Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.     

Stasis ulcers: the role of compliance in healing

The goal in treating a stasis ulcer is rapid and permanent reepithelialization of the ulcer bed. The patient can reach this goal by strict compliance with a program taught and continually reinforced by the physician. The program teaches about the effects of the force of gravity on the flow of blood and lymph in the lower extremities in various positions. The program consists of three rules for the patient to follow: (1) Never sit with legs below heart level. (2) Never stand still. Walk in place or even while sitting (if sitting is necessary). (3) Always wear compressive stockings or pneumatic leggings when walking. I present four case histories demonstrating the different rates of healing of stasis ulcers during noncompliance and during compliance with the physiologic methods of controlling edema and venous stasis in the legs.     

BMP‐7 protects against progression of cartilage degeneration after impact injury

In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 µg of rhBMP‐7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase‐3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous (pro‐) form of BMP‐7 protein. Knee joints that received rhBMP‐7 immediately after injury had small focal lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP‐7 3 weeks after injury were improved and had limited progression compared to controls, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP‐7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 602–611, 2009     

The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins

A primary pathologic component of Alzheimer's disease (AD) is the formation of neurofibrillary tangles composed of hyperphosphorylated tau (p-tau). Expediting the removal of these p-tau species may be a relevant therapeutic strategy. Here we report that inhibition of Hsp90 led to decreases in p-tau levels independent of heat shock factor 1 (HSF1) activation. A critical mediator of this mechanism was carboxy terminus of Hsp70-interacting protein (CHIP), a tau ubiquitin ligase. Cochaperones were also involved in Hsp90-mediated removal of p-tau, while those of the mature Hsp90 refolding complex prevented this effect. This is the first demonstration to our knowledge that blockade of the refolding pathway promotes p-tau turnover through degradation. We also show that peripheral administration of a novel Hsp90 inhibitor promoted selective decreases in p-tau species in a mouse model of tauopathy, further suggesting a central role for the Hsp90 complex in the pathogenesis of tauopathies. When taken in the context of known high-affinity Hsp90 complexes in affected regions of the AD brain, these data implicate a central role for Hsp90 in the development of AD and other tauopathies and may provide a rationale for the development of novel Hsp90-based therapeutic strategies.