Ischaemic preconditioning is a process by which exposure of a tissue to a short period of non-damaging ischaemic stress leads to resistance to the deleterious effects of a subsequent prolonged ischaemic stress. It has been extensively described in the heart, but few studies have examined the possibility that it can occur in skeletal muscle. We have used a rat model of ischaemia of one limb to examine this possibility. Exposure of the hind limb to a period of ischaemia of five minutes and reperfusion for five minutes significantly protected the tibialis anterior muscle against the structural damage induced by a subsequent period of limb ischaemia for four hours and reperfusion for one hour. This protection was evident on examination of the muscle by both light and electron microscopy. Longer or shorter times of prior ischaemia had no effect

Immobilisation causes denervation-like changes in the motor endplates, decreases the content of IGF-I, and increases the number of IGF-I receptors in the spinal cord. In the rat we investigated whether similar changes occur after a fracture of the midshaft of the femur which had been treated by intramedullary fixation with adequate or undersized pins. A more pronounced reduction in muscle wet weight was seen after fixation by undersized pins as well as decreased ash density of the ipsilateral tibia which did not completely return to normal within the 12-week experimental period. The nicotinic cholinergic receptors in the motor endplates of tibialis anterior were increased (p < 0.01) and there was a significant increase (p < 0.02) in IGF-I receptors in the lumbar spinal cord ipsilateral to the fracture after treatment by undersized nails. These changes may be associated with the impaired proprioception, co-ordination and motor activity which are sometimes seen after fractures

We have previously shown that prior exposure of rat hind limbs to ischaemia for five minutes and reperfusion for five minutes reduced the structural damage to skeletal muscle which followed a subsequent period of ischaemia for four hours and reperfusion for one hour. We have now examined the potential mechanisms by which this ischaemic preconditioning protocol may be effective in reducing damage to skeletal muscle induced by prolonged ischaemia and reperfusion. Prior exposure of the hindlimb to ischaemia for five minutes and reperfusion for five minutes did not prevent the fall in the ATP content of tibialis anterior which occurred after a subsequent period of ischaemia for four hours and reperfusion for one hour. Similarly, no effect of the preconditioning protocol was seen on the elevated muscle myeloperoxidase, indicative of an elevated neutrophil content, or abnormal muscle cation content. Reperfused ischaemic muscle was also found to have an increased content of heat-shock protein (HSP) 72, but the preconditioning protocol did not further increase the content of this or other HSPs indicating that it was not acting by increasing the expression of these cytoprotective proteins. The protective effects of preconditioning appeared to be mimicked by the infusion of adenosine to animals immediately before exposure to the four-hour period, indicating a potential mechanism by which skeletal muscle may be preconditioned to maintain structural viability

Injection or aspiration of the ankle may be performed through either an anteromedial or an anterolateral approach for diagnostic or therapeutic reasons. We evaluated the success of an intra-articular puncture in relation to its site in 76 ankles from 38 cadavers. Two orthopaedic surgical trainees each injected methylene blue dye into 18 of 38 ankles through an anterolateral approach and into 20 of 38 through an anteromedial. An arthrotomy was then performed to confirm the placement of the dye within the joint.

Of the anteromedial injections 31 of 40 (77.5%, 95% confidence interval (CI) 64.6 to 90.4) were successful as were 31 of 36 (86.1%, 95% CI 74.8 to 97.4) anterolateral injections. In total 62 of 76 (81.6%, 95% CI 72.9 to 90.3) of the injections were intra-articular with a trend towards greater accuracy with the anterolateral approach, but this difference was not statistically significant (p = 0.25). In the case of trainee A, 16 of 20 anteromedial injections and 14 of 18 anterolateral punctures were intra-articular. Trainee B made successful intra-articular punctures in 15 of 20 anteromedial and 17 of 18 anterolateral approaches. There was no significant difference between them (p = 0.5 and p = 0.16 for the anteromedial and anterolateral approaches, respectively). These results were similar to those of other reported studies. Unintended peri-articular injection can cause complications and an unsuccessful aspiration can delay diagnosis. Placement of the needle may be aided by the use of ultrasonographic scanning or fluoroscopy which may be required in certain instances.

We evaluated two reconstruction techniques for a simulated posterolateral corner injury on ten pairs of cadaver knees. Specimens were mounted at 30° and 90° of knee flexion to record external rotation and varus movement. Instability was created by transversely sectioning the lateral collateral ligament at its midpoint and the popliteus tendon was released at the lateral femoral condyle. The left knee was randomly assigned for reconstruction using either a combined or fibula-based treatment with the right knee receiving the other. After sectioning, laxity increased in all the specimens. Each technique restored external rotatory and varus stability at both flexion angles to levels similar to the intact condition. For the fibula-based reconstruction method, varus laxity at 30° of knee flexion did not differ from the intact state, but was significantly less than after the combined method.

Both the fibula-based and combined posterolateral reconstruction techniques are equally effective in restoring stability following the simulated injury.

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff.

We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis).

The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears.

These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.

The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry.

We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008).

These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies.