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.

Formation of mineralized nodules by bone derived cells in vitro: a model of bone formation?

Abstract: The identification of the factors which regulate the proliferation and differentiation of cells of the osteoblast lineage remains one of the major challenges in the field of bone cell biology. Although considerable progress has been made in the isolation and culture of cells of the osteoblast lineage from both animal and, more recently, human bone, uncertainties have persisted as to the extent to which these cell populations retain the ability to differentiate into functional osteoblasts in vitro. The formation in vitro of mineralized nodules that exhibit the morphological, ultrastructural and biochemical characteristics of embryonic/woven bone formed in vivo, represents the first evidence that the differentiation of functional osteoblasts can occur in cultures of isolated animal bone-derived cell populations. It is clear, however, that the culture conditions employed at present only permit a small number of cells to differentiate to the extent of being capable of organising their extracellular matrix into a structure that resembles that of bone. Moreover, it has generally been found that the reproducible mineralization of this extracellular matrix requires supplementation of the culture medium with mM concentrations of beta-GP, which raises doubts as to the physiological relevance of this process. The formation of nodules has also been observed in cultures of human bone-derived cells. As found in cultures of animal bone-derived cells, reproducible mineralization of these nodules will occur in the presence of beta-GP. We have shown, however, that in the presence of the long acting ascorbate analogue Asc-2-P, the formation and mineralization of nodules can occur in the absence of beta-GP. The nodules formed in human bone-derived cell cultures have yet to be characterized as rigorously as those formed in cultures of animal bone-derived cells and thus it remains to be shown that they resemble bone formed in vivo.

The effects of hyaluronic acid on articular chondrocytes

Abstract: The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes. There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.

Diagnosis and management of prosthetic joint infection.

Abstract: Joint replacement is safe, cost effective,1 and widely undertaken. Most prosthetic joint replacements are hips and knees; more than 130 000 people underwent such procedures in England and Wales in the 12 months from April 2006.w1 Subsequent prosthetic joint infection is uncommon—the incidence varies between 0.6% and 2% per joint per year.2 3 4 5 However, this complication is associated with substantial morbidity and economic cost ($30 000 (£20 500; €22 800) to $50 000 per patient).3 4 6 w2 The diagnosis of prosthetic joint infection is difficult,w2 because symptoms, signs, and investigations may all be non-specific.7 w3 Defining diagnostic criteria and optimum management is complicated by patient heterogeneity and the small numbers in many published studies.w4 However, prompt recognition and diagnosis of prosthetic joint infection facilitates timely intervention to salvage infected joints, preserve joint function, prevent morbidity, and reduce costs. #### Summary points #### Sources and selection criteria We performed Medline searches between November 2008 and January 2009 using the search terms “prosthetic joint” and “arthroplasty” combined with “infection”, “guidelines”, “septic arthritis”, “infection diagnosis”, “infection epidemiology”, and “infection revision arthroplasty”. Where possible, we focused on articles published in the past five years and restricted our search to literature published in English. We also drew from the experience of, and articles and documents published by, our multidisciplinary bone infection unit in the United …

Genetics of neuroendocrine and carcinoid tumours.

Abstract: Neuroendocrine tumours (NETs) originate in tissues that contain cells derived from the embryonic neural crest, neuroectoderm and endoderm. Thus, NETs occur at many sites in the body, although the majority occur within the gastro-entero-pancreatic axis and can be subdivided into those of foregut, midgut and hindgut origin. Amongst these, only those of midgut origin are generally argentaffin positive and secrete serotonin, and hence only these should be referred to as carcinoid tumours. NETs may occur as part of complex familial endocrine cancer syndromes, such as multiple endocrine neoplasia type 1 (MEN1), although the majority occur as non-familial (i.e. sporadic) isolated tumours. Molecular genetic studies have revealed that the development of NETs may involve different genes, each of which may be associated with several different abnormalities that include point mutations, gene deletions, DNA methylation, chromosomal losses and chromosomal gains. Indeed, the foregut, midgut and hindgut NETs develop via different molecular pathways. For example, foregut NETs have frequent deletions and mutations of the MEN1 gene, whereas midgut NETs have losses of chromosome 18, 11q and 16q and hindgut NETs express transforming growth factor-alpha and the epidermal growth factor receptor. Furthermore, in lung NETs, a loss of chromosome 3p is the most frequent change and p53 mutations and chromosomal loss of 5q21 are associated with more aggressive tumours and poor survival. In addition, methylation frequencies of retinoic acid receptor-beta, E-cadherin and RAS-associated domain family genes increase with the severity of lung NETs. Thus the development and progression of NETs is associated with specific genetic abnormalities that indicate the likely involvement of different molecular pathways.

Muscle action, bone rarefaction and bone formation

Abstract: 1. In five series of experiments in eighty-two rabbits we succeeded in causing rarefaction of the calcaneum of all the animals soon after it was relieved from muscular compressing forces; new bone was generated when the calcaneum was subjected again to the stresses and strains of muscle contraction.2. We found evidence that during muscle action pressure forces are transmitted through the bone, and that the presence or absence of these pressure forces conditions the balance between bone formation and bone removal.3. In the calcaneum of the rabbit lack of muscular action seems to be the most important factor inducing osteoporosis. It is possible that the origin of post-traumatic osteoporosis has the same basis.4. In our experiments bone rarefaction was characterised by a great increase in the vascularity of the bone; this increase ceased when the bone reached its final precarious bone density. Thus, vascular over-activity accompanied the removal of bone; but bone reconstruction was also seen to be accompani...