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.

Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures

Abstract: We have examined the ability of dexamethasone, retinoic acid, and vitamin D3 to induce osteogenic differentiation in rat marrow stromal cell cultures by measuring the expression of mRNAs associated with the differentiated osteoblast phenotype as well as analyzing collagen secretion and alkaline phosphatase activity. Marrow cells were cultured for 8 days in primary culture and 8 days in secondary culture, with and without 10 nM dexamethasone or 1 microM retinoic acid. Under all conditions, cultures produced high levels of osteonectin mRNA. Cells grown with dexamethasone in both primary and secondary culture contained elevated alkaline phosphatase mRNA and significant amounts of type I collagen and osteopontin mRNA. Addition of 1,25-dihydroxyvitamin D3 to these dexamethasone-treated cultures induced expression of osteocalcin mRNA and increased osteopontin mRNA. The levels of alkaline phosphatase, osteopontin, and osteocalcin mRNAs in Dex/Dex/VitD3 cultures were comparable to those of 1,25-dihydroxyvitamin D3-treated ROS 17/2.8 osteosarcoma cells. Omitting dexamethasone from either primary or secondary culture resulted in significantly less alkaline phosphatase mRNA, little osteopontin mRNA, and no osteocalcin mRNA. Retinoic acid increased alkaline phosphatase activity to a greater extent than did dexamethasone but did not have a parallel effect on the expression of alkaline phosphatase mRNA and induced neither osteopontin or osteocalcin mRNAs. In all conditions, marrow stromal cells synthesized and secreted a mixture of type I and III collagens. However, dexamethasone-treated cells also synthesized an additional collagen type, provisionally identified as type V. The synthesis and secretion of collagens type I and III was decreased by both dexamethasone and retinoic acid. Neither dexamethasone nor retinoic acid induced mRNAs associated with the chondrogenic phenotype. We conclude that dexamethasone, but not retinoic acid, promotes the expression of markers of the osteoblast phenotype in cultures of rat marrow stromal fibroblasts.

"Asymptomatic" pseudotumors after metal-on-metal hip resurfacing arthroplasty: prevalence and metal ion study.

Abstract: Symptomatic abnormal periprosthetic soft-tissue reactions ("pseudotumors") have been reported after metal-on-metal hip resurfacing arthroplasty (MoMHRA). The aims of this study were (1) to determine the prevalence of asymptomatic pseudotumors after MoMHRA and (2) to measure metal ion levels in these patients. A total of 201 hips in 158 patients were evaluated at a mean follow-up of 61 months (range, 36-88) using ultrasound/magnetic resonance imaging and serum/hip aspirate cobalt and chromium measurements. Pseudotumors found in 7 patients (4%) were associated with significantly higher cobalt and chromium levels and inferior functional scores. Elevated levels of cobalt and chromium ions suggest that pseudotumors are associated with increased wear generated from metal-on-metal articulations. Clinicians need to be aware of pseudotumors as a differential diagnosis during clinical evaluation of MoMHRA patients, and further imaging such as ultrasound or magnetic resonance imaging is recommended to confirm the diagnosis.

Osteoarthritis of the hip: a study of the nature and evolution of the disease.

Abstract: Osteoarthritis, as seen in the hip, is a disease which eventually embraces all the tissues of the joint but begins as a reaction of the juxta-chondral blood vessels to a degeneration of the articular cartilage; this reaction results in a hyperaemia of the bone. To our surprise we found that daily use preserves rather than "wears out" articular cartilage; indeed inadequate use is the commonest cause of cartilage degeneration and ensuing vascular invasion. To this factor are added the effects of excessive pressure in the many patients who require surgical treatment for advanced osteoarthritis of a hip the seat of some anatomical incongruity. This etiology based on cartilage suffering does not exclude, but indeed explains, the osteoarthritis implanted on joints of a normal shape which have been previously affected by acute or chronic inflammation or by hormonal dysfunction, such as acromegalic osteoarthritis. The stimulus to vessel growth and invasion is the same in all these cases—namely cartilage damage. Once the vessels have entered the cartilage the bone and marrow of the osteophyte are inevitably laid down. What is so damaging in osteoarthritis seems to be not the degeneration of the cartilage but the vigorous and persistent attempt at repair, an attempt which aggravates the already disordered function of the joint not only by osteophyte formation but by the hypervascularity which weakens the structure of the bone beyond the point where it can carry its increased load. The collapse that follows provokes further reparative efforts with the same deplorable results. The osteoarthritic process thus appears to be an attempt to transform a decaying joint into a youthful one and for this, as in the miraculous rejuvenation depicted in Goethe9s Faust, a high price must ultimately be paid.

Prosthetic Joint Infection.

Abstract: Total joint replacement has been one of the most remarkable successes of modern medical technology. Once John Charnley had solved the problems of implant design, choice of materials, implant fixation, and infection (initial rates of infection were approximately 10%), the way was clear for the widespread use of this valuable treatment, which is highly effective at removing pain and restoring function. Unfortunately, infection still remains an important, though less common, problem. It is associated with serious morbidity (pain, loss of function, wound breakdown, wound discharge, implant failure) and sometimes mortality. It may be impossible to eradicate or suppress infection in the long term without removal of the prosthesis, and most clinicians would consider it unwise to re-implant a new prosthesis in the presence of infection. Hence, patients with infected prosthetic joints generally require multiple additional operations and prolonged periods of antibiotic therapy. Even radical attempts at cure may fail (in 10% to 15% of cases in most series), requiring further cycles of treatment with progressively deteriorating function. Thus, the treatment of prosthetic joint infection is arduous for the patient and the health care team, with no guarantee of success.