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.     

Regulation of peripheral-type benzodiazepine receptors in cultured astrocytes by monoamine and amino acid neurotransmitters

Exposure of primary cultured astrocytes for 3 days to 1 μM of either dopamine, serotonin or norepinephrine resulted in upregulation (25–34% increase in B_max) of the peripheral-type benzodiazepine receptors (PBRs) labeled with [³H]Ro5-4864. A similar treatment with γ-aminobutyric acid [GABA] caused a 2-fold increase in the affinity (K_d) of [³H]Ro5-4864. The monoamines tested and GABA had no effect on the binding parameters of [³H]PK 11195, another selective PBR ligand. The present study indicates that Ro5-4864 binding sites are susceptible to regulation by specific neurotransmitters and provides further evidence for the distinction between Ro5-4864 and PK 11195 binding sites of the PBRs in cultured astrocytes.     

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%).     

Administration of Half-Dose Theophylline Together with Ketotifen to Asthmatic Children—A Double-Blind, Placebo-Controlled Study

Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 μg/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T + K-Placebo (T group); T + K (T + K group); half-dose T + K (T/ 2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T + P, T + K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.     

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.     

Immediate root canal disinfection with ultraviolet light: an ex vivo feasibility study.

OBJECTIVE: The study was designed to test application of ultraviolet light to root canal walls, as a mean of complementary immediate disinfection after the use of sodium hypochlorite. STUDY DESIGN: Root canals were infected ex vivo with Enterococcus faecalis for 48 hours. Non-attached bacteria were washed away, and the remaining attached bacteria were subjected to disinfection, with 5% sodium hypochlorite alone or followed by exposure to ultraviolet light (254 nm, 300 mJ/cm(2)). Root canals were then tested for remaining viable bacteria. Canals were obturated and tested again after 14 days. RESULTS: Sodium hypochlorite alone achieved negative cultures in only 47% of the cases, but 96% was achieved with sodium hypochlorite followed by ultraviolet light (P < .001). This status was also maintained after 14 days. CONCLUSIONS: Illumination of root canals with ultraviolet light may be an effective supplementary means to achieve immediate disinfection of infected root canals.     

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.