We studied the effect of a lipid clearing agent (clinofibrate) on the osteocytes of rabbits treated with corticosteroids. Thirty-one rabbits were divided into four groups: (A) steroid-treated with a normal diet, (B) steroid-treated and one a diet with added clinofibrate, (C) non-steroid-treated, on a diet with clinofibrate; and (D) non-steroid-treated on a normal diet. All the steroid-treated animals demonstrated hyperlipidaemia and fatty degeneration of the liver. Lipid-containing osteocytes were seen in the femoral heads of these animals. However, those which received clinofibrate (group B) had less severe lipidaemia, and less severe degeneration of the liver. In them, only the osteocytes around the haversian canals exhibited lipid inclusions. Clinofibrate appears to modify lipid metabolism, diminishing the steroid induced accumulation of lipids within osteocytes. This effect may protect against steroid-mediated osteonecrosis

We prospectively studied 50 patients with the diagnosis of primary frozen shoulder. The serum lipid levels were measured in 43 of these patients and compared with those in 43 age-matched and sex-matched control subjects. The fasting serum triglyceride and cholesterol levels were significantly elevated in the frozen-shoulder group (cholesterol p < 0.01; triglyceride p < 0.02)

We have used Fourier transform infrared spectroscopy (FTIR) to characterise the chemical and structural composition of the tendons of the rotator cuff and to identify structural differences among anatomically distinct tears. Such information may help to identify biomarkers of tears and to provide insight into the rates of healing of different sizes of tear. The infrared spectra of 81 partial, small, medium, large and massive tears were measured using FTIR and compared with 11 uninjured control tendons. All the spectra were classified using standard techniques of multivariate analysis. FTIR readily differentiates between normal and torn tendons, and different sizes of tear. We identified the key discriminating molecules and spectra altered in torn tendons to be carbohydrates/phospholipids (1030 cm. −1. to 1200 cm. −1. ), collagen (1300 cm. −1. to 1700 cm. −1. and 3000 cm. −1. to 3350 cm. −1. ) and lipids (2800 cm. −1. to 3000 cm. −1. ). Our study has shown that FTIR spectroscopy can identify tears of the rotator cuff of varying size based upon distinguishable chemical and structural features. The onset of a tear is mainly associated with altered structural arrangements of collagen, with changes in lipids and carbohydrates. The approach described is rapid and has the potential to be used peri-operatively to determine the quality of the tendon and the extent of the disease, thus guiding surgical repair

Free radicals, such as reactive oxygen species (ROS) which are released abruptly after deflation of an ischaemic tourniquet, cause reperfusion injuries. Ischaemic precondition (IPC), however, can reduce the injury. In clinical practice, the sequential application and release of tourniquets is often used in bilateral total knee replacement (TKR) to obtain a clearer operative field, but the effects on the production of free radicals and lipid peroxidation have not been studied. In this study, we have observed the production of free radicals and the subsequent lipid peroxidation in bilateral TKR with sequential application of a tourniquet to examine the effect of IPC. Patients undergoing elective TKR under intrathecal anaesthesia were studied. Blood samples were obtained after spinal anaesthesia, one minute before and five and 20 minutes after release of each tourniquet. We used the lucigenin chemiluminescence analysis and the phosphatidylcholine hydroperoxide (PCOOH) assay to measure the production of ROS and lipid peroxidation. Our results showed that production of ROS significantly increased at five and 20 minutes after release of the first tourniquet and at five minutes after release of the second tourniquet, but returned to normal at 20 minutes after the second reperfusion. The peak production of ROS was at 20 minutes after the first reperfusion; lipid peroxidation did not change significantly. We conclude that in spite of significant production of ROS after the release of tourniquet, the IPC phenomenon occurs during bilateral TKR with sequential application of a tourniquet

We studied prospectively the relationship between serum lipids and Dupuytren's disease of the hand in 85 patients, 65 men and 20 women. The Dupuytren patients had significantly higher fasting serum cholesterol and triglyceride levels than did the controls (p < 0.001). The raised levels of serum lipids appeared to be associated with the pathogenesis of Dupuytren's disease, and this may help to explain the high incidence of Dupuytren's disease in alcoholic, diabetic and epileptic patients, since these conditions are also associated with raised serum lipid levels

Aims

The influence of metabolic syndrome (MetS) on the outcome after hip and knee arthroplasty is debated. We aimed to investigate the change in patient-reported outcome measure (PROM) scores after hip and knee arthroplasty, comparing patients with and without MetS.

We examined soft tissue biopsies from 26 patients with symptomatic nerve root fibrosis and arachnoiditis after a previous laminectomy. Dense fibrous connective tissue was found about the nerve roots and in 14 cases (55%) fibrillar foreign material was seen within it. This material had the histochemical characteristics of cotton fibres from swabs and neurosurgical patties. In two other cases nerve root fibrosis was associated with residual radiopaque lipid thought to derive from earlier myelography. Our findings suggest that risks may be associated with the introduction of foreign material into the vertebral canal, and that microscopic fragments of surgical swabs and patties may have a role in the pathogenesis of postoperative periradicular fibrosis

Aims

Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm.

High-pressure lavage produces greater visible damage to bone at a macroscopic and microscopic level when compared with low-pressure lavage and can result in delay in the healing of fractures. Osteoblasts and adipocytes are derived from mesenchymal stem cells. Conditions which lead to bone loss often involve a switch from the osteoblast to adipocyte lineage. We have therefore examined the effect of high- and low-pressure irrigation on the differentiation of adipocytes. Calvaria-derived bone cells were exposed to either low-pressure or high-pressure irrigation with normal saline. After 14 days the cells were fixed and the osteoblasts and adipocytes quantified using Oil Red O to stain cytoplasmic lipid droplets (triglycerides) in the cells. Osteoblasts were quantified using a commercially available alkaline-phosphatase staining assay. A standard quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed. Messenger RNA levels for osteocalcin, a marker of osteoblasts, and PPARγ2, a marker of adipocytes, were measured. High-pressure lavage resulted in an increase in adipogenesis of 50% when compared with low-pressure lavage. Our findings suggest that high-pressure lavage may promote differentiation of mesenchymal stem cells towards the adipoctye lineage. This may have clinical significance in the development of delayed and nonunion after treatment of fractures of long bones

1. The surface of mature adult human articular cartilage from the knee has been studied by electron microscopy in eleven patients ranging in age from thirty-seven to eighty-three years. The ultrastructural appearance varies from person to person and often from area to area in the same specimen. These variations range from an intact surface to one showing overt fibrillation visible with the light microscope. 2. In areas where the articular surface appears intact the underlying superficial matrix consists of closely packed collagen fibres with only a small amount of interfibrillary ground substance. The collagen fibres show a predominantly tangential orientation in this region of the cartilage. Osmophilic lipidic bodies are sometimes seen in the matrix very close to the joint surface. 3. The appearances under the electron microscope are altered in what is interpreted as an early ultrastructural change in the development of cartilage fibrillation. In the affected areas the collagen fibres show abnormally wide separation by an excessive amount of interfibrillary matrix. Collagen fibres become directly exposed to the joint cavity, and the surface can also show accumulations of finely granular material and sometimes tuft-like projections containing collagen fibres and fine fibrils. At a slightly later stage shallow clefts and steeply sloping curves are apparent at the surface. It is suggested that these various alterations precede the development of overt fibrillation visible under the light microscope. 4. Electron micrographs occasionally show small "blisters" at the articular surface. Electron microscopy has not given evidence of shedding of cells into the joint cavity from non-fibrillated areas of adult human articular cartilage. Cells can, however, sometimes become exposed at the surface in fibrillated areas

Aims

Patients who sustain neck of femur fractures are at high risk of malnutrition. Our intention was to assess to what extent malnutrition was associated with worse patient outcomes.

Aims

Vitamin E-diffused, highly crosslinked polyethylene (VEPE) and porous titanium-coated (PTC) shells were introduced in total hip arthroplasty (THA) to reduce the risk of aseptic loosening. The purpose of this study was: 1) to compare the wear properties of VEPE to moderately crosslinked polyethylene; 2) to assess the stability of PTC shells; and 3) to report their clinical outcomes at seven years.

Aims

Our aim in this study was to describe a continuing review of 11 total hip arthroplasties using 22.225 mm Alumina ceramic femoral heads on a Charnley flanged femoral component, articulating against a silane crosslinked polyethylene.

Aims

The objective of this five-year prospective, blinded, randomised controlled trial (RCT) was to compare femoral head penetration into a vitamin E diffused highly cross-linked polyethylene (HXLPE) liner with penetration into a medium cross-linked polyethylene control liner using radiostereometric analysis.

The widespread use of MRI has revolutionised the diagnostic process for spinal disorders. A typical protocol for spinal MRI includes T1 and T2 weighted sequences in both axial and sagittal planes. While such an imaging protocol is appropriate to detect pathological processes in the vast majority of patients, a number of additional sequences and advanced techniques are emerging. The purpose of the article is to discuss both established techniques that are gaining popularity in the field of spinal imaging and to introduce some of the more novel ‘advanced’ MRI sequences with examples to highlight their potential uses.

Cite this article: Bone Joint J 2015;97-B:1683–92.

Aims

The aim of this study was to analyse human muscle tissue before and after rotator cuff repair to look for evidence of regeneration, and to characterise the changes seen in the type of muscle fibre.

Aims

Chronic conditions of the wrist may be difficult to manage because pain and psychiatric conditions are correlated with abnormal function of the hand. Additionally, intra-articular inflammatory cytokines may cause pain.

We aimed to validate the measurement of inflammatory cytokines in these conditions and identify features associated with symptoms.

Peri-tendinous injection of local anaesthetic, both alone and in combination with corticosteroids, is commonly performed in the treatment of tendinopathies. Previous studies have shown that local anaesthetics and corticosteroids are chondrotoxic, but their effect on tenocytes remains unknown. We compared the effects of lidocaine and ropivacaine, alone or combined with dexamethasone, on the viability of cultured bovine tenocytes. Tenocytes were exposed to ten different conditions: 1) normal saline; 2) 1% lidocaine; 3) 2% lidocaine; 4) 0.2% ropivacaine; 5) 0.5% ropivacaine; 6) dexamethasone (dex); 7) 1% lidocaine+dex; 8) 2% lidocaine+dex; 9) 0.2% ropivacaine+dex; and 10) 0.5% ropivacaine+dex, for 30 minutes. After a 24-hour recovery period, the viability of the tenocytes was quantified using the CellTiter-Glo viability assay and fluorescence-activated cell sorting (FACS) for live/dead cell counts. A 30-minute exposure to lidocaine alone was significantly toxic to the tenocytes in a dose-dependent manner, but a 30-minute exposure to ropivacaine or dexamethasone alone was not significantly toxic.

Dexamethasone potentiated ropivacaine tenocyte toxicity at higher doses of ropivacaine, but did not potentiate lidocaine tenocyte toxicity. As seen in other cell types, lidocaine has a dose-dependent toxicity to tenocytes but ropivacaine is not significantly toxic. Although dexamethasone alone is not toxic, its combination with 0.5% ropivacaine significantly increased its toxicity to tenocytes. These findings might be relevant to clinical practice and warrant further investigation.

Cardiac disease in patients with ankylosing spondylitis (AS) has previously been studied but not in patients with a kyphosis or in those who have undergone an operation to correct it.

The aim of this study was to measure the post-operative changes in cardiac function of patients with an AS kyphosis after pedicle subtraction osteotomy (PSO).

The original cohort consisted of 39 patients (33 men, six women). Of these, four patients (two men, two women) were lost to follow-up leaving 35 patients (31 men, four women) to study. The mean age of the remaining patients was 37.4 years (22.3 to 47.8) and their mean duration of AS was 17.0 years (4.6 to 26.4). Echocardiographic measurements, resting heart rate (RHR), physical function score (PFS), and full-length standing spinal radiographs were obtained before surgery and at the two-year follow-up.

The mean pre-operative RHR was 80.2 bpm (60.6 to 112.3) which dropped to a mean of 73.7 bpm (60.7 to 90.6) at the two-year follow-up (p = 0.0000). Of 15 patients with normal ventricular function pre-operatively, two developed mild left ventricular diastolic dysfunction (LVDD) at the two-year follow-up. Of 20 patients with mild LVDD pre-operatively only five had this post-operatively. Overall, 15 patients had normal LV diastolic function before their operation and 28 patients had normal LV function at the two-year follow-up.

The clinical improvement was 15 out of 20 (75.0%): cardiac function in patients with AS whose kyphosis was treated by PSO was significantly improved.

Cite this article: Bone Joint J 2015;97-B:1405–10.

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells.

Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis.

Drug therapy forms an integral part of the management of many orthopaedic conditions. However, many medicines can produce serious adverse reactions if prescribed inappropriately, either alone or in combination with other drugs. Often these hazards are not appreciated. In response to this, the European Union recently issued legislation regarding safety measures which member states must adopt to minimise the risk of errors of medication.

In March 2014 the Medicines and Healthcare products Regulatory Agency and NHS England released a Patient Safety Alert initiative focussed on errors of medication. There have been similar initiatives in the United States under the auspices of The National Coordinating Council for Medication Error and The Joint Commission on the Accreditation of Healthcare Organizations. These initiatives have highlighted the importance of informing and educating clinicians.

Here, we discuss common drug interactions and contra-indications in orthopaedic practice. This is germane to safe and effective clinical care.

Cite this article: Bone Joint J 2015;97-B:434–41.

Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH.

Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).

Cite this article: Bone Joint J 2014;96-B:259–62.

Total hip replacement in patients with Gaucher’s disease with symptomatic osteonecrosis of the femoral head is controversial because of the high early failure rates. We describe four patients who had an uncemented total hip replacement following enzyme replacement therapy for a median of two years and one month (1 to 9.8 years) prior to surgery, and who remained on treatment. At operation, the bone had a normal appearance and consistency. Histopathological examination showed that, compared with previous biopsies of untreated Gaucher’s disease, the Gaucher cell infiltrate had decreased progressively with therapy, being replaced by normal adipose tissue. The surfaces of viable bone beyond the osteonecrotic areas showed osteoblasts, indicating remodelling. In one case acetabular revision was carried out after 11 years and eight months. The three remaining patients had a mean follow-up of six years and four months (3.3 to 12 years). We recommend initiating enzyme replacement therapy at least one to two years prior to total hip replacement to facilitate bone remodelling and to allow implantation of uncemented components in these young patients.

The clinical and radiological results of 50 consecutive acetabular reconstructions in 48 patients using impaction grafting have been retrospectively reviewed. A 1:1 mixture of frozen, ground irradiated bone graft and Apapore 60, a synthetic bone graft substitute, was used in all cases. There were 13 complex primary and 37 revision procedures with a mean follow-up of five years (3.4 to 7.6). The clinical survival rate was 100%, with improvements in the mean Harris Hip Scores for pain and function. Radiologically, 30 acetabular grafts showed evidence of incorporation, ten had radiolucent lines and two acetabular components migrated initially before stabilising.

Acetabular reconstruction in both primary and revision surgery using a 1:1 mixture of frozen, ground, irriadiated bone and Apapore 60 appears to be a reliable method of managing acetabular defects. Longer follow-up will be required to establish whether this technique is as effective as using fresh-frozen allograft.

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight.

Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A₂, nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid.

This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome.

The long-term effects of metal-on-metal arthroplasty are currently under scrutiny because of the potential biological effects of metal wear debris. This review summarises data describing the release, dissemination, uptake, biological activity, and potential toxicity of metal wear debris released from alloys currently used in modern orthopaedics. The introduction of risk assessment for the evaluation of metal alloys and their use in arthroplasty patients is discussed and this should include potential harmful effects on immunity, reproduction, the kidney, developmental toxicity, the nervous system and carcinogenesis.

The systemic use of steroids and habitual alcohol intake are two major causative factors in the development of idiopathic osteonecrosis of the femoral head (ONFH). To examine any interaction between oral corticosteroid use and alcohol intake on the risk of ONFH, we conducted a hospital-based case-control study of 71 cases with ONFH (mean age 45 years (20 to 79)) and 227 matched controls (mean age 47 years (18 to 79)). Alcohol intake was positively associated with ONFH among all subjects: the adjusted odds ratio (OR) of subjects with ≥ 3032 drink-years was 3.93 (95% confidence interval (CI) 1.18 to 13.1) compared with never-drinkers. When stratified by steroid use, the OR of such drinkers was 11.1 (95% CI 1.30 to 95.5) among those who had never used steroids, but 1.10 (95% CI 0.21 to 4.79) among those who had. When we assessed any interaction based on a two-by-two table of alcohol and steroid use, the OR of those non-drinkers who did use steroids was markedly elevated (OR 31.5) compared with users of neither. However, no further increase in OR was noted for the effect of using both (OR 31.6). We detected neither a multiplicative nor an additive interaction (p for multiplicative interaction 0.19; synergy index 0.95), suggesting that the added effect of alcohol may be trivial compared with the overwhelming effect of steroids in the development of ONFH.

Cite this article: Bone Joint J 2013;95-B:320–5.

An increasing number of patients are treated by autologous chondrocyte implantation (ACI). This study tests the hypothesis that culture within a defined chondrogenic medium containing TGF-β enhances the reexpression of a chondrocytic phenotype and the subsequent production of cartilaginous extracellular matrix by human chondrocytes used in ACI. Chondrocytes surplus to clinical requirements for ACI from 24 patients were pelleted and cultured in either DMEM (Dulbecco’s modified eagles medium)/ITS+Premix/TGF-β1 or DMEM/10%FCS (fetal calf serum) and were subsequently analysed biochemically and morphologically.

Pellets cultured in DMEM/ITS+/TGF-β1 stained positively for type-II collagen, while those maintained in DMEM/10%FCS expressed type-I collagen. The pellets cultured in DMEM/ITS+/TGF-β1 were larger and contained significantly greater amounts of DNA and glycosaminoglycans. This study suggests that the use of a defined medium containing TGF-β is necessary to induce the re-expression of a differentiated chondrocytic phenotype and the subsequent stimulation of glycosaminoglycan and type-II collagen production by human monolayer expanded chondrocytes.

An international faculty of orthopaedic surgeons presented their work on the current challenges in hip surgery at the London Hip Meeting which was attended by over 400 delegates. The topics covered included femoroacetabular impingement, thromboembolic phenomena associated with hip surgery, bearing surfaces (including metal-on-metal articulations), outcomes of hip replacement surgery and revision hip replacement. We present a concise report of the current opinions on hip surgery from this meeting with appropriate references to the current literature.

The World Health Organization (WHO) launched the first Global Patient Safety Challenge in 2005 and introduced the ‘5 moments of hand hygiene’ in 2009 in an attempt to reduce the burden of health care associated infections. Many NHS trusts in England adopted this model of hand hygiene, which prompts health care workers to clean their hands at five distinct stages of caring for the patient. Our review analyses the scientific foundation for the five moments of hand hygiene and explores the evidence, as referenced by WHO, to support these recommendations. We found no strong scientific support for this regime of hand hygiene as a means of reducing health care associated infections. Consensus-based guidelines based on weak scientific foundations should be assessed carefully to prevent shifting the clinical focus from more important issues and to direct limited resources more effectively.

We recommend caution in the universal adoption of the WHO ‘5 moments of hand hygiene’ by orthopaedic surgeons and other health care workers and emphasise the need for evidence-based principles when adopting hospital guidelines aimed at promoting excellence in clinical practice.

The identification of the extent of neural damage in patients with acute or chronic spinal cord injury is imperative for the accurate prediction of neurological recovery. The changes in signal intensity shown on routine MRI sequences are of limited value for predicting functional outcome. Diffusion tensor imaging (DTI) is a novel radiological imaging technique which has the potential to identify intact nerve fibre tracts, and has been used to image the brain for a variety of conditions. DTI imaging of the spinal cord is currently only a research tool, but preliminary studies have shown that it holds considerable promise in predicting the severity of spinal cord injury.

This paper briefly reviews our current knowledge of this technique.

The scarcity of mesenchymal stem cells (MSCs) in iliac crest bone marrow aspirate (ICBMA), and the expense and time in culturing cells, has led to the search for alternative harvest sites. The reamer-irrigation-aspirator (RIA) provides continuous irrigation and suction during reaming of long bones. The aspirated contents pass via a filter, trapping bony fragments, before moving into a ‘waste’ bag from which MSCs have been previously isolated. We examined the liquid and solid phases, performed a novel digestion of the solid phase, and made a comparative assessment in terms of number, phenotype and differentiation capacity with matched ICBMA.

The solid fraction from the filtrate was digested for 60 minutes at 37°C with collagenase. Enumeration was performed via the colony-forming unit fibroblast (CFU-F) assay. Passage (P2) cells were differentiated towards osteogenic, adipogenic and chondrogenic lineages, and their phenotypes assessed using flow cytometry (CD33, CD34, CD45, CD73, CD90, and CD105).

MSCs from the RIA phases were able to differentiate at least as well as those from ICBMA, and all fractions had phenotypes consistent with other established sources. The median number of colonies for the three groups was: ICBMA = 8.5 (2 to 86), RIA-liquid = 19.5 (4 to 90), RIA-solid = 109 (67 to 200) per 200 μl. The mean total yield of cells for the three groups was: ICBMA = 920 (0 to 4275), RIA-liquid = 114 983 (16 500 to 477 750), RIA-solid = 12 785 (7210 to 28 475).

The RIA filtrate contains large numbers of MSCs that could potentially be extracted without enzymatic digestion and used for bone repair without prior cell expansion.

We describe a 63-year-old man who had xanthomatosis of the right tendo Achillis. He had undergone excision of the left tendo Achillis 17 years earlier without reconstruction for the same condition. The neurological history and examination were normal. Blood investigations showed hypercholestrolaemia, for which he was being treated with statins.

He was referred with pain in the right tendo Achillis and problems with footwear.

He was treated by excision of the right tendo Achillis, the xanthomatous nodules and the involved skin, followed by reconstruction with a cadaver bone-tendon graft. At follow-up eight months postoperatively, the scar had healed well. He walked without pain and could wear any type of shoe. Plain radiographs showed that the bone graft had healed. The American Orthopaedic Foot and Ankle Society hindfoot score was 95/100. The patient’s subjective evaluation of the result was very good.

In this study of 41 patients, we used proteomic, Western blot and immunohistochemical analyses to show that several reactive oxygen species scavenging enzymes are expressed differentially in patients with primary osteoarthritis and those with non-loosening and aseptic loosening after total hip replacement (THR). The patients were grouped as A (n = 16, primary THR), B (n = 10, fixed THR but requiring revision for polyethylene wear) and C (n = 15, requiring revision due to aseptic loosening) to verify the involvement of the identified targets in aseptic loosening. When compared with Groups A and B, Group C patients exhibited significant up-regulation of transthyretin and superoxide dismutase 3, but down-regulation of glutathione peroxidase 2 in their hip synovial fluids. Also, higher levels of superoxide dismutase 2 and peroxiredoxin 2, but not superoxide dismutase 1, catalase and glutathione perioxidase 1, were consistently detected in the hip capsules of Group C patients.

We propose that dysregulated reactive oxygen species-related enzymes may play an important role in the pathogenesis and progression of aseptic loosening after THR.

We undertook a study of the anti-tumour effects of hyperthermia, delivered via magnetite cationic liposomes (MCLs), on local tumours and lung metastases in a mouse model of osteosarcoma. MCLs were injected into subcutaneous osteosarcomas (LM8) and subjected to an alternating magnetic field which induced a heating effect in MCLs. A control group of mice with tumours received MCLs but were not exposed to an AMF. A further group of mice with tumours were exposed to an AMF but had not been treated with MCLs. The distribution of MCLs and local and lung metastases was evaluated histologically. The weight and volume of local tumours and the number of lung metastases were determined. Expression of heat shock protein 70 was evaluated immunohistologically. Hyperthermia using MCLs effectively heated the targeted tumour to 45°C. The mean weight of the local tumour was significantly suppressed in the hyperthermia group (p = 0.013). The mice subjected to hyperthermia had significantly fewer lung metastases than the control mice (p = 0.005). Heat shock protein 70 was expressed in tumours treated with hyperthermia, but was not found in those tumours not exposed to hyperthermia.

The results demonstrate a significant effect of hyperthermia on local tumours and reduces their potential to metastasise to the lung.

We report a case of osteonecrosis of the femoral head in a young man who is a carrier of the prothrombin gene mutation. We suggest that an electrical injury to his lower limb may have triggered intravascular thrombosis as a result of this mutation with subsequent osteonecrosis of the femoral head. No case of osteonecrosis of the femoral head secondary to a distant electrical injury has previously been reported.

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing.

The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-α) and appears to impair the blood supply of bone.

Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.

Technological advances and shorter rescue times have allowed early and effective resuscitation after trauma and brought attention to the host response to injury. Trauma patients are at risk of progressive organ dysfunction from what appears to be an uncontrolled immune response. The availability of improved techniques of molecular diagnosis has allowed investigation of the role of genetic variations in the inflammatory response to post-traumatic complications and particularly to sepsis.

This review examines the current evidence for the genetic predisposition to adverse outcome after trauma. While there is evidence supporting the involvement of different polymorphic variants of genes in determining the post-traumatic course and the development of complications, larger-scale studies are needed to improve the understanding of how genetic variability influences the responses to post-traumatic complications and pharmacotherapy.

Polymethylmethacrylate remains one of the most enduring materials in orthopaedic surgery. It has a central role in the success of total joint replacement and is also used in newer techniques such as percutaneous vertebroplasty and kyphoplasty.

This article describes the current uses and limitations of polymethylmethacrylate in orthopaedic surgery. It focuses on its mechanical and chemical properties and links these to its clinical performance. The behaviour of antibiotic-loaded bone cement are discussed, together with areas of research that are now shedding light upon the behaviour of this unique biomaterial.

Avascular necrosis of the femoral head creates considerable morbidity in successful renal transplant recipients who are generally young and expect active lifestyles. Total hip replacement is considered the treatment of choice in these patients, but surgeons may be wary because of a supposed increase in the risk of infection and other complications.

A review of the literature reveals that cemented hip arthroplasty provides good to excellent functional outcomes for renal transplant patients. Most authors have found that the risk of infection is not increased despite chronic immunosuppression, but the rates of general complications are and should be anticipated and treated. There is a high rate of early failure in these patients because of their young age and diffuse osteopenia as a result of secondary hyperparathyroidism related to the underlying renal disease and chronic steroid use. Recent studies have found that despite decreased bone stock in these patients, porous-coated prostheses are not contraindicated.

The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats.

Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month.

The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.

Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low.

Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal (sd 15.7) to 124.6 (sd 46.2) in periosteal bone for gentamicin and 31.9 (sd 8.9) in endosteal and 2.9 (sd 1.1) in periosteal bone for flucloxacillin. The antibiotics remained active against bacteria in vitro after iontophoresis and continued to elute from the allograft for up to two weeks.

Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.

We evaluated the concentrations of chromium and cobalt ions in blood after metal-on-metal surface replacement arthroplasty using a wrought-forged, high carbon content chromium-cobalt alloy implant in 64 patients. At one year, mean whole blood ion levels were 1.61 μg/L (0.4 to 5.5) for chromium and 0.67 μg/L (0.23 to 2.09) for cobalt. The pre-operative ion levels, component size, female gender and the inclination of the acetabular component were inversely proportional to the values of chromium and/or cobalt ions at one year postoperatively. Other factors, such as age and level of activity, did not correlate with the levels of metal ions. We found that the levels of the ions in the serum were 1.39 and 1.37 times higher for chromium and cobalt respectively than those in the whole blood.

The levels of metal ions obtained may be specific to the hip resurfacing implant and reflect its manufacturing process.