We performed a retrospective review of the case notes of 84 consecutive patients who had suffered a severe (Gustilo IIIb or IIIc) open fracture of the tibia after blunt trauma between 1990 and 1998. All had been treated by a radical protocol which included early soft-tissue cover with a muscle flap by a combined orthopaedic and plastic surgery service. Our ideal management is a radical debridement of the wound outside the zone of injury, skeletal stabilisation and early soft-tissue cover with a vascularised muscle flap. All patients were followed clinically and radiologically to union or for one year.

After exclusion of four patients (one unrelated death and three patients lost to follow-up), we reviewed 80 patients with 84 fractures. There were 67 men and 13 women with a mean age of 37 years (3 to 89). Five injuries were grade IIIc and 79 grade IIIb; 12 were site 41, 43 were site 42 and 29 were site 43. Debridement and stabilisation of the fracture were invariably performed immediately. In 33 cases the soft-tissue reconstruction was also completed in a single stage, while in a further 30 it was achieved within 72 hours. In the remaining 21 there was a delay beyond 72 hours, often for critical reasons unrelated to the limb injury. All grade-IIIc injuries underwent immediate vascular reconstruction, with an immediate cover by a flap in two. All were salvaged. There were four amputations, one early, one mid-term and two late, giving a final rate of limb salvage of 95%. Overall, nine pedicled and 75 free muscle flaps were used; the rate of flap failure was 3.5%. Stabilisation of the fracture was achieved with 19 external and 65 internal fixation devices (nails or plates). Three patients had significant segmental defects and required bone-transport procedures to achieve bony union. Of the rest, 51 fractures (66%) progressed to primary bony union while 26 (34%) required a bone-stimulating procedure to achieve this outcome. Overall, there was a rate of superficial infection of the skin graft of 6%, of deep infection at the site of the fracture of 9.5%, and of serious pin-track infection of 37% in the external fixator group. At final review all patients were walking freely on united fractures with no evidence of infection.

The treatment of these very severe injuries by an aggressive combined orthopaedic and plastic surgical approach provides good results; immediate internal fixation and healthy soft-tissue cover with a muscle flap is safe. Indeed, delay in cover (> 72 hours) was associated with most of the problems. External fixation was associated with practical difficulties for the plastic surgeons, a number of chronic pin-track infections and our only cases of malunion. We prefer to use internal fixation. We recommend primary referral to a specialist centre whenever possible. If local factors prevent this we suggest that after discussion with the relevant centre, initial debridement and bridging external fixation, followed by transfer, is the safest procedure.

We assessed factors which may affect union in 32 patients with nonunion of a fracture of the diaphysis of the femur and 67 comparable patients whose fracture had united. These included gender, age, smoking habit, the use of non-steroidal anti-inflammatory drugs (NSAIDs) the type of fracture (AO classification), soft-tissue injury (open or closed), the type of nail, the mode of locking, reaming v non-reaming, infection, failure of the implant, distraction at the fracture site, and the time to full weight-bearing. Patients with severe head injuries were excluded. Both groups were comparable with regard to gender, Injury Severity Score and soft-tissue injury.

There was no relationship between the rate of union and the type of implant, mode of locking, reaming, distraction or smoking. There were fewer cases of nonunion in more comminuted fractures (type C) and in patients who were able to bear weight early. There was a marked association between nonunion and the use of NSAIDs after injury (p = 0.000001) and delayed healing was noted in patients who took NSAIDs and whose fractures had united.

It has been suggested that reamed intramedullary nailing of the femur should be avoided in some patients with multiple injuries. We have studied prospectively the effect of femoral reaming on the inflammatory process as implicated in the pathogenesis of acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF). We studied changes in the levels of serum interleukin-6 (IL-6) (proinflammatory cytokine), neutrophil CD11b (C3) receptor expression (activated neutrophil adhesion molecule), serum soluble intracellular adhesion molecule (s-ICAM-1), serum soluble E-selectin (the soluble products of endothelial adhesion molecules) and plasma elastase (neutrophil protease) in a series of patients with femoral fractures treated by nailing. We have also compared reamed nailing with unreamed nailing.

We found that the levels of serum IL-6 and elastase rose significantly during the nailing procedure indicating a measurable ‘second hit’. There was no clear response in leukocyte activation and no difference in the release of endothelial adhesion molecule markers. There was no significant difference between groups treated by reamed and unreamed nailing. Although clinically unremarkable, the one patient who died from ARDS was shown to be hyperstimulated after injury and again after nailing, suggesting the importance of an excessive inflammatory reaction in the pathogenesis of these serious problems.

Our findings have shown that there is a second hit associated with femoral nailing and suggest that the degree of the inflammatory reaction may be important in the pathogenesis of ARDS and MOF.

We obtained samples of spinal accessory nerve from patients undergoing radical surgery for tumours or nerve grafting in the neck. These were analysed by light and electron microscopy for the type of fibre. All contained fibres consistent with non-proprioceptive sensory function including pain.

We have studied the influence of weight-bearing on the measurement of wear of the polyethylene acetabular component in total hip arthroplasty using two techniques. The measured vertical wear was significantly greater when radiographs were taken weight-bearing rather than with the patient supine (p = 0.001, method 1; p = 0.007, method 2). Calculations of rates of linear wear of the acetabular component were significantly underestimated (p < 0.05) when radiographs were taken supine. There are two reasons for this. First, a change in pelvic orientation when bearing weight ensures that the thinnest polyethylene is brought into relief, and secondly, the head of the femoral component assumes the position of maximal displacement along its wear path. Interpretation of previous studies on both linear and volumetric polyethylene wear in total hip arthroplasty should be reassessed in the light of these findings.

Particulate wear debris is associated with periprosthetic inflammation and loosening in total joint arthroplasty. We tested the effects of titanium alloy (Ti-alloy) and PMMA particles on monocyte/macrophage expression of the C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), monocyte inflammatory protein-1 alpha (MIP-1α), and regulated upon activation normal T expressed and secreted protein (RANTES). Periprosthetic granulomatous tissue was analysed for expression of macrophage chemokines by immunohistochemistry. Chemokine expression in human monocytes/macrophages exposed to Ti-alloy and PMMA particles in vitro was determined by RT-PCR, ELISA and monocyte migration.

We observed MCP-1 and MIP-1α expression in all tissue samples from failed arthroplasties. Ti-alloy and PMMA particles increased expression of MCP-1 and MIP-1α in macrophages in vitro in a dose- and time-dependent manner whereas RANTES was not detected. mRNA signal levels for MCP-1 and MIP-1α were also observed in cells after exposure to particles. Monocyte migration was stimulated by culture medium collected from macrophages exposed to Ti-alloy and PMMA particles. Antibodies to MCP-1 and MIP-1α inhibited chemotactic activity of the culture medium samples.

Release of C-C chemokines by macrophages in response to wear particles may contribute to chronic inflammation at the bone-implant interface in total joint arthroplasty.

The interactions between the different cell types in periprosthetic tissue are still unclear. We used a non-contact coculture model to investigate the effects of polymethylmethacrylate (PMMA) particles and human macrophage-derived soluble mediators on fibroblast activation. Macrophages were either exposed or not exposed to phagocytosable PMMA particles, but fibroblasts were not. Increasing numbers of macrophages were tested in cocultures in which the fibroblast cell number was held constant and cultures of macrophages alone were used for comparison of cytokine release. We used the release of interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α), lysosomal enzyme and metalloproteinase activity to assess the cultivation of macrophages and fibroblasts.

In cocultures, IL-6 release was increased 100-fold for both unchallenged and particle-challenged cultures when compared with macrophage cultures alone. Furthermore, particle-challenged cocultures had threefold higher IL-6 levels than unchallenged cocultures. Release of TNF-α was similar in cocultures and in macrophage cultures. IL-1β release in cocultures was independent of the macrophage-fibroblast ratio. Lysosomal enzyme activity and metalloproteinase activity were increased in cocultures.

Our data show that macrophages and fibroblasts in coculture significantly increase the release of IL-6 and to a less degree other inflammatory mediators; particle exposure accentuates this effect. This suggests that macrophage accumulation in fibrous tissue may lead to elevated IL-6 levels that are much higher than those caused by particle activation of macrophages alone. This macrophage-fibroblast interaction represents a novel concept for the initiation and maintenance of the inflammatory process in periprosthetic membranes.

We exposed human macrophages isolated from the peripheral blood of healthy donors to metal and bone-cement particles from 0.2 to 10 μm in size.

Zymography showed that macrophages exposed to titanium alloy and polymethylmethacrylate (PMMA) particles released a 92- and 72-kDa gelatinase in a dose- and time-dependent manner. Western immunoblotting confirmed that the 92- and 72-kDa gelatinolytic activities corresponded to matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9, MMP-2), respectively. Western immunoblotting also indicated that titanium alloy and PMMA particles increased the release of MMP-1. Northern blotting showed elevated mRNA signal levels for MMP-1, MMP-2, and MMP-9 after exposure to both types of particle. Collagenolytic activity also increased in the macrophage culture medium in response to both types of particle.

Our findings support the hypothesis that macrophages release MMPs in proportion to the amount of particulate debris within periprosthetic tissues.

We performed a retrospective analysis to evaluate the ability of whole-body ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) to identify local recurrence and pulmonary metastases in patients with soft-tissue tumours after treatment. We compared the results of FDG PET with those of MRI for the detection of local recurrence, and with CT of the chest for pulmonary metastases.

We assessed 62 patients of mean age 51 years, who had 15 types of soft-tissue sarcoma, after a mean follow-up of 3 years 2 months. For the detection of local disease, 71 comparisons showed that the sensitivity and specificity of FDG PET were 73.7% and 94.3%, respectively; there were 14 true-positive and five false-negative results. MRI had a sensitivity and specificity of 88.2% and 96.0% respectively. For the identification of lung metastases, 70 comparisons showed that the sensitivity and specificity of FDG PET were 86.7% and 100%, with 13 true-positive results and two false-negative results. CT of the chest had a sensitivity and specificity of 100% and 96.4%. Thirteen other sites of metastases were identified by FDG PET.

FDG PET can identify both local and distant recurrence of tumour as a one-step procedure and will detect other metastases. It seems that all three methods of imaging are needed to define accurately the extent of disease, both at initial staging and during follow-up.