Browsing by Author "Thomas, P."

gamma-Aminobutyric acid type A receptors (GABA(A)Rs) are the major sites of fast synaptic inhibition in the brain. An essential determinant for the efficacy of synaptic inhibition is the regulation of GABA(A)R cell surface stability. Here, we have examined the regulation of GABA(A)R endocytic sorting, a critical regulator of cell surface receptor number. In neurons, rapid constitutive endocytosis of GABA(A)Rs was evident. Internalized receptors were then either rapidly recycled back to the cell surface, or on a slower time scale, targeted for lysosomal degradation. This sorting decision was regulated by a direct interaction of GABA(A)Rs with Huntingtin-associated protein 1 (HAP1). HAP1 modulated synaptic GABA(A)R number by inhibiting receptor degradation and facilitating receptor recycling. Together these observations have identified a role for HAP1 in regulating GABAAR sorting, suggesting an important role for this protein in the construction and maintenance of inhibitory synapses.

Background: In 16 patients with revised metal-on-metal arthroplasty and peri-implant lymphocytic inflammation, we verified the role of metal hypersensitivity by patch testing (PT) and lymphocyte transformation test (LTT). Methods: In the 16 patients with lymphocyte dominated periprosthetic inflammation, allergy history was obtained by a questionnaire, specific serum IgE to aeroallergens was measured to assess atopy, PT to standard and metal series was performed and metal sensitivity was further assessed by LTT using blood mononuclear cells. Results: Revision surgery was performed because of pain (8/16), osteolysis (4/16), dislocation (3/16) and loosening of the stem (1/16). Histological examination showed perivascular infiltrates of T lymphocytes, high endothelial venules, fibrin exudation and accumulation of macrophages with drop-like inclusions. Five patients had a history of cutaneous metal allergy and atopy was found in 25% of the patients. In 13/16 patients (81%), systemic metal sensitivity was found based on PT and/or LTT. Patch test reactions were seen in 11/16 patients (69%; partly multiple reactions/patient): 7/16 to Cobalt (Co), 7/16 to Chromium (Cr), 4/16 to Nickel (Ni), and one each to Molybdenum (Mo) and Manganese (Mn). Ten of 16 patients (62%) showed enhanced LTT reactivity to metals: 7/16 to Ni, 7/16 to Co, 5/16 to Cr, 5/16 to Mo and 4/16 to Mn. Conclusions: The lymphocyte dominated peri-implant inflammation may well reflect an allergic hyper-reactivity in these patients, given the high rate of concomitantly found metal allergy. Despite the overall incidence of metal implant allergy being low, allergic reactions should be included as differential diagnosis in failed metal-on-metal arthroplasty.

Intolerance reactions to metal implants may be caused by metal allergy. However, prior to implantation, patch testing should not be done in a prophylactic-prophetic approach. Pre-implant patch testing should only be performed to verify or exclude metal allergy in patients with a reported respective history. In the case of implant-in particular arthroplasty-related complications like, for example, pain, effusion, skin changes, reduced range of motion, or loosening, orthopedic-surgical differential diagnostics should be performed first. Allergological workup of suspected metal implant allergy should be done with the DKG baseline series which contains nickel-, cobalt- and chromium-preparations. Various studies assessing the usefulness of metal alloy discs for patch testing proved that this approach does not give reliable information about metal allergy. Positive patch test reactions to the discs cannot be assigned to a specific metal within the disc alloy components. Furthermore, availability of such metal discs might be an invitation to uncritical testing. Accordingly, due to lack of benefit in comparison to patch testing with standardized metal salt preparations, we do not recommend patch testing with metal alloy discs.