A paciente veio a óbito em março/14 vítima de choque séptico refratário.Discussão: As lesões nas neoplasias císticas mucinosas podem se diferenciar transformando-se em um tumor maligno, sendo então um consenso entre os cirurgiões, sua remoção. Apesar da baixa mortalidade, a causa mais comum de complicação é o vazamento de fluído do ducto pancreático na margem de ressecção resultando na formação de fístula, como ocorreu no caso relatado, levando a paciente ao óbito por choque séptico

  10. Psoríase com eosinofilia: relato de caso

    Directory of Open Access Journals (Sweden)

    Thays Brunelli Pugliesi

    2015-10-01

    Full Text Available A psoríase, doença inflamatória crônica é caracterizada por lesões dérmicas sobrepostas a áreas de lesões eritematosas ou pustulares. Ocorre pela alteração no ciclo de crescimento das células epidérmicas, levando ao espessamento epidérmico decorrente da hiperproliferação celular e vascular com presença de infiltrado linfocitário. Pode desencadear manifestações como febre, mal-estar, fraqueza e outros. Seu diagnóstico é predominantemente clínico, podendo ser complementado pela biópsia das lesões. Entretanto, alguns casos encontrados na literatura e no caso que será relatado existe a presença de eosinofilia, mesmo na ausência de fatores que justificariam o surgimento desse sinal em pacientes portadores da psoríase. Objetivo: Relatar o caso de paciente encaminhado à hematologia com quadro de psoríase concomitante à eosinofilia. Relato de Caso: Paciente de 67 anos, masculino, vem encaminhado com hipótese diagnóstica de Síndrome Hipereosinofílica. Queixa de eosinofilia persistente (>1500 por mais de seis meses tendo realizado tratamento com Albendazol e Metronidazol, sem êxito. Concomitantemente, apresenta psoríase em acompanhamento da dermatologia sem sintomas sistêmicos. Exames laboratoriais: NR para Hepatite B ou C, HIV ou Toxocara canis. Ausência de população celular com imunofenótipo anômalo. Aumento do percentual de granulócitos eosinófilos. Coleta de JAK2 e BLC/ABR negativos. Tratamento da psoríase é realizado com shampoo indicado. Após dois meses, ainda apresenta eosinófilos = 1820. Conclusão: Recentemente, estabeleceu-se uma relação entre a eosinofilia e o aparecimento da psoríase. Não encontramos mais nenhuma causa possível que explique a eosinofilia deste paciente. Pretendemos acompanhá-lo e avaliar se o tratamento da psoríase relaciona-se com a diminuição da eosinofilia

  11. Síndrome de HETT - um relato de caso

    Directory of Open Access Journals (Sweden)

    Izilda das Eiras Tâmega

    2016-10-01

    Full Text Available Introdução: Em 1966, Andreas Rett descreveu pela primeira vez a síndrome de Rett, através de um estudo com 31 meninas que desenvolveram quadro de regressão mental, deterioração neuromotora e hiperamonemia. “Atrofia cerebral associada a hiperamonemia. No Brasil os primeiros casos foram identificados em 1986. Cerca de 95% das meninas que preenchem os critérios diagnósticos para a SR, tem uma alteração genética identificável no gene methyl-CpG-binding protein 2 (MECP2 do cromossomo X. Objetivo: Relatar um caso de uma criança admitida no Conjunto Hospitalar de Sorocaba . Metodologia: As informações contidas nesse trabalho foram obtidas por meio de análise de prontuário e revisão de literatura. Relato de caso: K.L.R, sexo feminino, branca, 6 anos e 7 meses, proveniente de Tatuí (SP com queixa de crise convulsiva com 1 ano e 6 meses de idade, encaminhada para o CHS devido a um episódio de vômito, hipotermia e flacidez muscular , esteve internada na origem por 10 dias. A mãe relatou que: que paciente começou a apresentar movimentos repetitivos de cruzar os dedos e “bater palmas”; não conseguia mais segurar objetos. Passou a rejeitar alimentos sólidos. Deixou de falar “mamãe” e “papai” e passou apenas a balbuciar. Os pais ainda relataram que com cerca de 02 anos de idade, passou em consulta com Médico Geneticista, que avaliou a paciente e solicitou Exame Molecular, pensando se tratar de Síndrome de Rett. Com 03 anos e 5 meses, teve episódio súbito de nistago vertical bilateral e rigidez muscular generalizada, com duração de poucos minutos. Foi ajustada a dose da carbamazepina. Conclusão: A síndrome de Rett é uma das causas mais frequentes de deficiência múltipla severa em crianças do sexo feminino, desta forma, os critérios clínicos constituem a base para o diagnóstico. É fundamental o diagnóstico precoce. Além disso, também é importante o apoio às famílias.

  12. Síndrome de Kinsbourne: relato de caso

    Directory of Open Access Journals (Sweden)

    Marcius Vinícius M. Maranhão

    2013-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A síndrome de Kinsbourne é uma doença neurológica rara que afeta, principalmente, crianças previamente hígidas, na faixa etária entre seis e trinta e seis meses, caracterizada pela presença de opsoclonia (movimentos oculares rápidos, irregulares, horizontais e verticais, mioclonias que podem afetar tronco, extremidades ou face e ataxia cerebelar. Pode ser considerada uma síndrome paraneoplásica pela associação com neuroblastomas, ganglioneuroma e raramente hepatoblastomas. Foi objetivo deste artigo apresentar os aspectos mais relevantes da síndrome de Kinsbourne, bem como a técnica anestésica usada para ressecção de tumor de mediastino em uma criança portadora desta síndrome. RELATO DO CASO: Criança de um ano e cinco meses com diagnóstico de tumor do mediastino posterior portadora de síndrome de Kinsbourne. Pré-medicação com midazolam oral. Indução da anestesia com sevoflurano, óxido nitroso, fentanil e rocurônio. Manutenção da anestesia com sevoflurano, óxido nitroso, fentanil e rocurônio. Reversão do bloqueio neuromuscular com neostigmina associado à atropina. Analgesia pós-operatória com o uso de dipirona, cetoprofeno e morfina. Levada para a Unidade de Terapia Intensiva extubada, com parâmetros hemodinâmicos e respiratórios estáveis. Alta da UTI quatro dias após a cirurgia e alta hospitalar no sétimo dia de pós-operatório sem intercorrências. Anátomo-patológico evidenciou para ganglioneuroblastoma. CONCLUSÕES: A síndrome de Kinsbourne é uma doença neurológica rara. As drogas usadas em nosso paciente mostraram ser seguras e permitiram uma anestesia sem intercorrências. Drogas que desencadeiam ou agravam opsoclonia e mioclonias, como cetamina e etomidato, deverão ser evitadas nesses pacientes.

  13. Síndrome 5q-: um relato de caso

    Directory of Open Access Journals (Sweden)

    Marcelo Gil Cliquet

    2015-10-01

    Full Text Available As síndromes mielodisplásicas (SMD se caracterizam por hematopoiese ineficaz, citopenias, distúrbios qualitativos de uma ou mais linhagens de células do sangue periférico, anormalidades cromossômicas e uma predileção variável de evolução para leucemias mielóides agudas. As anormalidades mais freqüentemente observadas incluem a deleção do braço longo do cromossomo 5 (5q-. O tratamento com novas drogas vem mudando as perspectivas de tratamento. A lenalidomida é um fármaco que fica reservada para o tratamento das síndromes mielodisplásicas 5q- e mieloma múltiplo. Objetivo: Relatar o uso do fármaco lenalidomida por um paciente portador de SMD com a síndrome 5q-, avaliando o impacto na necessidade transfusional. Relato de caso: Paciente de 64 anos, sexo masculino, encaminhado por apresentar anemia (8,2g/dl macrocítica (VCM=109fl. Série branca e plaquetária normais. Após investigação para hemólise, carência de B12, ácido fólico e Ferro sem anormalidades, foi solicitada avaliação de medula óssea que revelou hipercelularidade (relação G/E=4/1, aumento de mieloblastos e prómielocitos, e cariótipo mostrando 46XY del(5(q15q33{6} e 46XY{14}. Prescrito Lenalidomida (10mg VO/dia em ciclos de 21 dias com intervalo de uma semana. Desde a primeira consulta até o início do tratamento, o paciente recebeu 16 unidades de concentrados de hemácias. Após dois ciclos, observou-se elevação da hemoglobina, sem transfusões, chegando a 12,3g/dl. Apresentou, no entanto, redução de neutrófilos (970/mm³ e de plaquetas (107.000/mm3. Conclusão: O uso do fármaco pode melhorar a qualidade de vida e a sobrevida dos pacientes portadores da síndrome 5q-, tendo em vista a redução de transfusões de sangue, evitando, assim, a sobrecarga de ferro e ainda pode diminuir a taxa de transformação em LMA.

  14. Die Rolle von RANK-Ligand und Osteoprotegerin bei Osteoporose

    Directory of Open Access Journals (Sweden)

    Hofbauer LC

    2004-01-01

    Full Text Available Receptor activator of nuclear factor (NF- κB ligand (RANKL, sein zellulärer Rezeptor RANK und der Decoy-Rezeptor Osteoprotegerin (OPG stellen ein essentielles Zytokinsystem für die Zellbiologie von Osteoklasten dar. Verschiedene Untersuchungen belegen die Bedeutung von Störungen des OPG/RANKL/RANK-Systems bei der Pathogenese metabolischer Knochenerkrankungen. In dieser Arbeit werden die wichtigsten Störungen des OPG/RANKL/RANK-Systems bei verschiedenen Osteoporoseformen dargestellt. Östrogenrezeptor- (ER- Agonisten wie 17 β-Östradiol, Raloxifen und Genistein stimulieren die osteoblastäre Produktion von OPG durch Aktivierung von ER- α in vitro, während Lymphozyten von Patientinnen mit Östrogenmangel RANKL überexprimieren. Die parenterale Gabe von OPG vermag den mit Östrogenmangel assoziierten Knochenverlust im Tiermodell und in einer kleineren klinischen Studie zu verhindern. Glukokortikoide und Immunsuppressiva steigern gleichzeitig die RANKL-Expression und hemmen die OPG-Produktion in osteoblastären Zellen in vitro. Glukokortikoide sind auch in vivo imstande, die OPG-Serumspiegel deutlich zu reduzieren. Dagegen hemmen biomechanische Reize in vitro die RANKL-Produktion und steigern die OPG-Produktion. Ein Fehlen dieser biomechanischen Reize bei längerer Immobilisierung kann daher den RANKL/OPG-Quotienten steigern, während die tierexperimentelle Immobilisierungs-Osteoporose durch die parenterale Gabe von OPG gemildert werden kann.

  15. Drei Dimensionen von filmischem Archivmaterial. Die Untersuchung von Archivfilmen aus der Zeit des Holocaust

    Directory of Open Access Journals (Sweden)

    Tobias Ebbrecht-Hartmann

    2017-04-01

    Full Text Available Filmisches Archivmaterial aus der Zeit des Holocaust ist eine ambivalente Quelle. Daher sind spezifische Ansätze notwendig, um dieses Material zu ‘lesen’. Es geht darum, den besonderen Inhalt der Bilder zu analysieren, den Kontext ihrer Entstehung zu bestimmen, aber auch, ihre spätere Verwendung und Zirkulation in der visuellen Kultur und damit auch ihren wechselnden Status mit einzubeziehen. Am Beispiel ausgewählter Filmfragmente aus dem Warschauer Ghetto und dem Ghetto Theresienstadt skizziert der Artikel einen Ansatz, wie man diese drei Dimensionen von filmischem Archivmaterial analysieren kann und schlägt damit eine entsprechende Historiographie von Archivfilmen aus der Zeit des Holocaust vor.

  16. Modellierung von Angebots- und Nachfrageverhalten zur Analyse von Agrarpolitiken: Theorie, Methoden und empirische Anwendungen

    OpenAIRE

    Henningsen, Arne

    2006-01-01

    Die Analyse der Auswirkungen von Agrarpolitiken ist in der Regel sehr komplex und erfordert eine detaillierte Modellierung des Angebots- und Nachfrageverhaltens im Agrarsektor. Eine empirische Anwendung setzt daher eine angemessene ökonomische Theorie sowie fortgeschrittene quantitative Methoden voraus. Alle neun Aufsätze dieser Dissertation lassen sich in diese Themengebiete einordnen. Zunächst werden die Nachfrage nach Bananen und die Folgen der EU Bananenmarktordnung für deutsche Konsument...

  17. Charakterisierung von Mutanten im Lösungsmittelstoffwechsel von Clostridium acetobutylicum

    OpenAIRE

    Hönicke, Daniel

    2015-01-01

    Im Rahmen dieser Arbeit wurden insgesamt neun durch ClosTron-basierte Mutagenese erhaltene Insertionsmutanten von C. acetobutylicum ATCC 824 einer umfangreichen Charakterisierung unterzogen. Für alle im Batch-Fermentationsmaßstab und/oder in kontinuierlicher Kultur fermentierten Stämme erfolgte eine globale Analyse des Transkriptoms unter Verwendung der DNA-Microarray-Technologie. Für eine Analyse des Acetat- und Aceton-Stoffwechsels wurden Stämme mit einer inaktivierten Phosphotransacetyl...

  18. Informationssuchverhalten als Grundlage für die Gestaltung von Veranstaltungen zum Erwerb von Informationskompetenz

    Directory of Open Access Journals (Sweden)

    Martin Wollschläger-Tigges

    2015-09-01

    Full Text Available Für die Gestaltung bibliothekarischer Veranstaltungen zum Erwerb von Informationskompetenz stellen die bisherigen Ergebnisse und Befunde der Forschung zum Informationssuchverhalten eine wertvolle Grundlage dar, indem bestimmte und v.a. typische Verhaltensmuster, Routinen und Präferenzen im Umgang mit Informationsressourcen und Informationen in konzeptionelle und inhaltliche Anpassungen von IK- Veranstaltungen eingebracht und eingesetzt werden. Das Informationssuchverhalten untersucht sowohl individuelle als auch kollektive Informationsprozesse und Faktoren, die diese maßgeblich beeinflussen. Hierzu werden der gesamte Informationsprozess oder einzelne Abschnitte untersucht, die den Information Need, Seeking und Using (INSU-Prozess bilden. Die Befunde der einzelnen INSU-Prozesses-Einheiten zeigen, dass Faktoren wie Informationsbedarf, Informationsart und -form sowie die Einbindung in übergeordnete Arbeitsprozesse wesentlichen Einfluss auf das Informationssuchverhalten haben. Des Weiteren konnte die ISB-Forschung eine Klassifizierung von Benutzergruppen entwickeln und z.B. Fast Surfers, Broad Scanners und Deep Divers charakterisieren bzw. auch das Bouncing oder Flicking Behavior beschreiben. Hinzu kommen mehrere Modelle, die Informationssuchverhalten und Informationsverhalten in bestimmten Situationen nachbilden und darstellen können.

  19. Tragverhalten von Verbunddübeln unter Zugbelastung

    OpenAIRE

    Appl, Jörg-Jochen

    2009-01-01

    Im Bauwesen werden in zunehmendem Maße Dübel zur Einleitung von Lasten in den erhärteten Beton eingesetzt. Vor allem Befestigungssysteme auf der Grundlage chemischer Mörtel werden vermehrt verwendet. Allerdings fehlte bisher ein genügend genaues Berechnungsmodell zur Bemessung von beliebigen Befestigungen mit Verbunddübeln für unterschiedliche Verankerungstiefen und für verschiedene Verbundfestigkeiten. In der vorliegenden Arbeit wurde das Tragverhalten von Verbundübeln unter Zugbelastung...

  20. A von Bertalanffy growth model with a seasonally varying coefficient

    Science.gov (United States)

    Cloern, James E.; Nichols, Frederic H.

    1978-01-01

    The von Bertalanffy model of body growth is inappropriate for organisms whose growth is restricted to a seasonal period because it assumes that growth rate is invariant with time. Incorporation of a time-varying coefficient significantly improves the capability of the von Bertalanffy equation to describe changing body size of both the bivalve mollusc Macoma balthicain San Francisco Bay and the flathead sole, Hippoglossoides elassodon, in Washington state. This simple modification of the von Bertalanffy model should offer improved predictions of body growth for a variety of other aquatic animals.

  1. Abenteuer Alexander-von-Humboldt-Bibliographie

    Directory of Open Access Journals (Sweden)

    Christian Suckow

    2002-04-01

    Full Text Available Article in German; Abstracts in English and German.The two attempts (1860 and 1872 to compile a bibliography of all works of Alexander von Humboldt have to be regarded as failures. Due to Humboldt’s scientific methods, the contemporary popularity of his writings, and the conditions of book publishing and selling, it has been difficult to achieve an overview of his œuvre. Thus each attempt to write a reliable or at least partially complete bibliography of Humboldt’s works constituted an adventure. Horst Fiedler and Ulrike Leitner have mastered this undertaking. As a result of their efforts over more than two decades, a bibliography of those works by Humboldt which were published in book form appeared in the year 2000.

  2. Johann von Lamont: A Pioneer in Geomagnetism

    Science.gov (United States)

    Soffel, Heinrich

    2006-06-01

    The 200th birthday of John Lamont (1805-1879, Figure 1), a pioneer in the study of geomagnetism, was marked on 13 December 2005. Lamont founded the Munich Geomagnetic Observatory in 1840 and was a member of the group of scientists including Carl Friedrich Gauss, Alexander von Humboldt, Eduard Sabine, Jonas Angstrøm, Humphret Lloyd, Adolf Kupffer, Karl Kreil, and Adolphe Quetelet who composed the Göttingen Magnetic Union. They organized an international network of geomagnetic observatories [Barraclough et al., 1992]. The present knowledge of the geomagnetic field and its secular variation is largely based on the data collected by the global network of geomagnetic observatories during the last 170 years. Lamont's talents and his dedication and enthusiasm for discovery are reflected in the depth and scope of his contributions to a broad variety of natural sciences such as astronomy, meteorology, geomagnetism, and geodesy. However, this article just touches on his merits in geomagnetism.

  3. Bertha von Suttner 1843-1914

    OpenAIRE

    Hoock-Demarle, Marie-Claire; Hessel, Stéphane

    2016-01-01

    Née dans « le monde d'hier » cher à son compatriote Stefan Zweig, morte le 21 juin 1914 à la veille du déclenchement d’une guerre qu’elle appelle Weltkrieg, Bertha von Suttner témoigne d’un parcours hors du commun dans un moment crucial où s’amorcent les conflits générés par les militarismes et les nationalismes menant inexorablement à la catastrophe. Arpenteuse d’Europe, voyageuse du Nouveau Monde, elle voit dans « l’américanisation du monde » une raison de construire dans la paix et la coop...

  4. Modernisation of ventilation systems; Modernisierung von Lueftungsanlagen

    Energy Technology Data Exchange (ETDEWEB)

    Richter, W. [Technische Univ. Dresden (Germany). Inst. fuer Thermodynamik und Technische Gebaeudeausruestung

    1997-12-31

    When redeveloping buildings it is common to use window constructions with air-tight rabbets which obviate the inflow of fresh air almost entirely. This leads to the well-known structural-physics and hygienic consequences. As an added effect, the distinctly enhanced thermal insulation results in changes in dynamic heat loss. The paper focuses on the issues of how to safeguard the inflow of fresh air, and the heating capacity of radiators. (MSK) [Deutsch] Da die bei Gebaeudesanierungen eingesetzten fugendichten Fensterkonstruktionen die Nachstroemmoeglichkeiten fuer die Zuluft fast ganz unterbinden, fuehrt das zu den bekannten bauphysikalischen und hygienischen Konsequenzen. Dazu kommen veraenderte dynamische Waermverlustverhaeltnisse aufgrund der deutlich verbesserten Waermedaemmung. Im Folgenden wird schwerpunktmaessig auf die Probleme Zuluftsicherung und Waermeleistung von Heizkoerpern eingegangen.

  5. Hepatische Effekte von Wachstumshormon auf den Glukosestoffwechsel

    Directory of Open Access Journals (Sweden)

    Rufinatscha K

    2015-01-01

    Full Text Available Untherapierter Wachstumshormonmangel im Erwachsenenalter (AGHD ist mit viszeraler Adipositas, Dyslipidämie, Insulinresistenz und Fettleber verbunden. Interessanterweise finden sich viele der AGHD-Merkmale auch bei Patienten mit metabolischem Syndrom. Die nichtalkoholische Fettlebererkrankung (NAFLD gilt als hepatische Manifestation des metabolischen Syndroms. In einigen Studien wurden bei Patienten mit NAFLD verminderte Konzentrationen von zirkulierendem IGF-1, dessen Synthese zu einem großen Teil durch Wachstumshormon (GH reguliert wird, beschrieben. Mäuse, welche eine hepatische Wachstumshormondefizienz aufweisen, zeigen zahlreiche phänotypische Charakteristika des metabolischen Syndroms, unter anderen auch eine Fettlebererkrankung. Dies legt einen Zusammenhang zwischen dem Wachstumshormon und der Entstehung einer NAFLD nahe. Ziel unserer Studie ist es, in einem Zellkulturmodell die Effekte des Wachstumshormons auf den intrazellulären Glukosestoffwechsel näher zu untersuchen. Im Detail sollen Auswirkungen einer verminderten Wachstumshormonrezeptorexpression auf den Insulinsignaltransduktionsweg, den Glykogengehalt und auf Schlüsselenzyme der Glukoneogenese untersucht werden. Präliminäre Daten zeigen, dass eine verminderte Wachstumshormonrezeptorexpression mit intrazellulären Veränderungen des hepatischen Glukosestoffwechsels verbunden ist. Die verminderte Insulinsensitivität könnte auf Alterationen im Insulinsignaltransduktionsweg und Änderungen der Glukoneogenese zurückzuführen sein. Diese präliminären Daten weisen darauf hin, dass Wachstumshormon einen direkten Einfluss auf den Glukosestoffwechsel in der Leber hat. Zudem legen sie nahe, dass Veränderungen im Wachstumshormonstoffwechsel einen wichtigen pathophysiologischen Mechanismus in der Entstehung der Fettlebererkrankung bei Patienten mit metabolischem Syndrom darstellen könnten. Der folgende Artikel soll einen kurzen Überblick über die Effekte von Wachstumshormon

  6. Síndrome de Kinsbourne: relato de caso Síndrome de Kinsbourne: relato de caso Kinsbourne syndrome: case report

    Directory of Open Access Journals (Sweden)

    Marcius Vinícius M. Maranhão

    2013-06-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: A síndrome de Kinsbourne é uma doença neurológica rara que afeta, principalmente, crianças previamente hígidas, na faixa etária entre seis e trinta e seis meses, caracterizada pela presença de opsoclonia (movimentos oculares rápidos, irregulares, horizontais e verticais, mioclonias que podem afetar tronco, extremidades ou face e ataxia cerebelar. Pode ser considerada uma síndrome paraneoplásica pela associação com neuroblastomas, ganglioneuroma e raramente hepatoblastomas. Foi objetivo deste artigo apresentar os aspectos mais relevantes da síndrome de Kinsbourne, bem como a técnica anestésica usada para ressecção de tumor de mediastino em uma criança portadora desta síndrome. RELATO DO CASO: Criança de um ano e cinco meses com diagnóstico de tumor do mediastino posterior portadora de síndrome de Kinsbourne. Pré-medicação com midazolam oral. Indução da anestesia com sevoflurano, óxido nitroso, fentanil e rocurônio. Manutenção da anestesia com sevoflurano, óxido nitroso, fentanil e rocurônio. Reversão do bloqueio neuromuscular com neostigmina associado à atropina. Analgesia pós-operatória com o uso de dipirona, cetoprofeno e morfina. Levada para a Unidade de Terapia Intensiva extubada, com parâmetros hemodinâmicos e respiratórios estáveis. Alta da UTI quatro dias após a cirurgia e alta hospitalar no sétimo dia de pós-operatório sem intercorrências. Anátomo-patológico evidenciou para ganglioneuroblastoma. CONCLUSÕES: A síndrome de Kinsbourne é uma doença neurológica rara. As drogas usadas em nosso paciente mostraram ser seguras e permitiram uma anestesia sem intercorrências. Drogas que desencadeiam ou agravam opsoclonia e mioclonias, como cetamina e etomidato, deverão ser evitadas nesses pacientes.JUSTIFICATIVA Y OBJETIVOS: El síndrome de Kinsbourne es una enfermedad neurológica rara que afecta principalmente a los niños anteriormente sanos, en una franja etaria

  7. Von Krahli Teatri lavastus pääses tippfestivalile

    Index Scriptorium Estoniae

    1999-01-01

    Von Krahli Teatri uuendatud lavastus "Eesti mängud. Pulm" esietendub festivalil Theater Der Welt Berliinis. Peeter Jalaka multimeediaetendus Eesti ajaloost ja traditsioonidest osaleb ka suveteatrite festivalil Hamburgis, seejärel antakse kuus etendust Amsterdamis

  8. La actualidad del pensamiento de Carl von Clausewitz

    National Research Council Canada - National Science Library

    Borrero Mansilla, Armando

    2003-01-01

    The article presents the validity of the thought of Carl von Clausewitz, which application, beyond the wars among national States, can be extended to the analysis of the confrontation among political...

  9. Lexikon lesbischer Frauen im Film von Daniela Sobek

    Directory of Open Access Journals (Sweden)

    Karin Windt

    2002-03-01

    Full Text Available Das Lexikon stellt ein neues Basiswerk über lesbische Figuren im Film dar. Neben zahlreichen Artikeln von Anbeginn der Filmgeschichte bis heute gibt es Features über bekannte Schauspielerinnen und lesbische role models.

  10. Magnus Georg von Paucker (1787-1855) / Eckhard Spring

    Index Scriptorium Estoniae

    Spring, Eckhard

    2013-01-01

    Eestis sündinud ja Tartu Ülikoolis õppinud silmapaistvast baltisaksa teadlasest ja tema lapselapsest Alexandrine Pauckerist. 23. novembril 2012 Jelgavas/Mitaus toimunud Magnus Georg von Pauckerile pühendatud teaduskonverentsist

  11. Von Krahli Teater toob Eestisse erakordse auhinna / Tiit Tuumalu

    Index Scriptorium Estoniae

    Tuumalu, Tiit, 1971-

    2004-01-01

    Bessie-auhinna puhul, millega New Yorgis pärjati Von Krahli Teatri lavastust "Luikede järv." Mõjukuselt on seda võrreldud Broadway teatriauhinna Tonyga. Lisatud lühiandmed P. Jalaka ja S. Pepeljajevi kohta

  12. Politische Bildung im Kontext von Regierung, Unterricht und Zucht

    National Research Council Canada - National Science Library

    Thomas Rucker

    2014-01-01

    .... In diesem Beitrag wird zu zeigen versucht, dass Herbart die Unterstützung politischer Bildung als eine Aufgabe von Regierung, Unterricht und Zucht bestimmt und in seinem Werk wichtige „Bausteine...

  13. Die zentrale Wirkung von Candesartan in der Schlaganfalltherapie

    OpenAIRE

    Maydowski, Katja

    2011-01-01

    Ziel der vorliegenden Arbeit war es, die Auswirkungen des AT1-Blockers Candesartan auf einen ischämischen Insult durch eine rein zentrale AT1-Blockade am Tiermodell mit direkter intracerebroventrikulärer Applikation von Candesartan zu untersuchen.

  14. Zur sportlichen Laufbahn von Marathonläufern

    OpenAIRE

    Rümmele, Edgar

    1984-01-01

    Zur sportlichen Laufbahn von Marathonläufern : e. Beitr. zur Psychologie d. Marathonläufers. - Thun u.a. : Deutsch, 1984. - 253, 14 S. - Zugl.: Tübingen, Univ., Diss. - (Beiträge zur Sportwissenschaft ; 1)

  15. Warum das Controlling den systematischen Einsatz von Simulationen vorantreiben sollte

    DEFF Research Database (Denmark)

    Spitzner, Jan; Schneider, Melanie L.

    2017-01-01

    Simulationen werden in der Unternehmenssteuerung heutzutage noch nicht systematisch eingesetzt. Dass sich jedoch die existierenden Hemmnisse durchaus überwinden lassen, legen die Antworten von Studienteilnehmern nahe, die Simulationen häufig einsetzen. Dabei kann Controlling eine Vorreiterrolle e...

  16. Von Krahli Teater viis Helsingisse kaks menulavastust / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2003-01-01

    Von Krahli Teater esineb 29. nov. Helsingis "Baltic Circle" festivalil lavastustega "Luikede järv" ja "Taksojuhid". Tutvustatakse lühidalt ka paari olulisemat soome lavastust ("Puksiirabi" ja "Hamlet"), mis tulevad festivalil esitamisele

  17. Un relato sobre los 'miserables': Para una tumba sin nombre de Juan Carlos Onetti

    Directory of Open Access Journals (Sweden)

    María Teresa Gabriela Basile

    1999-11-01

    Full Text Available En el interior del proyecto fundacional de Onetti es posible leer tanto sus elecciones como sus exclusiones, su apuesta a la invención ficcional y su rechazo de las estéticas que califica de "nativistas" y "criollistas" así como su crítica al "compromiso literario". Tracé un itinerario de las huellas de estas exclusiones en sus textos, trayecto que se inicia en El pozo (1939 y en sus escritos contemporáneos de Marcha para articularse en Para una tumba sin nombre (1959. Propongo leer esta última nouvelle a partir de la siguiente pregunta: ¿cómo es posible armar un relato sobre "los miserables" en contra del relato realista y fuera de los mandatos del compromiso político?

  18. Un relato sobre los 'miserables': Para una tumba sin nombre de Juan Carlos Onetti

    Directory of Open Access Journals (Sweden)

    María Teresa Gabriela Basile

    2000-11-01

    Full Text Available En el interior del proyecto fundacional de Onetti es posible leer tanto sus elecciones como sus exclusiones, su apuesta a la invención ficcional y su rechazo de las estéticas que califica de "nativistas" y "criollistas" así como su crítica al "compromiso literario". Tracé un itinerario de las huellas de estas exclusiones en sus textos, trayecto que se inicia en El pozo (1939 y en sus escritos contemporáneos de Marcha para articularse en Para una tumba sin nombre (1959. Propongo leer esta última nouvelle a partir de la siguiente pregunta: ¿cómo es posible armar un relato sobre "los miserables" en contra del relato realista y fuera de los mandatos del compromiso político?

  19. Relato y discurso en los orígenes del Reino Asturleonés

    Directory of Open Access Journals (Sweden)

    Arsenio DACOSTA

    2009-12-01

    Full Text Available RESUMEN: El presente trabajo trata de analizar el relato de Pelayo en su contexto. Volviendo sobre el texto y sobre el discurso que genera el relato, se analiza su estructura íntima y la correlación e interdependencia de sus elementos. Aparte de revisar la estructura épica del mismo, se ahondará en la noción de arquetipo y en su papel como imagen política al filo del año 900.ABSTRACT: This work attempts at analysing the story of Pelayo in its context. Going back to the text and the discourse generated by the story, an analysis is undertaken about its inner structure and the correlation and interdependence of its elements. Apart from revising its epic structure, there is an in-depth study of the archetype notion and its role in political image around the year 900.

  20. Zur Dialektik von Soft Skills und fachlicher Kompetenz

    OpenAIRE

    Jendrowiak, Hans-Werner

    2010-01-01

    [Der Autor stellt folgende Thesen zur Dialektik von Soft Skills und fachlicher Bildung auf:] 1. Soft Skills sind normale Bildungskategorien und Teil einer Allgemeinen Bildung. […] 2. Soft Skills sind als personalgebundene Kriterien auch immer schon Gegenstand bildungstheoretischer Debatten. […] 3. Soft Skills ist eine trendorientierte Bezeichnung für Bildung. […] 4. Soft Skills sind Ausdruck von Vorstellungen, Ideen und Theorien (Schulkultur, Unternehmenskultur, Unternehmensphilosophie). 5. S...