We analysed the outcome of the Coonrad-Morrey total elbow replacement used for fracture of the distal humerus in elderly patients with no evidence of inflammatory arthritis and compared the results for early versus delayed treatment.

We studied a total of 32 patients with 15 in the early treatment group and 17 in the delayed treatment group. The mean follow-up was 56.1 months (18 to 88). The percentage of excellent to good results based on the Mayo elbow performance score was not significantly different, 84% in the early group and 79% in the delayed group. Subjective satisfaction was 92% in both the groups. One patient in the early group developed chronic regional pain syndrome and another type 4 aseptic loosening. Two elbows in the early group also showed type 1 radiological loosening. Two patients in the delayed group had an infection, two an ulnar nerve palsy, one developed heterotopic ossification and one type 4 aseptic loosening. Two elbows in this group also showed type 1 radiological loosening. The complication rates in the early and delayed treatment group were 13% and 29% respectively. The Kaplan-Meier survivorship analysis for the early and delayed treatment groups was 93% at 88 months and 76% at 84 months, respectively. No statistically significant difference was found between the two groups.

We conclude that total elbow replacement provides a preditable and reproducible outcome in terms of pain relief and functional range of movement in elderly osteoporotic patients with difficult distal humerus fractures.

Skeletal metastases are an increasing sequaelae for patients with a wide range of neoplastic lesions owing to the increasing incidences of cancer. The diagnosis of a skeletal metastasis is, however, at present a terminal diagnosis representing uncontrolled tumour dissemination. The metastatic destruction of the bone reduces its load bearing capabilities progressing to the principle orthopaedic complication, that of complete loss of cortical integrity.

Aim: We examine the population suffering a complication of skeletal metastasis in terms of their mortality and morbidity. We compare patients who underwent surgical stabilization as a result of a fracture through a metastatic lesion against those who underwent prophylactic stabilization.

This is a retrospective study of all patients within the Cardiff centre who underwent an operation for a metastatic bone lesion over a 10 year period (n=140). The patients were identified using pathological records created when samples were sent at the time of the operations. The patients were all followed up for a minimum of 24 months. The demographics of the patients were collected and a detailed analysis of the primary tumour, the surgical procedure, the mobility, and survival of the patients was undertaken. The patients data was then cross referenced with the database at the regional cancer centre and the post operative radiotherapy treatment regimen were collected.

Patients who underwent prophylactic surgical stabilization had a significant survival advantage compared to those stabilized following a fracture (p=0.002). The morbidity postoperatively, defined by the patients functional mobility, also shows the benefits of prophylactic stabilization with significantly improved mobility when compared to the mobility following fracture stabilization (p=0.033). It has also been shown that there is a significant postoperative survival benefit for those patients who were able to regain mobility (p< 0.01).

Our results show a significant survival benefit of prophylactic fixation rather than fixation following fracture which is in line with previous studies We have also, for the first time in a large number study, shown that there is a survival benefit for patients who are able to mobilize following surgery and if prophylactic stabilization was undertaken patients were significantly more mobile postoperatively.

Activated leukocyte cell adhesion molecule (ALCAM) has been shown to be involved in cell migration and in both homotypic/homophilic adhesion and heterotypic/heterophilic adhesion. It has been shown that a decreased level of ALCAM expression in human breast cancer tissue correlated with a significantly poor prognosis.

Aim: Previous studies have looked at nodal and general metastasis; in this analysis using an expanded tumour cohort, we, for the first time, specifically identified patients who went on to develop skeletal metastasis.

Primary breast cancer tissues (n=234) and non-neoplastic mammary tissue (n=34) were collected and patients were routinely followed up clinically after surgery. The immunohistochemical distribution and location of ALCAM was assessed in the normal breast tissue and carcinoma and the level of ALCAM transcripts in the frozen tissue was determined using real-time quantitative PCR. The results were analysed against the clinical data looking principally at the levels in patients with skeletal metastasis but also in relation to the nodal involvement, ER status, Nottingham Prognostic Index and survival.

The immunohistochemical staining intensity shows that the cytoplasmic staining in normal breast tissue is significantly stronger than that in breast cancer tissue (p=0.023) and also the breast cancer tissue from patients who went onto develop skeletal metastasis (p=0.048). The ALCAM transcript levels were the lowest in patient with skeletal metastasis (p=0.0048) compared to those who were disease free. Significantly lower transcript levels were also found the patients who developed local recurrence (p=0.040), and who died from breast cancer (p= 0.0075). Other indicators of poor prognosis show a significant difference: patients with moderate and poor NPI prognosis lower levels than those with a good prognosis (p=0.05, p=0.0089 respectively); and lower in patients with a positive ER status than those ER negative patients (p=0.043).

This study has for the first time shown that the patient who went on to develop skeletal metastasis tended to have the lowest levels of ALCAM transcript in their breast cancers. This fact could be used to provide patient with a more accurate prognosis and identify those who may benefit enhanced monitoring and early medical and orthopaedic treatment.

Paratenonitis describes inflammation of the paratenon and commonly presents as an overuse injury. The paratenon is the connective tissue sheath that surrounds tendons - including tendo Achilles, and serves to minimise friction with the outer layer of the tendon, the epitenon. Whilst this conjunction allows the tendon to glide smoothly on muscular contraction, the presentation of paratenonitis typically follows periods of frequent, repetitive musculoskeletal movements; hence, paratenonitis commonly afflicts the elite and, albeit to a lesser extent, amateur athlete. The extent to which friction at the epitenon-paratenon juncture contributes to this tendinopathy remains unclear, and this study is therefore concerned with the coefficient of friction and the lubrication regime.

By using a specially designed and validated apparatus, the in vivo paratenon-epitenon conjunction was approximated using bovine flexor tendon paratenon and a glass disc; this is being an equivalent experimental set-up to that used in other studies exploring soft tissue contacts. Bovine synovial fluid was used to lubricate the conjunction at 37 deg C, and the frictional characteristics were analysed over a range of sliding speeds and loads.

The coefficient of friction was found to generally lie between 0.1 – 0.01. This range suggests that a system of mixed lubrication applies - where the synovial fluid is causing partial separation of the two surfaces. However, when the data is plotted in the form of a Stribeck curve, the trend suggests that boundary lubrication prevails - where lubrication is determined by surface-bound proteins.

The coefficient of friction at the epitenon-paratenon interface appears to be approximately one order of magnitude greater than that typically reported within the healthy synovial joint. Additionally, the synovial joint is thought to exhibit some fluid film lubrication (i.e. total surface separation), whereas the epitenon-paratenon lubrication regime appears to vary only between the inferior mixed and boundary systems - depending on the specific biomechanical conditions. This data would suggest that the coefficient of friction at the epitenon-paratenon interface is relatively high and thus is potentially significant in the incidence of paratenonitis. Such a hypothesis could be of particular interest to sports-medicine and orthopaedic specialists.

Introduction: Monoclonal antibodies (mAbs) recognizing linear sulphation motifs in keratan sulphate (KS) were first developed in the early 1980’s. Over the years, ELISAs using 5-D-4 or other related anti-KS mAbs have been used in many studies monitoring increased cartilage aggrecan degradation with the onset of degenerative joint diseases. However, whilst these studies have in general been useful for monitoring some aspects of disease progression (usually in parallel with other biomarker assays), many longitudinal studies have shown efficacy in only the transient (early, mid or late) stages of the degenerative joint disease process. During the onset of degenerative joint disease, the pathological tissue attempts to repair/regenerate the cartilage, the chondrocytes thus synthesizing cartilage aggrecan with KS substitution [and chondroitin sulphate (CS) isomer composition] that is more like that found in developing or immature cartilage. This immature cartilage aggrecan contains much less KS substitution with shorter chain size and less linear sulphation motifs. Thus, during the different stages of degenerative joint disease progression one would expect to find variable changes in different linear sulphation epitopes present in the serum or synovial fluids. The aim of this study was to investigate the use of several monoclonal antibodies that recognise different sulphation epitopes [high sulphation (5-D-4), low sulphation (1-B-4) and KS-stubs (BKS-1)] to see if patterns of their expression could be used to distinguish different stages of degenerative joint disease. We have also developed ELISAs using mAbs recognising the KS-proteoglycans, keratocan (Ker 1) and lumican (Lum 1) for their quantification as potential biomarkers of osteoarthritis.

Methods: Competitive ELISAs were developed using monoclonal antibodies (mAbs) 5-D-4, 1B4, BKS-1, Ker-1 and Lum-1. Bovine corneal KS-proteoglycans pre-treated with keratanase were used as both the coating antigen and “standard” antigen on the same ELISA plate. Blood, synovial fluid and cartilage samples (surgical waste) obtained from patients undergoing arthroplasty with different Kellgren & Lawrence grades were analysed.

Results and Discussion: 5-D-4 and BKS-1 showed similar inhibition curves and relative 50% inhibition points. However, the curve obtained with 1B4 indicated lower relative expression of 1B4 epitope. Analysis of serum and synovial fluid sample with 5-D-4 mAb showed the presence of the epitope in both samples, but there was significantly less KS in serum than in the synovial fluid. Our results show that competitive ELISA for quantification of several different KS sulphation or “stub” epitopes and two KS-proteoglycans can all be quantified and compared using the same experimental conditions. These studies are ongoing as part of an Arthritis Research Campaign (UK) funded study. In addition the data indicates that keratocan and lumican are also increased in their expression with the progression of disease. Future studies will be performed in an attempt to quantify increased keratocan and lumican expression as potential biomarkers of degenerative joint disease.

Introduction- Proximal humeral fractures remain a challenging problem. Most authors agree that anatomical reduction and stable fixation are essential to allow early range of motion. A variety of techniques have been described such as threaded pins, tension band wiring, screws, nails, plates and primary prosthesis. Locking plates score over other implants by the virtue of providing greater angular stability and better biomechanical properties. The Aim of the Study is to evaluate the functional outcome of PHILOS plate Osteosynthesis of displaced proximal humeral fractures.

Materials and Methods- A retrospective study of 50 patients treated with PHILOS plating for the 2 part, 3part and 4 part proximal humeral fractures with a minimum follow up of 1 year. All the patients were assessed in clinic by Constant Murley and ASES scoring systems. X-ray evaluation was done for fracture healing, AVN, mal-union, non-union, collapse of head, screw penetration and impingement of plate.

Results- Total of 50 acute displaced fractures of proximal humerus treated with PHILOS plating between 2003–2005 were assessed. Mean age was 64 years (15–86) Male to female ratio was 12:38, dominant to non-dominant ratio was 32:18. According to Neer’s classification 16 fractures were 2 part, 24 fractures were 3 part and 10fractures were 4 part. The overall mean Constant score was 73.4(range20–100) and ASES score was 71.7(range 25–98). Under 60 years of age the mean Constant and ASES scores were 83.5 and 83, over 60 years of age scores were 63.1 and 60.4 respectively. The complications include two deep infections which needed excision arthroplasty, one malunion, one subacromial impingement which needed plate removal after fracture healing. No mechanical failure, no non-union, no ANV was noted.

Conclusions- PHILOS plate Osteosynthesis is a reliable method of treating complex proximal humeral fractures. It provides good mechanical stability and allows rapid mobilization with out compromising fracture healing.

Introduction: Several small leucine-rich proteoglycans (SLRPs) are involved in the regulation of collagen fibril size(s) in a variety of different soft and hard musculosk-eletal tissues. In the intervertebral disc (IvD) the major SLRPs involved in regulation of types I & II collagen fibril size are believed to be decorin, fibromodulin and lumican. Research into IvD degeneration and backpain is hampered by a lack of specific biomarkers to detect and monitor the disease process. We have discovered that two keratan sulphate (KS) substituted members of the SLRP family, Keratocan and Lumican (that are major KS-pro-teoglycans found in cornea) were unusually expressed in extracts from degenerative disc tissues.

Methods: Non-degenerate disc tissue (n=10) was obtained from 2 scoliosis patients and degenerate disc tissue from 11 patients undergoing surgery. The degenerate discs were graded using criteria described by Pfir-rman et al (Spine26: 1873; 2001). Tissue samples were extracted with 4M guanidine HCl and after dialysis subjected to SDS-PAGE and Western blot analyses using monoclonal antibodies that recognise epitopes on kera-tocan and lumican.

Results & Discussion: Keratocan was not found in the non-degenerate disc tissue but was present in all degenerate IvD tissues tested. Lumican showed and increased expression in extracts of degenative IvD tissues. Our working hypothesis is that the increased expression of these two SLRPs in degenerative disc tissue results from a reparative depostion of a type I collagen fibrillar ‘scar’. This unusual expression suggests their potential as biomarkers for detecting the onset of degenrative disc disease.

To study the survival analysis of the Accord TKR and to analise the causes for its failure. 111 Accord knees were implanted in 106 patients between 1986 and 1996. All components were cemented. Eighty-seven patients were followed up and assessed according to the Knee Society Clinical Rating System.

Life table analysis of this implant using revision as the end point shows a survival of 25% at 11–12 years.

Of the 87 knees, only 31 were still in situ and of these 7 showed radiographic signs of severe loosening. However, the average knee score for these 31 was only 65/100 and average functional score was down to 42/100.

56 implants have been revised, 21 due to aseptic loosening, 11 due to gross valgus/varus instability, 9 due to deep infection, 8 due to loosening of the patella liner and 7 due to mobile bearing complications.

All 21 (24%) cases of aseptic loosening were found to have a loose femoral component; however, 56% of the total showed significant radiographic osteolysis around the stem of the tibial implants.

Retrieved implants in 5 patients showed significant delamination of the UHMWP at its margins and also revealed a track through the tibial baseplate into the medullary cavity of the tibia.

Conclusion: Early failure of this implant is due to increased debris formation from the UHMWP due to edge loading and early delamination probably as a consequence of the shape of its articulating surface. This situation was significantly aggravated by a design fault in the tibial baseplate, which encouraged unrestricted access of debris into the medullary cavity of the tibia and hence early and severe osteolysis.

Introduction: Elevated plasma elastase levels have been reported following major trauma and isolated femoral fracture. Reamed femoral nailing has been shown to further increase plasma elastase levels. The aim of this study was to investigate neutrophil (PMN) priming for degranulation following major trauma and isolated long-bone pelvis fracture by assessing the ability of PMN to release elastase in-vitro in response to phorbol myristate acetate (PMA) an analogue of dia-cylglycerol (DAG) a component of the “second messenger” system.

Methods: 11 major trauma (ISS≥18) patients and 18 patients with isolated long-bone/pelvis fracture, were consented to enter the study. Patients in the isolated fracture group were further stratified depending upon the type of fracture stabilization they underwent [reamed nail (n=12), Ex-Fix (n=6)]. Blood samples were obtained on admission, at 24 hours post injury, at day 3 and day 5. 11 healthy volunteers were used as controls. PMN were isolated by dextran sedimentation and ficoll-hypaque density gradient centrifugation. The ability of PMN to degranulate was assessed by an elastase substrate assay.

Results: A significant increase in the capacity of PMN to release elastase in response to a PMA stimulus was seen in major trauma patients on admission as compared with healthy volunteers. However in patients with isolated long-bone/pelvis fracture, there was no difference in levels of elastase release. Further no difference in the ability of PMN to release elastase was seen between the reamed nail and Ex-Fix groups.

Conclusions: In conclusion we show that PMN are primed for increased degranulation (elastase release) following major trauma but not following isolated long-bone/pelvis fracture. These primed PMN are capable of increased tissue damage following major trauma thus increasing the risk of development of multiple organ failure.

Introduction: Kashin-Beck disease (KBD) is a special endemic osteoarthropathy whose main pathologic changes occur in growth plate cartilage and articular cartilage of human limbs and joints where it is manifested as cartilage degeneration and necrosis. Past and current research suggests that KBD, and its endemic geographic distribution in China, is due to the combined presence of fungal mycotoxins (on stored food ingested by affected populations) and a regional selenium deficiency in the environment providing local food sources. Thus, we hypothesise that the presence of fungal mycotoxins and the absence of selenium in the diet specifically affects chondrocyte metabolism in the growth plate during limb and joint development and in articular cartilage of adults, which leads to localised tissue necrosis, and the onset of degenerative joint disease. The aim of this study was to examine the effects of mycotoxins; e.g. Nivalenol (NIV), selenium and NIV in the presence of selen! ium in in vitro chondrocyte culture systems to better understand cellular and molecular mechanisms underlying the pathogenesis of KBD.

Methods: Chondrocyte tissue cultures were established using cartilage explant cultures either in the presence or absence of selenium (0.5–1.5 microg/ml) and the mycotoxin nivalenol (0.5–1.5 microg/ml) and culture for 1 to 4 days. Medium was harvested daily at day 1 through 4 and analysed for glycosaminoglycan (GAG) release and the presence of aggrecanase or MMP activity using RT-PCR for gene expression and monoclonal antibodies that detect their respective enzyme-generated neo-epitopes on cartilage aggrecan metabolites.

Results: Our studies to date have shown that NIV exposure induces catabolic changes in chondrocyte metabolism with an increased expression of aggrecanase activity. Addition of selenium did not affect mRNA expression of the aggrecanases ADAMTS-4 & 5. Parallel studies involving immunohistochemical analyses of articular cartilage from KBD showed an increase in aggrecanase activity.

Conclusions: These studies demonstrate that induction of aggrecanase activity as one of the molecular mechanisms involved is the pathogenesis of KBD. However, the addition of selenium does not alter aggrecanase gene expression indicating that its beneficial effects are occurring in other areas of cartilage metabolism.

Degenerative joint disease (DJD) involves the proteolysis of many extracellular matrix molecules (ECM) present in articular cartilage and other joint tissues such as tendon, meniscus and ligaments. Recent research has identified key enzymes involved in the catabolism of ECM. Two classes of enzyme the Matrix Metalloproteinases (MMP’s) MMP-2, MMP-3, MMP-13 and the ADAMTS family (a disintegrin and metalloproteinase with thrombospondin motifs) of proteinases most notably, ADAMTS-1, -4 and −5, have been shown to be involved in the catabolism of ECM (such as type II collagen and cartilage aggrecan). The presence of several MMPs in the synovial fluid has been reported; however, little data has yet been gathered on the presence of ADAMTS-1, -4 or −5 (the aggrecanases) in synovial fluids. In this study we have used a recombinant artificial substrate and specific neoepitope antibodies that recognise either MMP- generated or aggrecanase -generated degradation products to measure the relative activity of these two enzyme families in the synovial fluid from human patients.

Methods: A recombinant substrate containing the interglobular domain of cartilage aggrecan , flanked by a complement regulator and the Fc region of IgG has been stably transfected into CHO cells. The recombinant protein has been purified from the medium using a Protein A column followed by gel chromatography using a Superose 12 column. Synovial fluid samples were depleted of serum immunoglobulin by pre-absorption with ProSepA. The recombinant substrate was then added to synovial fluid samples and incubated overnight as 37?C. The recombinant substrate was recovered from samples using ProsepA and then separated by SDS-PAGE (10% gels). Gels were transferred to nitrocellulose membranes and immunoblotted with antibodies recognising the undigested substrate and using neoeptiope antibodies specifically recognising MMP or aggrecanase –generated catabolites.

Results: Preliminary analysis by Western blot using the anti IGD neoepitopes BC-14 (detecting cleavage at the major MMP site) and BC-3 (detecting cleavage at the aggrecanase site) demonstrated that enzymes in human synovial fluid collected from patients diagnosed with rheumatoid arthritis cleaved the pro-drug at the MMP site with little or no evidence of aggrecanase catabolism. In contrast, synovial fluid collected from patients diagnosed with osteoarthritis indicted that there was cleavage at the aggrecanase site. In these preliminary studies we have also examined the enzyme activity in a set of clinical samples collected from patients that have undergone knee replacement surgery having been given either n-3 fatty acids or a placebo 10 weeks prior to surgery. Results indicate that aggrecanase generated fragments were found in synovial fluid from placebo patients, and reduced levels of enzyme activity were apparent in fluids tested from patients that had received n-3 fatty acids prior to surgery.

Discussion: This data suggests that the recombinant substrate will aid in the detection of MMP or aggrecanase activities in synovial fluid samples. The ratio of MMP to aggrecanase activity has potential as a biomarker for the severity of cartilage degeneration in degenerative joint diseases.

Introduction: Kashin-Beck disease (KBD) is an endemic osteoarthropathy with pathological changes occurring in growth plate and articular cartilage in humans. It manifests as cartilage degeneration and necrosis. It is postulated that KBD is due to fungal mycotoxins infiltrating the diet and a regional selenium deficiency in the environment providing food sources in a broad belt across China. Previous work has established an in vitro system in which chondrocytes are cultured and an ex vivo cartilage graft is produced. Subjecting these chondrocytes to either selenium (SEL), Nivalenol (NIV) or in combination during the growth of the graft was found to alter the morphology of the cartilage graft. In addition, the quantity of the large aggregating proteoglycan, was significantly reduced in a dose dependent manner in the presence of Nivalenol. This study aimed to examine the composition of aggrecan from grafts grown in the presence of NIV or SEL alone, or in combination to better understand cellular and molecular mechanisms underlying the pathogenesis of KBD.

Methods: Chondrocytes (from 7 day old bovine cartilage) were seeded at high density in MilliCell filter inserts (12mm diameter; Millipore, MA). Cultures were maintained for 4 weeks in DMEM supplemented with 20% heat–inactivated FBS, ascorbate (100μg/ml) and TGFß2 (5ng/ml) or additionally supplemented with either SEL , NIV or both at concentrations of 0.01, 0.05 and 0.1μg/ml. Media was refreshed thrice weekly and later analysed. At 4 weeks the cartilage grafts were harvested, weighed and extracted in 4M guanidium chloride (with an inhibitor cocktail) for biochemical analysis of matrix molecules. Residues were papain digested. Glycosaminoglycan concentration was determined using the DMMB assay in all media samples, guanidine extracts and papain digests. Aggrecan and GAG composition was determined using Western blotting with a panel of antibodies recognising chondroitin sulphate (CS), keratan sulphate (KS) and protein core epitopes present in aggrecan.

Results: The total GAG synthesised in a 4week period was substantially reduced in chondrocytes cultured in the presence of NIV at 0.05 and 0.1μg/ml and to a lesser extent in those cultures exposed to the highest dose of SEL. However, the amount of GAG released into the media remained fairly constant within the treatment groups, but a marked reduction was apparent in the guanidine extracts of the cartilage grafts. Western blot analysis with a series of antibodies on guanidine extracted aggrecan showed no substantial changes in the core protein molecular weights however analysis demonstrated that KS was reduced in NIV treated cultures. Results also indicated that NIV treated cultures appeared to contain less CS substitutions on the aggrecan core protein.

Discussion: The GAG concentration data indicates that there is an inability of the GAG to remain within the cartilage grafts extracellular matrix. when treated with NIV. Western blot analysis indicates minor changes in the composition of the aggrecan in relation to protein core length and CS/KS side chain substitutions or length. Further work will investigate the proportion of aggrecan able to form high molecular weight aggregates, the metabolism of link protein and hyaluronan.

Introduction: Osteoarhthritis is a degenerative disease affecting a large proportion of the population. Recently, there has been renewed interest in the use of neutraceuticals (such as glucosamine) for the treatment of symptomatic pain and pathology in arthritic joints. However, little research has been carried out to assess the biochemical mechanisms by which glucosamine imparts its effects on the disease process. Biochemically, an early change in the cartilage metabolism is a loss of the large aggregating proteoglycan, aggrecan. Functionally, this loss results in a decreased capacity for the tissue to sustain mechanical loading that leads to cartilage destruction and a painful joint. The enzymes responsible for the loss of aggrecan from the tissue are commonly referred to as the aggrecanases and are members of the ADAMTS family of enzymes. Degradation of aggrecan by the aggrecanases can be detected using a specific neoepitope monoclonal antibody BC-3 (1). Model systems using cartilage explant cultures that mimic the degradative processes seen in osteoarthritis have been developed in which cytokine such as IL-1 are used to initiate the catabolic processes leading to cartilage degradation.

Methods: Cartilage explant cultures (bovine) were established using published methodologies (1). Explants were then incubated in either DMEM, DMEM supplemented with a chemically modified glucosamine (0.5–15mM) or DMEM supplemented with glucosamine hydrochloride (0.5–15mM) for 1 hour. IL-1 (10ng/ml) was then added to half of the explant cultures in each experimental group. Cultures were maintained for 4 days in the experimental media after which media and explants were harvested for analysis. Glycosaminoglycan (GAG) concentrations of media samples and cartilage extracts were determined using the DMMB assay. RNA was extracted from cartilage explants and RT-PCR was performed using primers to cartilage matrix molecules, ADAMTS and MMPs. Western blot analysis was performed on the experimental media using MAb BC-3 to determine the presence of aggrecanase-generated aggrecan catabolites.

Results: Experiments show that glucosamine hydrochloride (0.5–15mM) was unable to inhibit the release of GAG from explant cultures induced by treatment with IL-1. However, explant cultures preincubated with 10–15mM chemically-modified glucosamine were able to inhibit the release of GAG induced by IL-1 to that of control culture levels. The decreased release of GAG corresponded to a decrease in the detection of aggrecanase-generated aggrecan catabolites as assessed by Western blotting with MAb BC-3.

Discussion: This data questions the effectiveness of glucosamine hydrochloride in the inhibition of biochemical mechanisms involved in the IL-1 induced degradation of aggrecan in articular cartilage. However, the data suggests a role for a chemically modified glucosamine in the IL-1 induced degradative pathways involved in the loss of aggrecan from cartilage. The use of glucosamine in the treatment of arthritic diseases is controversial, however, the modified form of glucosamine used in this study helps to support the potential use of the dietary ingestion of glucosamine and its beneficial effects in arthritis patients. 1. Hughes, C.E., et al. (1995). Biochem. Journal. 305, 799–80

This study aimed to explore the relationship between the geometry of the tuberosity located superior to the Achilles tendon enthesis and the thickness of its fibro-cartilaginous periosteum. The tuberosity acts as a pulley for the tendon during dorsiflexion of the foot and is thus compressed by the overlying tendon. This can result in pressure-related injuries which account for a significant number of Achilles-related problems among sportsmen or women. We postulated that variations in the contact area between the tendon and the tuberosity (and consequently the pressure exerted by the tendon) affects the periosteum thickness. Here, we report four methods of portraying the two dimensional geometry of the superior tuberosity. Material was obtained from 10 elderly dissecting room cadavers donated to the Cardiff University for anatomical examination and prepared for routine histology. Serial sagittal sections were collected at 1 mm intervals, and stained with Masson’s trichrome, toluidine blue and haematoxylin & eosin. In the first method, the area of the bursal cavity was measured between the deep surface of the tendon and the tuberosity within a 9mm radius of the proximal part of the attachment site. The second technique was similar, though used the long axis of the tendon as a reference, rather than its deep surface. The third technique measured the area of the tuberosity within 20 degrees of the tendon long axis. The final technique measured the cumulative gradient of the first 5 mm of the tuberosity, with reference to the tendon long axis. The periosteum thickness was measured at 500 μm intervals from the proximal part of the enthesis and mean values calculated. A good correlation was seen between all techniques, with the tuberosities having the most localised area of contact with the tendon, showing the thickest periosteum.

We propose a grading system for contrast free MRI images of tennis elbow and evaluate the inter and intra observer variability of their interpretation.

Methods: Three senior orthopaedic surgeons were asked to blindly grade 0.2T dedicated extremity contrast free MRI images of elbows of patients who presented with varying degrees of symptomatic tennis elbow.

Our proposed grading system of 1 to 5 based on the pattern around the common extensor tendon was used.

Images of the symptomatic and contralateral non symptomatic elbows were graded blindly twice with an interval of 1 month by each surgeon.

Each surgeon graded 176 MRI images twice.

The grades were subsequently grouped into (I) grades 1 to 2 and (II) grades 3 to 5

Results: With regards to the intra observer agreement, consultant A showed 90.1% agreement, consultant B showed 90.6% agreement and consultant C 96.0% agreement. The mean intra observer agreement rate was 92.2%.

The inter observer agreement between consultant A and B was 82.46%, between A and C 67.1% and between B and C 80.1%.

It was also noted that there were systematic differences to the inter observer variability. Consultant A graded the images 3 to 5 on both occasions 52.9% of the time, consultant B graded 3 to 5 on both occasions 37.8% of the time and consultant C graded 3 to 5 on both occasions 23.3% of the time.

Conclusion: The intra observer agreement rate is high. There is however a greater inter observer variation but this variation is consistent. We suggest that the inter observer differences can be improved by (1) reducing the grades to positive or negative and (2) by group reeducation of the observers.

Introduction: Previous studies have demonstrated that exposure of normal bovine and human osteoarthritic cartilage to n-3 polyunsaturated fatty acids (PUFAs) such as those present in fish oils can modulate the expression and activity of the degradative and inflammatory factors that are responsible for cartilage destruction [1,2]. In these studies, supplementation of cartilage explant cultures with n-3 PUFAs resulted in an abrogation of aggrecanase activity as well as mRNA expression of mediators of inflammation. To date, few studies have examined the effect of PUFAs on the metabolism of other tissues within the musculoskeletal system, therefore the present work examines the effect of n-3 PUFA supplementation on tendon metabolism.

Methods: Bovine deep digital flexor tendon explants were obtained from the compressed region of young metacarpophalangeal joints (2-week-old) and supplemented with eicosapentaenoic acid (EPA), as previously described [2]. Release of proteoglycan metabolites was analysed using Western blotting whilst RT-PCR analysis was used to examine the mRNA expression patterns of matrix proteases and inflammatory agents.

Results: Exposure to the n-3 fatty acid, EPA, markedly changed the overall lipid composition profile of the tendon with major changes occurring in the supplemented fatty acid (i.e., EPA), with a concomitant percentage reduction in other polyunsaturated fatty acids. Aggrecanase activity was present in the media from control cultures, as expected [3]. However, supplementation with EPA had no effect on this activity, in contrast to articular cartilage where aggrecanase catabolites were absent from the conditioned media following treatment with n-3 PUFAs [1,2]. mRNA expression for the inflammatory mediators (COX-2, IL-1β, TNF), ADAMTS-5, MMPs and TIMPs was also unchanged following supplementation with EPA, again contrasting with articular cartilage where mRNA expression was abolished.

Discussion: This study demonstrates that exposure of bovine tendon explant cultures to an n-3 PUFA, EPA, had no effect on the mRNA expression or activity of aggrecanases; similarly, expression of the inflammatory mediators was also unaffected. Importantly, within this musculoskeletal tissue, aggrecanases are constitutively active and appear to be involved in normal, everyday turnover of aggrecan, in contrast to non-pathological articular cartilage where aggrecanase-generated metabolites are only detected following treatment with catabolic agents. Similarly, COX-2 mRNA expression is present constitutively within tendons whereas in cartilage it is absent under basal (unstimulated) conditions. These data demonstrate that the incorporation of n-3 PUFAs have a differential effect on the regulatory mechanisms which control gene expression within articular cartilage versus tendon.

Traditionally midshaft clavicle fractures have been treated conservatively. It is recognized that displaced and shortened fractures may be better treated operatively. In particular, patients with greater than 20 mm of shortening and 100 percent displacement have a symptomatic non union rate of 30 percent. The standard technique used previously has been via plate fixation with LC-DCP or DCP. However in the last 5 years intramedullary fixation has been popularized. “Rockwood intramedulary clavicular pin” remedies the past treatment issues including poor blood supply, painful prominent hardware and stress raiser related to removal of metal work.

Aim: The aim of this study was to assess the functional outcome following intramedullary fixation of clavicle using Rockwood pin.

Method: We retrospectively evaluated 17 patients with displaced and shortened mid-shaft clavicular fractures who underwent intramedullary pinning using Rock-wood pins. Each patient was assessed using the ASES, Constant and SF36 scoring system. A physical examination was performed and individual radiographs were assessed to determine union.

Results: The mean age of the patients was 28 (range 15–56). All patients went into union within 2 to 4 months. They had a shorter stay in hospital, earlier mobilization and no scar related paraesthesia. The average ASES score 98.2 (range 92–100) and constant 95.3 (range 89–100).

Summary: Displaced and shortened mid clavicular fractures require operative fixation. Plates and screws on the clavicle requires significant soft tissue stripping leading to compromised blood supply to the bone and multiple bi-cortical screws act as stress raisers. Previous intra-medullary devices presented with the problem of pin migration. Rockwood pins are designed with a differential pitch which leads to compression at the fracture site and prevent pin migration. From this study we now recommend the use of the Rockwood Pin for the management of displaced mid-shaft clavicle fractures.

Aim: To assess the functional outcome following internal fixation with the PHILOS® plating system for displaced proximal humeral fractures by using the ASES and Constant scoring system.

Background: Controversy exists with regards to the management of displaced proximal humeral fractures and many methods of treatment have been proposed over the years. In particular, the role of surgery has not been clearly defined. The current trend is toward limited dissection of the soft tissues with the use of minimal amounts of hardware to gain stability.

Methods: We performed a retrospective analysis of 30 consecutive patients treated surgically with the PHILOS ® plate for a displaced proximal humeral fracture between February 2002 and October 2003. Patients were assessed clinically and radio graphically at an average follow-up time of 9 months. Functional outcome was determined utilising the American Shoulder and Elbow Society score (ASES) and Constant Murley score. The injury was classified using Neer’s 4 part classification.

Results: Average age of the patients was 58 years (19 to 92). There were 6 two part, 14 three part and 10 four part fractures. All the fractures were radio graphically united by 10 weeks. The average overall ASES score is 66.5%. The average overall Constant score is 55%. The average external rotation at 90 of abduction for the ages 15–55 was 55°–64° and the ages 56–95 was 25°–34°. The average forward elevation for the ages 15–55 was 85°–95° and the ages 76–95 was 55°–64°. The most difficult movement for the older subgroup of patients was internal rotation which was up to the sacrum.

Conclusion: Our results show that good fracture stability and functional outcome can be obtained from the use of the PHILOS® plate. Early mobilisation of the shoulder can be achieved without compromising fracture union. We would recommend the use of the PHILOS® plate for the management of displaced fractures of the proximal humerus.

Aim: To evaluate the functional outcome of patients following intra-osseous suturing for repair of distal biceps tendon ruptures, using the Mayo scoring system. Subsequent analysis of mRNA expression; in the ruptured biceps tendons was performed.

Methods: We operated on 8 patients who had ruptured their biceps tendon. The average ages of the patients were 36 (Range 22–50). The technique involved using intrasosseous suturing via a single anterior skin crease incision. The functional outcome of these patients was scored by using the Mayo elbow performance score. The average follow-up was 7 months. (Range 5–8 months). The tendons were processed for RNA isolation and reverse -transcription – polymerase chain reaction (RT-PCR).

Results: The average subjective assessment (pain and function) of these patients was 63/70 (Range 57–68). The average objective assessment (motion and stability) was 24/30 (Range 22–27). The overall average was 87/100. None of the patients had any complications postoperatively. Our results showed that in the samples of ruptured biceps tendon there was mRNA expression of ECM structural components, especially aggrecan and the small proteoglycans biglycan and decorin. Interestingly, these samples also showed a high expression for the enzymes commonly involved in articular cartilage degradation and turnover, the aggrecanases (ADAMTS-4 and ADAMTS-5) and the matrix metalloproteinases (MMP-3 and MMP-13).

Conclusion: We demonstrated that intrasosseous suturing via a single anterior incision, in-patients with ruptured biceps tendons could provide a good functional outcome. This technique should therefore be considered as one of the surgical options in the management of this condition. We know clinically that patients can rupture their biceps tendon either due to trauma if not due to degenerative conditions. In our study we wanted to know if the subset of patients how ruptured their tendons traumatically had any pre-existing degenerative conditions leading on to the rupture compared to the normal subjects. Interestingly our study has shown that there is mRNA expression of degradative enzymes (aggrecanases and MMPs) in the samples of ruptured biceps tendon. Furthermore, our samples also showed mRNA expression for factors involved in the inflammatory response. In conclusion, mRNA expression of the factors involved in degradation and inflammation may suggest a phenotype that predisposes the biceps tendon to rupture, although further studies are required in order to investigate this.

Aim: To study mRNA expression in ruptured biceps tendon.

Methods: Our study was carried out in the University College of Medicine. We took the biceps tendon of 5 patients who had traumatic ruptures. The age of the patients ranged from 35–53. The tendons were processed for RNA isolation and reverse-transcription-polymerase chain reaction (RT-PCR) carried out in order to investigate the mRNA gene expression in ruptured biceps tendon of extra cellular matrix (ECM) components (e.g. proteoglycans and collagens); ECM degradative components (e.g. aggrecanases and MMPs); inflammatory components (e.g. cytokines and cyclooxygenases); and factors involved in the apoptotic response.

Results: Our results showed that in the samples of ruptured biceps tendon there was a good mRNA expression of ECM structural components, especially aggrecan and the small proteoglycans biglycan and decorin. Interestingly, these samples also showed a high expression for the enzymes commonly involved in articular cartilage degradation and turnover, the aggrecanases (ADAMTS-4 and –5) and the matrix metalloproteinases (MMP-3 and –13). As has been recently reported for Achilles tendon rupture (Cetti et al, 2003), an inflammatory reaction was also observed in these ruptured bicep tendons with expression of the inflammatory cytokines IL-1α and TNFα and the enzyme cyclooxygenase-2.

Conclusion: We know clinically that patients can rupture their biceps tendon either due to trauma if not due to degenerative conditions. In our study we wanted to know if the subset of patients who ruptured their tendons traumatically had any pre-existing degenerative conditions leading on to the rupture compared to the normal subjects. Interestingly our study has shown that there is mRNA expression of degradative enzymes (aggrecanases and MMPs) in the samples of ruptured biceps tendon. Whether these mRNA levels equate to increased enzyme activity of these molecules warrants further investigation. Furthermore, our samples also showed mRNA expression for factors involved in the inflammatory response. In conclusion, mRNA expression of the factors involved in degradation and inflammation may suggest a phenotype that predisposes the bicep tendon to rupture, although further studies are required in order to investigate this further.

Aim: To ascertain the accuracy of partial weight bearing.

Method: 6 healthy volunteers with a below knee plaster cast, 10 patients with uncemented hip replacements and 12 patients with lower limb fractures were trained to partial weight bear. They were asked to place the affected leg on a bathroom scale and to press on it till the prescribed limit. This process was repeated till the subject formed a mental image of the amount of load they must put through the limb. The ability to partial weight bear was tested in a gait lab by making them walk on a walkway incorporating a Bertec force platform. Exact magnitude of weight bearing was calculated from the vertical ground reaction forces produced.

Results: 4 out of 6 volunteers exerted mean weight of 20.3 kg above and the remaining 2 exerted 5.6 kg below that prescribed. Of the 22 patients, 19 exerted mean weight of 24.3 kg above and 3 patients exerted mean weight of 7.5 kg below that prescribed. As per Spearmanñs rank correlation test, the relationship between the prescribed weight bearing and the actual weight bearing was non-signiþcant (p=0.399) i.e., there is little relationship between the prescribed and actual weight bearing.

Conclusions: Neither patients nor healthy volunteers could partial weight bear to the extent required. They were either above or below the prescribed level of partial weight bearing. Current method of teaching partial weight bearing is inaccurate and has poor reproducibility. Such methods use static loading situations whereas walking is a dynamic activity. An inexpensive, easy to use, dynamic device is required to train patients to partial weight bear.

Aims: Neutrophil (PMN) dysfunction is implicated in both acute respiratory distress syndrome (ARDS) and sepsis. We aimed to determine the PMN response following isolated long-bone/pelvic fracture by investigating temporal changes in PMN migration and surface receptor expression (CXCR1, PECAM- 1, & CD18/ CD11b) following injury. Methods: Of the 20 patients consented to enter the study, 14 underwent reamed nailing/ORIF within 24 hours, and 6 were treated with an Ex-Fix or conservatively. 11 normal volunteers (NLV) were used as controls. Blood samples were obtained within 2 hours of admission, at 24 hours, at day 3 and day 5. PMN were isolated and the number of PMN migrating across porous collagen IV coated tissue culture inserts, in response to IL-8 were quantitated by myeloperoxidase activity. PMN surface receptor expression was assessed by whole blood FACScan analysis. Results: Signiþcantly greater numbers of fracture patient PMN migrated on admission as compared with NLV. In the Ex-Fix group the numbers migrating declined steadily and showed a hypo-response on day 5. In the reamed nailing group there was a further elevation in the PMN numbers migrating post-operatively. CXCR1 & CD18 expression was signiþcantly increased on admission. PECAM-1 was signiþcantly down-regulated on admission.

Conclusions: Following isolated long-bone/pelvic fracture PMN are primed for increased migration in response to IL-8. This is associated with up-regulation of CXCR1 and CD18, and down-regulation of PECAM-1. Treatment by reamed nailing and ORIF confers a Ç second hit È manifest as a further increase in IL-8 mediated PMN migration.