Characterisations of human prostate stem cells reveal deficiency in class I UGT enzymes as a novel mechanism for castration-resistant prostate cancer.

BACKGROUND: Evidence increasingly supports that prostate cancer is initiated by the malignant transformation of stem cells (SCs). Furthermore, many SC-signalling pathways are shown to be shared in prostate cancer. Therefore, we planned transcriptome characterisation of adult prostate SCs as a strategy to consider new targets for cancer treatment. METHODS: Intuitive pathway analysis was used for putative target discovery in 12 matched selections of human prostate SCs, transiently amplifying cells and terminally differentiated cells. These were pooled into three groups according to the stage of differentiation for mRNA microarray analysis. Targets identified were validated using uncultured primary tissue (n=12), functional models of prostate cancer and a tissue microarray consisting of benign (n=42) and malignant prostate (n=223). RESULTS: A deficiency in class 1 UDP glucuronosyltransferase (UGT) enzymes (UGT1A) was identified in prostate SCs, which are involved in androgen catabolism. Class 1 UGT enzyme expression was also downregulated in cancer SCs and during progression to metastatic castration-resistant prostate cancer (CRPC). Reduction of UGT1A expression in vitro was seen to improve cell survival and increase androgen receptor (AR) activity, as shown by upregulation of prostate-specific antigen expression. INTERPRETATION: Inactivation of intracellular androgen catabolism represents a novel mechanism to maintain AR activity during CRPC.

A bench-top method for evaluating modular total hip component combinations.

A modular total hip prosthesis allows the surgeon to vary head size, neck length, and acetabular coverage. Different combinations, however, may increase the risk of impingement of the prosthesis neck on the acetabular liner, leading to dislocation. We developed a bench-top model to test different modular component combinations to determine how far the femoral component could travel within the acetabular liner before impingement led to dislocation. We tested two hip systems, each from a different manufacturer. Certain components increased the risk of impingement and dislocation: skirted necks, smaller heads, and lipped liners. While the contribution of each component was small, the risk was additive, so that the combination of a small head with a skirted neck in a lipped liner actually reduced the available range of motion by 18 degrees, from 146 degrees to 128 degrees, in the first system, and by 13 degrees, from 156 degrees to 143 degrees in the other. This method could be adapted to test a wide range of component configurations, from a number of manufacturers. These findings may be useful in avoiding potentially unstable configurations when given a choice of modular components.

Dorsal capsulodesis using suture anchors.

Scapholunate instability can be treated by stabilizing the scaphoid with the dorsal wrist capsule, which acts as a tether to control palmar rotation. We began using suture anchors instead of pull-out wires to secure the dorsal capsule to the scaphoid. Thirty-eight patients were treated with this method, and 35 were followed an average of 24 months. Sixteen were pain free, 12 had pain with activity, and 7 required additional surgical treatment. Patients regained 85% of expected grip strength, with 25 of the 35 returning to their preinjury job. The scapholunate gap, reduced at the time of surgery, recurred in 31 of the 35 patients, but this alone did not correlate with symptoms. This procedure improves symptoms in a majority of patients, but like other procedures described for scapholunate instability, it does not completely cure the problem.

Extensor tendon ruptures in rheumatoid arthritis.

The best treatment for extensor tendon rupture is prevention, either by medical management or surgical tenosynovectomy before tendon ruptures occur. Once a rupture has occurred, tendon transfer or free tendon grafting can provide acceptable restoration of extensor function. Communication with the rheumatologist is necessary to provide timely treatment for chronic dorsal tenosynovitis (and impending tendon rupture) or for single finger extension loss before the disease progresses to multiple finger extension loss. Consideration always must be given to associated joint involvement when planning surgical treatment.

Ejection of the proximal scaphoid in a trans-scaphoid perilunate fracture dislocation. A case report.

Trans-scaphoid perilunate fracture dislocations are difficult injuries to treat. Described herein is the unusual case of a trans-scaphoid perilunate fracture dislocation in which the proximal scaphoid fragment was ejected into the volar aspect of the distal forearm. The significant displacement of the proximal fragment represented complete devascularization of this piece. This unique fracture raised difficult management issues in the treatment of this injury. A primary proximal row carpectomy was performed, with a successful clinical result.

Difficult reductions in traumatic patellar dislocation.

A traumatic lateral dislocation with internal rotation of the patella can be unreducible using conventional maneuvers. These unusual dislocations may involve locking of the patella on the lateral femoral condyle. In these cases, reduction can be achieved by applying a downward force to the lateral aspect of the patella, which reduces the rotational deformity and unlocks the medial patellar facet.

An overview of muscle strengthening.

This article gives an overview of muscle strengthening. In this review, we explore the underlying rationale, the process, and the physiologic adjustments that occur as muscles are trained to become stronger. Although controversy surrounds methods used to strengthen muscles, most agree that regular strength training exercises, regardless of the type, can be beneficial.

Computerized analysis of isokinetic torque curves for muscle strengthening.

Isokinetic exercise measurements are widely used in rehabilitation medicine for evaluation and treatment planning. Computerized peak torque, work, and power measurements in isokinetic exercise can be obtained reliably when testing muscles that cross the knee and elbow joints. Important technical considerations in torque curve analysis are axis alignment, instrument calibration, and damp and gravity correction factors. The usefulness of these measurements has been limited by the small number of accurate scientific studies providing valid normative data on healthy individuals.

Modern concept for a new, improved microporous skin-closure tape.

A new improved skin-closure tape, Proxi-Strip, has been developed. It has unique performance and handling characteristics that are ideally suited for wound closure. Most importantly, its adhesive provides a strong level of shear adherence to the skin. Its backing is extensive under low forces to accommodate swelling of the underlying tissue. Its great air porosity and water transmission rates augur well for the presence of dry skin under the tape. An antistatic compound has been added to the tape that maintains its flat configuration and facilitates its application to skin. On the basis of these unique performance and handling characteristics, Proxi-Strip skin-closure tape is recommended for wound closure.