Permeability of muscle capillaries to microperoxidase

In this study we attempted to identify a morphologic counterpart of the small pore of muscle capillaries. The existence of such a pore has been postulated by physiologists to explain the permeability of muscle capillaries to small macromolecules. We injected mice intravenously with microperoxidase (MP) and fixed specimens of diaphragm at intervals of 0-250 s after the injection to localize the tracer by electron microscopy. The small size of MP (1,900 mol wt and 20 A molecular diameter [MD]) ensures its ready passage through the small pore since the latter is thought to be either a cylindrical channel 90 A in diameter or a slit 55 A wide. MP appears in the pericapillary interstitium within 30 s of initiation of its intravenous injection. The patterns of localization of MP observed within clefts between adjacent capillary endothelial cells indicate that some endothelial junctions are permeable to this tracer. Although small vesicles transfer MP across the endothelium, we do not believe that the vesicles transfer substantial amounts of MP into the pericapillary interstitium. We did not obtain evidence that MP crosses the endothelium of capillaries through channels formed either by a single vesicle or by a series of linked vesicles opening simultaneously at both surfaces of the endothelial cell. From our observations we conclude that some endothelial junctions of capillaries are permeable to MP, and that these permeable junctions are a plausible morphologic counterpart of the small pore

Defining an International Standard Set of Outcome Measures for Patients With Hip or Knee Osteoarthritis: Consensus of the International Consortium for Health Outcomes Measurement Hip and Knee Osteoarthritis Working Group

Objective: To define a minimum Standard Set of outcome measures and case-mix factors for monitoring, comparing, and improving health care for patients with clinically diagnosed hip or knee osteoarthritis (OA), with a focus on defining the outcomes that matter most to patients. Methods: An international working group of patients, arthroplasty register experts, orthopedic surgeons, primary care physicians, rheumatologists, and physiotherapists representing 10 countries was assembled to review existing literature and practices for assessing outcomes of pharmacologic and nonpharmacologic OA therapies, including surgery. A series of 8 teleconferences, incorporating a modified Delphi process, were held to reach consensus. Results: The working group reached consensus on a concise set of outcome measures to evaluate patients’ joint pain, physical functioning, health-related quality of life, work status, mortality, reoperations, readmissions, and overall satisfaction with treatment result. To support analysis of these outcome measures, pertinent baseline characteristics and risk factor metrics were defined. Annual outcome measurement is recommended for all patients. Conclusion: We have defined a Standard Set of outcome measures for monitoring the care of people with clinically diagnosed hip or knee OA that is appropriate for use across all treatment and care settings. We believe this Standard Set provides meaningful, comparable, and easy to interpret measures ready to implement in clinics and/or registries globally. We view this set as an initial step that, when combined with cost data, will facilitate value-based health care improvements in the treatment of hip and knee OA

fMRI adaptation revisited

Adaptation has been widely used in functional magnetic imaging (fMRI) studies to infer neuronal response properties in human cortex. fMRI adaptation has been criticised because of the complex relationship between fMRI adaptation effects and the multiple neuronal effects that could underlie them. Many of the longstanding concerns about fMRI adaptation have received empirical support from neurophysiological studies over the last decade. We review these studies here, and also consider neuroimaging studies that have investigated how fMRI adaptation effects are influenced by high-level perceptual processes. The results of these studies further emphasize the need to interpret fMRI adaptation results with caution, but they also provide helpful guidance for more accurate interpretation and better experimental design. In addition, we argue that rather than being used as a proxy for measurements of neuronal stimulus selectivity, fMRI adaptation may be most useful for studying population-level adaptation effects across cortical processing hierarchies