Epidemiological Challenges in Rare Bleeding Disorders: FVIII Inhibitor Incidence in Haemophilia A Patients-A Known Issue of Unknown Origin.

There is a broad range of factor products approved in Germany for haemophilia A treatment. Since the introduction of recombinant coagulation factor VIII (FVIII) products in the 1990s, there has been substantial debate whether there is a difference in inhibitor incidence between single FVIII products or product classes. Neither haemophilia registries nor clinical studies, including a randomised controlled clinical trial, provided a consistent and definite answer.

The German Hemophilia Registry: Growing with Its Tasks.

Hemophilia is a rare heredity bleeding disorder that requires treatment for life. While few therapeutic options were available in the past, multiple recent breakthroughs have fundamentally altered and diversified hemophilia therapy, with even more new therapeutic options forthcoming. These changes are mirrored by significant regulatory and legal changes, which have redefined the role of hemophilia registries in the European Union (EU).

Annual Bleeding Rates: Pitfalls of Clinical Trial Outcomes in Hemophilia Patients.

Emerging treatment options for hemophilia, including gene therapy, modified factor products, antibody-based products, and other nonreplacement therapies, are in development or on their way to marketing authorization. For proof of efficacy, annual bleeding rates (ABRs) have become an increasingly important endpoint in hemophilia trials. We hypothesized that ABR analyses differ substantially between and within medicinal product classes and that the ABR observation period constitutes a major bias.

Electrophysiological characterization of ATPases in native synaptic vesicles and synaptic plasma membranes.

Vesicular V-ATPase (V-type H+-ATPase) and the plasma membrane-bound Na+/K+-ATPase are essential for the cycling of neurotransmitters at the synapse, but direct functional studies on their action in native surroundings are limited due to the poor accessibility via standard electrophysiological equipment. We performed SSM (solid supported membrane)-based electrophysiological analyses of synaptic vesicles and plasma membranes prepared from rat brains by sucrose-gradient fractionation. Acidification experiments revealed V-ATPase activity in fractions containing the vesicles but not in the plasma membrane fractions.

Administration of low-dose FK 506 accelerates histomorphometric regeneration and functional outcomes after allograft nerve repair in a rat model.

A substantial loss of peripheral nerves requires grafts for repair. In animal experiments, the use of allografts is successful only when rejection of the transplant is prevented and nerve regeneration is improved by the administration of the immunosuppressant FK 506 used in high doses. In this study, we examined the functional and morphometric outcome after allograft transplantation of the sciatic nerve in rats at low doses of FK 506.

Muscarinic acetylcholine receptors potentiate the GABAergic transmission in the developing rat inferior colliculus.

Postsynaptic currents (PSCs) were recorded using the patch-clamp technique in neurons of the rat inferior colliculus (IC) to investigate the muscarinic modulation of the GABAergic transmission. In the presence of strychnine (0.5 microM) and kynurenic acid (1 mM), spontaneous GABAergic PSCs were observed in all IC neurons investigated.