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Biomedical subjects

D W Murray

Publications and source records attributed to D W Murray.

At least 91 records · Page 5Linked to original sources
PubMed1997

Human arthroplasty derived macrophages differentiate into osteoclastic bone resorbing cells.

OBJECTIVE: In aseptic loosening, a heavy macrophage response to biomaterial wear particles is commonly found in arthroplasty tissues. The aim of this study was to discover if these cells contribute to the bone resorption of aseptic loosening by differentiating into osteoclasts. METHODS: Macrophages were isolated from the pseudocapsule and pseudomembrane of loose cemented and uncemented hip arthroplasties at the time of revision surgery and then co-cultured on glass coverslips and dentine slices with UMR 106 rat osteoblast-like cells, both in the presence and absence of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. Macrophages isolated from the synovial membrane of patients with osteoarthritis (OA) undergoing hip replacements were similarly studied as a control group. RESULTS: After 24 hours incubation, most cells isolated from the above periprosthetic tissues strongly expressed macrophage (CD11b, CD14) but not osteoclast markers. However, after 14 days incubation, numerous multinucleated cells showing the phenotypic features of osteoclasts (that is, positive for tartrate resistant acid phosphatase, the vitronectin receptor, and capable of extensive lacunar resorption) formed in co-cultures of arthroplasty derived macrophages and UMR 106 cells, in the presence of 1,25(OH)2D3. The addition of an antibody to macrophage colony stimulating factor (M-CSF) considerably reduced macrophage-osteoclast differentiation and hence the lacunar resorption seen in these co-cultures. In contrast, OA synovial macrophage/UMR 106 co-cultures showed little or no evidence of macrophage-osteoclast differentiation and this was only seen when human M-CSF was added to the co-cultures. CONCLUSION: This is the first report showing that human macrophages isolated directly from periprosthetic tissues surrounding loosened implants can differentiate into multinucleated cells showing all the functional and cytochemical characteristics of osteoclasts. In contrast with other macrophage populations, exogenous M-CSF is not required for this to occur. In the context of the heavy macrophage response to wear particles in periprosthetic tissues macrophage-osteoclast differentiation may represent an important cellular mechanism whereby osteolysis is effected in aseptic loosening.

Aged↗
PubMed1997

Pain levels after total hip replacement: their use as endpoints for survival analysis.

We have assessed the relative value of various outcome measures after THR, by the analysis of follow-up data from over 2000 patients. They had been reviewed clinically and radiologically six months after operation, at one year, and then every two years, some for 16 years. At each review their pain level, stiffness and opinion of progress were scored and a radiograph taken. We found that pain level was the most informative outcome as a predictor of revision and correlated well with the patients' opinions. We made a comparison between the six types of implant in the series, using survival analysis and log-rank testing with different pain levels as endpoints. This analysis revealed differences which were not detected by survival analysis using the traditional endpoint of revision. We therefore recommend the use of different levels of pain as the main outcome measures after total hip replacement.

Adolescent↗
PubMed1997

Radio-opaque agents in bone cement increase bone resorption.

A heavy infiltrate of foreign-body macrophages is commonly seen in the fibrous membrane which surrounds an aseptically loose cemented implant. This is in response to particles of polymethylmethacrylate (PMMA) bone cement and other biomaterials. We have previously shown that monocytes and macrophages responding to particles of bone cement are capable of differentiating into osteoclastic cells which resorb bone. To determine whether the radio-opaque additives barium sulphate (BaSO4) and zirconium dioxide (ZrO2) influence this process, particles of PMMA with and without these agents were added to mouse monocytes and cocultured with osteoblast-like cells on bone slices. Osteoclast differentiation, as shown by the presence of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and lacunar bone resorption, was observed in all cocultures. The addition of PMMA alone to these cocultures caused no increase in TRAP expression or bone resorption relative to control cocultures. Adding PMMA particles containing BaSO4 or ZrO2, however, caused an increase in TRAP expression and a highly significant increase in bone resorption. Particles containing BaSO4 were associated with 50% more bone resorption than those containing ZrO2. Our results suggest that radio-opaque agents in bone cement may contribute to the bone resorption of aseptic loosening by enhancing macrophage-osteoclast differentiation, and that PMMA containing BaSO4 is likely to be associated with more osteolysis than that containing ZrO2.

Acid Phosphatase↗
PubMed1997

Loss to follow-up matters.

Survival analysis of joint replacement relies on the assumption that surgical procedures in patients lost to follow-up have the same chance of failing as those in patients who continue to be assessed. Our study questions that assumption. During the 16-year follow-up of 2268 patients who had received total hip replacements 142 (6%) were lost to follow-up. The cumulative loss at 15 years was 20%. At their last assessment, patients who subsequently failed to attend for follow-up had significantly worse pain, range of movement and opinion of their progress (p < 0.001) and significantly worse radiological features than a matched control group (p < 0.01). Patients lost to follow-up have a worse outcome than those who continue to be assessed. Consequently, a survival analysis that does not take into account such patients is likely to give falsely optimistic results. It is therefore essential that vigorous attempts are made to minimise loss to follow-up, and that the rate of such loss is quoted. The overall loss to follow-up disguises the magnitude of the problem, which is best quantified by a cumulative rate of follow-up. The reliability of a study can be assessed by a loss-to-follow-up quotient, calculated by the number of failures: the lower the quotient the more reliable the data. Ideally, the quotient should be less than 1.

Aged↗
PubMed1997

Which primary total knee replacement? A review of currently available TKR in the United Kingdom.

Comparative information on total knee replacements (TKRs) is not readily available. With the help of implant manufacturers and distributors, we have compiled a list of TKRs on the market in the UK and summarised the information about these implants in a table. There are 37 different TKRs, marketed by 14 companies; 54% have been introduced since 1990. The number of different implants is increasing. At least eight designs have undergone major modifications, while many have had minor alterations. Of the TKRs on the market, 60% are modular. Some 54% of TKRs have no published results in peer-reviewed journals; only one of the four most widely used prostheses has published survival figures. New and modified implants are introduced without clinical evidence of their superiority over other available designs. Published results in peer-reviewed journals are currently the best evidence available on the reliability of an implant. When selecting an implant, surgeons should be aware if the prosthesis has any such results, the length of the follow-up, and the survival rates that are achieved. More detailed interpretation is difficult because of the different combinations used in modular implants and because of the frequent modification of existing designs. Properly conducted long-term clinical trials should be encouraged as they are the only means of evaluating new designs.

Costs and Cost Analysis↗
PubMed1996

The development of adolescent idiopathic scoliosis.

There are many conflicting actiological theories for adolescent idiopathic scoliosis. We present a simple new model of scoliosis and a mechanism by which it is initiated and progresses. This mechanism provides a final common pathway for the multiple aetiological factors. A simple model of the spine, incorporating its fundamental mechanical features, was constructed. The model consisted of interconnected anterior compression and posterior tension columns. It allowed normal spinal movements, with flexion limited by the posterior column and rotation centered around the anterior column. It also allowed deformities to develop. The ends of the model were fixed in the position of the vertebrae they represented. Overgrowth of the anterior column relative to the posterior column caused the model to take up the shape of an idiopathic scoliosis. The greater the overgrowth, the more marked the deformity. Normally anterior and posterior column growth are coupled. During the growth spurt the thoracic kyphosis flattens indicating that anterior growth temporarily exceeds posterior growth. If this over-growth is marked a scoliosis will develop, as demonstrated by the model. Once this occurs the coupling is lost, anterior growth further outstrips posterior growth and the deformity progresses. Not all scolioses worsen, as the tendency to progress is balanced by neuromuscular factors and remodelling. Factors that increase the growth rate, induce asymmetry or decrease the inherent stability of the spine all encourage the development and progression of a scoliosis. This explains the complex biomechanics of scoliosis and provides a final common pathway by which the multiple aetiological factors can induce idiopathic scoliosis. It has important implications for the understanding and treatment of this condition.

Adolescent↗
PubMed1996

Arthroplasty implant biomaterial particle associated macrophages differentiate into lacunar bone resorbing cells.

OBJECTIVE: To study the pathogenesis of aseptic loosening: in particular, to determine whether macrophages responding to particles of biomaterials commonly used in arthroplasty surgery for arthritis are capable of differentiating into osteoclastic bone resorbing cells, and the cellular and hormonal conditions required for this to occur. METHODS: Biomaterial particles (polymethylmethacrylate, high density polyethylene, titanium, chromium-cobalt, stainless steel) were implanted subcutaneously into mice. Macrophages were isolated from the foreign body granulomas that resulted, cultured on bone slices and coverslips, and assessed for both cytochemical and functional evidence of osteoclast differentiation. RESULTS: Tartrate resistant acid phosphatase (TRAP) negative macrophages isolated from granulomas containing particles of all types of biomaterial composition were capable of differentiating into TRAP positive cells capable of extensive lacunar bone resorption (assessed by scanning electron microscopy). The presence of both UMR106 rat osteoblast-like cells and 1,25-dihydroxy vitamin D3 was necessary for this to occur. CONCLUSION: All implant materials produce wear particles that are the focus of a heavy foreign body macrophage response in the fibrous membrane between a loose implant component and the host bone undergoing resorption. These findings underline the importance of biomaterial wear particle generation and the macrophage response to different types of biomaterial wear particles in the pathogenesis of aseptic loosening.

Animals↗
PubMed1996

Femoral remodelling after subtrochanteric osteotomy for developmental dysplasia of the hip.

Children who present late with hip dislocation may require femoral osteotomy after reduction, to correct valgus and anteversion deformity of the femoral neck. After these procedures proximal femoral growth is unpredictable. We have studied proximal femoral growth in 40 children who had been treated by femoral osteotomy. Preoperatively, the mean femoral neck-shaft angle was 5 degrees greater on the affected side than on the contralateral side. Postoperatively, it was 28 degrees less. There was progressive recorrection; after five years the angle was not significantly different from that on the contralateral side. In our series 70% of the capital epiphyses became abnormally shaped, taking the appearance of a 'jockey's cap'. All the growth plates became angulated but this corrected with time. Correction of the neck-shaft angle probably results from the more normal mechanical environment provided by reduction. The abnormal radiographic appearance of the epiphysis and growth plate is probably due to the rotation produced by the osteotomy.

Bone Remodeling↗
PubMed1996

Thromboprophylaxis and death after total hip replacement.

The recommendation that patients having a total hip replacement should receive pharmacological thromboprophylaxis is based on the belief that fatal pulmonary embolism is common, and that prophylaxis will decrease the death rate. To investigate these assumptions we performed a meta-analysis of all studies on hip replacement which included information about death or fatal pulmonary embolism. A total of 130 000 patients was included. The studies were so varied in content and quality that the results of our analysis must be interpreted with some caution. The fatal pulmonary embolism rate was 0.1% to 0.2% even in patients who received no prophylaxis. This is an order of magnitude lower than that which is generally quoted, and therefore the potential benefit of prophylaxis is small and may not justify the risks. To balance the risks and benefits we must consider the overall death rate. This was 0.3% to 0.4%, and neither heparin nor any other prophylactic agent caused a significant decrease. Our study demonstrates that there is not enough evidence in the literature to conclude that any form of pharmacological thromboprophylaxis decreases the death rate after total hip replacement. For this reason guidelines which recommend their routine use to prevent death after hip replacement are not justified.

Hip Prosthesis↗
PubMed1996

Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4 and leukemia inhibitory factor.

To determine the influence of polymethylmethacrylate (PMMA) wear particles on macrophage-osteoclast differentiation, PMMA particles were added to mouse monocytes which were cocultured with UMR 106 osteoblast-like cells in the presence of 1,25 dihydroxy vitamin D3[1,25(OH)2D3] for up to 7 days on glass coverslips and for up to 14 days on human cortical bone slices. An increase in osteoclast differentiation, as evidenced by the expression of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and the extent of lacunar bone resorption, was observed in monocyte cultures to which PMMA had been added. Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) added to these cocultures caused considerably less expression of TRAP and significant inhibition of lacunar bone resorption. This inhibitory effect was reversed by the addition of specific neutralizing antibodies to LIF and IL-4. These findings show that PMMA-wear particle-associated macrophages exhibit an enhanced capacity for differentiation to osteoclastic bone-resorbing cells.

Acid Phosphatase↗
PubMed1996

Migration of cemented femoral components after THR. Roentgen stereophotogrammetric analysis.

We studied the migration of 58 cemented Hinek femoral components for total hip replacement, using roentgen stereophotogrammetric analysis over four years. The implants migrated faster during the first year than subsequently, and the pattern of migration in the second period was very different. During the first year they subsided, tilted into varus and internally rotated. After this there was slow distal migration with no change in orientation. None of the prostheses has yet failed. The early migration is probably caused by resorption of bone damaged by surgical trauma or the heat generated by the polymerisation of bone cement. Later migration may be due to creep in the bone cement or the surrounding fibrous membrane. The prosthesis which we studied allows the preservation of some of the femoral neck, and comparison with published migration studies of the Charnley stem suggests that this decreases rotation and may help to prevent loosening.

Adult↗
PubMed1996

Long-term comparison of Charnley and Stanmore design total hip replacements.

We reviewed the records of the long-term outcome of 208 Charnley and 982 Stanmore total hip replacements (THR) performed by or under the supervision of one surgeon from 1973 to 1987. The Stanmore implant had a better survival rate before revision at 14 years (86% to 79%, p = 0.004), but the difference only became apparent at ten years. The later Stanmore implants did better than the early ones (97% to 92% at ten years, p = 0.005), the improvement coinciding with the introduction of a new cementing technique using a gun. Most of the Charnley implants were done before most of the Stanmore implants so that the difference between the results may in part be explained by improved methods, but this is not the complete explanation since a difference persisted for implants carried out during the same period of time. We conclude that improved techniques have reduced failure rates substantially. This improvement was much greater than that observed between these two designs of implant. Proof of the difference would require a very large randomised controlled trial over a ten-year period.

Bone Cements↗
PubMed1996

Bone growth and remodelling after fracture.

We used a rabbit model to investigate the mechanism by which the angulation of fractures is corrected in children. We produced a transverse proximal tibial fracture in one leg of 12 eight-week-old New Zealand white rabbits and measured bone alignment and length and the patterns of bone growth and remodelling. The angle between the joint surfaces changed rapidly to correct the alignment of the limb as a result of asymmetrical growth of epiphyseal plates. In an adult with closed plates, the angle between the joint surfaces cannot therefore improve. The angle at the fracture itself showed slow improvement because of bone drift and the asymmetrical growth of the epiphyseal plates. Remodelling corrected the shape of the bone in the region of the fracture. Periosteal division on the convex side increased the growth of the epiphyseal plate on that side, thus slowing the correction. The effect was relatively small, providing an indication that factors other than the periosteum are important in inducing correction. External torsional deformities developed because of helical growth at the plate. This was probably caused by abnormal posture which induced a torque at the growth plate. Helical growth is the mechanism by which rotational deformities can occur and correct.

Age Factors↗
PubMed1995

Use of the Russell-Taylor reconstruction nail in femoral shaft fractures.

Of 242 patients with injuries treated by locked intramedullary nailing of the femur, 52 (22 percent) were considered suitable for insertion of the reconstruction nail. The Russell-Taylor reconstruction nail was found to be useful in a greater variety of fractures than those for which it was originally designed. In addition to ipsilateral neck and shaft fractures, the Russell-Taylor reconstruction nail proved successful in high-energy comminuted subtrochanteric fractures, elderly subtrochanteric fractures and pathological lesions. In two cases, problems were encountered due to the relative straightness of the nail, but in the remaining patients there were no technical problems. In the 43 elderly patients and those with pathological lesions, seven complications occurred: a number which compares favourably with published reports for extramedullary devices. There were no cases of implant failure and in all patients the device supported the fracture to union or death.

Adult↗
PubMed1995

Roentgen stereophotogrammetric analysis for assessing migration of total hip replacement femoral components.

A new Roentgen stereophotogrammetric analysis system, using a biplane technique, has been developed to determine the migration and rotation of total hip replacement (THR) femoral components in three dimensions. Stainless steel marker balls were injected into the femur during the operation. The patients stood within a calibration frame during the X-ray. The two exposures were taken consecutively allowing radio-opaque shutters to be moved in front of the films to prevent fogging. Studies with a model demonstrated that the system was capable of measuring the position of an implant to better than 0.11 mm (2 SD). In vivo measurements demonstrated that the migration rate of the different parts of the femoral component could be determined with an accuracy of 0.25 to 0.50 mm/year. By considering the accuracy determined in different ways, methods for improving the system have been identified. The migration and rotation rate of 58 Hinek cemented femoral components was studied for four years. Migration was three to five times greater (p < 0.001) during the first year than subsequently. The prosthesis head moved the most during the first year (0.94 mm). A better understanding of the cause of implant failure could be obtained by studying the early migration of different types of prosthesis and comparing this with their clinical results and design features.

Algorithms↗
PubMed1995

Which primary total hip replacement?

To assist surgeons to select a total hip replacement (THR) we present comparative information on all such implants on the market in the UK. We identified 62 different primary THRs, manufactured by 19 companies; half had been introduced in the last five years, and only 30% have any results published in peer-reviewed journals. The prices range from 250 pounds to 2000 pounds, and the two cheapest implants have the longest reported follow-up. The number of THR implants available in the UK, and presumably the rest of the world, is rapidly increasing, but there is little or no scientific evidence that the newer, more expensive, implants are better than established designs. Some will undoubtedly be worse. We believe that this situation is unsatisfactory and make recommendations for improvement, in particular that preference be given to implants with good results in published peer-reviewed long-term clinical trials.

Evaluation Studies as Topic↗