A new approach for evaluating antigen-specific T cell responses to myelin antigens during the course of multiple sclerosis

We used a flow cytometry assay to measure proliferation and cytokine production of self-antigen-specific T cells in individual patients during the clinical course of multiple sclerosis (MS). Myelin-associated oligodendrocytic basic protein (MOBP) was selected for proof of principles in the assay, along with myelin basic protein (MBP) to assess specific activated T cells in 10 MS patients over an 18-month period, in parallel with brain magnetic resonance imaging (MRI) scans and clinical rating scale. A positive correlation occurred between antigen-specific T cell proliferation and interferon-gamma production with clinical relapses and MRI lesion activity that was absent when the same patients were in remission.     

A pilot feasibility study of the effects of touch therapy on nurses

The White House Commission on Complementary Alternative Medicine (CAM) has recommended that safe and effective CAM practices be evaluated to determine their role in maintaining wellness and promoting health. There is little research on individual bodywork/energy therapies and their effects on wellness. The purpose of this pilot study was to assess the effect of AMMA treatments on relaxation and anxiety in staff nurses, and to examine themes describing the nurses' experiences. It was hypothesized that nurses receiving AMMA treatments would demonstrate reduced anxiety, as measured by a Visual Analog Scale (VAS) and increased relaxation, measured by physiologic parameters. The study was designed as a prospective, randomized, blinded clinical trial, with convenience sampling of 24 nurses working 12-hour shifts. While both groups demonstrated decreased anxiety after intervention, the experimental group consistently showed greater differences between pre- and post-treatment anxiety scores. The mean change in physiologic parameters between groups was not significant. Themes derived from a final interview included: importance of touch in nursing care, stress reduction, increased self-awareness, the need for self-care and a new understanding of the mind-body connection. Outcomes suggest the need for further research with a larger population to assess this intervention's impact on anxiety, stress, self-care and caring relationships.     

Mechanism of the inhibition of lysosomal functions in the retinal pigment epithelium by lipofuscin retinoid component A2-E

BACKGROUND: Excessive accumulation of lipofuscin in the retinal pigment epithelium with age and in various hereditary and degenerative retinal diseases, is of pathogenetic significance. We have shown that the major lipofuscin fluorophor A2-E (N-retinylidene-N-retinylethanolamine) affects the lysosomal degradation of human RPE cells and damages the cellular metabolism by phototoxic properties. Herein we sought to determine mechanisms for the inhibitory effect on lysosomal function apart from pH elevation. METHODS: Potter-Elvejem homogenates of RPE cells were used to measure the activity of 24 lysosomal enzymes before and after incubation with A2-E. RESULTS: This is the first time that RPE cells have been screened for a large spectrum of lysosomal hydrolases including proteases, lipidases, glycosidases, nucleases, sulfatases and phosphatases. The activities of these hydrolases were readily detectable in cultured RPE cells. Incubation of RPE cell homogenates even with high A2-E concentrations (up to 10 microM) did not affect the activity of isolated lysosomal enzymes. CONCLUSIONS: The results suggest that a direct inhibition of lysosomal enzyme activity would not explain the inhibitory effect on lysosomal degradation. A2-E increases the acidic intralysosomal pH thereby probably hindering pH-dependent lysosomal enzymatic activities. The understanding of the inhibitory effects of A2-E on RPE cell metabolism may contribute to new approaches for treatment of retinal diseases with excessive lipofuscin accumulation such as ARMD or M. Stargardt.     

Die Implantation einer unikondyl?ren Schlittenprothese

Zusammenfassung Operationsziel Wiederherstellung einer geraden Beinachse und schmerzfreien Gelenkfunktion. Indikationen Mediale oder laterale, auf eine Gelenkhälfte beschränkte Arthrose mit Fehlstellung der Beinachse unter 20°, bei der eine sog. Umstellungsosteotomie nicht in Frage kommt. Osteonekrose des medialen Femurkondylus (Morbus Ahlbäck). Voraussetzung: Alter über 60 Jahre. Kontraindikationen Panarthrose. Instabilität des Kniegelenks (abgesehen von relativer Aufklappbarkeit wegen Knorpelschwunds). Polyarthritis. Systemische Gelenkerkrankung wie z. B. Hämophilie. Neuropathische Arthropathie. Starke Adipositas. Fehlstellung der Beinachse über 20°, Beugekontraktur über 20°. Operationstechnik Darstellung des Kniegelenks über einen medianen Zugang. Horizontale Resektion des betroffenen Tibiaplateaus unter Erhalt der Kreuz- und Seitenbänder. Zurichtung des Femurkondylus zur Aufnahme des entsprechenden Prothesenteils. Einzementierung der Prothesenkomponenten in achsengerechter Position. Ergebnisse Retrospektive Studie an 149 Patienten (34 Männer und 115 Frauen im Alter zwischen 62 und 86 Jahren), die in den Jahren 1986-1990 operiert wurden. Der Nachuntersuchungszeitraum betrug 8-12 Jahre, durchschnittlich 10,07 Jahre. 44 Patienten sind zwischenzeitlich an knieunabhängigen Erkrankungen gestorben. 23 Prothesen wurden aus unterschiedlichen Gründen gewechselt. Die Ergebnisse wurden bei 35 Patienten telefonisch erfragt, bei 45 nach klinischen und radiologischen Untersuchungen sowie nach dem HSS-Score festgestellt: Bei 80% der Patienten fanden sich sehr gute und gute, bei 7,5% mäßige und bei 12,5% schlechte Resultate. Hauptgründe für die schlechten Ergebnisse waren ungünstige Ausgangssituationen wie z. B. rheumatische Polyarthritis, zu weit fortgeschrittene Gonarthrose, Lockerung oder Einsinken der tibialen Prothesenkomponente. Die Überlebensrate ("survival rate") betrug bei 84 Patienten nach mehr als 10-jähriger Laufzeit und Revisionserfordernis als Endpunkt 83,7%. Abstract Objectives Correction of axial malalignment and restoration of a normal pain-free joint function through insertion of a unicompartmental runner. Indications Medial or lateral unicompartmental osteoarthritis. Osteonecrosis of the medial femoral condyle. Age over 60 years. Contraindications Osteoarthritis of more than one compartment. Ligamentous instability (instability due to cartilage loss is not a contraindication). Rheumatoid arthritis. Chronic synovitis. Systemic affections of joints (i. e., hemophilia). Neuropathic joint diseases. Obesity. Axial malalignment exceeding 20°. Flexion contracture exceeding 20°. Sugical Technique Medial approach. After visual confirmation that only one compartment is affected, resection of the tibial plateau while preserving cruciate and collateral ligaments. Preparation of the femoral condyle and restoration of axial alignment through insertion of the unicompartmental components. Avoid overcorrection. Results Between 1986 and 1990 a unicompartmental arthroplasty was done in 34 men and 115 women (62-86 years). 44 had died for unrelated reasons. 35 answered a questionnaire by phone, 45 could be examined clinically and radiologically. 23 patients had undergone a revision surgery for various reasons. The duration of follow-up varied between 8 and 12 years. The clinical assessment was based on the HSS score. Results were good to excellent in 80%, moderate in 7.5%, and poor in 12.5%. Patients with a poor result were scrutinized paying special attention to the surgical indication. Main reasons for poor results were rheumatoid arthritis, advanced osteoarthritis, loosening and subsidence of the tibial component. The survival rate after more than 10 years of 84 patients at risk, with the need of revision as endpoint, was 83.7%.     

Calcium-independent receptor for alpha-latrotoxin and neurexin 1alpha [corrected] facilitate toxin-induced channel formation: evidence that channel formation results from tethering of toxin to membrane

alpha-Latrotoxin binding to the calcium-independent receptor for alpha-latrotoxin (CIRL-1), a putative G-protein-coupled receptor, stimulates secretion from chromaffin and PC12 cells. Using patch clamp techniques and microspectrofluorimetry, we demonstrate that the interaction of alpha-latrotoxin with CIRL-1 produces a high conductance channel that permits increases in cytosolic Ca(2+). alpha-Latrotoxin interaction with CIRL-1 transiently expressed in bovine chromaffin cells produced a 400-pS channel, which rarely closed under Ca(2+)-free conditions. The major effect of overexpressing CIRL-1 was to greatly increase the sensitivity of chromaffin cells to channel formation by alpha-latrotoxin. alpha-Latrotoxin interaction with CIRL-1 transiently overexpressed in non-neuronal human embryonic kidney 293 (HEK293) cells produced channels that were nearly identical with those observed in chromaffin cells. Channel currents were reduced by millimolar Ca(2+). At alpha-latrotoxin concentrations below 500 pM, channel formation occurred many seconds after binding of toxin to CIRL-1 indicating distinct steps in channel formation. In all cases there was a rapid, sequential addition of channels once the first channel appeared. An analysis of CIRL-1 mutants indicated that channel formation in HEK293 cells is unlikely to be transduced by a G-protein-dependent mechanism. alpha-Latrotoxin interaction with a fusion construct composed of the extracellular domain of CIRL-1 anchored to the membrane by the transmembrane domain of vesicular stomatitis virus glycoprotein, and with neurexin 1alpha, an alpha-latrotoxin receptor structurally unrelated to CIRL-1, produced channels virtually identical with those observed with wild-type CIRL-1. We propose that alpha-latrotoxin receptors recruit toxin to facilitate its insertion across the membrane and that alpha-latrotoxin itself controls the conductance properties of the channels it produces.     

Experimentelle Nachweise adrenergischer Fasern und deren Aufteilung in der Cochlea

Ohne Zusammenfassung     

Komplikationen und Spätschäden bei Verletzungen des Ellbogens

Trauma und Berufskrankheit - Zusammenfassung Unfallbedingte Komplikationen bei Verletzungen des Ellbogens betreffen v. a. die Gefäße und Nerven zur Hand; sie sind relativ selten....     

Die Implantation der trabekulär orientierten Hüfttotalendoprothese

Operationsprinzip Zementfreie Implantation eines kraftflu?orientierten Hüfttotal-Endoprothesensystems mit weitgehender Erhaltung der ?Substantia spongiosa?, welche die kraftübertragenden elastomechanischen und biodynamischen Elemente enth?lt. Die dauerhafte Verankerung der Endoprothesenpfanne geschieht über eine gro?fl?chige Integration in der Spongiosa am Acetabulum. Die Femurkomponente der Endoprothese besteht aus einer Tragplatte und verstrebten Pfeilern, die in der gesamten Trochanterregion verankert werden. Der Schenkelhals wird weitgehend erhalten. Die Vernetzung der Endoprothese in der Spongiosa, eine prim?re Rotationsstabilit?t und die Aufnahme von Zugkr?ften im Trochantermassiv erm?glichen eine ann?hernd physiologische Kraftübertragung am Hüftgelenk.