Objectives

Experimental studies indicate that non-steroidal anti-inflammatory drugs (NSAIDs) may have negative effects on fracture healing. This study aimed to assess the effect of immediate and delayed short-term administration of clinically relevant parecoxib doses and timing on fracture healing using an established animal fracture model.

1. One hundred and seventy-nine cases of primary malignant bone tumour and giant-cell tumour seen at the Middlesex Hospital since 1925 are reviewed. Tumours arising from non-skeletal tissues in bone have been excluded. 2. The following histological classification is used. Osteosarcoma (osteoblast sarcoma): This tumour is not synonymous with osteogenic (bone-forming) sarcoma. The essential feature is the formation of osteoid tissue by malignant osteoblasts, with no intermediate matrix of cartilage or fibrous tissue. It is the most malignant bone tumour and only four of the thirty-two patients survived three years. Chondrosarcoma: These tumours are composed of cartilage, and some show secondary ossification. The behaviour of this group is related to the degree of cartilaginous differentiation. In general, compared with the osteosarcoma, it is of low-grade malignancy. More than half of the sixty-eight patients survived four years. Fibrosarcoma: The essential feature of this tumour is the production of collagen by malignant fibroblastic tumour cells. Tumours of this type invading the medullary cavity have an average prognosis between that of an osteosarcoma and a chondrosarcoma. Nine of the thirty-four patients survived three years. Spindle-cell sarcoma: These tumours are composed of spindle cells which produce no diagnostic matrix. In spite of the lack of differentiation the outlook is not hopeless. Six of the eleven patients survived for five years or more. Giant-cell tumour: This tumour is composed of a cellular stroma with diagnostic giant cells resembling osteoclasts. It is by no means a benign lesion, for half the tumours recurred after treatment and a quarter of the patients died with metastases. 3. The subdivision of primary malignant skeletal tumours into groups according to the histological pattern appears to be reflected in the behaviour of the individual tumours after treatment. The prognosis of each group has been stated in the appropriate sections

Aims

Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.

We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45°C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia. The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung

Aims

Preoperative diagnosis is important for revision surgery after prosthetic joint infection (PJI). The purpose of our study was to determine whether reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which is used to detect bacterial ribosomal RNA (rRNA) preoperatively, can reveal PJI in low volumes of aspirated fluid.

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches

Objectives

Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that ^99mTc-methylene diphosphonate (^99mTc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA).

We evaluated the diagnostic accuracy of fine-needle aspiration biopsy in a prospective study of 300 patients with previously undiagnosed bone lesions. Patients with suspected local recurrence of a primary bone tumour or a metastatic lesion of a previously diagnosed malignancy were excluded. Fine-needle aspiration biopsy was performed under radiological control as an outpatient procedure. The series was grouped into three major categories: 1) benign bone lesions including infections; 2) primary malignant bone tumours; and 3) metastases including lymphomas and myelomas. We compared the cytological diagnosis with the final diagnosis as assessed by histological examination and/or the clinical and radiological features. Material considered conclusive for cytological diagnosis was obtained from 251 of the 300 patients. Of the 49 failures, there were 24 aspirates with insufficient cellular yield and 25 in which a diagnosis could not be made although the cytological material was adequate in quantity. Most of the inconclusive aspirates (36/49) were obtained from benign bone lesions. The diagnosis was correct in 239 (95%) of the 251 cases providing adequate cytological material. There were eight (3%) falsely benign diagnoses, one (0.3%) falsely malignant, and three cases in which we were unable to differentiate between sarcoma and a metastasis. Chondrosarcoma (2/12) gave the greatest diagnostic difficulty and Ewing’s sarcoma the least (0/9). There were no decisive errors of treatment. All falsely benign or malignant diagnoses were questioned, and led to open biopsy since they did not correlate with the clinical and radiological features. Our study suggests that fine-needle aspiration biopsy is a valid option for the diagnosis of bone tumours. It is a simple outpatient procedure which gives sufficient cytological material for the correct diagnosis in 80% of cases. As with histological analysis of material from open biopsy, the cytological assessment must agree with the clinical and radiological findings

Aims

The use of frozen tumour-bearing autograft combined with a vascularized fibular graft (VFG) represents a new technique for biological reconstruction of massive bone defect. We have compared the clinical outcomes between this technique and Capanna reconstruction.

We hypothesised that meniscal tears treated with mesenchymal stem cells (MSCs) together with a conventional suturing technique would show improved healing compared with those treated by a conventional suturing technique alone. In a controlled laboratory study 28 adult pigs (56 knees) underwent meniscal procedures after the creation of a radial incision to represent a tear. Group 1 (n = 9) had a radial meniscal tear which was left untreated. In group 2 (n = 19) the incision was repaired with sutures and fibrin glue and in group 3, the experimental group (n = 28), treatment was by MSCs, suturing and fibrin glue. At eight weeks, macroscopic examination of group 1 showed no healing in any specimens. In group 2 no healing was found in 12 specimens and incomplete healing in seven. The experimental group 3 had 21 specimens with complete healing, five with incomplete healing and two with no healing. Between the experimental group and each of the control groups this difference was significant (p < 0.001). The histological and macroscopic findings showed that the repair of meniscal tears in the avascular zone was significantly improved with MSCs, but that the mechanical properties of the healed menisci remained reduced

1. A radiographic investigation of a group of 241 men who had worked in compressed air at pressures up to 35 pounds per square inch gauge on the construction of tunnels under the River Clyde showed that forty-seven men (19 per cent) had one or more lesions of aseptic necrosis of bone. 2. The radiological lesions have been classified as juxta-articular, which may lead to pain and limitation of movement, and head, neck and shaft lesions, which are usually symptomless. In 10 per cent of the men the lesions were juxta-articular and therefore potentially disabling. The treatment ofjuxta-articular lesions is described and reviewed. 3. The environmental factors associated with the occurrence of aseptic necrosis of bone, the radiological and histological appearances, and the pathogenesis of the lesions are discussed. Bone lesions were found to be related directly to the number of times a man had been decompressed, to the height of pressure at which he had worked and to attacks of bends for which treatment was given. 4. When the histological and radiographic appearances of aseptic necrosis of bone in compressed air workers are compared it is clear that a radiograph may not always reveal the full extent of the lesion, and some lesions may not show up at all. The cause of the necrosis is obscure because experimental and direct evidence of bone infarction by gas bubbles is lacking. 5. The currently accepted decompression procedures and treatment of bends used in civil engineering practice, do not prevent the occurrence of aseptic necrosis of bone in compressed air workers. 6. It is suggested that periodic radiological examination of the bones of compressed air workers should be carried out and the results correlated with other information about the men and the contracts on which they have worked in order to elucidate the causative factors in aseptic necrosis of bone. A central registry has been set up by the Medical Research Council in the University of Newcastle upon Tyne to fulfil this function

Two Durasul highly crosslinked polyethylene liners were exchanged during revision surgery four and five years after implantation, respectively. The retrieved liners were evaluated macroscopically and surface analysis was performed using optical and electron microscopy. A sample of each liner was used to determine the oxidation of the material by Fourier transform infrared spectroscopy. Samples of the capsule were examined histologically. The annual wear rate was found to be 0.010 and 0.015 mm/year, respectively. Surface analysis showed very little loss of material caused by wear. Histological evaluation revealed a continuous neosynovial lining with single multinucleated foreign-body giant cells. Our findings showed no unexpected patterns of wear on the articulating surfaces up to five years after implantation and no obvious failure of material

Objectives

Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study.

1 . The magnitude of the problem of congenital anomalies becomes evident when one takes into consideration the fact that they cause the death of approximately one quarter of the human race either before or shortly after birth, and handicap an appreciable proportion of the survivors throughout their lives. Further, a significant percentage of infants judged to be normal at birth are found in later life to suffer from "disguised" anomalies of the skeleton and soft tissues. Though the study of genetic factors leading to congenital defects has attracted a great deal of attention during the last few decades, the importance of environmental causes of human malformations has received relatively less emphasis. The association of congenital anomalies such as cataract and cardiac septal defects with maternal intercurrent infection of rubella during the early months of pregnancy demonstrates clearly that changes in the germplasm cannot always be invoked as the cause of developmental abnormalities. Congenital malformations that are sometimes genetically determined, such as microphthalmos, cleft palate, and certain skeletal abnormalities, can be caused in the offspring not only by maternal nutritional deficiencies and x-radiation but also, at least in some animals, such as chickens, rats and rabbits, by the introduction of certain substances like insulin into the environment of the embryo during its development. 2. Since very little is known of the detailed histology of the early human embryo, the histological examination of cases of perverted growth is mainly limited to aborted foetuses which, unfortunately, tend to present varying degrees of post-mortem degeneration before accurate histological methods can be applied. It is exactly in this field that animal experiments can offer valuable help. According to Mall and other embryologists the pathological changes that take place in human foetuses and those obtained experimentally in animals are not merely "analogous or similar but identical.". 3. An attempt has been made to review, in some detail, the more important work which has been carried out on experimental teratogenesis, on the epidemiological implications of developmental arrests in humans, and on foetal abnormalities associated with maternal metabolic and hormonal disorders during pregnancy. 4. The technique employed for injection of insulin into the egg yolk has been described. Methods used for the estimation of blood sugar in chick embryos at various stages after injection of insulin and special histochemical techniques for localising polysaccharides in cartilage have been outlined. 5. A few salient experimental results have been tabulated, and some of the insulin-induced abnormalities have been illustrated. 6. The possible mechanism of action of insulin in the causation of the various developmental anomalies has been discussed. Broadly speaking, insulin seems to affect primarily the part or tissue which is in the most active stage of growth or differentiation at the time of the injection. Within the range of 0·05 to 6 units of insulin employed, the incidence, severity and distribution of the deformities appear to increase with the dose of the hormone. It has been observed that the hypoglycaemia caused by insulin injection is not counteracted till about the twelfth day of incubation, presumably because of excessive accumulation of glycogen in the yolk-sac membrane immediately after the injection, and because of lack of glycogen storage in the embryonic liver and the absence of active secretion in the endocrine glands concerned with the carbohydrate metabolism of the embryo. It has been suggested that this unchecked hypoglycaemia may deprive the mesenchyme, pre-cartilage and cartilage of glycogen and mucopolysaccharides (chondroiten-sulphuric acid complexes), depending on the time of injection and the dose of insulin, and thus not only give rise to a variety of single and multiple deformities in the cartilaginous skeleton but also interfere with the normal endochondral ossification, resulting in a generalised developmental disturbance of bone resembling osteogenesis imperfecta in the human. 7. Insulin-induced abnormalities can be prevented to a remarkable extent by injecting nicotinamide and riboflavin into eggs along with insulin. 8. The question of the practical application of the knowledge gained from experimental observations on insulin-induced developmental abnormalities in explaining the possible causation of congenital anomalies in humans by genetic and environmental teratogenic factors, has been discussed. It is suggested that the orderly progression from the mesenchymatous condensation to cartilage, and then through calcified cartilage to bone, may be disturbed by these teratogenic factors at critical phases during the development of the embryo, and a variety of single and multiple skeletal deformities may thus be induced. 9. A plea is made for routine pathological and radiological examination of aborted foetuses and stillborn infants more or less on the lines followed for experimentally induced deformities with a view to applying the knowledge gained from animal experiments to a better understanding of the etiology and pathology of human congenital anomalies. 10. As regards the possible prevention of these deformities, it is not always easy to offer sound eugenic advice in the cases of congenital malformations determined partly or completely by genetic factors, for two important reasons. First, it is often difficult to distinguish between genetically determined congenital anomalies and their phenocopies. Secondly, genetically determined developmental defects sometimes show surprisingly variable expressivity and penetrance. For the conditions in which both genetic and environmental factors are involved, the most profitable immediate line of attack would be on the environmental factors. A relatively simpler problem is presented by the malformations which are, for all practical purposes, entirely caused by environmental factors. Measures to prevent congenital anomalies caused by prenatal rubella, such as exposure of girls to the disease during childhood and protection of pregnant women during the early stages of pregnancy by immune serum, are under active consideration. 11 . Further energetic investigation of the causes of permaturity, stillbirths, monstrosities and congenital malformations is urgently needed, before embarking on a successful programme for prevention. "The day of successful prophylaxis is not yet, but it is much nearer than seemed possible a few years ago."

Aims

The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels.

Aims

We analyzed the long-term outcomes of patients observed over ten years after resection en bloc and reconstruction with extracorporeal irradiated autografts

Aims

The consensus is that bipolar hemiarthroplasty (BHA) in allograft-prosthesis composite (APC) reconstruction of the proximal femur following primary tumour resection provides more stability than total hip arthroplasty (THA). However, no comparative study has been performed. In this study, we have compared the outcome and complication rates of these two methods.

Aims

Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure.