37 research outputs found
An Aggressive Course of Transformed Splenic Diffuse Red Pulp Small B-Cell Lymphoma With Novel Somatic Loss-of-Function Mutation in RB1
Deep sequencing reveals different compositions of mRNA transcribed from the F8 gene in a panel of FVIII-producing CHO cell lines
mRNA expression of genes involved in inflammation and haemostasis in equine fibroblast-like synoviocytes following exposure to lipopolysaccharide, fibrinogen and thrombin
Preliminary references under TEC article 177 : a comparative study of the practice of the Danish and Swedish courts
Award date: 31 December 1998Supervisor: Prof. R. DehoussePDF of thesis uploaded from the Library digitised archive of EUI PhD theses completed between 2013 and 201
Haemarthrosis and arthropathy do not favour the development of factor VIII inhibitors in severe haemophilia A mice
Cesarean section in twin pregnancies in two Danish counties with different cesarean section rates
Hemostatic effect of recombinant factor VIIa, NN1731 and recombinant factor VIII on needle-induced joint bleeding in hemophilia A mice
IL-6 receptor antagonist as adjunctive therapy with clotting factor replacement to protect against bleeding-induced arthropathy in hemophilia
BACKGROUND: The major morbidity of hemophilia is bleeding induced hemophilic arthropathy (HA) which once established may not be interrupted completely even by prophylactic clotting factor replacement. Specific therapies to oppose inflammatory cytokines, including Interleukin 6 (IL-6) receptor antagonists, have become important in the management of inflammatory arthritides. OBJECTIVES: We investigated combining therapy using MR16-1, a rat IgG antibody directed against mouse IL-6 receptor (anti-IL-6R), with factor VIII (FVIII) replacement to protect against bleeding induced arthropathy in hemophilia A mice. METHODS: Three recurrent hemarthroses were induced in the knee joint capsule of factor VIII knockout mice. Treatment at the time of each hemorrhage included either: No treatment; FVIII replacement given at the time of hemorrhage; FVIII replacement at hemorrhage plus anti-IL-6R as four weekly injections; FVIII replacement with non-specific control antibody (rat IgG); anti-IL-6R alone without FVIII replacement. Six weeks following the first hemarthosis joints were harvested and histopathology was scored for synovitis, for cartilage integrity and for macrophage infiltration. RESULTS: Animals that received anti-IL-6R as an adjunct to FVIII replacement demonstrated the best survival and the least acute joint swelling and pathology on histologic examination of synovium and cartilage (P<0.05 for each parameter). All histopathologic parameters in the mice receiving FVIII+anti-IL-6R were limited and were comparable to findings in injured hemostatically normal mice. The major benefits of adjunctive anti-IL-6R were decreasing synovial hyperplasia, hemosiderin deposition and macrophage infiltration. CONCLUSIONS: Short-course specific inhibition of inflammatory cytokines as an adjunct to replacement hemostasis may be an approach to minimize hemophilic joint degeneration