Transplanting the Highly Sensitized Patient: The Emory Algorithm

Renal transplant patients sensitized to HLA antigens comprise nearly one-third of the UNOS wait-list and receive 14% of deceased donor (DD) transplants, a rate half that of unsensitized patients. Between 1999 and 2003, we performed 492 adult renal transplants from DD; 120 patients (approximately 25%) had a panel reactive antibody (PRA) of >30%, with nearly half (n = 58) having a PRA of >80%. Our approach is based upon high-resolution solid-phase HLA antibody analysis to identify class I/II antibodies and a 'virtual crossmatch' to predict compatible donor/recipient combinations. Recipients are excluded from the United Network for Organ Sharing match run if donors possess unacceptable antigens. Thus, when sensitized patients appear on the match run, they have a high probability of a negative final crossmatch. Here, we describe our 5-year experience with this approach. Five-year graft survival ranged from 66% to 70% among unsensitized (n = 272), moderately sensitized (PRA < 30%, n = 100) and highly sensitized (>30% PRA; n = 120) patients, equal to the average national graft survival (65.7%). The application of this approach (the Emory Algorithm) provides a logical and systematic approach to improve the access of sensitized patients to DD organs and promote more equitable allocation to a highly disadvantaged group of patients awaiting renal transplantation.     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

Demonstration of cardiac arrhythmias in multi-infarct dementia and ischemic stroke using Holter monitoring.]

The occurrence of the cardiac arrhythmias was estimated by using 24-hour ECG Holter monitoring in 30 patients with multi-infarct dementia and in 30 with ischaemic stroke. Holter monitoring revealed pathological cardiac arrhythmias in 36.7% patients with multi-infarct dementia and in 40% with single ischaemic focus in the brain. It also allowed to reveal more frequent occurrence of cardiac arrhythmias in patients with ischaemic stroke (40%), than standard ECG (17%).     

Ruptur der langen Bizepssehne und operative Therapiestrategien

Zusammenfassung Die Ruptur der langen Bizepssehne beruht auf ihrer anatomischen Disposition und, bedingt durch die biomechanische Belastung, zu 90% auf degenerativen Veränderungen. In der Regel finden sich begleitende Verschleißschäden anderer Strukturen des Schultergelenks wie der Rotatorenmanschette. Es wird ein Überblick über die Häufigkeit und den Entstehungsmechanismus von Rupturen der langen Bizepssehne sowie gängige operative Behandlungskonzepte gegeben. Die Rolle und das anatomisch-funktionelle Prinzip der Sehne des Caput longum im komplexen dynamischen System des Schultergelenks werden erläutert. Eingang finden die klinische Symptomatik, Beschreibungen sowie Wertungen apparativer diagnostischer Verfahren. Der Stand derzeit etablierter Operationstechniken wird unter Darstellung von Vor- und Nachteilen beleuchtet und diskutiert. Des Weiteren werden die selbst favorisierte Methode und die gesammelten Erfahrungen dargestellt.     

Rescue of lethal molybdenum cofactor deficiency by a biosynthetic precursor from Escherichia coli

Substitution therapies for orphan genetic diseases, including enzyme replacement methods, are frequently hampered by the limited availability of the required therapeutic substance. We describe the isolation of a pterin intermediate from bacteria that was successfully used for the therapy of a hitherto incurable and lethal disease. Molybdenum cofactor (Moco) deficiency is a pleiotropic genetic disorder characterized by the loss of the molybdenum-dependent enzymes sulphite oxidase, xanthine oxidoreductase and aldehyde oxidase due to mutations in Moco biosynthesis genes. An intermediate of this pathway-'precursor Z'-is more stable than the cofactor itself and has an identical structure in all phyla. Thus, it was overproduced in the bacterium Escherichia coli, purified and used to inject precursor Z-deficient knockout mice that display a phenotype which resembles that of the human deficiency state. Precursor Z-substituted mice reach adulthood and fertility. Biochemical analyses further suggest that the described treatment can lead to the alleviation of most symptoms associated with human Moco deficiency.