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Showing papers by "Nuffield Orthopaedic Centre published in 2002"


Journal ArticleDOI
TL;DR: Patients with spondylarthritis express both HLA-B27 heavy-chain homodimers and receptors for HLA -B27 homodimer structure lacking beta(2)-microglobulin, of significance with regard to disease pathogenesis.
Abstract: Objective. HLA–B27 is capable of forming in vitro a heavy-chain homodimer structure lacking 2microglobulin. We undertook this study to ascertain if patients with spondylarthritis express 2-microglobulin– free HLA–B27 heavy chains in the form of homodimers and receptors for HLA–B27 homodimers. Methods. Expression of HLA–B27 heavy chains by mononuclear cells was analyzed by fluorescenceactivated cell sorter staining, Western blotting with the monoclonal antibody HC-10, and 2-dimensional isoelectric focusing. Fluorescence-labeled tetrameric complexes of HLA–B27 heavy-chain homodimers were constructed in which each dimer comprised one His-tagged heavy chain and one biotinylated heavy chain, and were used to stain patient and control mononuclear cells and transfected cell lines. Results. Patients with spondylarthritis expressed cell-surface HLA–B27 homodimers. Populations of synovial and peripheral blood monocytes, and B and T lymphocytes from patients with spondylarthritis, and controls carried receptors for HLA–B27 homodimers. Experiments with transfected cell lines demonstrated that KIR3DL1 and KIR3DL2, and immunoglobulin-like transcript 4 (ILT4), but not ILT2, are receptors for HLA–B27 homodimers. Conclusion. Patients with spondylarthritis express both HLA–B27 heavy-chain homodimers and receptors for HLA–B27 homodimers. This may be of significance with regard to disease pathogenesis.

244 citations


Journal ArticleDOI
TL;DR: It is suggested that, in the presence of M‐CSF, TNFα is sufficient for inducing human osteoclast differentiation from circulating precursors by a process which is distinct from the RANK/RANKL signalling pathway.
Abstract: TNFalpha and IL-1alpha are potent stimulators of bone resorption in vivo and in vitro. Recently, it has been demonstrated that these two cytokines directly induce osteoclastogenesis in mouse marrow cultures. This study determined whether TNFalpha (+/- IL-1alpha) is also capable of inducing human osteoclastogenesis. The CD14(+) monocyte fraction of human peripheral mononuclear cells was cultured with TNFalpha +/- IL-1alpha in the presence of M-CSF. TNFalpha induced the formation of multinucleated cells (MNCs) which were positive for TRAP, VNR and cathepsin K and showed evidence of resorption pit formation. IL-1alpha stimulated TNFalpha-induced lacunar resorption two- to four-fold. Osteoprotegerin, the decoy receptor for RANKL, did not inhibit this process. Anti-human IL-1alpha neutralizing antibodies significantly inhibited resorption without inhibiting the formation of TRAP(+)/VNR(+) MNCs. These results suggest that, in the presence of M-CSF, TNFalpha is sufficient for inducing human osteoclast differentiation from circulating precursors by a process which is distinct from the RANK/RANKL signalling pathway.

225 citations


Journal ArticleDOI
01 Jan 2002-Spine
TL;DR: In this paper, the Shuttle Walking Test (SWT), the Swiss Spinal Stenosis (SSS) Questionnaire, the Oxford Claudication Score (OCS), and the Oswestry Disability Index (ODI) were administered to patients with lumbar spinal stenosis and neurogenic claudication.
Abstract: Study Design. The Shuttle Walking Test (SWT), the Swiss Spinal Stenosis (SSS) Questionnaire, the Oxford Claudication Score (OCS), and the Oswestry Disability Index (ODI) were administered to patients with lumbar spinal stenosis and neurogenic claudication. Objective. To determine reliability of the SWT, the SSS (Q1-12), the OCS, and the ODI in lumbar spinal stenosis assessment. Summary of Background Data. Reliability data for exercise tests in lombar spinal stenosis are lacking. Methods. To determine reliability, 32 clinic patients with lumbar spinal stenosis were assessed twice, with 1 week between assessments. Retrospective data from 17 patients assessed before surgery and 18 months after surgery for lumbar spinal stenosis were used to investigate the use of reliability in a clinical setting. Results. Test-retest reliability in terms of the intraclass correlation co-efficiant (ICC) was 0.92 for the SWT, 0.92 for the SSS, 0.83 for the OCS and 0.89 for the ODI. The mean percentage scores were 51 for the SSS, 45 for the OCS, and 40 for the ODI. To achieve 96% certainty of change between assessments for a single patient, the SSS would need to change by 15, the OCS by 20, and the ODI by 16. The mean SWT was 150 m, with a change of 76 m required for 95% confidence. Cronbach's alpha was 0.91 for the SSS, 0.90 for the OCS, and 0.89 for the ODI. The change in ODI correlated most strongly with patient satisfaction after surgery (ρ = 0.80; P < 0.001). Conclusions, Fluctuations in a patient's symptoms result in wide individual confidence intervals. Performance on the SSS, OCS, and ODI questionnaires are broadly similar, the most precise being the condition-specific SSS. The SWT gives a snapshot of physical function, which is acceptable for group analysis. Use of the SWT for individual assessment after surgery is feasible.

213 citations


Journal ArticleDOI
TL;DR: It is suggested that increased osteoclast functional activity rather than osteoclasts formation is more likely to play a role in the generalized bone loss that occurs in RA, and that corticosteroids stimulate osteOClast formation and resorption.
Abstract: OBJECTIVE: Rheumatoid arthritis (RA) is often complicated by generalized osteopenia due to increased bone resorption by osteoclasts. We analysed a number of cellular and humoral factors that influence osteoclast formation from circulating precursors in RA patients. METHODS: Monocytes isolated from RA patients and normal controls were cultured with macrophage colony-stimulating factor (M-CSF) and nuclear factor-kappaB ligand (RANKL), or with RANKL-expressing UMR106 cells and 1,25 dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. Osteoclast differentiation was assessed by expression of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptors (VNR) and lacunar resorption. RESULTS: Osteoclasts formed from RA patients exhibited increased resorptive activity but there was no difference in the relative proportion of circulating osteoclast precursors between RA patients and normal controls. Osteoclast precursors in RA patients were not more sensitive to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF or RANKL. Dexamethasone, but not interleukin (IL) 1beta, tumour necrosis factor alpha and IL-6, increased osteoclast formation and lacunar resorption. CONCLUSION: There is an increase in the extent of lacunar resorption carried out by osteoclasts formed from circulating precursors in RA patients. This is not due to an increase in the number of circulating precursors or increased sensitivity to the osteoclastogenic effects of 1,25(OH)(2)D(3), M-CSF, RANKL or inflammatory cytokines. Our findings suggest that increased osteoclast functional activity rather than osteoclast formation is more likely to play a role in the generalized bone loss that occurs in RA, and that corticosteroids stimulate osteoclast formation and resorption.

126 citations


Journal ArticleDOI
TL;DR: The effects of growth pre-dispose children with neurological impairments to the sec-ondary problems of muscle contractures, bony deformities, and unusual gait abnormalities.
Abstract: Children with cerebral palsy (CP) are functionally limited to varying degrees because of their decreased central control and coordination of their movements. The effects of growth predispose children with neurological impairments to the secondary problems of muscle contractures, bony deformities, and unusual gait abnormalities. Health care programmes aim to prevent deformities and encourage the development of functional and independent skills and abilities. Orthoses continue to have an important role in many therapeutic regimens for children with CP, however, there have been differences in designs of orthoses prescribed for the common problem of spastic equinus. This is because different treatment paradigms have evolved which advocate different designs of ankle–foot orthoses (AFOs).

108 citations


Journal ArticleDOI
TL;DR: In this paper, a mutation in the ANKH gene was identified that causes increased extracellular pyrophosphate (PPi) levels, predisposing to CPPD crystal deposition.
Abstract: Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) chondrocalcinosis has previously been mapped to chromosome 5p15. We have identified a mutation in the ANKH gene that segregates with the disease in a family with this condition. ANKH encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of ANKH causes elevated extracellular PPi levels, predisposing to CPPD crystal deposition.

103 citations


Journal ArticleDOI
TL;DR: It is concluded that established atrophic non-unions can be well vascularised and that measurements of serum levels of ESAF could not distinguish between those osteotomies that would unite and those that would progress to non-union.
Abstract: The objective of this study was to assess the vascularity of atrophic non-unions using an experimental animal model. Twenty skeletally mature female rabbits were randomly divided into control and experimental groups that were killed 1, 8, or 16 weeks after surgery. The experimental groups underwent surgery to induce an atrophic non-union whereas the control groups underwent a similar operation but which resulted in union. Using immunocytochemical techniques blood vessels were identified in histological sections obtained from the osteotomy site. The concentration of the vessels within the osteotomy gaps was measured, as was the serum concentration of an important angiogenic factor: endothelial cell-stimulating angiogenesis factor (ESAF). The results demonstrated a significant difference between the control and the experimental groups in the concentration of vessels within the gap at 1 week but there was no significant difference between those groups at 8 weeks. There were no significant differences in the ESAF concentration between the groups at any time points. We concluded that established atrophic non-unions can be well vascularised and that measurements of serum levels of ESAF could not distinguish between those osteotomies that would unite and those that would progress to non-union.

94 citations


Journal ArticleDOI
TL;DR: The findings suggest that current classification systems for the analysis of congenital talipes equinovarus are not entirely satisfactory.
Abstract: We have assessed the reliability of four classification systems for club foot. Four observers evaluated nine children (18 feet) at different stages in the first six months of life, a total of 180 examinations. Each observer independently assessed all feet according to the classification systems described by Catterall, Dimeglio et al, Harrold and Walker, and Ponseti and Smoley. The variation between observers was assessed using the kappa test which for no more agreement than chance has a value of 0, and for complete agreement between observers a value of 1. The kappa values varied between 0.14 and 0.77 depending on which classification system was used. The system of Dimeglio et al was found to have the greatest reliability. Our findings suggest that current classification systems for the analysis of congenital talipes equinovarus are not entirely satisfactory.

90 citations


Journal ArticleDOI
TL;DR: Osteoclast precursors in synovial tissues are CD14+ monocyte/macrophages, pointing to a role for CD14− cells in promoting osteoclast differentiation and bone resorption in inflamed synovials by a mechanism which does not involve a direct effect of proinflammatory cytokines/prostaglandins on RANKL-induced macrophage-osteoclast differentiate.
Abstract: Background: Pathological bone resorption (marginal erosions and juxta-articular osteoporosis) by osteoclasts commonly occurs in rheumatoid arthritis (RA). Objectives: To define the nature of the mononuclear precursor cells from which osteoclasts are formed in inflamed synovial tissues and to determine the cellular and humoral factors which influence osteoclast differentiation. Method: Macrophage (CD14+), non-macrophage (CD14-), and unsorted (CD14+/CD14-) synovial cell populations from RA and inflammatory/non-inflammatory osteoarthritis (OA) synovium were cultured in the presence of receptor activator for nuclear factor κB ligand (RANKL) and monocyte-colony stimulating factor (M-CSF; in the presence/absence of prostaglandin E2 (PGE2), interleukin 1s (IL1s), tumour necrosis factor α (TNFα), and IL6). Osteoclast differentiation was assessed by expression of tartrate resistant acid phosphatase (TRAP), vitronectin receptor (VNR), and lacunar resorption. Results: TRAP+ and VNR+ multinucleated cells capable of lacunar resorption were only formed in cultures of CD14+-containing synovial cell populations (that is, CD14+ and CD14+/CD14- cells). No difference in the extent of osteoclast formation was noted in cultures of CD14+ cells isolated from RA, inflammatory OA, and non-inflammatory OA synovium. However, more TRAP+/VNR+ cells and more lacunar resorption was noted in CD14+/CD14- cells from RA and inflammatory OA synovial tissues. The addition of PGE2, IL1s, TNFα, and IL6 did not increase RANKL/M-CSF-induced osteoclast formation and lacunar resorption of both CD14+/CD14- and CD14+ synovial cell populations. Conclusions: Osteoclast precursors in synovial tissues are CD14+ monocyte/macrophages. The increase in osteoclast formation in cultures of CD14+/CD14- compared with CD14+ synovial cells in RA and inflammatory OA points to a role for CD14- cells in promoting osteoclast differentiation and bone resorption in inflamed synovial tissues by a mechanism which does not involve a direct effect of proinflammatory cytokines/prostaglandins on RANKL-induced macrophage-osteoclast differentiation.

89 citations


Journal ArticleDOI
TL;DR: In this article, the postoperative radiographs of 46 lateral unicompartmental arthroplasties were analyzed and five variables related to the position and alignment of the components were measured.
Abstract: When the Oxford unicompartmental meniscal bearing arthroplasty is used in the lateral compartment of the knee, 10% of the bearings dislocate. A radiological review was carried out to establish if dislocation was related to surgical technique. The postoperative radiographs of 46 lateral unicompartmental arthroplasties were analysed. Five variables which related to the position and alignment of the components were measured. Dislocations occurred in six knees. Only one of the five variables, the proximal tibial varus angle, had a statistically significant relationship to dislocation. This variable quantifies the height of the lateral joint line. The mean proximal tibial varus angle for knees the bearings of which had dislocated was 9 degrees and for those which had not it was 5 degrees. In both groups it was greater than would be expected in the normal knee (3 degrees). Our study suggests that a high proximal tibial varus angle is associated with dislocation. The surgical technique should be modified to account for this, with care being taken to avoid damage to or overdistraction of the lateral soft tissues.

87 citations


Journal ArticleDOI
TL;DR: A single-blind randomized controlled trial comparing two types of exercise regime aiming to improve mobility and function following knee arthroplasty found trends in favour of the FEG that were of clinical relevance.
Abstract: Objective: To assess the feasibility of comparing two types of exercise regime aiming to improve mobility and function following knee arthroplasty.Design: A single-blind randomized controlled trial.Subjects: Patients with primary, unilateral knee osteoarthritis undergoing elective knee joint replacement.Intervention: Home-based traditional exercise group (TEG) or home-based functional exercise group (FEG) following discharge from hospital.Outcome measures: These included goniometry; a knee-specific pain score, leg extensor power and a walking test. Patients were followed up at three, six and 12 months after surgery.Results: Forty-seven patients met the study criteria, 24 were randomized to the TEG and 23 to the FEG. There were marked improvements in mobility, leg extensor power and pain in the year after surgery (MANOVA p < 0.001). There were no statistically significant differences between the two exercise groups. Knee flexion decreased during the follow-up period and had not recovered by 12 months. Rete...

Journal ArticleDOI
TL;DR: In this article, the effect of synthetic glucocorticoid, dexamethasone, on human osteoclast formation and bone-resorbing activity was examined.
Abstract: Chronic corticosteroid treatment is known to induce bone loss and osteoporosis. Osteoclasts are specialised bone-resorbing cells that are formed from mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have examined the effect of the synthetic glucocorticoid, dexamethasone, on human osteoclast formation and bone-resorbing activity. Human monocytes were cultured for up to 21 days on glass coverslips and dentine slices, with soluble receptor activator for nuclear factor kappaB ligand (RANKL; 30 ng/ml) and human macrophage-colony stimulating factor (M-CSF; 25 ng/ml) in the presence and absence of dexamethasone (10(-8) M). The addition of dexamethasone over a period of 7 and 14 days of culture of monocytes (during which cell proliferation and differentiation predominantly occurred) resulted in a marked increase in the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and an increase in lacunar resorption. The addition of dexamethasone to monocyte cultures after 14 days (when resorptive activity of osteoclasts had commenced) reduced the extent of lacunar resorption compared with cultures to which no dexamethasone had been added. The addition of dexamethasone to osteoclasts isolated from giant cell tumours of bone significantly inhibited resorption pit formation. Our findings indicate that dexamethasone has a direct effect on osteoclast formation and activity, stimulating the proliferation and differentiation of human osteoclast precursors and inhibiting the bone-resorbing activity of mature osteoclasts.

Journal ArticleDOI
TL;DR: In this paper, the authors studied 17 cases of GCT-TS of the foot and ankle in which treatment was by excision and found that the lesion was associated with sensory deficit of a digital nerve and pain on walking.
Abstract: Giant-cell tumour of the tendon sheath (GCT-TS) is a benign solitary tumour which usually arises in the limbs. It occurs most often in the hand where local recurrence after excision has been reported in up to 45% of cases. It is less common in the foot where the biological behaviour and risk of local recurrence have not been defined. We have studied 17 cases of GCT-TS of the foot and ankle in which treatment was by excision. Fifteen presented as a solitary, painless, slow-growing soft-tissue swelling. One lesion was associated with sensory deficit of a digital nerve and one with pain on walking. Thirteen cases originated from the periarticular tendon-sheath complex of the small joints of the toes and four from the capsule or long tendons of the ankle. A correct preoperative diagnosis was made in only three cases. MRI proved to be the most useful preoperative investigation as GCT-TS has a characteristic appearance which allows planned local excision to be carried out. None of the patients with histologically confirmed GCT-TS required further surgery. There was no local recurrence in 15 patients who were available for follow-up at a mean of 85 months.

Journal ArticleDOI
TL;DR: An improvement in all muscle functions in both the operated and unoperated legs during the recovery period was found and continued to improve in all muscles and actions between 6 months and 1 year.
Abstract: We designed a prospective study to examine the influence of graft type (hamstring or patella tendon) on thigh muscle torque recovery after anterior cruciate ligament reconstruction. 60 patients undergoing ACL reconstruction, using a hamstring or patella tendon graft, were studied and 45 were followed up to 1 year. Concentric and eccentric quadriceps and hamstring torque were recorded, using an isokinetic dynamometer preoperatively, 6 and 12 months after ACL reconstruction. We found an improvement in all muscle functions in both the operated and unoperated legs during the recovery period. Graft type had no effect on recovery. During the first 6 months, torque was restored to preoperative levels and continued to improve in all muscles and actions between 6 months and 1 year.

Journal ArticleDOI
01 Sep 2002-Knee
TL;DR: A pilot study assessed the feasibility of discharging NHS patients undergoing knee replacement within a day of surgery and found that the new protocol allows for early, safe discharge of patients undergoing unicompartmental knee replacement.
Abstract: A pilot study assessed the feasibility of discharging NHS patients undergoing knee replacement within a day of surgery. Seven patients with medial compartment osteoarthritis were recruited after fulfilling strict exclusion criteria. Pre-operative assessment revealed that all patients had significant dysfunction and pain before operation. They had medial unicompartmental replacement through a short incision without dislocation of the patella. Each patient underwent an accelerated recovery program that included pain control, physiotherapy and self-assessment. Patients were mobilised immediately after operation. Follow-up assessment was performed at 1, 2 and 6 weeks after surgery. All patients, except one (who failed to go home because of an administrative error), returned home the day after surgery. The average pain score for the first 2 weeks after surgery was 2/10. At 6 weeks, knee flexion averaged 125 degrees and all patients were walking independently and painfree. The new protocol allows for early, safe discharge of patients undergoing unicompartmental knee replacement.

Journal ArticleDOI
TL;DR: The role of ATPase pumps is reviewed in the context of their expression in bone cells, their contribution to ion homeostasis and their relation to other transport systems regulating bone turnover.

Journal ArticleDOI
TL;DR: Calcium gluconate is used as a secretagogue to treat gastrinomas with high extracellular calcium concentrations, which cause degranulation of neuroendocrine cells and subsequent release of hormone.
Abstract: BACKGROUND Preoperative localisation is important for successful surgical treatment of gastrinomas. However, a satisfactory method that achieves this has not been defined, and at present somatostatin receptor scintigraphy and selective intra-arterial stimulation testing with secretin have the greatest sensitivities. As secretin is now difficult to obtain, we decided to explore the use of calcium gluconate as a secretagogue. High extracellular calcium concentrations cause degranulation of neuroendocrine cells and subsequent release of hormone. METHODS Two patients with biochemically proven gastrinomas were investigated pre-operatively. Under angiographic control calcium gluconate was injected into the arteries supplying the pancreas and duodenum, gastrin levels were then determined in hepatic vein samples obtained before and 30, 60, 90, 120 and 180 seconds after each injection. One of the patients had also previously undergone selective intra-arterial stimulation testing with secretin. RESULTS Calcium gluconate produced sharp peaks of gastrin which unequivocally localised the tumour to a specific vascular territory in each case. Furthermore, surgery confirmed the localisations of the gastrinomas. Calcium injection, unlike secretin, into vascular territories without gastrinomas caused no rise in gastrin, thereby demonstrating calcium's greater specificity. CONCLUSIONS Calcium gluconate is a highly sensitive and specific alternative secretagogue to secretin for localisation of pancreatic and duodenal gastrinomas. Furthermore calcium gluconate was found to demonstrate the territory of the tumour more accurately than secretin.

Journal ArticleDOI
TL;DR: The natural immunological function of HLA-B27 is set out to define, and then to apply this knowledge to understand its pathogenic role, and a number of lines of evidence from the laboratory and other laboratories have suggested that HLA -B27 has unusual cell biology.
Abstract: The human leukocyte antigen HLA-B27 is strongly associated with development of a group of inflammatory arthritides collectively known as the spondyloarthritides. We have set out to define the natural immunological function of HLA-B27, and then to apply this knowledge to understand its pathogenic role. Human leukocyte antigen class 1 molecules bind antigenic peptides for cell surface presentation to cytotoxic T lymphocytes. HLA-B27 binds and presents peptides from influenza, HIV, Epstein-Barr virus, and other viruses. This leads to vigorous and specific cytotoxic T lymphocyte responses, which play an important role in the body's immune response to these viruses. HLA-B27 thus carries out its natural function highly effectively. Although many theories have been proposed to explain the role of HLA-B27 in the pathogenesis of spondyloarthropathy, we favour those postulating that the pathogenic role of HLA-B27 stems from its natural function. For example, the 'arthritogenic' peptide hypothesis suggests that disease results from the ability of HLA-B27 to bind a unique peptide or a set of antigenic peptides. Additionally, a number of lines of evidence from our laboratory and other laboratories have suggested that HLA-B27 has unusual cell biology. We have recently demonstrated that HLA-B27 is capable of forming disulfide-bonded homodimers. These homodimers are expressed on the cell surface and are ligands for a number of natural killer and related immunoreceptors, expressed on a variety of cell types including natural killer cells, T lymphocytes and B lymphocytes, and members of the monocyte/macrophage lineage. We are currently investigating the possibility that such interactions could be involved in disease pathogenesis.

Journal ArticleDOI
TL;DR: A new control model for the study of biomechanical simulation of human movement was investigated using rowing as an example to explore biological and mechanical alternatives to optimal control methods and is believed to be significant from the point of view of fundamental biological theories of movement.
Abstract: A new control model for the study of biomechanical simulation of human movement was investigated using rowing as an example. The objectives were to explore biological and mechanical alternatives to optimal control methods. The simulation methods included simple control mechanisms based on proportional and derivative (PD) control, consideration of a simple neural model, introduction of an inverse dynamics system for feedback, and computational adjustment of control parameters by using an evaluative criterion and optimization method. By using simulation, appropriate rowing motions were synthesized. The generated rowing motion was periodic, continuous, and adaptable so that the pattern was stable against the mechanical force and independent of the initial condition. We believe that the simulation model is not only practical as a computational research tool from a biomechanical-engineering viewpoint but also significant from the point of view of fundamental biological theories of movement.



Journal ArticleDOI
TL;DR: The shoulder-specific measures had greater sensitivity than the SF-36 in registering significant differences in outcomes between comparison groups at 6 months and 4 years.
Abstract: Objective To compare different assessments following shoulder surgery for impingement syndrome with or without rotator cuff tear or repair. Methods A prospective study of 93 patients was conducted. Standard assessments were performed before, at 6 months, and at 4 years following shoulder surgery using the patient-based Oxford Shoulder Score (OSS), the Medical Outcomes Study Short Form-36 (SF-36) questionnaire, and a surgeon-assessed Constant Shoulder Score. Patients were categorized according to the surgery received in relation to the presence of cuff tears: full repair, partial repair, cuff tear/no repair, no tear/no repair. Results Most patients (57%) received subacromial decompression for impingement with no cuff tear. This group had the fewest pre- and postoperative symptoms. The category of patients who received only partial repair of a cuff tear had worse scores on all outcome assessments compared with other groups. Patient-based measures were more stable over time than the Constant. Conclusion The shoulder-specific measures had greater sensitivity than the SF-36 in registering significant differences in outcomes between comparison groups at 6 months and 4 years.

Journal ArticleDOI
TL;DR: In this article, the frequency of the C282Y and H63D polymorphisms in the disease, and to assess the risk of hereditary haemochromatosis in heterozygotes for the polymorphism were determined, and 128 patients were recruited because of either radiographic chondrocalcinosis or CPPD pseudogout.
Abstract: Hereditary haemochromatosis (HH) is the most common lethal monogenic human disease, affecting roughly 1 in 300 white northern Europeans. Homozygosity for the C282Y polymorphism within the HFE gene causes more than 80% of cases, with compound heterozygosity of the C282Y and H63D polymorphism also increasing susceptibility to disease. The aim of this study was to determine the frequency of the C282Y and H63D polymorphisms in the disease, and to assess the risk of HH in heterozygotes for the C282Y polymorphism. 128 patients were recruited because of either radiographic chondrocalcinosis (at least bicompartmental knee disease or joints other than the knee involved) or CPPD pseudogout. Genotyping of the HFE C282Y and H63D mutations was performed using PCR/SSP and genotypes for the C282Y polymorphism confirmed by PCR/RFLP. Historical white European control data were used for comparison. Two previously undiagnosed C282Y homozygotes (1.6%), and 16 C282Y heterozygotes (12.5%), including four (3.1%) C282Y/H63D compound heterozygotes were identified. This represents a significant overrepresentation of C282Y homozygotes (relative risk 3.4, p=0.037), but the number of heterozygotes was not significantly increased. At a cost per test of £1 for each subject, screening all patients with chondrocalcinosis using the above ascertainment criteria costs only £64 for each case of haemochromatosis identified, clearly a highly cost effective test given the early mortality associated with untreated haemochromatosis. Routine screening for haemochromatosis in patients with appreciable chondrocalcinosis is recommended.

Journal ArticleDOI
TL;DR: The results show that there are specific gender/age-related differences in osteoclast formation and bone resorption and have implications for evaluating osteOClastogenesis in skeletal diseases such as primary osteoporosis and Paget's disease.
Abstract: A number of bone diseases characterised by excessive osteolysis (e.g. osteoporosis and Paget’s disease) exhibit a marked gender difference in prevalence and are more common in the elderly population. Bone resorption is carried out by osteoclasts, which are formed by fusion of circulating mononuclear precursor cells of haematopoietic origin. In this study, we have determined whether there are gender- and age-related differences in osteoclast formation from circulating precursors. Peripheral blood mononuclear cells (PBMCs) were co-cultured with UMR106 osteoblast-like cells in the presence of macrophage-colony stimulating factor (M-CSF) and 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) or cultured alone in the presence of sRANKL (soluble receptor activator of nuclear factor B ligand) and M-CSF. As assessed by the formation of tartrate resistant acid phosphatase (TRAP)positive (TRAP + ) and vitronectin receptor-positive (VNR + ) multinucleated cells (MNCs), there was no

Journal ArticleDOI
TL;DR: Polished collarless tapered stems such as the Exeter seem to have enhanced rotational stability, and increasing anteversion of the Elite was associated with decreasing PHM and increased stability, while conventional stems are recommended to be anteverted 20 degrees.
Abstract: Internal rotation of a femoral stem within the femur, with posterior migration of the femoral head (PHM) relative to the femur, is an important mode of failure. The relationship between anteversion and rotational stability for the Exeter (Howmedica International Ltd, London, UK) and Charnley Elite (DePuy International Ltd, Leeds, UK) stems was investigated using radiostereometric analysis (RSA). For the Elite, there was a significant (P=.01) correlation between anteversion and PHM, whereas for the Exeter, there was no significant correlation (P=.6). Increasing anteversion of the Elite was associated with decreasing PHM and increased stability. Of stems, 20% of the Elite and none of the Exeter were classified as having reduced rotational stability because their PHM was >2 SDs from the mean. All reduced rotational stability implants had anteversion substantially <20 degrees. Polished collarless tapered stems such as the Exeter seem to have enhanced rotational stability. For conventional stems, increasing anteversion increases stability. It is recommended that these stems are anteverted 20 degrees.

Journal ArticleDOI
TL;DR: While for some common limb fractures there is a clear body of opinion supporting safety to drive, for other common fractures opinion is less clear cut and has important financial, medico-legal and legal implications that could be resolved by formal testing.
Abstract: One hundred Orthopaedic Consultants in the UK were randomly selected and asked to complete a postal questionnaire indicating when they felt patients with treated, pain free, common limb fractures could return to driving. Seventy-two questionnaires were returned. Six were not completed leaving 66 completed questionnaires. Analysis revealed a clear mandate to allow or prevent driving in patients with certain treatment modalities and stages of union. In the lower limb there was majority agreement of suitability to drive in 61% of the 28 presented scenarios. Opinion was more divided for the upper limb, with only 43% of the scenarios having majority agreement. Our results show that while for some common limb fractures there is a clear body of opinion supporting safety to drive, for other common fractures opinion is less clear cut. This has important financial, medico-legal and legal implications that could be resolved by formal testing.

Journal ArticleDOI
01 Sep 2002-Knee
TL;DR: In this paper, a fluoroscopic study was performed to investigate if abnormal mid-sagittal plane kinematics was related to bearing dislocation in meniscal bearing arthroplasty.
Abstract: When the Oxford unicompartmental meniscal bearing arthroplasty (UCA) is used in the lateral compartment 10% of the bearings dislocate. A fluoroscopic study was performed to investigate if abnormal mid-sagittal plane kinematics was related to bearing dislocation. Video fluoroscopy is an accepted means of determining in-vivo knee kinematics in the sagittal plane. Video fluoroscopy was obtained of 5 Oxford lateral UCAs 10 years post-operatively and of five normal knees. Patellar tendon angle (PTA), derived from dynamic fluoroscopic images, was used to describe the joint kinematics. This in-vivo experiment demonstrated that the PTA/knee relationship for the Oxford lateral UCA is similar to the normal knee. Both the normal knee ( r 2 =0.99) and the Oxford lateral UCA ( r 2 =0.98) demonstrated a linear relationship between flexion angle and PTA. No significant difference in PTA was found between the normal knee and the Oxford lateral UCA. This study demonstrated normal kinematics, as indicated by PTA, ten years after implantation of the Oxford lateral UCA. It is therefore reasonable to suggest that abnormal kinematics is not a significant factor relating to meniscal bearing dislocation in the lateral compartment.

Journal ArticleDOI
TL;DR: Soft tissue infections are common and usually respond rapidly to oral antibiotics; if empirical therapy fails then exposure to unusual organisms should be considered.
Abstract: Soft tissue infections are common and usually respond rapidly to oral antibiotics; if empirical therapy fails then exposure to unusual organisms should be considered. Septic arthritis requires early recognition, identification of the infecting pathogen and urgent joint washout to prevent irreversible cartilage and bone destruction. Prosthetic joint infection is uncommon but has high morbidity; the best outcomes are achieved with removal of the prosthesis and replacement after at least six weeks of antibiotic therapy. Osteomyelitis often complicates diabetic foot infection with ulceration and is rarely cured by antibiotics alone; early surgical intervention achieves the best outcome.

Journal ArticleDOI
01 Feb 2002-Knee
TL;DR: The use of the posterior border of the lower femoral diaphysis to represent the axis is accurate, simple, reliable and can be used by researchers studying knee joint kinematics using dynamic video fluoroscopy.
Abstract: The methodological detail about determining the femoral axis on lateral fluoroscopic images of the knee is lacking. This paper reports on the use of the posterior border of the lower femoral diaphysis to represent the axis. This method is accurate, simple, reliable and can be used by researchers studying knee joint kinematics using dynamic video fluoroscopy. It is also useful in the outpatient clinic to assess the flexion/extension position of femoral components after knee arthroplasty.

Journal ArticleDOI
TL;DR: MRI can successfully segregate patients with a clinical diagnosis of mechanical locking into those who have a true mechanical block and those who can be treated conservatively, and should precede arthroscopy in this clinical setting.
Abstract: Objective. To explore prospectively the hypothesis that MRI of the acutely locked knee can alter surgical decision-making. Design and patients. The study group comprised patients with a clinical diagnosis of knee locking requiring arthroscopy. The decision to carry out arthroscopy was made by an experienced consultant orthopaedic surgeon specialising in trauma and recorded in the patient's notes prior to MRI. Preoperative MRI was carried out using a 1.5 T system. The management was altered from surgical to conservative treatment in 20 (48%) patients on the basis of the MR findings. Arthroscopy was limited to patients with an MR diagnosis of a mechanical block, usually a displaced meniscal tear or loose body. Both patient groups were followed clinically until symptoms resolved. Results. Forty-two patients were entered into the study. MRI identified a mechanical cause for locking in 22 patients (21 avulsion meniscal tears and 1 loose body). All were confirmed at arthroscopy. Twenty patients were changed from operative to non-operative treatment on the basis of the MRI findings. One patient in this group required a delayed arthroscopy for an impinging anterior cruciate ligament stump. The sensitivity/specificity/accuracy of MRI in identifying patients who require arthroscopy was therefore 96%/100%/98% respectively. Conclusion. MRI can successfully segregate patients with a clinical diagnosis of mechanical locking into those who have a true mechanical block and those who can be treated conservatively. MRI should precede arthroscopy in this clinical setting.