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Biomedical subjects

D W Murray

Publications and source records attributed to D W Murray.

At least 55 records · Page 3Linked to original sources

Hydroxyapatite particles are capable of inducing osteoclast formation.

Hydroxyapatite (HA) coatings have been used to improve implant fixation by promoting bone formation around the prosthesis. A macrophage response to HA particulates has been noted around loosened HA-coated prostheses. As biomaterial wear particle-associated macrophages are known to be capable of differentiating into osteoclasts that are capable of bone resorption, we examined whether particulate HA could similarly induce macrophage-osteoclast differentiation. HA-associated macrophages were isolated from granulomas, formed by subcutaneous implantation of HA, and co-cultured with UMR 106 osteoblast-like cells in the presence of 1,25-dihydroxyvitamin D(3) for up to 14 days on glass coverslips and bone slices. HA-associated macrophage-osteoclast differentiation was evidenced by the formation of numerous multinucleated tartrate resistant acid phosphatase (TRAP)-positive cells which formed lacunar resorption pits on bone slices. Polymethylmethacrylate (PMMA) particle-associated macrophages, isolated from subcutaneous PMMA-containing granulomas, caused significantly more osteoclast formation and bone resorption than HA-associated macrophages. These results indicate that macrophages responding to HA particles are capable of osteoclast differentiation. They also suggest that particles derived from uncemented (HA-coated) implants are likely to induce less osteoclast formation and osteolysis than cemented implants.

Journal Article↗

Should total hip arthroplasty femoral components be designed to subside? A radiostereometric analysis study of the Charnley Elite and Exeter stems.

The Charnley Elite and the Exeter stems have different design concepts: The former is designed not to subside, whereas the latter is expected to subside. This radiostereometric analysis study compares the early migration of the 2 stems. For both implants, the 1st year migration was about 4 times faster than the 2nd year. The Exeter migration was predominantly distal (1 mm/y in the 1st year). It also showed slight collapse into valgus, and the head migrated slowly posteriorly (0.3 mm/y in the 1st year). In contrast, the Elite had slow distal migration (0.2 mm/y in the 1st year) and rapid posterior head migration (0.8 mm/y in the 1st year). Four Elites and no Exeters had rapid posterior head migration rates (mean 2.8 mm/y in the 1st year and 0.8 mm/y in the 2nd year). The Elite and the Exeter stems have fundamentally different early patterns of migration, which affect their long-term function; 20% of the Elites and none of the Exeters had rapid posterior head migration in the 1st year and the 2nd year and are likely to fail early. Polished, collarless, tapered designs, such as the Exeter, may be more forgiving than conventional stems designed not to subside.

Activities of Daily Living↗

Rapid recovery after oxford unicompartmental arthroplasty through a short incision.

Forty Oxford medial unicompartmental arthroplasties (UCAs) were performed through a short incision medial to the patellar tendon, without dislocation of the patella, using updated instruments (Oxford Knee Phase III, Biomet Ltd., Bridgend, UK). The rate of recovery of these knees (measured by the time taken to achieve straight-leg raising, 70 degrees of flexion, and independent stair climbing) was compared with that of 20 Oxford UCAs performed through an open approach with dislocation of the patella. Both groups were compared with 40 AGC (Biomet) total knee arthroplasties performed for osteoarthritis during the same time period. The average rate of recovery after the short-incision UCA was twice as fast as after open UCA and 3 times as fast as after total knee arthroplasty. Accuracy of implantation, assessed from 11 variables seen on fluoroscopically centered postoperative radiographs, was the same after UCA by the short-incision approach as after the open approach, suggesting that the short-term advantage of increased speed of recovery was gained without affecting the long-term results. We now employ the short incision with the phase III instruments for all UCAs.

Aged↗

Microanatomy of the acetabular cavity and its relation to growth.

The anatomy and development of the growing acetabulum are not clearly understood. We dissected and studied histologically two acetabula from the pelvis of a three-month-old infant. Relative rates of growth at the different growth plates were assessed by comparing the height of the proliferative layer with that of the hypertrophic layer. The three bones which form the acetabulum are surrounded by growth plates on all sides except medially. These face towards the centre of the triradiate cartilage, the limbs of the triradiate cartilage and the articular surface and each may be divided into four distinct areas according to the orientation of its cell columns which reflect the direction of growth. Growth was particularly rapid at the ischial growth plates directed towards the centre and the articular cartilage, add on both sides of the anterior limb of the triradiate cartilage. These findings may explain the mechanism by which the acetabulum changes orientation and inclination with growth.

Acetabulum↗

Medial unicompartmental arthroplasty after failed high tibial osteotomy.

Satisfactory selection criteria are essential for the successful outcome of unicompartmental knee arthroplasty (UCA). We report the frequency of revision of the Oxford medial unicompartmental arthroplasty in knees previously treated for anteromedial osteoarthritis by high tibial osteotomy (HTO). The combined results from three sources were used to allow statistical analysis of this uncommon subgroup. In the combined series of 631 knees (507 patients) which had medial unicompartmental replacement, 613 were primary procedures and 18 were for a failed HTO. The mean follow-up times of the two groups were similar (5.8 years and 5.4 years, respectively). At review, 19 (3.1%) of the primary procedures and five (27.8%) of those undertaken for a failed HTO had been revised to total knee replacement. Survival analysis revealed the ten-year cumulative survivals to be 96% and 66%, respectively. The log-rank comparison of these survivals revealed a highly significant difference (p < 0.0001). We recommend that the Oxford UCA should not be used in knees which have previously undergone an HTO.

Adult↗

Reconstruction does not reduce tibial translation in the cruciate-deficient knee an in vivo study.

We have assessed the effectiveness of reconstruction of the anterior cruciate ligament (ACL) in reducing functional tibial translation (TT). The gait of 11 ACL-deficient patients was studied using Vicon equipment before and after surgery. Measurements of the angle between the patellar tendon and the long axis of the tibia were obtained in order to calculate TT in the sagittal plane relative to the uninjured limb during standing and walking. Before surgery, patients did not show abnormal TT on the injured side, but after surgery significant anterior TT was found in the operated limb for every parameter of gait. Abnormal anterior TT occurring during activity does not seem to be reduced by reconstruction; rather, it increases. It may be that the increased translation results from relaxation of excess contraction of the hamstring muscles, since compensatory muscle activity no longer is required in a reconstructed knee. The reduction of TT may not be an appropriate objective in surgery on the ACL.

Adult↗

Mobile-bearing knee replacement: concepts and results.

In summary, if TKRs are to be performed in patients who are younger and more active than those who had the initial procedures in the 1970s and 1980s, better wear performance is imperative for long-term durability, especially if surgeons continue to consider the versatility associated with modular knee-replacement systems to be a necessity. At least with some designs, including the Oxford knee and the LCS knee, the results after a minimum follow-up of 10 years are comparable with the best results after arthroplasty with fixed-bearing designs in terms of wear, loosening, and osteolysis (Table 7). As with fixed-bearing designs, there are additional challenges in terms of optimizing bearing-surface conformity and improving kinematics. Improvements in future designs of mobile-bearing total knee replacements should include better control of bearing mobility patterns to reduce the prevalence of the abnormal kinematic motions that have been observed in fluoroscopic evaluations.

Adult↗

Primary total hip replacement: variations in patient management in Oxford & Anglia, Trent, Yorkshire & Northern 'regions'.

OBJECTIVES: To examine national practice, and variations in practice, concerning total hip replacement; in particular the choice of prosthesis and the involvement of consultants in NHS operations. DESIGN: Pre-operative survey of patients undergoing total hip replacement. SETTING: Five English regions serving combined population of 16.8 million people. SUBJECTS: 13,343 total hip replacement operations in one year commencing September 1996, either in NHS or private sector. MAIN OUTCOME MEASURES: Prosthesis used for surgery, status of surgeons involved in operation, use of laminar flow operating theatre. RESULTS: Prostheses without well documented 5-year survival were used in 5504 (58%) of 9417 operations for which information was available. The consultant was the operator in 4810 (64%) of 7499 NHS operations. In 1352 trainee-led operations, the consultant was present for only 637 (47%); this figure was 54% for trainees in years 1-4 of their training. Substantial variation between NHS consultant firms occurred both for use of prostheses with well documented survival data, and supervision of trainees by the consultant. CONCLUSIONS: This large study is the first attempt to describe national practice for primary total hip replacement. Substantial variation among consultant firms was observed for all indices of practice reported.

Adult↗

Rheumatoid arthritis synovial macrophage-osteoclast differentiation is osteoprotegerin ligand-dependent.

Osteoprotegerin ligand (OPGL) is a newly discovered molecule which is essential for osteoclast differentiation. Both OPGL and its soluble decoy receptor, osteoprotegerin (OPG), which inhibits osteoclast formation, are known to be produced by osteoblasts and inflammatory cells found in the rheumatoid arthritis (RA) synovium. In this study, RA synovial macrophages were incubated in the presence or absence of OPGL, macrophage-colony stimulating factor (M-CSF), and dexamethasone for various time points. The results indicated that osteoclast formation from RA synovial macrophages is OPGL-dependent and that OPGL and M-CSF are the only humoral factors required for RA synovial macrophage-osteoclast differentiation. OPG was found to inhibit osteoclast formation by RA synovial macrophages in a dose-dependent manner. This study has shown that macrophages isolated from the synovium of RA patients are capable of differentiating into osteoclastic bone-resorbing cells; this process is OPGL- and M-CSF-dependent and is modulated by corticosteroids. Cellular (T and B cells, dendritic cells) and humoral factors in RA synovium and bone may influence osteoclast formation and bone resorption by controlling OPGL/OPG production.

Aged↗

The effect of particle phagocytosis and metallic wear particles on osteoclast formation and bone resorption in vitro.

Osteoclasts are multinucleated bone-resorbing cells that are formed from precursors that circulate in the monocyte fraction. This study has determined the effect of phagocytosis of metal particles on osteoclast formation and bone resorption in vitro. Human peripheral blood monocytes were cocultured for 21 days with osteoblast-like UMR 106 cells, in the presence of 1,25-dihydroxyvitamin D3, dexamethasone, and human macophage colony-stimulating factor. Cobalt-chrome alloy (CoCr), stainless steel (316L-SS), titanium alloy (TiAlV), and commercially pure titanium (cpTi) particles (size range, 0.5-3.0 microm) and 1.0-microm latex particles were added to the cocultures as a single dose at the beginning of each experiment. All 5 types of particles were readily phagocytosed by the monocytes. After 4 days' exposure to high concentrations of all the metal particles, some cell death was found in the cocultures. After 14 days, a reduction in the number of CD14+ cells was seen in cocultures exposed to high concentrations of metal particles, particularly CoCr and 316L-SS particles. Phagocytosis of latex particles by osteoclast precursors did not affect the ability of these cells to undergo osteoclast differentiation. In contrast, exposure to metal wear particle preparations caused a dose-dependent reduction in the number of vitronectin receptor-positive osteoclastic cells formed and a dose-dependent reduction in the bone resorption produced by these cells. This decrease in resorption was greater after exposure to CoCr and 316L-SS particles compared with TiAlV and cpTi particles. This in vitro cell culture system may provide a useful model to compare the effect of different prosthetic materials on human osteoclast formation and bone resorption.

Alloys↗

Macrophage-osteoclast differentiation and bone resorption in osteoarthrotic subchondral acetabular cysts.

A macrophage infiltrate is commonly found in enlarging subchondral cysts in osteoarthrosis (OA) and the surrounding bone. To determine whether osteoclast differentiation by these cells contributes to the increase in the number of osteoclasts and bone resorption that accompanies OA cyst enlargement, we isolated macrophages from the wall of OA cysts and co-cultured them with osteoblast-like UMR106 cells in the presence or absence of 1,25(OH)2D3 and M-CSE After 14 days of incubation, co-cultures of UMR106 cells and cyst-derived macrophages showed evidence of osteoclast differentiation by expression of TRAP, VNR and formation of numerous lacunar pits. We found that, unlike osteoclast precursors in monocyte and other tissue macrophage populations, the addition of M-CSF to medium is not required for osteoclast differentiation. Our findings suggest that macrophage-osteoclast differentiation is one means whereby the osteolysis associated with the enlargement of OA cysts could be effected.

Acetabulum↗

Effect of osteoprotegerin and osteoprotegerin ligand on osteoclast formation by arthroplasty membrane derived macrophages.

OBJECTIVE: Osteoprotegerin ligand (OPGL) is a newly discovered molecule, which is expressed by osteoblasts/bone stromal cells. This ligand and M-CSF are now known to be essential for osteoclast differentiation from marrow and circulating precursors. This study examined whether OPGL and its soluble receptor osteoprotegerin (OPG), influenced osteoclast formation from human arthroplasty derived macrophages, to determine if the effects of OPGL and OPG on these cells could contribute to the osteolysis of aseptic loosening. METHODS: OPGL (+/- dexamethasone/M-CSF) was added to cultures of macrophages isolated from the pseudomembrane of loosened hip arthroplasties incubated on glass coverslips and dentine slices. OPG was added to cocultures of arthroplasty derived macrophages and UMR106 osteoblast-like cells. Osteoclast differentiation in long term cultures was assessed by expression of macrophage (CD14) and osteoclast markers (tartrate resistant acid phosphatase (TRAP), vitronectin receptor (VNR) and lacunar resorption). RESULTS: In the absence of osteoblastic cells, the addition of OPGL alone was sufficient to induce differentiation of macrophages (CD14(+), TRAP(-), VNR(-)) into TRAP(+) and VNR(+) multinucleated cells, capable of extensive lacunar resorption. OPG was found to inhibit osteoclast formation by arthroplasty macrophages in a dose dependent manner. OPG (100 ng/ml) more than halved the formation of TRAP(+) and VNR(+) cells and the extent of lacunar resorption in co-cultures of UMR106 cells and arthroplasty macrophages. CONCLUSIONS: This study has shown that macrophages, isolated from the pseudomembrane surrounding loose arthroplasty components, are capable of differentiating into osteoclastic bone resorbing cells and that OPGL is required for this to occur. OPG inhibits this process, most probably by interrupting the cell-cell interaction between osteoblasts and mononuclear phagocyte osteoclast precursors present in the pseudomembrane.

Aged↗

The value of short and simple measures to assess outcomes for patients of total hip replacement surgery.

OBJECTIVES: To evaluate the performance of a patient assessed outcome measure, the Oxford Hip Score, in a national study of primary hip replacement surgery. DESIGN: A survey of patients' health status before undergoing primary hip replacement surgery and three months and one year after surgery. SETTING: 143 hospitals in three NHS English regions. PATIENTS: 7151 patients admitted for primary total hip replacement surgery over a period of 13 months from September 1996. MAIN MEASURES: For patients, Oxford Hip Score and satisfaction with hip replacement and, for surgeons, American Anesthesiologists' Society (ASA) classification of physical status. RESULTS: The response rates to the postal questionnaire at three and 12 months follow up were 85.2% and 80.7%, respectively. Including all three administrations of the questionnaire, all except two items of the Oxford Hip Score were completed by 97% or more respondents and only one item at one administration appeared marginally to reduce the reliability of the score. The effect sizes for changes in the score from baseline to three months was 2.50 and to 12 months was 3.05. Patients rated by surgeons as being healthy preoperatively by the ASA classification were somewhat more likely to return a completed questionnaire at three months (79.4% versus 75.3%) and 12 months (72.4% versus 70.3%) than those rated as having poorer health. CONCLUSIONS: Overall there was little evidence of difficulties for patients in completing the Oxford Hip Score or of unreliable data, except in relation to one questionnaire item. The instrument was very responsive to change over time and score changes for the Oxford Hip Score related well to patients' satisfaction with their surgery. The instrument is an appropriate measure in terms of validity, responsiveness, and feasibility for evaluating total hip replacement from the

Aged↗

Human bone-derived cells support formation of human osteoclasts from arthroplasty-derived cells in vitro.

Mononuclear osteoclast precursors are present in the wear-particle-associated macrophage infiltrate found in the membrane surrounding loose implants. These cells are capable of differentiating into osteoclastic bone-resorbing cells when co-cultured with the rat osteoblast-like cell line, UMR 106, in the presence of 1,25(OH)2 vitamin D3. In order to develop an in vitro model of osteoclast differentiation which more closely parallels the cellular microenvironment at the bone-implant interface in situ, we determined whether osteoblast-like human bone-derived cells were capable of supporting the differentiation of osteoclasts from arthroplasty-derived cells and analysed the humoral conditions required for this to occur. Long-term co-culture of arthroplasty-derived cells and human trabecular-bone-derived cells (HBDCs) resulted in the formation of numerous tartrate-resistant-acid-phosphatase (TRAP) and vitronectin-receptor (VNR)-positive multinucleated cells capable of extensive resorption of lacunar bone. The addition of 1,25(OH)2 vitamin D3 was not required for the formation of osteoclasts and bone resorption. During the formation there was release of substantial levels of M-CSF and PGE2. Exogenous PGE2 (10(-8) to 10(-6) M) was found to stimulate strongly the resorption of osteoclastic bone. Our study has shown that HBDCs are capable of supporting the formation of osteoclasts from mononuclear phagocyte precursors present in the periprosthetic tissues surrounding a loose implant. The release of M-CSF and PGE2 by activated cells at the bone-implant interface may be important for the formation of osteoclasts at sites of pathological bone resorption associated with aseptic loosening.

Acid Phosphatase↗

Radiological changes five years after unicompartmental knee replacement.

Failure of a unicompartmental knee replacement (UKR) may be caused by progressive osteoarthritis of the knee and/or failure of the prosthesis. Limb alignment can influence both of these factors. We have examined the fate of the other compartments and measured changes in leg alignment after UKR. A total of 50 UKRs was carried out on 45 carefully selected patients between 1989 and 1992. At operation, deliberate attempts were made to avoid overcorrection of the deformity. Four patients died, one patient was lost to follow-up and two knees were revised before review which was at a minimum of five years. Standard long-leg weight-bearing anteroposterior views of the knee and skyline views of the patellofemoral joint were taken before and at eight months and five years after operation. The radiographs of the remaining 43 knees were reviewed twice by blind and randomised assessment to measure the progression of osteoarthritis within the joints. Overcorrection of the deformity in the coronal plane was avoided in all but two knees. Only one showed evidence of progression of osteoarthritis within the patellofemoral joint, and this was only identified in one of the four assessments. Deterioration in the state of the opposite tibiofemoral compartment was not seen. Varus deformity tended to recur. Recurrent varus of 2 degrees was observed between eight months and five years after operation. There was no correlation between the postoperative tibiofemoral angle and the extent of recurrent varus recorded at five years. Changes in alignment may be indicative of minor polyethylene wear or of subsidence of the tibial component. The incidence of progressive osteoarthritis within the knee was very low after UKR. Patients should be carefully selected and overcorrection of the deformity be avoided.

Aged↗