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Showing papers by "Nuffield Orthopaedic Centre published in 1998"


Journal ArticleDOI
TL;DR: In this article, a 12-item questionnaire for patients having a total knee replacement (TKR) was developed and a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36.
Abstract: We have developed a 12-item questionnaire for patients having a total knee replacement (TKR). We made a prospective study of 117 patients before operation and at follow-up six months later, asking them to complete the new questionnaire and the form SF36. Some also filled in the Stanford Health Assessment Questionnaire (HAQ). An orthopaedic surgeon completed the American Knee Society (AKS) clinical score. The single score derived from the new questionnaire had high internal consistency, and its reproducibility, examined by test-retest reliability, was found to be satisfactory. Its validity was established by obtaining significant correlations in the expected direction with the AKS scores and the relevant parts of the SF36 and HAQ. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at follow-up. We also compared change in scores with the patients' retrospective judgement of change in their condition. The effect size for the new questionnaire compared favourably with those for the relevant parts of the SF36. The change scores for the new knee questionnaire were significantly greater (p < 0.0001) for patients who reported the most improvement in their condition. The new questionnaire provides a measure of outcome for TKR that is short, practical, reliable, valid and sensitive to clinically important changes over time.

2,177 citations


Journal ArticleDOI
TL;DR: It is recommended that five or six specimens be sent, that the cutoff for a definite diagnosis of infection be three or more operative specimens that yield an indistinguishable organism, and that because of its low level of sensitivity, Gram staining should be abandoned as a diagnostic tool at elective revision arthroplasty.
Abstract: A prospective study was performed to establish criteria for the microbiological diagnosis of prosthetic joint infection at elective revision arthroplasty. Patients were treated in a multidisciplinary unit dedicated to the management and study of musculoskeletal infection. Standard multiple samples of periprosthetic tissue were obtained at surgery, Gram stained, and cultured by direct and enrichment methods. With reference to histology as the criterion standard, sensitivities, specificities, and likelihood ratios (LRs) were calculated by using different cutoffs for the diagnosis of infection. We performed revisions on 334 patients over a 17-month period, of whom 297 were evaluable. The remaining 37 were excluded because histology results were unavailable or could not be interpreted due to underlying inflammatory joint disease. There were 41 infections, with only 65% of all samples sent from infected patients being culture positive, suggesting low numbers of bacteria in the samples taken. The isolation of an indistinguishable microorganism from three or more independent specimens was highly predictive of infection (sensitivity, 65%; specificity, 99.6%; LR, 168.6), while Gram staining was less useful (sensitivity, 12%; specificity, 98%; LR, 10). A simple mathematical model was developed to predict the performance of the diagnostic test. We recommend that five or six specimens be sent, that the cutoff for a definite diagnosis of infection be three or more operative specimens that yield an indistinguishable organism, and that because of its low level of sensitivity, Gram staining should be abandoned as a diagnostic tool at elective revision arthroplasty.

693 citations


Journal ArticleDOI
TL;DR: In this paper, the authors report the outcome of 143 knees with anteromedial osteoarthritis and normal anterior cruciate ligaments treated by unicompartmental arthroplasty using fully congruous mobile polyethylene bearings.
Abstract: Retrieval studies have shown that the use of fully congruent meniscal bearings reduces wear in knee replacements. We report the outcome of 143 knees with anteromedial osteoarthritis and normal anterior cruciate ligaments treated by unicompartmental arthroplasty using fully congruous mobile polyethylene bearings. At review, 34 knees were in patients who had died and 109 were in those who were still living. The mean elapsed time since operation was 7.6 years (maximum 13.8). We established the status of all but one knee. There had been five revision operations giving a cumulative prosthetic survival rate at ten years (33 knees at risk) of 98% (95% CI 93% to 100%). Considering the knee lost to follow-up as a failure, the 'worst-case' survival rate was 97%. No failures were due to polyethylene wear or aseptic loosening of the tibial component. One bearing which dislocated at four years was reduced by closed manipulation. The ten-year survival rate is the best of those reported for unicompartmental arthroplasty and not significantly different from the best rates for total knee replacement.

647 citations


Journal ArticleDOI
TL;DR: In this article, the authors report the outcome of 143 knees with anteromedial osteoarthritis and normal anterior cruciate ligaments treated by unicompartmental arthroplasty using fully congruous mobile polyethylene bearings.
Abstract: Retrieval studies have shown that the use of fully congruent meniscal bearings reduces wear in knee replacements. We report the outcome of 143 knees with anteromedial osteoarthritis and normal anterior cruciate ligaments treated by unicompartmental arthroplasty using fully congruous mobile polyethylene bearings. At review, 34 knees were in patients who had died and 109 were in those who were still living. The mean elapsed time since operation was 7.6 years (maximum 13.8). We established the status of all but one knee. There had been five revision operations giving a cumulative prosthetic survival rate at ten years (33 knees at risk) of 98% (95% CI 93% to 100%). Considering the knee lost to follow-up as a failure, the ‘worst-case’ survival rate was 97%. No failures were due to polyethylene wear or aseptic loosening of the tibial component. One bearing which dislocated at four years was reduced by closed manipulation. The ten-year survival rate is the best of those reported for unicompartmental arthroplasty and not significantly different from the best rates for total knee replacement.

259 citations


Journal ArticleDOI
01 Jan 1998-Spine
TL;DR: Oxygen concentrations in intervertebral discs were measured in 10 patients during discography and in 13 patients with scoliosis and 11 patients with back pain during spinal surgery to determine if oxygen and lactate levels in human discs vary with degree of degeneration.
Abstract: Study design Oxygen concentrations in intervertebral discs were measured in 10 patients during discography and in 13 patients with scoliosis and 11 patients with back pain during spinal surgery. Lactate concentration profiles were measured in 12 of these discs. The discs were graded for degeneration by magnetic resonance imaging and histology where possible. Objectives To determine if oxygen and lactate levels in human discs vary with degree of degeneration. Failure of nutrient transport is thought to lead to disc degeneration. Summary of background data The disc is avascular. Oxygen is used by the disc cells, and lactate is produced. Low oxygen and high lactate concentrations have been measured in the center of healthy animal discs. Methods Oxygen concentrations were measured amprometrically. The sterilized gold-needle electrode was introduced into the disc during discography or after the disc was exposed surgically via an anterior approach. Concentration profiles of each disc took approximately 5 minutes to measure. Lactate concentrations were measured biochemically on the excised disc segment. Results Oxygen concentrations were highest at the disc surface and fell toward the center. Lactate concentrations showed the reverse profile. Oxygen levels were very variable, ranging from 5-150 mm Hg in the center of the nucleus. No correlation was seen with age, pathology, or degree of degeneration. Lactate concentrations ranged for the most part from 2 mmol/L to 6 mmol/L. Conclusions Concentrations of metabolites depend on cellular activity and on transport of the metabolite between the blood supply and the cell. The correlation between degeneration and nutrition cannot be determined only from metabolite concentrations; measurements of metabolic activity and nutrient transport rates also are required.

219 citations


Journal ArticleDOI
TL;DR: Surgical treatment of idiopathic anterior knee pain in adolescents is not justified until a procedure has been shown to provide a better outcome than that reported here or until a way has been found to distinguish the few patients who will not get better spontaneously from the majority who will.
Abstract: We describe a consecutive series of girls with idiopathic anterior knee pain in adolescence and who were treated nonoperatively. At a mean follow-up of 16 years, 22% had no pain, 71% thought that their symptoms were better than at presentation, 88% used analgesics rarely or not at all, and 90% continued to participate regularly in sports. Nevertheless, about one in four of the patients continued to have significant symptoms for < or = 20 years after presentation. No features were identified that predicted those patients in whom symptoms would persist. We conclude that surgical treatment of idiopathic anterior knee pain in adolescents is not justified until a procedure has been shown to provide a better outcome than that reported here or until a way has been found to distinguish the few patients who will not get better spontaneously from the majority who will.

201 citations


Journal ArticleDOI
TL;DR: In unicompartmental knee replacement, careful implantation of fully congruous meniscal bearings can avoid failure due to polyethylene wear.
Abstract: Many designs of unicompartmental knee replacement show early and mid-term failure due to polyethylene wear. We studied the wear rate of congruent polyethylene meniscal bearings retrieved from failed Oxford unicompartmental knee replacements. We examined 16 bearings, 0.8 to 12.8 years after implantation, measuring their thickness and comparing it with that of 14 unused bearings. The mean rate of penetration, which included the effects of wear at both upper and lower surfaces, was 0.036 mm per year (maximum 0.08). Bearings as thin as 3.5 mm wore no faster than thicker models, but ten with evidence of impingement had greater wear. The six bearings with no impingement showed a mean rate of penetration of 0.01 mm per year. In unicompartmental knee replacement, careful implantation of fully congruous meniscal bearings can avoid failure due to polyethylene wear.

170 citations


Journal ArticleDOI
01 Jan 1998-Pain
TL;DR: Clinical effectiveness of a fitness programme 2 years after treatment is demonstrated but this needs to be replicated in a larger study which should include a cost effectiveness analysis, further analysis of objective functional status and a placebo intervention group.
Abstract: The aim of this study was to assess the long-term effect of a supervised fitness programme on patients with chronic low back pain. The design of the study was a single blind randomised controlled trial with follow-up, by postal questionnaire, 2 years after intervention. The Oswestry Low Back Pain Disability Index was used as the outcome measure to assess daily activity affected by back pain. Eighty-one patients with chronic low back pain, who were referred to the physiotherapy department of a National Health Service orthopaedic hospital, were randomised to either a supervised fitness programme or a control group. Patients in the intervention group and control group were taught specific exercises to be continued at home and referred to a backschool for back care education. In addition, the intervention group attended eight sessions of a supervised fitness programme. Sixty-two patients (76%) with a mean age of 37 years, returned the Oswestry Low Back Pain Disability Index questionnaire. Of these, 29 were in the intervention group and 31 in the control group. Patients in the intervention group demonstrated a mean reduction of 7.7% in the Oswestry Low Back Pain Disability Index score (95% confidence interval of mean paired difference 3.9, 11.6 P 0.05). Between group comparisons demonstrated a statistically significant difference in disability scores between the treatment and control group (mean difference 5.8, 95% confidence interval 0.3, 11.4 P < 0.04). This study supports the current trend towards a more active treatment approach to low back pain. We have demonstrated clinical effectiveness of a fitness programme 2 years after treatment but this needs to be replicated in a larger study which should include a cost effectiveness analysis, further analysis of objective functional status and a placebo intervention group.

161 citations


Journal ArticleDOI
TL;DR: It is concluded that precursor cells capable of osteoclast differentiation are present in the marrow compartment, the monocyte fraction of peripheral blood, and in the macrophage compartment of extraskeletal tissues and that these cells are capable of differentiating into mature functional osteoclasts.
Abstract: Mononuclear precursors of the human osteoclast have been identified in both bone marrow and the circulation in man, but osteoclast membership of the mononuclear phagocyte system (MPS) and its precise cellular ontogeny remain controversial. We isolated human hematopoietic marrow cells, blood monocytes, and peritoneal macrophages and incubated each of these cell populations with UMR106 osteoblast-like cells on glass coverslips and dentine slices in both the presence and absence of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), macrophage-colony stimulating factor (M-CSF), and dexamethasone. Cells isolated from peripheral blood and peritoneal dialysis fluid were positive only for monocyte/macrophage markers (CD11a, CD11b, CD14, and HLA-DR) and negative for osteoclast markers [tartrate-resistant acid phosphatase (TRAP), vitronectin reception (VNR), and calcitonin (CT) receptors and did not form resorption pits on dentine slices after 24 hours in culture. Similarly marrow cells did not form resorption pits on dentine slices after 24 hours in culture. However, after 14 days in co-culture with UMR106 cells, in the presence of 1,25(OH)2D3 and M-CSF, numerous TRAP, CT receptor, and VNR-positive multinucleated cells capable of extensive lacunar resorption were formed in co-cultures of all these preparations. The presence of 1,25 (OH)2D3, M-CSF, and UMR106 were absolute requirements for osteoclast differentiation. It is concluded that precursor cells capable of osteoclast differentiation are present in the marrow compartment, the monocyte fraction of peripheral blood, and in the macrophage compartment of extraskeletal tissues and that these cells are capable of differentiating into mature functional osteoclasts. These findings argue in favor of osteoclast membership of the human MPS.

125 citations


Journal ArticleDOI
TL;DR: This in vitro culture system demonstrates the use of human bone marrow cells for the potential evaluation of new biomaterials and the development of a novel carbonated apatite that may be of potential use in orthopaedic implants.

124 citations


Journal ArticleDOI
TL;DR: F fracture mechanics should be controlled more rigorously to provide amplitudes of movement in the first 4 to 6 weeks after fracture, and the rigidity of fixation should be increased in the subsequent weeks until the fracture has healed and the frame is removed.
Abstract: Selected studies are summarized that measure interfragmentary fracture displacements in 6 degrees of freedom at intervals throughout healing in groups of patients with tibial diaphyseal fractures treated by external skeletal fixation. The results are compared with those obtained from experimental studies in which the ideal mechanical conditions for fracture healing were predicted. A finite element analysis model of the healing tibial fracture also was developed. Measured data were used for the analysis, and stress and strain patterns were defined for different stages of healing. Interfragmentary movement measured in the first 6 weeks after injury usually is a magnitude smaller in patients treated by external fixation than in patients treated with cast immobilization. This movement can be much smaller than that predicted to be optimal by experimental studies. A greater amplitude can be achieved, even in stable fractures, by ensuring patient activity. The interfragmentary movement is elastic during loading activity and is generally sinusoidal during steady walking. At the time of dynamization (the unlocking of the frame), a permanent set occurs at the fracture site in all planes. The cyclical movement range in each plane often decreases immediately after unlocking. The model analysis study of fracture healing predicts that tissue damage may occur in the later (hard callus) phase of healing, even while the fixation device is in place, because of abnormally high stresses and strains. This study indicates that fracture mechanics should be controlled more rigorously to provide amplitudes of movement in the first 4 to 6 weeks after fracture. The rigidity of fixation should be increased in the subsequent weeks until the fracture has healed and the frame is removed.

Journal ArticleDOI
TL;DR: The injection of local anaesthetic into the hip is a reliable test, with low morbidity, and in difficult cases it will aid in the clarification of the cause of pain which possibly arises from the hip.
Abstract: We investigated 42 patients who were being considered for primary total hip arthroplasty (THA), but in whom it was uncertain whether the hip was the source of their pain. They were given an injection of local anaesthetic into the joint space. Of 33 patients who gained pain relief from their injection, 32 subsequently had successful THA. The remaining patient has not had surgery. The intra-articular injection of local anaesthetic is thus at least 96% sensitive. Of the nine patients who had no or only minimal pain relief from injection, one has had an unsuccessful THA, three have been successfully treated for other conditions and five have unresolved pain for which no organic basis has been established. We believe that the injection of local anaesthetic into the hip is a reliable test, with low morbidity. In difficult cases it will aid in the clarification of the cause of pain which possibly arises from the hip.

Journal ArticleDOI
TL;DR: It is found that it is difficult to discriminate between the various types of TKR, but this can be achieved using pain, and 30% of the patients reported moderate pain at some stage by seven years from operation.
Abstract: The results of total knee replacement (TKR) are commonly assessed by survival analysis using revision as the endpoint. We have used the assessment of pain by a patient-based questionnaire as an alternative. In one hospital, 1429 TKRs were inserted by 66 surgeons between 1987 and 1993. The survival at seven years, with revision as the endpoint, was 97.5% (CI 94 to 100). There were no significant differences between the three different types of implant used, the AGC, the IB2 and the Nuffield Knee. When the endpoint was the development of moderate pain, the survival at seven years for the AGC knee was 72% and that for the IB2 was similar. Significantly more patients (p = 0.007) with the Nuffield Knee, however, had developed moderate pain. Using revision as the endpoint, it is difficult to discriminate between the various types of TKR, but this can be achieved using pain. In this investigation 30% of the patients reported moderate pain at some stage by seven years from operation.

Journal ArticleDOI
TL;DR: The results demonstrate that with age or in scoliosis, some cells from the inner annulus or nucleus of the disc differentiate to the hypertrophic chondrocyte phenotype, which might be the initiating event for the abnormal calcification described in aged and scoliotic discs in other studies.
Abstract: The distribution and expression of type X collagen, a calcium-binding collagen, which is a marker of hypertrophic chondrocytes and thought to be involved in cartilage calcification, was examined in situ in nondegenerate (grade I or II) human discs taken at autopsy over a wide age range (fetal->80 years) and also in scoliotic discs removed at surgery. In the fetal vertebral column, type X collagen was strongly expressed in the hypertrophic chondrocytes of the endplate, but was not seen in other areas. In the cartilaginous endplate of adults, it was found over the whole age range examined, with intensity increasing with age. In the disc matrix itself, type X collagen was demonstrated around individual cells from all individuals older than 50 years, but not in any fetal or autopsy disc from individuals younger than 40 years. In scoliotic discs, however, focal type X collagen expression was seen in 3/8 patients younger than 40 years including one 12-year-old. No type X collagen was found in the outer annulus in any autopsy or scoliotic disc, supporting the idea that cells of the outer annulus are phenotypically distinct from cells of the inner annulus and the nucleus. Our results demonstrate for the first time that type X collagen is a possible gene product of the intervertebral disc cells and a potential biochemical component of the disc matrix. They indicate that with age or in scoliosis, some cells from the inner annulus or nucleus of the disc differentiate to the hypertrophic chondrocyte phenotype. This might be the initiating event for the abnormal calcification described in aged and scoliotic discs in other studies.

Journal ArticleDOI
01 Sep 1998-Robotica
TL;DR: The design requirements, the methods of detection of the signals and the training required to operate the hand are outlined, and more than one degree of freedom can be controlled and a greater and more natural functional range is possible.
Abstract: The current designs of commercial artificial hands have a low level of innovation. As feedback to the user is difficult to achieve reliably, most devices are simple in design and operation, and limited in functional range. If information on the state of the hand, the forces and any slippage that is occurring is fed back to a microcontroller then more than one degree of freedom can be controlled and a greater and more natural functional range is possible. This paper describes the development of such a device. It outlines the design requirements, the methods of detection of the signals and the training required to operate the hand.

Journal ArticleDOI
TL;DR: The abnormalities of the patellar tendon angle which resulted from implantation of the two total prostheses explain the observed changes in the PFF and show how the mechanics of thepatellofemoral joint depend upon the kinematics of the tibiofemoral articulation.
Abstract: Using a new, non-invasive method, we measured the patellofemoral force (PFF) in cadaver knees mounted in a rig to simulate weight-bearing. The PFF was measured from 20° to 120° of flexion before and after implanting three designs of knee prosthesis. Medial unicompartmental arthroplasty with a meniscal-bearing prosthesis and with retention of both cruciate ligaments caused no significant change in the PFF. After arthroplasty with a posterior-cruciate-retaining prosthesis and division of the anterior cruciate ligament, the PFF decreased in extension and increased by 20% in flexion. Implantation of a posterior stabilised prosthesis and division of both cruciate ligaments produced a decrease in the PFF in extension but maintained normal load in flexion. There was a direct relationship between the PFF and the angle made with the patellar tendon and the long axis of the tibia. The abnormalities of the patellar tendon angle which resulted from implantation of the two total prostheses explain the observed changes in the PFF and show how the mechanics of the patellofemoral joint depend upon the kinematics of the tibiofemoral articulation.

Journal ArticleDOI
TL;DR: The cold compression device appeared to reduce blood loss and pain following TKR, and a higher proportion of patients in the treatment group did not require blood transfusion postoperatively.
Abstract: This prospective, controlled study compared cold compressive dressings with wool and crepe in the postoperative management of patients undergoing total knee replacement (TKR). Forty TKR patients were assessed for blood loss, pain, swelling, and range of motion. Patients in the cold compression group had less blood loss through suction drainage (982 mL versus 768 mL). A higher proportion of patients in the treatment group did not require blood transfusion postoperatively. Mean opiate requirements were lower in the cold compression group (0.57 versus 0.71 mg/kg/48 hours). The cold compression device appeared to reduce blood loss and pain following TKR.

Journal ArticleDOI
01 Jun 1998-Bone
TL;DR: The results show that the application of highly controlled strains causes a significant effect on human bone cells, but only in a proportion of subjects, and the response is consistent between sequential explants derived from the same patient.

Journal ArticleDOI
TL;DR: In this article, the authors studied the wear rate of congruent polyethylene meniscal bearings retrieved from failed Oxford unicompartmental knee replacements, measuring their thickness and comparing it with that of 14 unused bearings.
Abstract: Many designs of unicompartmental knee replacement show early and mid-term failure due to polyethylene wear. We studied the wear rate of congruent polyethylene meniscal bearings retrieved from failed Oxford unicompartmental knee replacements.We examined 16 bearings, 0.8 to 12.8 years after implantation, measuring their thickness and comparing it with that of 14 unused bearings. The mean rate of penetration, which included the effects of wear at both upper and lower surfaces, was 0.036 mm per year (maximum 0.08). Bearings as thin as 3.5 mm wore no faster than thicker models, but ten with evidence of impingement had greater wear. The six bearings with no impingement showed a mean rate of penetration of 0.01 mm per year.In unicompartmental knee replacement, careful implantation of fully congruous meniscal bearings can avoid failure due to polyethylene wear.

Journal ArticleDOI
TL;DR: It is shown that particle phagocytosis by macrophages does not abrogate the ability of these cells to undergo osteoclast differentiation, emphasising the importance of the foreign-body macrophage response to biomaterial wear particles in the pathogenesis of aseptic loosening.
Abstract: Aseptic loosening of implant components is a common and important complication of both cemented and uncemented prosthetic joint replacements. Wear particles derived from organic polymer and metal implant biomaterials are commonly found within macrophages and macrophage polykaryons in the fibrous membrane between loose implant components and the host bone undergoing resorption. In order to determine whether biomaterial particle-containing, foreign-body macrophages may contribute to periprosthetic bone resorption, we cultured murine monocytes that had phagocytosed particles of biomaterials commonly employed in bone implant surgery [polymethylmethacrylate (PMMA), ultra-high molecular weight polyethylene (PE), titanium and chromium-cobalt] on bone slices and glass coverslips with UMR 106 osteoblast-like stromal cells in the presence of 1,25-dihydroxy-vitamin D3. Under these conditions, all biomaterial particle-containing, foreign-body macrophages differentiated into osteoclastic cells, i.e. tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells capable of extensive lacunar bone resorption. This study shows that particle phagocytosis by macrophages does not abrogate the ability of these cells to undergo osteoclast differentiation. These findings emphasise the importance of the foreign-body macrophage response to biomaterial wear particles in the pathogenesis of aseptic loosening.

Journal ArticleDOI
TL;DR: Despite the unique clinical features, the initial diagnosis of fibrodysplasia ossificans progressiva was often wrong and usually considerably delayed, and mistaken histologic diagnoses such as soft tissue sarcoma or fibromatosis could lead to inappropriate treatment.
Abstract: Fibrodysplasia (myositis) ossificans progressiva is a rare dominantly inherited disorder, in which defects in skeletal patterning particularly affecting the big toes, are associated with progressive endochondral ossification of the large striated muscles in a specific order leading to prolonged disability. A recent series of 28 patients studied for as many as 24 years exemplifies the presentation and course of this disease. Painful swelling of muscles (myositis) leading to ossification began at a mean age of 4.6 years (range, 0-16 years) initially in the neck and upper spine (in 25 subjects) and later around the hips, other major joints, and jaw. The rate and extent of disability was unrelated to the time of onset. No form of treatment produced consistent benefit. Despite the unique clinical features, the initial diagnosis of fibrodysplasia ossificans progressiva was often wrong and usually considerably delayed. Mistaken histologic diagnoses such as soft tissue sarcoma or fibromatosis could lead to inappropriate treatment.

Journal ArticleDOI
TL;DR: It would seem that in distracted muscle the connective tissue element adapts less readily than the contractile component, with prolonged stretch leading to damage to the perimysial and endomysial network, with subsequent fibrosis and loss of muscle compliance.
Abstract: When the tibialis anterior muscle of the rabbit is progressively stretched during surgical limb distraction, the muscle fibres lengthen by addition of new serial sarcomeres, provided that stretch is carried out at an appropriate rate. However, in spite of the apparent adaptation to the new functional length, range of joint movement is greatly decreased. In this study we have first, made measurements of the passive tension developed by distracted muscles over the range of joint movement and secondly made quantitative measurements of endomysial and perimysial connective tissue content. It was found that at all ankle joint angles greater than 90°, the passive tension developed by the distracted muscles was greater than both contralateral and sham-operated controls. Image analysis showed that the ratio of collagen to contractile material was increased in distracted muscles compared with muscles from sham-operated controls, due to increased deposition of collagen type III. Scanning electron microscopy showed the presence of a dense perimysial weave surrounding the distracted muscle fibres. These quantitative and qualitative changes in the connective tissue component could account for the increased stiffness demonstrated by the physiological measurements. It would seem that in distracted muscle the connective tissue element adapts less readily than the contractile component, with prolonged stretch leading to damage to the perimysial and endomysial network, with subsequent fibrosis and loss of muscle compliance. Such changes could help explain the loss of range of movement noted in the distracted limbs of patients undergoing surgical limb-lengthening and in other conditions that result in muscle contractures.

Journal ArticleDOI
TL;DR: Results indicate that by mixing a bisphosphonate with bone cement, it is possible to inhibit PMMA particle induced bone resorption and may provide a possible therapeutic strategy to prevent or to control the osteolysis of aseptic loosening.
Abstract: OBJECTIVE Wear particle induced bone resorption is thought to be one of the mechanisms that contribute to implant loosening. It has previously been shown that macrophages, in response to polymethylmethacrylate (PMMA) particles, differentiate into bone resorbing osteoclasts, and that this process is inhibited by a bisphosphonate, etidronate (EHDP). The aim of this study was to determine whether incorporating EHDP in bone cement could reduce PMMA associated bone resorption. METHODS Two concentrations of EHDP were mixed with PMMA monomer before polymerisation. Particles of PMMA (1–10 μm) were generated then added to mouse monocytes cocultured with UMR106 rat osteoblast-like cells and the extent of osteoclast differentiation was determined by assessing the extent of tartrate resistant acid phosphatase (TRAP) staining and measuring the amount of lacunar bone resorption. RESULTS The addition of PMMA to monocyte-UMR106 cocultures resulted in a marked increase in the number of TRAP positive osteoclast-like cells and a significant increase in the number of lacunar resorption pits compared with control cultures to which no particles had been added. After the addition of particles of PMMA + 20 mg EHDP, significantly fewer lacunar pits (p=0.00006) and fewer TRAP positive cells were noted compared with cocultures containing PMMA particles alone. CONCLUSIONS These results indicate that by mixing a bisphosphonate with bone cement, it is possible to inhibit PMMA particle induced bone resorption. This bisphosphonate inhibition of PMMA biomaterial wear particle containing macrophage-osteoclast differentiation and bone resorption may provide a possible therapeutic strategy to prevent or to control the osteolysis of aseptic loosening.

Journal ArticleDOI
TL;DR: The observations suggest that the BMP-4 gene product is one of the local contributing factors in regulating bone and cartilage formation in distraction osteogenesis.
Abstract: We characterized the presence and localization of bone morphogenetic protein 4 (BMP-4) mRNA in the regenerating tissues produced by distraction osteogenesis following tibial osteotomy in the rabbit. The findings are consistent with previous reports on the localization of BMP-4 mRNA expression during fracture repair. The BMP-4 gene is expressed by less differentiated osteoprogenitor cells (fibroblastic mesenchymal cells and preosteoblasts), and not by fully differentiated osteoblasts. BMP-4 gene expression is localized in callus-forming tissue (muscle, periosteum) during callus formation. Our observations suggest that the BMP-4 gene product is one of the local contributing factors in regulating bone and cartilage formation in distraction osteogenesis.

Journal ArticleDOI
TL;DR: It is exploited to demonstrate that the repertoire of clones expanded by in vitro tetanus toxoid stimulation shows stability within an individual, implying long‐term maintenance of multiple CD4+ clones.
Abstract: Oligoclonal or clonal T-cell expansions, presumed to be antigen driven, are frequently sought and followed for diagnostic and prognostic purposes, as well as to understand more about their natural history Techniques based on conservation of T-cell receptor CDR3 length are increasingly widely used, often without assessment of sensitivity or specificity We present a comparative evaluation of a novel modified heteroduplex technique and a CDR3-length-based assay Dilution of a known clone in a mixed T-cell population shows that in our hands the heteroduplex technique is at least 10-fold more sensitive than the CDR3-length-based assay However, even with this level of sensitivity, we do not detect clonal expansions in unstimulated CD4(+) T cells This contrasts with the frequent detection of CD8(+) clones in fresh samples and suggests different mechanisms of clonal homeostasis in the two subsets We show that both techniques detect functional expansions after in vitro stimulation with a recall antigen The distinct molecular footprint seen with the heteroduplex technique allows reproducible follow up of specific clonal expansions We have exploited this to demonstrate that the repertoire of clones expanded by in vitro tetanus toroid stimulation shows stability within an individual, implying long-term maintenance of multiple CD4(+) clones

Journal ArticleDOI
TL;DR: Recent research in non osteoporotic women shows that breast feeding maintains a low bone density; it is therefore contraindicated in pregnancy associated osteoporeosis.
Abstract: Osteoporosis leading to fracture can occur during pregnancy. Bone density may be low before pregnancy due to recognised causes such as coeliac disease, osteogenesis imperfecta and previous anorexia nervosa (secondary osteoporosis). In some patients there is no identifiable cause. This condition is referred to as "pregnancy associated or pregnancy related osteoporosis"; it is not known whether pregnancy causes the osteoporosis or merely coincides with it. Typically the loss of bone leads to vertebral fracture with loss of height or pain in the hips also sometimes with fracture. Symptoms most often begin in the third trimester of the first pregnancy and improve after delivery; they do not usually recur in subsequent pregnancies. The cause is unknown and there is no specific treatment; follow up bone density measurements show that the osteoporosis slowly improves post partum. Recent research in non osteoporotic women shows that breast feeding maintains a low bone density; it is therefore contraindicated in pregnancy associated osteoporosis.

Journal ArticleDOI
TL;DR: At 24 months after operation all patients had excellent knee stability, a high rate of return to sport and minimal radiological evidence of degenerative change, and the series represents a basis for comparison of results using other techniques and after more severe injuries.
Abstract: We treated 90 patients with an isolated injury to the anterior cruciate ligament (ACL) by reconstruction using a patellar tendon autograft and interference screw fixation. Of these, 82 (91%) were available for review at 24 months. Two grafts and two contralateral ACLs had ruptured during sport and there was one case of atraumatic graft resorption. Using the assessment of the International Knee Documentation Committee (IKDC), 86% of the remaining patients were normal or nearly normal. The median Lysholm knee score was 95/100 and 84% of patients were participating in moderate to strenuous activity. All had grade-0 or grade-1 Lachman, pivot-shift and anterior-drawer tests. Measurement with the KT1000 arthrometer gave a side-to-side difference of <3 mm of anterior tibial displacement in 90%. Sixty-six radiographs were IKDC grade A and one was grade B. Pain on kneeling was present in 31% and graft site pain in 44%. At 24 months after operation all patients had excellent knee stability, a high rate of return to sport and minimal radiological evidence of degenerative change. Our series therefore represents a basis for comparison of results using other techniques and after more severe injuries.

Journal Article
TL;DR: It is concluded that BMPs are subject to regulation by a variety of factors and that this is dependent on the stage of the cell in the osteogenic lineage.
Abstract: Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGF-beta) superfamily and are crucial factors in the process of bone formation. Despite knowledge on their wide distribution and expression, however, there is very little information on the biological factors that affect gene transcription of these osteoinductive agents. To investigate this aspect of BMP gene regulation we have studied the effect of a number of factors known to affect osteogenic cells. Northern analysis showed modulation of the expression of BMP-2 and BMP-4 mRNAs in two human osteosarcoma cell lines, MG63 and Saos-2, by prostaglandin E2 (PGE2), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interferon-alpha (IFN-alpha), retinoic acid and 1,25(OH)2 vitamin D3. mRNA expressions of the normally used "housekeeping genes", glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin, were found to be susceptible to influence by some of the factors used. Hence, an oligo(dT)15-18 probe was used to reliably estimate the relative quantities of mRNA present for normalization of data. In general, all factors down-regulated mRNA expressions of BMP-2 and BMP-4 in MG63 cells. IL-6 completely abolished detectable expression of BMP-2 mRNA, which was also greatly reduced by IL-1beta, retinoic acid and 1,25(OH)2 vitamin D3. PGE2 had similar influences on BMP-2 and BMP-4 expressions, showing reductions to approximately 60% of normal. In Saos-2 cells only 1,25(OH)2 vitamin D3 had any great effect on BMP-2 expression, which was down-regulated to approximately 60% of control values. BMP-4 was down-regulated by IFN-alpha (approximately 60%) and IL-1beta (approximately 20%). We conclude that BMPs are subject to regulation by a variety of factors and that this is dependent on the stage of the cell in the osteogenic lineage. Furthermore, the use of GAPDH and beta-actin genes as "housekeeping genes" in expression-modulation studies must be treated with care.

Journal ArticleDOI
TL;DR: Scapulectomy gives an excellent functional result if the glenohumeral joint is preserved, and the rotator cuff could be removed without a severe functional deficit provided that the deltoid was reattached to the scapular remnant and the trapezius.
Abstract: We describe the functional results in 14 patients (7 men, 7 women) after subtotal scapulectomy for primary bone and soft-tissue tumours at a specialist musculoskeletal oncology unit. Eight had chondrosarcomas, two Ewing’s sarcomas, one aggressive fibromatosis and three soft-tissue sarcomas. The mean follow-up was 52 months (6 to 120). Analysis of residual symptoms and of range and strength of movement by physicians used the Musculoskeletal Tumour Society rating scale (MSTS). Physical disability was measured by the patients using the Toronto Extremity Salvage Score (TESS). All 14 patients are still alive, two with systemic disease. Nine had more than 80% of their scapula resected but the glenohumeral joint was preserved in all cases. Eight had full movement and another two achieved 90° of flexion. The mean functional results were good to excellent in all except three patients (mean MSTS = 71.6 and TESS = 79.9). Two of these three patients had considerable pain as a result of brachial neuropathy. Scapulectomy gives an excellent functional result if the glenohumeral joint is preserved. The rotator cuff could be removed without a severe functional deficit provided that the deltoid was reattached to the scapular remnant and the trapezius.

Journal ArticleDOI
TL;DR: The transducer may be used to examine the correlation between impact force and fracture incidence for a variety of different floors in homes for the elderly.