Interaction of alpha-phenyl-N-tert-butyl nitrone and alternative electron acceptors with complex I indicates a substrate reduction site upstream from the rotenone binding site.

Mitochondrial complexes I, II, and III were studied in isolated brain mitochondrial preparations with the goal of determining their relative abilities to reduce O2 to hydrogen peroxide (H2O2) or to reduce the alternative electron acceptors nitroblue tetrazolium (NBT) and diphenyliodonium (DPI). Complex I and II stimulation caused H2O2 formation and reduced NBT and DPI as indicated by dichlorodihydrofluorescein oxidation, nitroformazan precipitation, and DPI-mediated enzyme inactivation. The O2 consumption rate was more rapid under complex II (succinate) stimulation than under complex I (NADH) stimulation. In contrast, H2O2 generation and NBT and DPI reduction kinetics were favored by NADH addition but were virtually unobservable during succinate-linked respiration. NADH oxidation was strongly suppressed by rotenone, but NADH-coupled H2O2 flux was accelerated by rotenone. Alpha-phenyl-N-tert-butyl nitrone (PBN), a compound documented to inhibit oxidative stress in models of stroke, sepsis, and parkinsonism, partially inhibited complex I-stimulated H2O2 flux and NBT reduction and also protected complex I from DPI-mediated inactivation while trapping the phenyl radical product of DPI reduction. The results suggest that complex I may be the principal source of brain mitochondrial H2O2 synthesis, possessing an "electron leak" site upstream from the rotenone binding site (i.e., on the NADH side of the enzyme). The inhibition of H2O2 production by PBN suggests a novel explanation for the broad-spectrum antioxidant and antiinflammatory activity of this nitrone spin trap.

Electronic communication with patients. Evaluation of distance medicine technology.

OBJECTIVE: To evaluate controlled evidence on the efficacy of distance medicine technologies in clinical practice and health care outcome. DATA SOURCES: Systematic electronic database and manual searches (1966-1996) were conducted to identify clinical trial reports on distance medicine applications. STUDY SELECTION: Three eligibility criteria were applied: prospective, contemporaneously controlled clinical trial with random assignment of the intervention; electronic distance technology application in the intervention group and no similar intervention in the control group; and measurement of the intervention effect on process or outcome of care. DATA EXTRACTION: Data were abstracted by independent reviewers using a standardized abstraction form and the quality of methodology was scored. Distance technology applications were described in 6 categories: computerized communication, telephone follow-up and counseling, telephone reminders, interactive telephone systems, after-hours telephone access, and telephone screening. DATA SYNTHESIS: Of 80 eligible clinical trials, 61 (76%) analyzed provider-initiated communication with patients and 50 (63%) reported positive outcome, improved performance, or significant benefits, including studies of computerized communication (7 of 7), telephone follow-up and counseling (20 of 37), telephone reminders (14 of 23), interactive telephone systems (5 of 6), telephone access (3 of 4), and telephone screening (1 of 3). Significantly improved outcomes were demonstrated in studies of preventive care, management of osteoarthritis, cardiac rehabilitation, and diabetes care. CONCLUSIONS: Distance medicine technology enables greater continuity of care by improving access and supporting the coordination of activities by a clinician. The benefits of distance technologies in facilitating communication between clinicians and patients indicate that application of telemedicine should not be limited to physician-to-physician communication.

An expert system for performance-based direct delivery of published clinical evidence.

OBJECTIVE: To develop a system for clinical performance improvement through rule-based analysis of medical practice patterns and individualized distribution of published scientific evidence. METHODS: The Quality Feedback Expert System (QFES) was developed by applying a Level-5 expert system shell to generate clinical direct reports for performance improvement. The system comprises three data and knowledge bases: 1) a knowledge base of measurable clinical practice parameters; 2) a practice pattern database of provider-specific numbers of patients and clinical activities; and 3) a management rule base comprising "redline rules" that identify providers whose practice styles vary significantly. Clinical direct reports consist of a table of practice data highlighting individual utilization vs recommendation and selected pertinent statements from medical literature. RESULTS: The QFES supports integration of recommendations from several guidelines into a comprehensive and measurable quality improvement plan, analysis of actual practice patterns and comparison with accepted recommendations, and generation of a confidential individualized direct report to those who significantly deviate from clinical recommendations. The feasibility of the practice pattern analysis by the QFES was demonstrated in a sample of 182 urinary tract infection cases from a primary care clinic. In a set of clinical activities, four questions/procedures were associated with significant (p < 0.001) and unexplained variation. CONCLUSION: The QFES provides a flexible tool for the implementation of clinical practice guidelines in diverse and changing clinical areas without the need for special program development. Preliminary studies indicate utility in the analysis of clinical practice variation and deviations. Using data obtained through a retrospective chart audit, the QFES was able to detect overutilization, and to identify nonrandom differences in practice patterns.