Pathological conditions of the hip joint may present with variable patterns of pain referral in the lower limb. Literature reports suggest that up to 35% of total hip arthroplasties are performed on patients whose primary compliant is obturator nerve referred “knee pain”. However the effect of varied pain patterns on patient outcome and satisfaction has not previously been examined. This prospective study was undertaken to determine the most common referral patterns of hip pain in patients scheduled to undergo primary total hip replacement and to examine whether initial pain referral pattern predicted ultimate patient outcome. Patients were assessed using the Harris Hip score, SF 36 and WOMAC scoring systems measured preoperatively, at 6 months, 1 and 2 years post operatively.

236 patients were identified with isolated single hip joint disease. Patients who demonstrated multi joint disease, and particularly ipsilateral knee pathology were excluded. Forty-five percent of patients with primary hip disease had pain primarily at or about the knee. There was no difference in preoperative demographics, physical function, social function, perceived general health, Harris Hip score (p=0.74), SF 36 (p=0.66) or WOMAC scores (p=0.81) between the pain pattern groups. Operator status and operative techniques were comparable. At 1 and 2 years postoperatively the groin and thigh pain groups were similar in all respects. However at 6 months, 12 months and 2 years, Harris hip scores (p=0.04, p=0.037, p=0.021) and SF 36 scores (p=0.035, p=0.027, p=0.01) were significantly lower in those patients presenting initially with knee pain. Multivariate regression analysis confirmed that no other confounding variables could account for the observed differences between the groups. These results indicate that, using current outcome measures, patients with “knee pain” who undergo total hip arthroplasty, and in whom ipsilateral knee disease has been excluded, have poorer long-term physical and social function and perceived general health. We believe this is the first report of its kind and suggest that patient and surgeon expectations of the results of total hip arthroplasty should be tailored according to the individual initial pain referral pattern.

Management of symptomatic residual acetabular dysplasia in adolescence and early adulthood remains a major therapeutic challenge. At our unit the two senior authors review all patients preoperatively and simultaneously perform each procedure. In the four years from 1998 forty-three Bernese osteotomies were performed in 40 patients with residual acetabular dysplasia. The mean average age at surgery was 21 years (range 12 – 43 years) and there were 34 female patients. The indication for surgery was symptomatic hip dysplasia (all idiopathic but for one male with a history of slipped capital femoral epiphysis) presenting with pain and restricted ambulation. 4 patients had previous surgery on the affected hip (2 Salter’s osteotomy, one Shelf procedure and one proximal femoral osteotomy). 27.5% of patients had symptomatic bilateral disease. 42% of patients had Severin class IV or V dysplasia at presentation. 100% of patients had preservation of the hip joint at last follow-up evaluation (mean 2.4 years), with excellent results in 82%, an average post-operative Harris hip score of 96, and an average d’Aubigne hip score of 16.1. The mean post-operative improvements in radiographic measures were as follows: Anterior centre edge angle +19.4°, Lateral centre angle +25.8°, Acetabular Index – 10.7°. Head to Ischial distance – 7.3mm. Surgical operative time decreased from 128 minutes to 43 minutes from the first to the most recent case. Average blood loss has reduced from 1850mls to 420mls over the four years experience. Predonation of 2 units of blood requested from all patients with baseline hemoglobin of > 12g/dl. When combined with intraoperative cell salvage the need for transfusion of homologous blood has been eliminated. All complications occurred in the first 9 patients: (one major – iliac vein injury requiring no further treatment; four moderate – lateral cutaneous nerve injuries; four minor – asymptomatic heterotopic ossification). Our experience confirms that the Ganz peri-acetabular osteotomy is an efficacious procedure for the treatment of the residually dysplastic hip, providing excellent clinical results, where early intervention is the key to improved outcome. It is a technically demanding procedure with a significant early learning curve and we believe that a two-surgeon approach is invaluable to the management of these difficult cases.

Background: Circulating endothelial precursor cells (CEPS) are thought to play a role in postnatal angiogenesis. We investigated the angiogenic stress of musculoskeletal trauma on CEP kinetics in trauma patients and their bone marrow progenitor populations in a murine model.

Methods: Peripheral blood mononuclear cells (PB-MNCs) were isolated from patients (n=12) on consecutive days following closed lower-limb diaphyseal fractures. CEP levels, defined by the surface expression patterns of VEGFR2, CD34 and AC133 were determined and cytokine analysis of collected serum was performed. Bone marrow precursors defined by Ly-6A/E and c-Kit expression were harvested following traumatic insult from the murine model and quantified on flow cytometry. Human and murine progenitor populations were cultured on fibronectin and examined for markers of endothelial cell linage (Ulexeuropaeus- agglutinin- 1 binding and acetylated-LDL uptake) and cell morphology. Statistical analysis was performed using variance analysis.

Results: A consistent increase in human CEPs levels was noted within 72 hours of the initial insult, the percentage increase over day 1 reaching 300%.

Conclusion: We propose that musculoskeletal trauma through the release of chemokines such as VEGF, promotes rapid mobilisation of CEP from born marrow, which have the potential to contribute to reparative neovascularisation. Strategies to enhance CEPs kinetics may accelerate this process and offer a therapeutic role in aberrant fracture healing.

Introduction: Patients with multiple skeletal injuries are susceptible to Systemic Inflammatory Response Syndrome (SIRS) and consequently Acute Respiratory Distress Syndrome (ARDS). Fracture haematoma contains pro-inflammatory mediators. The aim of our study was to show in vitro that fracture haematoma is implicated in neutrophil mediated injury, SIRS, ARDS and MOF.

Methods: Fracture haematoma was isolated from 10 patients at the time of surgery. Neutrophils (PMN) were isolated from 10 healthy volunteers. PMN were exposed to the fracture haematoma supernatant and PMN activation in both primed and unprimed neutrophils were examined (CD11b and CD18 adhesion receptor expression and respiratory burst). PMN phagocytosis and apoptosis were also assessed using flow cytometry. Transmigration across an endothelial barrier was also measured following exposure to fracture haematoma.

Results: Fracture haematoma had a marked effect on respiratory burst in primed PMNs (control = 100% vs 20% fracture haematoma = 1044% ± 405, p=0.04). CD11b and CD18 adhesion receptor expression were not upregulated in the fracture haematoma group. PMN phagocytosis of E coli was increased following treatment with fracture haematoma (control = 100% vs fracture haematoma = 171% ± 6SE, p=0.0001). Transendothelial migration of treated neutrophils was unaffected. Treatment of endothelial monolayers with fracture haematoma did not result in upregulated ICAM1 expression but was observed to induce significant endothelial cell death. PMN apoptosis was significantly delayed following exposure to fracture haematoma (control = 46% ± 5 vs fracture haematoma = 8% ±2, p=0.0005).

Discussion: We have shown that fracture haematoma activates neutrophils, increases phagocytosis and respiratory burst whilst delaying apoptosis. These effects, whilst beneficial at the site of injury, may cause neutrophil mediated tissue injury systemically.

To determine whether systemic nitric oxide production in tourniquet-induced skeletal muscle ischaemia-reper-fusion injury (SMRI) is dependent on release of vascular endothelial growth factor (VEGF), a modulator of nitric oxide cytoprotection in myocardial ischaemia-reperfusion injury.

Mice were randomised (n=10 per group) into: time controls (no tourniquet) and test animals (bilateral hindlimb tourniquet ischaemia). Blood samples were collected in test animals prior to ischaemia and after reper-fusion. In controls, blood samples were collected at the same corresponding time points. Serum VEGF, nitric oxide metabolites (nitrite and nitrate) and the proinflammatory cytokine tumour necrosis factor (TNF)-α (an indicator of systemic inflammation) were determined. At the end of reperfusion, the lungs and muscle (right gastrocnemius) were harvested and tissue injury determined by measuring myeloperoxidase (MPO) activity, a marker of neutrophil infiltration. Data are presented as mean ± SEM and statistical comparison was performed using one-way analysis of variance (ANOVA) with significance attributed to P < 0.05.

In comparison to control animals, muscle (4.9±0.3 versus 4±0.03 units/g of wet tissue; P=0.02) and lung (16.7±1.9 versus 10.4±0.5; P=0.005) MPO activity at the end of repercussion was significantly greater in test animals. The table shows the results with respect to serum cytokine levels and nitricxide metabolites.

These data demonstrate that SMRI results in local and systemic proinflammatory responses. In contrast to myocardial ischaemia-reperfusion injury, nitric oxide production in tourniquet-induced SMRI is VEGF-independent. Alternative mechanisms for nitric oxide production in tourniquet-controlled extremity surgery requires further evaluation.

Introduction: Limb reperfusion in patients following pneumatic tourniquet-controlled surgery is associated with nitric oxide (NO) generation. Meanwhile, NO mediates vascular endothelial growth factor (VEGF)-cytoprotection in myocardial ischaemia-reperfusion injury. In addition, VEGF is contributory in attenuating skeletal muscle ischaemia-reperfusion injury (SMRI). Whether this effect of VEGF is NO-mediated in SMRI is unknown. We investigate whether systemic nitric oxide production in tourniquet-induced SMRI is dependent on VEGF release.

Methods: Anaesthetised male C57BL/6 mice were randomised (n=10 per group) into two groups: time controls (no tourniquet) and test animals with bilateral hindlimb tourniquets (SMRI; 2 hours of ischaemia, 2 hours of reperfusion). Blood samples were collected in test animals prior to ischaemia and after 2 hours of reperfusion. In controls, blood samples were collected at the same corresponding time points. Serum VEGF, nitric oxide metabolites (nitrite and nitrate) and the proinflammatory cytokine tumour necrosis fractor (TNF)-α (an indicator of systemic inflammation) were determined. At the end of reperfusion, the lungs and muscle (right gastrocnemius) were harvested and tissue injury determined by measuring myeloperoxidase (MPO) activity, a marker of neutrophil infiltration. Data are presented as mean ± SEM and statistical comparison was performed using one-way analysis of variance (ANOVA) with significance attributed to P,0.05.

Results: In comparison to control animals, both the muscle (4.9±0.3 versus 4±0.03 units/g of wet tissue; P=0.02) and lung (16.7±1.9 versus 10.4±0.5; P=0.005) MPO activity at the end of reperfusion was significantly greater in test animals.

Conclusions: Our data demonstrates that SMRI results in local and systemic proinflammatory responses. In contrast to myocardial ischaemia-reperfusion injury, nitric oxide production in tourniquet-induced SMRI is VEGF-independent. Alternative mechanisms for nitric oxide production in tourniquet-controlled limb surgery requires further evaluation.

Background: Low molecular weight heparins (LMWH) are of undoubted efficacy as thromboprophylaxis in orthopaedic surgical practice. However, prolonged dosage inhibits bone nodule formation in vitro and we have previously reported that daily dosing significantly delays fracture healing. To further investigate these phenomena we hypothesised that LMWH’s would reduce osteoblast survival and thus bone formation by inducing programmed cell death (apoptosis).

Methods: Primary human osteoblasts were isolated from femoral heads excised during hip arthoplasty and cultured to passage 3–5. These were examined for VEGF receptor expression using a biotinylated binding assay on flow cytometry. Osteoblasts were grown to confluence and then incubated for 24 hours in control medium or medium treated with enoxaparin (200 – 2X10(−4) IU/mL) or combination of enoxaparin (200 – 2X10 (−4) IU/mL) and VEGF (1ng/ml). Apoptosis was determined by measuring cytosolic histone-associated DNA fragmentation using an enzyme linked immunosorbant assay. Results were confirmed by DNA fragmentation analysis on agarose gel electrophoresis. Cell functional viability was measured by a tetrazolium bioreduction colorimetric assay.

Results: Data is expressed as percentage of control apoptosis or viability, illustrates mean ± s.e.m. and n=4 experiments in each case. ANOVA was employed for statistical analysis; *versus control, #versus enoxaparin treated; p< 0.05 was considered significant.

Conclusions: Therapeutic doses of LMWH attenuate osteo-blast survival by inducing significant apoptosis. This effect is partly abrogated by VEGF, which independently enhances osteoblast viability, thus delaying spontaneous and enoxaparin induced apoptosis. These findings may explain the bone resorptive effects of prolonged LMWH therapy and suggest a potential therapeutic role for VEGF in conditions of delayed bone formation.