Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear. This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=11), and compares them with a control group with isolated long bone fractures (n=10). Serum was taken from these patients at five specific time intervals post injury (24hrs, 120hrs, 10 days, 6 weeks and 12 weeks). The time period most closely related to the end of the acute inflammatory reaction and the laying down of callus was the 10-day post injury time period. Serum samples taken at this time period were analysed for IGF-1 and TGF-β levels, both known to initiate osteoblastic activity, using ELISA kits. They were also exposed to an osteoblast cell culture line and cell proliferation was measured. Results show that the group with neurology has increased levels of IGF-1 compared to the other groups (p<
0.14, p<
0.18 respectively, Student’s t-test) but had lower TGF- (p<
0.05, p<
0.006) and osteoblast proliferation levels (p<
0.002, p<
0.001), despite having a significantly higher cell proliferation than a control group (p<
0.0001). When the neurology group is subdivided into complete (n=5) and incomplete (n=5), it was shown that the complete group had higher levels of both IGF-1 and TGF-. This trend is reversed in the osteoblast proliferation assay. This work, for the first time in human subjects, identifies a factor which may be regulating this complication of acute spinal cord injuries, namely IGF-1. Furthermore, the observed trend in the two cytokines seen in the complete neurology group may suggest a role for TGF-β. However, the results do show that a direct mediation of this unwanted side effect of spinal cord injuries is unlikely as seen in the proliferation assay. Further work remains to be done to fully understand the complexities of the excessive bone growth recognised in this patient group.
Aseptic loosening is currently the leading cause of failure of total hip arthroplasty. The aetiology of periprosthetic bone resorption is currently under intense investigation. Wear particles are produced from the articulating surface of the femoral and acetabular components. These particles gain access to the bone-cement interface where they are phagocytosed by macrophages. Particle stimulated macrophages differentiate into bone resorping osteoclasts. This leads to periprosthetic bone resorption and subsequent implant loosening. Nuclear factor kappa B (NFκB) is a transcription factor known to be activated by pathogenic stimuli in a variety of cells. The activation of NFkB would appear to be the primary event in the activation of particle stimulated macrophages in the periprosthetic membrane. NFκB subsequently causes a cascade of events leading to the release of bone resorbing cytokines, namely interleukin-6 (IL-6) and tumour necrosis factor α (TNFα). The aim of our study was to ascertain if bone resorption could be prevented in vitro by the addition of PDTC, an NFkB inhibitor to particle stimulated macrophages. Human monocytes were isolated and cultured from healthy volunteers. The monocyte/macrophage cell line was differentiated into osteoclasts by the addition of alumina particles and allowed to adhere onto bone slices. The NFkB inhibitor, PDTC, has added to the cultured osteoclasts. Bone resorption was analysed by counting the number of resorption pits in each bone slice. The addition of PDTC to stimulated macrophages reduced the number of resorption pits by greater than 40% compared to control. This is a unique and promising finding that may offer a future therapeutic strategy for the prevention of periprosthetic bone resorption and therefore aseptic loosening in total hip arthoplasty.
Aseptic loosening has become the single most important long-term complication of total joint replacements. The pathophysiology of this loosening is multifactorial in origin ranging from mechanical wear, poor surgical technique, thermal damage and the inflammatory response to particulate wear debris. Cytokines are released in response to macrophage activation by particulate wear debris (PWD), the resultant inflammatory cascade stimulates osteoclastic resorption of bone. The failure of remodelling and repair mechanisms may be as a result of Osteonecrosis from cement (PMMA).
Dupuytren’s disease is a benign fibroproliferative disease of unknown aetiology. It is often familial and commonly affects Northern European Caucasian men, but genetic studies have yet to identify the relevant genes. Transforming growth factor beta one (TGF-β1) is a multifunctional cytokine which plays a central role in wound healing and fibrosis. It stimulates the proliferation of fibroblasts and the deposition of extracellular matrix. Previous studies have implicated TGF-β1 in Dupuytren’s disease, suggesting that it may represent a candidate susceptibility gene for this condition. We have investigated the association of four common single nucleotide polymorphisms in TGF-β1 with the risk of developing Dupuytren’s disease. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping TGF-β1 polymorphisms. DNA samples from 135 patients with Dupuytren’s disease and 200 control subjects were examined. There was no statistically significant difference in TGF-β1 genotype or allele frequency distributions between the patients and controls for the codons 10, 25, −509 and −800 polymorphisms. Our observations suggest that common TGF-β1 polymorphisms are not associated with a risk of developing Dupuytren’s disease. These data should be interpreted with caution since the lack of association was shown in only one series of patients with only known, common polymorphisms of TGF-β1. To our knowledge, this is the first report of a case-control association study in Dupuytren’s disease using single nucleotide polymorphisms in TGF-β1.
Traditional biomedical/ergonomic occupational interventions to reduce work loss show limited success. Attention is now focussing on tackling the psychosocial factors that influence occupational back pain. A workforce survey of Glaxo Smith Kline (reported to the Society last year) established that clinical and occupational psychosocial factors (yellow &
blue flags) act independently and may represent obstacles to recovery. Consequently, a nurse-led intervention was devised. Occupational nurses at two manufacturing sites were trained to identify both clinical and occupational psychosocial factors, and address them using a basic ‘counselling’ technique that reinforces evidence-based messages and advice, along with availability of modified work. The program should ideally be implemented within the first days of absence, with ‘case-management’ by the nurse for a further 4 weeks. Control sites simply offer ‘usual management’. Outcomes at 12-month follow-up are rates for work loss/work retention. The target for contacting the worker (3 days) was achieved at one site, but not the other (mean 12 days), thus exerting a differential delay in delivering the intervention. The lack of early identification at the second site was due to local reporting/recording mechanisms. This study reveals a third class of obstacles to recovery – black flags – company policies/procedures that can impede occupational rehabilitation programs.
Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E2 (PGE2) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p <
0.006 and p <
0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.
A bipolar spacer was inserted for severe arthritic destruction of the shoulder in 14 patients, and followed up for a mean of 5.9 years. In one patient the operation failed because of infection. Two others required revision for loss of low-friction properties which caused loosening of the humeral component. At the end of the follow-up all the patients showed improvement. The Hospital for Special Surgery pain score had increased from 5.3 to 18.9 and the movement score from 7.5 to 20.1.
We dissected 105 cadaveric shoulders to study the origin of the tendon of the long head of biceps, and examined histologically the interrelationship between the tendon, the supraglenoid tubercle and the superior labrum of the glenoid. In all specimens approximately 50% of the biceps tendon arose directly from the superior glenoid labrum with the remainder attached to the supraglenoid tubercle. The main labral origin was from the posterior labrum in more than half of the specimens, and in a quarter this was the only labral attachment. On the basis of the biceps attachment to the anterior or posterior labrum, we distinguished four types of origin. These normal anatomical variations are significant for arthroscopic diagnosis and may help to explain the various patterns of injury seen in partial or complete detachment of the tendon, the labrum or both.
The long-term functional result of exposed total knee arthroplasty, treated by flap cover, is presented and the results compared with those of a randomly selected control group. The wound was successfully covered and the prosthesis was preserved in 76% of cases, but the final functional score was not as good as in those with primary wound healing.
Augmentation of the acetabular component of total hip replacements is a method of increasing stability and preventing recurrent dislocation. We report a series of mechanical experiments designed to evaluate the turning moments and angles required to dislocate standard, long posterior wall and two different augmented prostheses.
Thirty-three patients with impingement syndrome of the rotator cuff were studied before and at operation. It was shown that the rotator cuff lengthens and twists during elevation of the arm. Elevation is achieved by early glenohumeral abduction and continuous flexion and external rotation. The range of free rotation at the glenohumeral joint diminishes progressively during elevation. Rotator cuff impingement occurs towards the end of the early glenohumeral abduction. Excision arthroplasty of the acromioclavicular joint and anterior acromioplasty is highly effective for impingement under the acromion, but only moderately effective where impingement is under the acromioclavicular joint.
Major ruptures of the rotator cuff were repaired in 89 patients over a six-year period, using an approach through the split deltoid muscle and the bed of the excised outer centimetre of the clavicle. Review of these patients showed that poor results were associated with larger cuff defects, with more pre-operative steroid injections and with pre-operative weakness of the deltoid muscle. A randomised prospective study showed that repair followed by splinting in abduction gave no better results than repair followed by resting the arm at the side. Excision of the coraco-acromial ligament was associated with worse results than leaving its divided halves in situ. Follow-up showed that the results continued to improve for two years after operation; their quality was maintained in patients less than 60 years old, but in those over 60 there was deterioration with time.
Non-operative management has frequently been adopted for closed injuries of the infraclavicular brachial plexus and its branches in the belief that spontaneous recovery is likely to occur, and surgical exploration is performed only if recovery has not occurred in the expected time. This paper correlates the clinical and electrophysiological features with the operative findings in six patients with such injuries. The axillary nerve was ruptured in all six patients, the musculocutaneous nerve in two and the radial nerve in two. When the muscles supplied by a branch of the plexus were denervated, the differentiation between rupture of that branch and a lesion in continuity could only be made by surgical exploration, which should be performed as soon as other injuries permit.