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.

Infected joint replacements in HIV-positive patients with haemophilia

Abstract: Joint replacement in HIV-positive patients remains uncommon, with most experience gained in patients with haemophilia. We analysed retrospectively the outcome of 102 replacement arthroplasties in 73 HIV-positive patients from eight specialist haemophilia centres. Of these, 91 were primary procedures. The mean age of the patients at surgery was 39 years, and the median follow-up was for five years. The overall rate of deep sepsis was 18.7% for primary procedures and 36.3% for revisions. This is a much higher rate of infection than that seen in normal populations. A total of 44% of infections resolved fully after medical and/or surgical treatment. The benefits of arthroplasty in haemophilic patients are well established but the rates of complications are high. As this large study has demonstrated, high rates of infection occur, but survivorship analysis strongly suggests that most patients already diagnosed with HIV infection at the time of surgery should derive many years of symptomatic relief after a successful joint replacement. Careful counselling and education of both patients and healthcare workers before operation are therefore essential.

Development of osteogenic tissue in diffusion chambers from early precursor cells in bone marrow of adult rats

Abstract: Diffusion chambers containing bone marrow cells from adult rats were implanted intraperitoneally into rat hosts and cultured in vivo for up to 64 days. Biochemical and histological analyses of the contents of the chambers demonstrate that a connective tissue consisting of bone, cartilage and fibrous tissues is formed by precursor cells present in marrow stroma. The amounts of osteogenic tissue and DNA are directly correlated with time of implantation and with number of cells inoculated. In the chambers there is initial formation of fibrous tissue which is strongly reactive to collagen type III, laminin and fibronectin. In areas of osteogenesis which appear later within this fibrous anlage, expression of collagen type III, laminin and fibronectin decrease and collagen types I and II increase in association with bone and cartilage respectively. Where osteogenesis does not develop, fibrous tissue continues to express collagen type III. The sequential expression of the different extracellular matrix components is similar to that previously observed during osteogenic differentiation in embryonic and adult developmental systems. It is concluded that the formation of fibrous and osteogenic tissues in diffusion chambers by precursor cells present in adult marrow, resembles the normal developmental process.

Vascularity in a new model of atrophic nonunion

Abstract: Our aim was to develop a clinically relevant model of atrophic nonunion in the rat to test the hypothesis that the vessel density of atrophic nonunion reaches that of normal healing bone, but at a later time-point. Atrophic nonunion is usually attributed to impaired blood supply and is poorly understood. We determined the number of blood vessels at the site of an osteotomy using immunolocalisation techniques in both normally healing bones and in atrophic nonunion. At one week after operation there were significantly fewer blood vessels in the nonunion group than in the healing group. By eight weeks, the number in the atrophic nonunion group had reached the same level as that in the healing group. Our findings suggest that the number of blood vessels in atrophic nonunion reaches the same level as that in healing bone, but at a later time-point. Diminished vascularity within the first three weeks, but not at a later time-point, may prevent fractures from uniting.

Effects of Ingested Steak and Infused Leucine on Forelimb Metabolism in Man and the Fate of the Carbon Skeletons and Amino Groups of Branched-Chain Amino Acids

Abstract: 1. The effects of ingested grilled beef steak (250 g raw weight of lean meat) and infusion of leucine (3.8 g) on human forelimb metabolism were studied by monitoring the concentrations of various metabolites in arterial (A) and venous (V) blood of four overnight fasted and rested men. 2. The mean basal A—V for branched-chain 2-oxo acid (BCOA) was small (−3.6 μmol/l). After ingestion of steak or administration of leucine there were large positive increases in the A—V for branched-chain amino acid (BCAA) but increase in the negative A—V for BCOA was relatively small. 3. Within 2 h of ingestion of steak, BCAA accounted for approx. 50% of those amino acids with a positive A—V and glutamine for up to 75% of those with a negative A—V; the negative A—V for alanine decreased to 10% of its basal value. Infusion of leucine produced a large positive A—V for leucine by forelimb, a doubling in the negative A—V for glutamine and a rise in the blood glutamine concentration; the negative A—V for alanine was virtually unchanged and the blood alanine concentration showed a late significant decrease. 4. After ingestion of steak there was a two- to three-fold rise in the arterial insulin concentration, little change in the positive A—V for glucose and a decreased negative A—V for ‘glycolytic products’ (alanine + lactate + pyruvate), suggesting increased utilization of glucose carbon. Infusion of leucine doubled the arterial insulin concentration; the A—V for glucose decreased, that for lactate, pyruvate and alanine remained unchanged, suggesting decreased utilization of glucose carbon. 5. Circulating BCOA was distributed almost entirely in the plasma space. 6. in a variety of clinical conditions (insulin-dependent diabetes, cirrhosis, muscular dystrophy and starvation), the basal plasma concentrations of BCOA correlated well with those of BCAA ( r = 0.989). Infusion of leucine increased the plasma BCAA/BCOA ratio to the same extent (about 40%) in each clinical condition despite considerable variations in the rate of leucine clearance. 7. The observations indicate that both ingested steak and infused leucine produce important changes in the selection of respiratory fuels by the human forelimb, that BCOA is preferentially oxidized rather than released from human limb tissues, and that glutamine, not alanine, is the major amino group carrier leaving the forelimb both after a protein meal and after leucine administration. Changes in cellular uptake or transamination of leucine appear not to be responsible for the varied rates of leucine clearance in a variety of clinical conditions.

RANKL-dependent and RANKL-independent mechanisms of macrophage-osteoclast differentiation in breast cancer.

Abstract: The cellular and humoral mechanisms accounting for tumour osteolysis in metastatic breast cancer are uncertain. Osteoclasts, the specialised multinucleated cells responsible for tumour osteolysis, are derived from monocyte/macrophage precursors. Breast cancer-derived tumour-associated macrophages (TAMs) are capable of osteoclast differentiation but the cellular and humoral mechanisms controlling this activity are uncertain. In this study, TAMs were isolated from primary breast cancers and cultured in the presence and absence of cytokines/growth factors influencing osteoclastogenesis. Extensive TAM-osteoclast differentiation occurred only in the presence of RANKL and M-CSF; this process was inhibited by OPG and RANK:Fc, decoy receptors for RANKL. Breast cancer-derived fibroblasts and human bone stromal cells expressed mRNA for RANKL, OPG and TRAIL, and co-culture of these fibroblasts with human monocytes stimulated osteoclast formation by a RANKL-dependent mechanism. Osteoclast formation and lacunar resorption also occurred by a RANKL-independent mechanism when the conditioned medium from breast cancer cells, MDA-MB-231 and MCF-7, was added (with M-CSF) to monocyte cultures. Our findings indicate that TAMs in breast cancer are capable of osteoclast differentiation and that breast cancer-derived fibroblasts and breast cancer cells contribute to this process by producing soluble factors that influence osteoclast formation by RANKL-dependent and RANKL-independent mechanisms respectively.