Nuffield Orthopaedic Centre

About: Nuffield Orthopaedic Centre is a healthcare organization based out in Oxford, United Kingdom. It is known for research contribution in the topics: Population & Arthroplasty. The organization has 2082 authors who have published 2920 publications receiving 145718 citations.

Functional recovery in patients with nonunion treated with the Ilizarov technique.

Abstract: There are few reports on function after limb salvage surgery using the Ilizarov technique, and none that document the pattern of recovery or predict when maximum function returns. This prospective, longitudinal study documents the baseline functional abilities of 40 consecutive patients with nonunion of a fracture in the lower limb. Patients were studied for at least two and a half years following the completion of surgery. Function was measured by timed tests of functional performance and by the Toronto Extremity Salvage Score self-reported patient questionnaire. Recovery was slowest in the early stages after removal of the frame and greatest between six months and one year. Statistically significant improvement continued up to, but not beyond two years. This observation has important implications for the length of follow-up incorporated into the rehabilitation programmes for patients, predictions of patient status in regard to compensation and for the design of future studies to evaluate functional outcome.

Oxygen free radicals stimulate fibroblast proliferation

Abstract: Oxygen free radials, including superoxide (0; 1 and hydroxyl (OH.) radicals, and H 2 0 , in high concentrations are toxic in a number of ischaemic animal models and t o cultured cells. Here we report that oxygen free radicals in lower concentrations stimulate fibroblast proliferation. Passage 3-5 fibroblasts from skin biopsies or operative Dupuytren's contracture palmar fascia specimens (Murrell et ul., 1087) were cultured in Dulbecco's modification o f Eagle's medium supplemented with 10%, (v /v) fetal calf serum. Each well of a 1.6 cm 24 multiwcll tissue culture plate was seeded with 4 x 10\" fibroblasts and cultured for 48 h (near confluence). The medium was then replaced with 1.0 ml of medium containing the agents to be tested. In thymidine incorporation experiments, this medium also contained 1.0 pCi of [3H]thymidinc and carrier thymidine t o a final concentration of 5.0 pM-thymidine (Puzas & Brand. 1986). After 4 h of incubation at 37\"C, the cell layer was harvested, processed and the radioactive, acid-insoluble fraction measured by liquid scintillation spectrometry to give an estimation of the rate of cell proliferation. Cell density was determined using a 1 mm? eyepiece graticule at 6 and 24 h. Cell morphology parameters were calculated at 4 h using a Zeiss modulator system for quantitative digital image analysis (MOP AM02). Oxygen free radicals were generated by three systems (xanthine oxidase and hypoxanthine. glyceraldehyde in phosphate-buffered saline and H,O,). Oxygen free radicals in high concentrations ( > 10 units of xanthine oxidase/ml with lo' M-hypoxanthine; > lo' M H ~ O ? ; > lo' Mglyceraldehyde) visibly damaged cultured human fibroblasts, reduced cell density and inhibited thymidine incorporation. In contrast, lower concentrations of free radicals ( 10-'-10-' units xanthine oxidase/ml; IWJ10 -\" M-glyceraldehydc; 10 -' M-H~O:) stimulated thymidine incorporation and increased mean cell area, maximum length and cell density (Fig. 1). Both the stimulatory and inhibitory effects of xanthine oxidase were inhibited if xanthine oxidase was heat inactivated for 10 min at 1 00°C or lo' ~-allopurinol (a competitive inhibitor of xanthine oxidase) was added. or 0; and HzOz scavengers added (60 pg of superoxide dismutase/ ml and 250 units catalase/ml). The concentrations of free radicals which stimulated proliferation were similar to those produced by cultured fibroblasts themselves (Murrell et al., 1989b), a finding confirmed by the observation that free radical scavengers when added alone inhibit fibroblast proliferation (Murrell et al., 1 0 8 9 ~ ) . These results it7 vitro may help explain fibroblast proliferation in fibrotic conditions such as Dupuytren's contracture where localized hypoxia can induce free radical production (Murrell er ul., 1987). * * * T

Phenotypic and Molecular Heterogeneity in Fibrodysplasia Ossificans Progressiva

Abstract: Fibrodysplasia (myositis) ossificans progressiva (FOP) is an extremely rare inherited disorder in which progressive ossification of major striated muscles, often following injury, is associated with abnormal skeletal patterning. Altered expression of bone morphogenetic proteins may be a contributory cause. To examine this hypothesis, we compared the patterns of expression of bone morphogenetic proteins (BMPs) mRNAs from lymphoblastoid cell lines from two small multigenerational families with autosomal dominant transmission of FOP. Although affected members of both families showed the characteristic phenotype of FOP, one family was more severely affected than the other. Expression of mRNAs for BMP-1, 2, 3, 5, and 6 mRNAs were not detected within the more severely affected family, but BMP-4 mRNA was expressed in affected but not unaffected members of this family. The results of linkage exclusion analysis using a highly polymorphic microsatellite marker near the BMP-4 gene were consistent with linkage of FOP and BMP-4 in this family. Within the less severely affected family, affected and unaffected members showed similar levels of mRNA expression of BMPs 1, 2, 4, and 5, and linkage of FOP to the BMP-4 gene was excluded. It is concluded that clinical, radiographic, and biochemical data in these two families with FOP establish clinical and molecular heterogeneity and also suggest the possibility of genetic heterogeneity.