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.

Combined anterior cruciate reconstruction and Oxford unicompartmental knee arthroplasty.

Abstract: The options for treatment of the young active patient with isolated symptomatic osteoarthritis of the medial compartment and pre-existing deficiency of the anterior cruciate ligament are limited. The potential longevity of the implant and levels of activity of the patient may preclude total knee replacement, and tibial osteotomy and unicompartmental knee arthroplasty are unreliable because of the ligamentous instability. Unicompartmental knee arthroplasties tend to fail because of wear or tibial loosening resulting from eccentric loading. Therefore, we combined reconstruction of the anterior cruciate ligament with unicompartmental arthroplasty of the knee in 15 patients (ACLR group), and matched them with 15 patients who had undergone Oxford unicompartmental knee arthroplasty with an intact anterior cruciate ligament (ACLI group). The clinical and radiological data at a minimum of 2.5 years were compared for both groups. The groups were well matched for age, gender and length of follow-up and had no significant differences in their pre-operative scores. At the last follow-up, the mean outcome scores for both the ACLR and ACLI groups were high (Oxford knee scores of 46 (37 to 48) and 43 (38 to 46), respectively, objective Knee Society scores of 99 (95 to 100) and 94 (82 to 100), and functional Knee Society scores of 96 and 96 (both 85 to 100). One patient in the ACLR group needed revision to a total knee replacement because of infection. No patient in either group had radiological evidence of component loosening. The radiological study showed no difference in the pattern of tibial loading between the groups. The short-term clinical results of combined anterior cruciate ligament reconstruction and unicompartmental knee arthroplasty are excellent. The previous shortcomings of unicompartmental knee arthroplasty in the presence of deficiency of the anterior cruciate ligament appear to have been addressed with the combined procedure. This operation seems to be a viable treatment option for young active patients with symptomatic arthritis of the medial compartment, in whom the anterior cruciate ligament has been ruptured.

The Localization of the Functional Glucocorticoid Receptor α in Human Bone

Abstract: Glucocorticoids have well-documented effects on the skeleton, although their mechanism of action is still poorly understood. The actions of glucocorticoids on bone cells are mediated, in part, directly via specific receptors. The presence of these receptors has been demonstrated in both rodent and human osteoblastic cells in vitro, but their presence in human bone in vivo has not been reported. In this study, we have used specific affinity purified polyclonal antibodies to the functional glucocorticoid receptor alpha (GRalpha) to investigate its expression in both developing and adult human bone using sections of neonatal rib, calvarial, and vertebral bones, tibial growth plates from adolescents, and iliac crest biopsies from adults who were to undergo liver transplantation. In the tibial growth plates, GRalpha was predominantly expressed in the hypertrophic chondrocytes within the cartilage. In the primary spongiosa, the receptor was highly expressed by osteoblasts at sites of bone modeling. Within the bone marrow, receptors were also detected in mononuclear cells and in endothelial cells of blood vessels. In the neonatal rib and vertebrae, GRalpha was widely distributed at sites of endochondral bone formation in resting, proliferating, mature, and hypertrophic chondrocytes. They were also highly expressed in osteoblasts at sites of bone modeling. At sites of intramembranous ossification in neonatal calvarial bone and rib periosteum, GRa was widely expressed in cells within the fibrous tissue and in osteoblasts at both the bone-forming surface and at modeling sites. In the iliac crests from adults, GRalpha was predominantly expressed in osteocytes. The receptors were not detected in osteoclasts. Our results show for the first time the presence of the functional GRalpha in human bone in situ and suggest that the actions of glucocorticoids on bone may be mediated, in part, directly via the GR at different stages of life. The absence of receptor expression in osteoclasts also suggests that the effects of glucocorticoids on bone resorption may be mediated indirectly.

The correlation of wear with histological features after failed hip resurfacing arthroplasty

Abstract: Background: Tissue necrosis and a macrophage and perivascular lymphocytic infiltrate are commonly seen in periprosthetic tissues around metal-on-metal hip resurfacing implants, including pseudotumors associated with these implants. The purpose of the present study was to correlate pathological changes in periprosthetic tissues with clinical findings and the amount of implant-derived metal wear. Methods: We analyzed morphological changes in the periprosthetic soft tissues around fifty-six failed metal-on-metal hip resurfacing implants. The most common reason for failure was the presence of a symptomatic pseudotumor (n = 45). The extent of necrosis and the nature of the inflammatory cell infiltrate, including aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL), was evaluated semiquantitatively. Bearing surface wear was determined for all patients. Prostheses were considered to be highly worn if the total linear wear rate was ≥4 μm/yr. Results: Substantial necrosis and a heavy macrophage infiltrate were noted in most periprosthetic tissues, including all pseudotumors, many of which contained a prominent ALVAL infiltrate. Most pseudotumors (80%) were associated with highly worn prostheses. It was noted that the extent of necrosis and macrophage infiltration correlated with the volume of generated metal wear. Although increased wear volume moderately correlated with a high ALVAL response, all pseudotumors associated with low wear had a strong ALVAL response. Conclusions: The majority of pseudotumors are associated with increased implant wear. This increased wear is associated with soft-tissue necrosis and a heavy nonspecific foreign-body macrophage response coupled with a variable adaptive or specific immune response (ALVAL). A minority of pseudotumors are associated with low wear and a prominent immune response. These findings confirm that minimizing wear from metal-on-metal hip resurfacing arthroplasty prostheses would lead to a reduction in the incidence of pseudotumor. However, a small number of pseudotumors are still likely to occur, which may be due to an exacerbated adaptive immune response. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis

Abstract: Objective: To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis in a Finnish population. Methods: 673 individuals from 261 families with ankylosing spondylitis were genotyped for HLA-DRB1 alleles and HLA-B27 heterozygosity/homozygosity. The frequencies of HLA-B27 homozygotes in probands from these families were compared with the expected number of HLA-B27 homozygotes in controls under Hardy–Weinberg equilibrium (HWE). The effect of HLA-DRB1 alleles was assessed using a logistic regression procedure conditioned on HLA-B27 and case–control analysis. Results: HLA-B27 was detected in 93% of cases of ankylosing spondylitis. An overrepresentation of HLA-B27 homozygotes was noted in ankylosing spondylitis (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (odds ratio (OR) = 3.3 (95% confidence interval, 1.6 to 6.8), p = 0.002). HLA-B27 homozygosity was marginally associated with reduced BASDAI ( HLA-B27 homozygotes, 4.5 (1.6); HLA-B27 heterozygotes, 5.4 (1.8) (mean (SD)), p = 0.05). Acute anterior uveitis (AAU) was present in significantly more HLA-B27 positive cases (50%) than HLA-B27 negative cases (16%) (OR = 5.4 (1.7 to 17), p HLA-B27 positive cases had a lower average age of symptom onset (26.7 (8.0) years) compared with HLA-B27 negative cases (35.7 (11.2) years) (p Conclusions: HLA-B27 homozygosity is associated with a moderately increased risk of ankylosing spondylitis compared with HLA-B27 heterozygosity. HLA-B27 positive cases had an earlier age of onset of ankylosing spondylitis than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis.

Structural changes of the brain in rheumatoid arthritis.

Abstract: Objective To investigate whether structural changes are present in the cortical and subcortical gray matter of the brains of patients with rheumatoid arthritis (RA). Methods We used two surface-based style morphometry analysis programs and a voxel-based style analysis program to compare high-resolution structural magnetic resonance imaging data obtained for 31 RA patients and 25 age- and sex-matched healthy control subjects. Results We observed an increase in gray matter content in the basal ganglia of RA patients, mainly in the nucleus accumbens and caudate nucleus. There were no differences in the cortical gray matter. Moreover, patients had a smaller intracranial volume. Conclusion Our results suggest that RA is associated with changes in the subcortical gray matter rather than with cortical gray matter atrophy. Since the basal ganglia play an important role in motor control as well as in pain processing and in modulating behavior in response to aversive stimuli, we suggest that these changes may result from altered motor control or prolonged pain processing. The differences in brain volume may reflect either generalized atrophy or differences in brain development. © 2012 American College of Rheumatology.