Opening wedge trapezial osteotomy as possible treatment for early trapeziometacarpal osteoarthritis: a biomechanical investigation of radial subluxation, contact area, and contact pressure.

PURPOSE: Radial subluxation and cartilage thinning have been associated with initiation and accelerated development of osteoarthritis of the trapeziometacarpal joint. Few investigators have reported on the benefits of opening wedge trapezial osteotomy for altering the contact mechanics of the trapeziometacarpal joint as a possible deterrent to the initiation or progression of osteoarthritis. We used cadaveric specimens to determine whether opening wedge osteotomy of the trapezium was successful in reducing radial subluxation of the metacarpal base and to quantify the contact area and pressure on the trapezial surface during simulated lateral pinch. METHODS: We used 8 fresh-frozen specimens in this study. The flexor pollicis longus, abductor pollicis longus, adductor pollicis, abductor pollicis brevis, and flexor pollicis brevis/opponens pollicis tendons were each loaded to simulate the thumb in lateral pinch position. We measured radial subluxation from anteroposterior radiographs before and after placement of a 15° wedge. We used real-time sensors to analyze contact pressure and contact area distribution on the trapezium. RESULTS: Center of force in the normal joint under lateral pinch loading was primarily located in the dorsal region of the trapezium. After wedge placement, contact pressure increased in the ulnar-dorsal region by 76%. Mean contact area increased in the ulnar-dorsal region from 0.05 to 0.07 cm(2), and in the ulnar-volar region from 0.003 to 0.024 cm(2). The average reduction in joint subluxation was 64%. CONCLUSIONS: The 15° opening wedge osteotomy of the trapezium reduced radial subluxation of the metacarpal on the trapezium and increased contact pressure and contact area away from the diseased compartments of the trapezial surface. Trapezial osteotomy addresses the 2 preeminent theories about the initiation and progression of osteoarthritis. CLINICAL RELEVANCE: By reducing radial subluxation and altering contact pressure and contact area, trapezial osteotomy may prove an alternative to first metacarpal extension osteotomy or ligament reconstruction in early stages of degenerative arthritis of the trapeziometacarpal joint.

Incidence and survival rates for female malignant germ cell tumors.

OBJECTIVE: To evaluate 30-year, population-based trends in incidence and survival rates for malignant germ cell tumors originating within the female genital tract. METHODS: Surveillance, Epidemiology, and End Results data were used to identify malignant germ cell tumors (1973-2002). Overall and 5-year incidence rates, estimated annual percentage change, and survival rates were calculated and compared by age at diagnosis, race, stage, and histology. RESULTS: Of 1,262 cases, there were 414 (32.8%) dysgerminomas, 449 (35.6%) immature teratomas, 37 (2.9%) mature teratomas with malignant degeneration, and 362 (28.7%) mixed germ cell tumors. The 30-year, age-adjusted incidence rate per 100,000 women-years was 0.338, decreasing by 29.4% for dysgerminomas (P = .18) and by 31.5% for mixed germ cell tumors (P = .22). Other nonwhites had higher rates than whites and blacks, but dysgerminoma rates were higher in whites and other nonwhites than in blacks. Using the registries for expanded races, rates were higher for Asian/Pacific Islanders (P = .059) and Hispanics (P = .07). By age at diagnosis, 15-19 year olds had the highest rates and the only significant change in rates (37.5% increase, P = .008). The 5-year relative survival was 83.9%. Survival rates improved significantly over calendar time and varied by histologic subtype, race, stage of disease, and age at diagnosis. CONCLUSION: Over the past 30 years, germ cell tumor incidence rates have declined in women and differ from rising trends reported for testicular tumors. Survival rates have improved but were lower for older women and for nondysgerminoma subtypes.

Rat cytochrome P450C24 (CYP24A1) and the role of F249 in substrate binding and catalytic activity.

A high level of functional recombinant rat cytochrome P450C24 enzyme (CYP24A1) was obtained (40-50mg/L) using an Escherichia coli expression system. Purified enzyme was stable with retention of spectral and catalytic activity. The rate of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] side-chain oxidation and cleavage to the end-product calcitroic acid was directly related to the rate of electron transfer from the ferredoxin redox partner. It was determined from substrate-induced spectral shifts that the 1 alpha- and 25-hydroxyl groups on vitamin D(3) metabolites and analogs were the major determinants for high-affinity binding to CYP24A1. Lowest K(d) values were obtained for 1 alpha-vitamin D(3) (0.06 microM) and 1,25-dihydroxyvitamin D(3) (0.05 microM) whereas unmodified parental vitamin D(3) and the non-secosteroid 25-hydroxycholesterol had lower affinities with K(d) values of 1.3 and 1.9 microM, respectively. The lowest binding affinity for natural vitamin D metabolites was observed for 24,25-dihydroxyvitamin D(3) [24,25(OH)(2)D(3)] (0.43 microM). Kinetic analyses of the two natural substrates 25-hydroxyvitamin D(3) [25(OH)D(3)] and 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] revealed similar K(m) values (0.35 and 0.38 microM, respectively), however, the turnover number was higher for 25(OH)D(3) compared to 1,25(OH)(2)D(3) (4.2 and 1 min(-1), respectively). Mutagenesis of F249 within the F-helix of CYP24A1 altered substrate binding and metabolism. Most notable, the hydrophobic to polar mutant F249T had a strong impact on lowering substrate-binding affinity and catalysis of the final C(23) oxidation sequence from 24,25,26,27-tetranor-1,23-dihydroxyvitamin D(3) to calcitroic acid. Two other hydrophobic 249 mutants (F249A and F249Y) also lowered substrate binding and expressed metabolic abnormalities that included the C(23)-oxidation defect observed with mutant F249T plus a similar defect involving an earlier pathway action for the C(24) oxidation of 1,24,25-trihydroxyvitamin D(3). Therefore, Phe-249 within the F-helix was demonstrated to have an important role in properly binding and aligning substrate in the CYP24A1 active site for C(23) and C(24) oxidation reactions.