The aims of the study were to evaluate the clinical, radiological and ultrasonographical images of knee joints in children with severe haemophilia and von Willebrand's disease, to determine the correlation between these images and to assess the usefulness of ultrasonography (USG) in evaluating the intensity of haemophilic arthropathy. Thirty-nine boys were included in the study, all of them with a past history of knee bleeds. The average age of the children was 10.02 +/- 3.01 years. In patients with slight (1-3 points) and moderate (4-7 points) radiological changes in knee joint bones, an increase in synovial fluid, considerable hypertrophy and inflammation of the synovium were observed in USG. In haemophilic patients with severe (8-13 points) bone changes, the amount of fluid was usually normal and there was slight inflammation but considerable hypertrophy of the synovium. Radiological evaluation of haemophilic arthropathy was made according to the Pettersson classification. A good correlation between the degree of cartilage damage in USG and the progression of bone changes in radiographs was found. Cartilage and bone damage progressed with the increase in the number of intra-articular haemorrhages into the knee joint. In our opinion USG is useful in evaluating the fluid, synovium and cartilage of joints in haemophiliacs.

Introduction:Nuwiq â (Human-cl rhFVIII) is a new-generation recombinant factor VIII (rFVIII) protein, without chemical modification or fusion to any other protein, produced in a human cell line. Aim/Methods: This prospective, open-label, multinational phase III study assessed the efficacy and safety of Human-cl rhFVIII in 59 previously treated patients (PTPs) with severe haemophilia A aged 2-12 years (2-5 [N = 29]; 6-12 [N = 30]) during standard prophylaxis (≥50 exposure days and ≥6 months). Efficacy in treating breakthrough bleeds and during surgical prophylaxis was also assessed. Results: An initial pharmacokinetic assessment (N = 13 per age subgroup) demonstrated comparable results with the one-stage and chromogenic assays. Mean (SD) half-life was 11.9 (5.4) and 13.1 (2.6) hours in children aged 2-5 years and 6-12 years respectively (one-stage assay). Prophylactic efficacy, based on mean monthly bleeding rate, was 'excellent' or 'good' in 91.5% of children for all bleeds and in 96.6% of children for spontaneous bleeds. Mean (SD) annualized bleeding rate was 4.12 (5.22) [median 1.9] for all bleeds, 1.50 (3.32) [median 0] for spontaneous bleeds and 2.34 (3.54) [median 1.57] for traumatic bleeds. There were no major, life-threatening bleeds. Efficacy was 'excellent' or 'good' in the treatment of 82.4% of breakthrough bleeds. Overall efficacy during five major surgeries was rated as 'excellent'. There were no FVIII inhibitors or treatment-related serious adverse events. Conclusion: These results in paediatric PTPs indicate that Human-cl rhFVIII is effective for the prevention and treatment of bleeds.

Introduction/background: Development of neutralizing inhibitors against factor VIII (FVIII) is a major complication of haemophilia A treatment. Aim: The ongoing, international, open-label, uncontrolled, observational immune tolerance induction (ObsITI) study evaluates ITI, the standard of care in patients with inhibitors. Patients/methods: Forty-eight prospective patients in this interim analysis received a single plasmaderived, von Willebrand factor-stabilized, FVIII concentrate (pdFVIII/VWF) for ITI. According to recommended Bonn protocol, 'low responders' at ITI start (<5 BU) received 50-100 IU FVIII kg À1 daily, or every other day; 'high responders' (≥5 BU) received 100 IU FVIII kg À1 every 12 h. Results: Forty of 48 patients (83.3%), had at least one risk factor for poor ITI-prognosis at ITI start (i.e. age ≥7 years, >2 years since inhibitor diagnosis, inhibitor titre ≥10 BU at the start of ITI, or prior ITI failure). Nonetheless, 34 patients (70.8%) achieved complete success, 3 (6.3%) partial success, 1 (2.1%) partial response; ITI failed in 10 patients (20.8%), all with poor prognosis factors. All six low responders achieved complete success. ITI outcome was significantly associated with inhibitor titre level at ITI start (P = 0.0068), number of poor prognosis factors for ITI success (P = 0.0187), monthly bleeding rate during ITI (P = 0.0005) and peak inhibitor titre during ITI (P = 0.0007). Twenty-two of 35 high responder patients (62.9%) with ≥1 poor prognosis factor achieved complete success. Conclusion: Treatment with a single pdFVIII/VWF concentrate, mainly according to the Bonn protocol, resulted in a high ITI success rate in haemophilia A patients with inhibitors and poor prognosis for ITI success.

We present results regarding the fast and inexpensive fabrication of polymer biochips for investigating the statics and dynamics of DNA confined in nanochannels. The biochips have been fabricated by means of nanoimprint lithography (NIL) in low molecular weight polymethyl methacrylate (PMMA) using a 4 inch diameter two-level hybrid stamp. The fluidic structures were sealed using thermal polymer fusion bonding. The stamp has nanometer-and micrometer-sized protrusions defined in a thermally grown SiO 2 layer and the sol-gel process derived duromeric hybrid polymer Ormocomp, respectively. The stamp is compatible with molecular vapor deposition (MVD), used for applying a durable chlorosilane based antistiction coating, and allows for imprint up to a temperature of 270 • C. The extension of YOYO-1 stained T4 GT7 bacteriophage DNA inside the PMMA nanochannels has been experimentally investigated using epi-fluorescence microscopy. The measured average extension length amounts to 20% of the full contour length with a standard deviation of 4%. These results are in good agreement with results obtained by stretching DNA in conventional fused silica nanochannels.

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