We have performed a prospective double-blind, randomised controlled trial over two years to evaluate the efficacy and safety of an intra-operative peri-articular injection of triamcinolone acetonide in patients undergoing medial unicondylar knee replacement. We randomised 90 patients into two equal groups. The study group received an injection of triamcinolone acetonide, bupivacaine, and epinephrine into the peri-articular tissues at the end of the operation. The control group received the same injection mixture but without the addition of triamcinolone. The peri-operative analgesic regimen was standardised.

The study group reported a significant reduction in pain (p = 0.014 at 12 hours, p = 0.031 at 18 hours and p = 0.031 at 24 hours) and had a better range of movement (p = 0.023 at three months). There was no significant difference in the rate of infection and no incidence of tendon rupture in either group.

The addition of corticosteroid to the peri-articular injection after unicondylar knee replacement had both immediate and short-term benefits in terms of relief from pain, and rehabilitation with no increased risk of infection.

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p = 0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.

Despite local treatment with systemic chemotherapy in Ewing’s sarcoma family tumours (ESFT), patients with detectable metastases at presentation have a markedly worse prognosis than those with apparently localised disease. We investigated the clinical, pathological and laboratory differences in 888 patients with ESFT, 702 with localised disease and 186 with overt metastases at presentation, seen at our institution between 1983 and 2006.

Multivariate analyses showed that location in the pelvis, a high level of serum lactic dehydrogenase, the presence of fever and a short interval between the onset of symptoms and diagnosis were indicative of metastatic disease. The rate of overt metastases at presentation was 10% without these four risk factors, 22.7% with one, 31.4% with two, and 50% for those with three or four factors. We concluded that in ESFT the site, the serum level of lactic dehydrogenase, fever, and the interval between the onset of symptoms and diagnosis are indicators of tumours having a particularly aggressive metastatic behaviour.

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells.

Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation.

A rat model of lumbar root constriction with an additional sympathectomy in some animals was used to assess whether the sympathetic nerves influenced radicular pain. Behavioural tests were undertaken before and after the operation.

On the 28th post-operative day, both dorsal root ganglia and the spinal roots of L4 and L5 were removed, frozen and sectioned on a cryostat (8 μm to 10 μm). Immunostaining was then performed with antibodies to tyrosine hydroxylase (TH) according to the Avidin Biotin Complex method. In order to quantify the presence of sympathetic nerve fibres, we counted TH-immunoreactive fibres in the dorsal root ganglia using a light microscope equipped with a micrometer graticule (10 x 10 squares, 500 mm x 500 mm). We counted the squares of the graticule which contained TH-immunoreactive fibres for each of five randomly-selected sections of the dorsal root ganglia.

The root constriction group showed mechanical allodynia and thermal hyperalgesia. In this group, TH-immunoreactive fibres were abundant in the ipsilateral dorsal root ganglia at L5 and L4 compared with the opposite side. In the sympathectomy group, mechanical hypersensitivity was attenuated significantly.

We consider that the sympathetic nervous system plays an important role in the generation of radicular pain.

We have studied the effects of bupivacaine on human and bovine articular chondrocytes in vitro. Time-lapse confocal microscopy of human articular chondrocytes showed > 95% cellular death after exposure to 0.5% bupivacaine for 30 minutes. Human and bovine chondrocytes exposed to 0.25% bupivacaine had a time-dependent reduction in viability, with longer exposure times resulting in higher cytotoxicity. Cellular death continued even after removal of 0.25% bupivacaine. After exposure to 0.25% bupivacaine for 15 minutes, flow cytometry showed bovine chondrocyte viability to be 41% of saline control after seven days. After exposure to 0.125% bupivacaine for up to 60 minutes, the viability of both bovine and human chondrocytes was similar to that of control groups.

These data show that prolonged exposure 0.5% and 0.25% bupivacaine solutions are potentially chondrotoxic.

We studied bone-tendon healing using immunohistochemical methods in a rabbit model.

Reconstruction of the anterior cruciate ligament was undertaken using semitendinosus tendon in 20 rabbits. Immunohistochemical evaluations were performed at one, two, four and eight weeks after the operation. The expression of CD31, RAM-11, VEGF, b-FGF, S-100 protein and collagen I, II and III in the bone-tendon interface was very similar to that in the endochondral ossification. Some of the type-III collagen in the outer layer of the graft, which was deposited at a very early phase after the operation, was believed to have matured into Sharpey-like fibres. However, remodelling of the tendon grafted into the bone tunnel was significantly delayed when compared with this ossification process. To promote healing, we believe that it is necessary to accelerate remodelling of the tendon, simultaneously with the augmentation of the ossification.

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches.

The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.

In order to clarify the role of cytokines in the remodelling of the grafted tendon for ligament reconstruction we compared the responses to interleukin (IL)-1β, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-β1 of extrinsic fibroblasts infiltrating the frozen-thawed patellar tendon in rats with that of the normal tendon fibroblasts, in regard to the gene expression of matrix metalloproteinase (MMP)-13, using Northern blot analysis. We also examined, immunohistologically, the local expression of IL-1β, PDGF-BB, and TGF-β1 in fibroblasts infiltrating the frozen-thawed patellar tendon.

Northern blot analysis showed that fibroblasts derived from the patellar tendon six weeks after the freeze-thaw procedure in situ showed less response to IL-1β than normal tendon fibroblasts with respect to MMP-13 mRNA gene expression. The immunohistological findings revealed that IL-1β was over-expressed in extrinsic fibroblasts which infiltrated the patellar tendon two and six weeks after the freeze-thaw procedure in situ, but neither PDGF-BB nor TGF-β1 was over-expressed in these extrinsic fibroblasts. Our findings indicated that IL-1β had a close relationship to matrix remodelling of the grafted tendon for ligament reconstruction, in addition to the commencement of inflammation during the tissue-healing process.

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (sd 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis.

We stably transfected early passage chondrocytes with an anti-apoptotic Bcl-2 gene in vitro using a retrovirus vector. Samples of articular cartilage were obtained from 11 patients with a mean age of 69 years (61 to 75) who were undergoing total knee replacement for osteoarthritis. The Bcl-2-gene-transfected chondrocytes were compared with non-transfected and lac-Z-gene-transfected chondrocytes, both of which were used as controls. All three groups of cultured chondrocytes were incubated with nitric oxide (NO) for ten days. Using the Trypan Blue exclusion assay, an enzyme-linked immunosorbent assay and flow cytometric analysis, we found that the number of apoptotic chondrocytes was significantly higher in the non-transfected and lac-Z-transfected groups than in the Bcl-2-transfected group (p < 0.05). The Bcl-2-transfected chondrocytes were protected from NO-induced impairment of proteoglycan synthesis.

We conclude that NO-induced chondrocyte death involves a mechanism which appears to be subject to regulation by an anti-apoptotic Bcl-2 gene. Therefore, Bcl-2 gene therapy may prove to be of therapeutic value in protecting human articular chondrocytes.

This prospective study evaluates the role of new laboratory markers in the diagnosis of deep implant infection in 78 patients (41 men and 37 women) with a revision total knee or hip replacement.

The mean age at the time of operation was 64.0 years (19 to 90). Intra-operative cultures showed that 21 patients had a septic and 57 an aseptic total joint replacement. The white blood cell count, the erythrocyte sedimentation rate and levels of C-reactive protein, interleukin-6, procalcitonin and tumour necrosis factor (TNF)-α were measured in blood samples before operation. The diagnostic cut-off values were determined by Received Operating Characteristic curve analysis.

C-reactive protein (> 3.2 md/dl) and interleukin-6 (> 12 pg/ml) have the highest sensitivity (0.95). Interleukin-6 is less specific than C-reactive protein (0.87 vs 0.96). Combining C-reactive protein and interleukin-6 identifies all patients with deep infection of the implant. Procalcitonin (> 0.3 ng/ml) and TNF-α (> 40 ng/ml) are very specific (0.98 vs 0.94) but have a low sensitivity (0.33 vs 0.43).

The combination of C-reactive protein and interleukin-6 measurement provide excellent screening tests for infection of a deep implant. A highly specific marker such as procalcitonin and pre-operative aspiration of the joint might be useful in identifying patients with true positive C-reactive protein and/or interleukin-6 levels.

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.

The subject of central nervous system damage includes a wide variety of problems, from the slow selective ‘picking off’ of characteristic sub-populations of neurons typical of neurodegenerative diseases, to the wholesale destruction of areas of brain and spinal cord seen in traumatic injury and stroke. Experimental repair strategies are diverse and the type of pathology dictates which approach will be appropriate. Damage may be to grey matter (loss of neurons), white matter (cutting of axons, leaving neurons otherwise intact, at least initially) or both. This review will consider four possible forms of treatment for repair of the human central nervous system.

We describe a method of reconstruction using tumour-bearing autograft treated by liquid nitrogen in 28 patients. The operative technique consisted of en bloc excision of the tumour, removal of soft tissue, curettage of the tumour, drilling and preparation for internal fixation or prosthetic replacement before incubation for 20 minutes in liquid nitrogen, thawing at room temperature for 15 minutes, thawing in distilled water for ten minutes, and internal fixation with an intramedullary nail, plate or composite use of prosthetic replacement. Bone graft or cement was used to augment bone strength when necessary.

The limb function was rated as excellent in 20 patients (71.4%), good in three (10.7%), fair in three (10.7%), and poor in two (7.1%). At the final follow-up six patients had died at a mean of 19.8 months after the operation, while 21 remained free from disease with a mean follow-up of 28.1 months (10 to 54). One patient is alive with disease. Bony union was seen at a mean of 6.7 months after the operation in 26 patients. Complications were encountered in seven patients, including three deep infections, two fractures, and two local recurrences. All were managed successfully. Our results suggest that this is a simple and effective method of biological reconstruction.

There is no diagnostic, non-invasive method for the early detection of loosening after total hip arthroplasty. In a pilot study, we have analysed two serum markers of bone remodelling, procollagen I C-terminal extension peptide (PICP) and cross-linked N-terminal telopeptide (NTx), as well as the diagnostic performance of NTx for the assessment of osteolysis. We recruited 21 patients with loosening (group I), 18 with a well-fixed prosthesis (group II) and 17 at the time of primary arthroplasty for osteoarthritis (OA) (group III). Internal normal reference ranges were obtained from 30 healthy subjects (group IV).

The serum PICP level was found to be significantly lower in patients with OA and those with loosening, when compared with those with stable implants, while the NTx level was significantly increased only in the group with loosening, suggesting that collagen degradation depended on the altered bone turnover induced by the implant. This hypothesis was reinforced by the finding that the values in the pre-surgery patients and stable subjects were comparable with the reference range of younger healthy subjects.

A high specificity and positive predictive value for NTx provided good diagnostic evidence of agreement between the test and the clinical and radiological evaluations. The NTx level could be used to indicate stability of the implant. However, further prospective, larger studies are necessary.

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors.

Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes.

There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism.