Ischaemic preconditioning protected skeletal myotubes against the effects of ischaemia-reperfusion in vitro. This protection was associated with increased Nrf2 signalling. Ischaemic preconditioning (IPC) is a well recognised and powerful phenomenon where a tissue becomes more tolerant to a period of prolonged ischaemia when it is first subjected to short bursts of ischaemia/reperfusion. While much is known about the ability of ischaemic preconditioning to protect myocardial tissue against ischaemia-reperfusion injury, its potential to confer benefit in an orthopaedic setting by protecting skeletal muscle remains relatively unexplored to date. One mechanism by which ischaemic preconditioning may induce protection is through a reduction in oxidative stress. Reactive oxygen species (ROS) are generated both during prolonged ischaemia and also upon reperfusion by infiltrating neutrophils, thereby leading to an increase in oxidative stress. The transcription factor, NF-E2-related factor 2 (Nrf2), is a key regulator of the cells response to oxidative stress as it regulates the expression of a network of anti-oxidant/detoxifying enzymes. Nrf2 signalling has recently been shown to protect against ischaemia-reperfusion injury in both a kidney cell line and in liver biopsies, indicating that this transcription factor may play a key role in the protection provided by ischaemic preconditioning. To date, the involvement of Nrf2 in the response of skeletal muscle to ischaemia-reperfusion has not been investigated. Thus, the aims of this study were to investigate the ability of ischaemic preconditioning to protect skeletal myotubes against ischaemia-reperfusion and to determine the role of Nrf2 signalling in this protection.Summary Statement
Introduction
The internet has revolutionized the way we live our lives. Over 60% of people nationally now have access to the internet. Healthcare is not immune to this phenomenon. We aimed to assess level of access to the internet within our practice population and gauge the level of internet use by these patients and ascertain what characteristics define these individuals. A questionnaire based study. Patients attending a mixture of trauma and elective outpatient clinics in the public and private setting were invited to complete a self-designed questionnaire. Details collected included basic demographics, education level, number of clinic visits, history of surgery, previous clinic satisfaction, body area affected, whether or not they had internet access, health insurance and by what means had they researched their orthopedic complaint.Background
Method
Ischaemic preconditioning (IPC) is a phenomenon whereby tissues develop an increased tolerance to ischaemia and subsequent reperfusion if first subjected to sublethal periods of ischaemia. Despite extensive investigation of IPC, the molecular mechanism remains largely unknown. Our aim was to show genetic changes that occur in skeletal muscle cells in response to IPC. We established an in-vitro model of IPC using a human skeletal muscle cell line. Gene expression of both control and preconditioned cells at various time points was determined. The genes examined were HIF-1?, EGR1, JUN, FOS, and DUSP1. HIF-1? is a marker of hypoxia. EGR1, JUN, FOS and DUSP1 are early response genes and may play a role in the protective responses induced by IPC. Secondly, the expression of HSP22 was examined in a cohort of preconditioned total knee arthroplasty patients.Objectives
Methods
Matrix metalloproteinases (MMP) play a key role in cartilage degradation in osteoarthritis. Statins are a potential suppressor of MMPs. The aim of this research was to assess the efficacy of Pravastatin in suppressing MMP gene and protein expression in an in vitro model. We stimulated normal human chondrocytes with IL-1b for 6 hours to induce MMP expression and then treated with Pravastatin (1, 5 & 10 mM) for a further 18 hours. Cells stimulated with IL-1b but not treated with Pravastatin served as controls. Real-time PCR was used to assess expression of MMP-3 and MMP-9 mRNA. MMP enzyme activity was assessed using a fluorescent MMP-specific substrate. Staistical analysis was performed using ANOVA.Introduction
Methods
Although chondrocytes have been used for autologous implantation in defects of articular cartilage, limited availability and donor-site morbidity have led to the search for alternative cell sources. Mesenchymal stem cells from various sources represent one option. The infrapatellar fat-pad is a promising source. Advantages include low morbidity, ease of harvest and ex-vivo evidence of chondrogenesis. Expansion of MSCs from human fat-pad in FGF-2 has been shown to enhance chondrogenesis. To further elucidate this process, we assessed the role of TGF-?3, FGF-2 and oxygen tension on growth kinetics of these cells during expansion. Infrapatellar fatpads were obtained from 4 donors with osteoarthritis. Cells were expanded in various media formulations (STD, FGF, TGF and FGF/TGF) at both 20% and 5% oxygen tensions. Colony forming unit fibroblast assays were performed for each expansion group and assessed with crystal violet staining. Cell aggregates from each group underwent chondrogenic differentiation in 5% and atmospheric oxygen tension. Pellets were analyzed on day 21. 5% Oxygen tension during expansion increased the colony size for both FGF and FGF/TGF groups. Cells expanded in FGF/TGF proliferated more rapidly. Biochemical analysis revealed that cells expanded in FGF-2 had higher glycosaminoglycan synthesis rates, a marker for chondrogenesis. Differentiation at 5% pO2 led to higher levels of sGAG but its effect was generally less potent compared to expansion in FGF-2.Methods
Results
Local anaesthetic has been reported to have a detrimental effect on human chondrocytes both Human chondrocytes were grown under standard conditions. Cells were exposed to either lignocaine (0.5, 1, 2%), levobupivacaine (0.125, 0.25, 0.5%), bupivacaine (0.125, −.25, 0.5%) or ropivacaine (0.1875, 0.375, 0.75%) for 15 minutes. Cells were also exposed to a local anesthetic agent with the addition of magnesium (10, 20, or 50%). Cells exposed to media or saline served as controls. The MTS assay was used to assess cell viability 24-hours after exposure.Introduction
Methods
Ischaemic preconditioning (IPC) is a phenomenon whereby a tissue is more tolerant to an insult if it is first subjected to short bursts of sublethal ischaemia and reperfusion. The potential of this powerful mechanism has been realised in many branches of medicine where there is an abundance of ongoing research. However, there has been a notable lack of development of the concept in Orthopaedic surgery. The routine use of tourniquet-controlled limb surgery and traumatic soft tissue damage are just two examples of where IPC could be utilised to beneficial effect in Orthopaedic surgery. We conducted a randomized controlled clinical trial looking at the role of a delayed remote IPC stimulus on a cohort of patients undergoing a total knee arthroplasty (TKA). We measured the effect of IPC by analysing gene expression in skeletal muscle samples from these patients. Specifically we looked at the expression of Heat shock protein-90 (HSP-90), Catalase and Cyclo-oxygenase-2 (COX-2) at the start of surgery and at one hour into surgery. Gene analysis was performed using real time polymerase chain reaction amplification. As a second arm to the project we developed an in-vitro model of IPC using a human skeletal muscle cell line. A model was developed, tested and subsequently used to produce a simulated IPC stimulus prior to a simulated ischaemia-reperfusion (IR) injury. The effect of this on cell viability was investigated using crystal violet staining.Introduction
Methods
Local anaesthetic has been reported to have a potentially detrimental effect on human chondrocytes both in vitro and in vivo. Due to chondroproliferative effects, magnesium may be an alternative intra-articular analgesic agent following arthroscopy. We aimed to examine the dose response effect of commonly used local anaesthetics on chondrocyte viability and also to report on the effect of adding magnesium to the local anesthetic agent. Human chondrocytes were grown under standard culture conditions. Cells were exposed to either lignocaine (0.5, 1, 2%), levobupivacaine (0.125, 0.25, 0.5%), bupivacaine (0.125, 0.25, 0.5%) or ropivacaine (0.1875, 0.375, 0.75%) for 15 minutes. Cells were also exposed to a local anesthetic agent with the addition of magnesium (10, 20, or 50%). Cells exposed to culture media or saline served as controls. The MTS assay was used to assess cell viability 24 hours after exposure. One-way ANOVA were used to test for statistical significance.Introduction
Methods
The IPC consisted of three five-minute periods of tourniquet insufflation on the operative limb, interrupted by five minute periods of reperfusion. The tourniquet was again insufflated and the operation started. The control group simply had tourniquet insufflation as normal prior to the start of surgery. Muscle samples were taken from the operative knee of all patients at the immediate onset of surgery (t=0), and again, at one hour into the surgery (t=1). Total RNA was extracted from the muscle samples, and the gene expression profiles were determined using microarray technology.
Slipped capital femoral epiphysis (SCFE) is the most common hip disorder in adolescents and its incidence is on the increase. Obesity is purported to be a significant risk factor in the pathogenesis of this condition. Measurements for weight and BMI’s are good techniques in identifying children at risk and those who are obese. In this retrospective review, we provide clear evidence of a relationship between SCFE and obesity based on weight-to-age percentiles. 64 patients with radiologically diagnosed SCFE were compared with 88 controls without histories of hip pathology. In the SCFE group, 45.3% were above the 95th percentile as opposed to 12.1% in the control group (P=<
0.0001). In addition, the obesity risk group (85–95th percentile) numbers were much higher in the SCFE group (15.6%) compared to controls (7.7%) (P=<
0.0001). Obesity is a modifiable risk factor in most cases and thus, identifying children at risk using weight-to-age percentile charts correcting for gender is potentially beneficial in reducing the incidence of SCFE.
The mean length of stay for revision due to aseptic loosening in 1997 was 14.3 days. The average length of stay for revision for infected arthroplasty was 35 days. In 2006, the length of stay increased to 65 days for infected arthroplasty and 15.03 days for aseptic cases. The mean total cost of aseptic revision per patient was 12,409.92 (range 8,822.58–13,559.65) euro in 1997 with revisions for infection costing 20,888.66 euro, a difference of 68.32%. The industry cost of implants increased by 32–35% (€3119–€4371 and €4216–€5800) between 1999 and 2006 depending on implant selection. There was a 20– 42% increase in generic hospital costs (admission, investigation and treatment related costs) in the same period.
In the Irish orthopaedic unit 42 consecutive hip and knee arthroplasty patients from a single consultant were included. There were 26 women and 16 men with average age of 63.9 years (range 36 to 88 years). The average LOS was 6.5 days (range, 3 to 10 days), with 24 patients going to a rehabilitation facility and 18 directly home. There was no correlation found between LOS and either comorbidities, social factors or complications, in both groups although one patient had a delayed discharge due to haematoma and wound drainage in the US. Prolonged LOS in both groups was correlated with delays in rehabilitation bed and transportation availability, reported short staffing in hospital and weekend stays. Both groups were well matched for comparison. The average shorter LOS noted in the US unit appears to be almost entirely attributable to an implemented perioperative care pathway and a more proactive coordinated approach to discharge planning.
As the numbers of revision total knee arthroplasty (RTKA) rise, we continually need current information regarding the etiology/modes of failure and functional disability of patients presenting for RTKA. We used a prospective cohort study to assess these fundamental aspects of RTKA. 290 consecutive subjects presenting for RTKA had relevant clinical information, including modes of failure, collected from surgeon-completed documents. Patients themselves also completed quality of life and functional questionnaires, including the SF-36 and WOMAC Osteoarthritis Index. Mean patient age was 68.6 years (55 to 79 years). Mean SF-36 and WOMAC score at baseline indicated significant functional disability. The mean time from primary procedure to RTKA was 7.9 years (6 months to 27 years). Our series included 31 percent ‘early’ (under 2 years) revisions and 69 percent ‘late’ revisions. Sepsis was the cause of 10.4 percent revisions. The tibia needed revision in 78 percent, femur in 71 percent and patella in 31 percent of cases. The predominant modes of failure (non-exclusive frequency values as patients could have more than one cause) were (in percentages): instability (28.9), malalignment (27.5), tibial osteolysis (27.5), polyethylene wear (24.5), femoral osteolysis (22.5) and tibial loosening (22.2). These patients are relatively young, and considerably disabled by their failed primary procedure. Many modes of failure are within surgical control and direct us toward improved techniques and approaches. Other modes confirm the need for continued development of implants and materials. Information gained here will allow better formulation of measures and resource allocation that may prevent RTKAs.
46.4% of the cases had positive cultures from the deep tissues. Staphylococcus species were responsible for 62% of cases, while enterococci, pseudomonas, streptococcus pneumonia, and MRSA have similar occurrences. The mean total cost per case was € 21,895 (13,597 for aseptic revision) a 61% increase in cost for cases revised for non septic reasons.
Total knee arthroplasty revisions (TKAR) are increasing in incidence. These complex and demanding procedures are typically associated with a higher complication rate than primaries. We report on the actual complications encountered in a prospective study of TKAR patients to determine the current nature and incidence of these problems. 230 consecutive patients undergoing TKAR were enrolled to our database and had information on demographics, comorbidities, outcomes (WOMAC and SF-36) and complications recorded. Baseline information and data from 2 month, 6 month and 1 year follow up was collated. Mean patient age was 68.0 and clinical outcomes scores showed significant improvements for function, stiffness and pain at all points of follow-up. The total number of complications was 131 in 97 (42.2%) patients (48 by 2 months, 46 at 6 months and 32 at 1 year). Systemic complications comprised 41 of these, many being relatively minor. There were no deaths, 4 deep vein thromboses and 3 myocardial infarctions. The majority of complications (90) were local, including 2 patellar dislocations, 3 periprosthetic fractures, 3 peroneal nerve injuries, 2 ‘late’ patellar tendon ruptures and 1 patellar avascular necrosis, 9 wound hematomas, and a substantial rate of 21 superficial or deep wound infections. Although patients experience significant improvement in function, activity and pain following TKAR, there is a considerable incidence of complications up to 1 year following TKAR. This is important in terms of resources, patient counseling and also in identifying and instituting preventive measures where possible in order to improve outcomes for these patients.
Although conventional thinking and teaching have implicated weight and body mass index (BMI) in premature failure of total knee arthroplasty (TKA) there is scant evidence based confirmation of this belief. Furthermore, there is little knowledge regarding the precise effect of BMI on functional outcomes following TKA. We performed this study to assess the effect of weight on the longevity of TKA and on outcomes following TKA revision (TKAR). 186 consecutive subjects undergoing TKAR in a 17-center prospective cohort study, had data collected on weight (pounds), BMI and time elapsed between primary and revision surgery (T). The Physical Component Score (PCS) of the Short Form-36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, and the Knee Society Score (KSS) were also collected preoperatively and at 6-month follow-up. Univariate, bivariate and multivariate statistical methods were used in the analysis. The mean BMI and weight were 31.8 (54% of subjects had a BMI >
30) and 200 pounds (range 107–350) respectively. The distribution of both measures of excessive weight was close to normal. Average time between primary and revision procedures (T) was 7.3 years (range 6 months to 27 years). Using linear regression, T significantly decreased as weight (BMI) increased. Mean SF-36 PCS, WOMAC and KSS-Function scores were significantly improved 6 months after revision surgery. However, BMI and, in particular, weight were predictive of worse physical functional outcomes. This study demonstrates the deleterious effect of weight on both the longevity of primary TKA as assessed at the time of revision and on functional outcomes following TKAR. Although further prospective data regarding this population is indicated, the current findings direct us towards better outcomes prediction for overweight patients and more effective counselling and appropriate management of these patients.
Percutaneous wiring is a successful technique for the management of distal radial fractures. Practice differs according to surgeon preference as to whether the wires used are buried or protruding. To assess patient satisfaction with wither technique, we prospectively randomised 52 consecutive patients undergoing percutaneous wiring for distal radius fractures with regard to whether the wires were buried or not. Patients with a distal radial fracture managed with percutaneous wire fixation and casting only were randomly allocated to have the wires buried or protruding. The fractures were classified according to Frykmn’s classification of fractures of the distal radius, and there were no differences between the groups (p=0.9). The total number of patients studied was 52, with a mean age of 56.6 years (range 19–84). The female: male ratio was 38:13. Twenty-five (48%) patients had percutaneous wiring of their fracture with the Kirschner wires buried and 27 (52%) had the wires protruding. Cast and wire fixation were removed at a mean duration of 5.8 weeks in an outpatient setting. Patients recorded whether they experienced pain during the period of wire fixation or pain during the removal of wires on a visual analogue scale. Fifteen patients reported pain during the period of fixation (55.5%), the severity ranged between 2–8 (mean 3.8) with no significant difference between the groups (p=0.8). All patients with buried wires compared with 10% of those protruding wires required local anaesthesia in the operating theatre for removal (p=0.03). Superficial infection was diagnosed in 4 patients with no significant difference between groups (p=0.14). Buried wires are typically advocated to prevent pin site infections and to improve patient comfort and satisfaction. However, we found no difference between the study groups with regard to patient satisfaction, pain during the period of fixation or pin-site infections. Furthermore, all patients in the buried wire group required local anaesthesia for removal with some of these necessitating a visit to the operating theatre. We therefore feel that burying these wires confers no advantage while adding to the complexity, time and cost of removal and recommend leaving wires protruding through the skin.
Spinal injuries are among the most devastating injuries related to recreational sport. There are few studies specifically on spinal injuries in horseback riding. The purpose of our study was to determine the factors contributing to horse-riding accidents and to assess the usefulness of wearing protectors while horse riding. All patients with spinal injuries admitted to our unit over a six-year period (1993–1998) were reviewed. Of 957 patients admitted to the National Spinal Injuries Unit from 1993–1998, 25 patients incurred spinal injury while horse riding. Age, sex, occupation and injury details were collected for all patients. All 25 patients were also contacted retrospectively to collect further details in relation to the specifics of the horse-riding event. There were 16 male and 9 female patients with a mean age of 35 years (range 17–61). There were nine cervical fractures/dislocations, eleven thoracic fractures, and eight lumbar fractures. Four patient sustained injuries at more than one level. In relation to spinal cord injury, two patients had complete neurological deficit, a further ten had incomplete lesions. Thirteen patients had no neurological deficit. Surgical intervention was required in eleven patients. Only six riders, all of who were either jockeys or horse trainers, wore back protectors. Of the 19 patients without a back protector there were 5 cervical, 10 thoracic and 6 lumbar injuries. Two patients sustained injuries at more than one level. However, of the six riders wearing a protective jacket there was a completely different fracture pattern level with 4 cervical injuries, only one thoracic injury and on e lumber injury. The variation in injury level between the group wearing protective back supports and those without is noteworthy. While the numbers are too small to draw a significant conclusion it would appear that there is a trend for riders wearing a back protector to suffer less thoracic and lumbar injuries relative to cervical injuries.
The number of skate related injuries has seen a resurgence in the western world with almost 51000 patients in 1999 presenting to US hospitals with a skateboard related injury, almost 90% of these being male and almost 70% of these are orthopaedic related injuries. Protection , particularly wrist guards, elbow pads, knee pads and recognized helmets are all necessary in protecting the young child against orthopaedic injuries. However despite these physical barriers little training or supervision exists in adequately educating children as to the dangers of these devices. Having observed an increased number of referrals to our Accident and Emergency Dept with fractures sustained whilst roller-blading and skateboarding we set about prospectively evaluating the epidemiology and nature of such injuries. 100 successive referrals to the orthopaedic service as a result of roller/skate injuries were evaluated. Childs age, sex, time using apparatus, mechanism of injury, and whether the injury occurred in a dedicated skatepark or on the street was recorded. Whether the child was wearing any form of protective gear and what type was also recorded. The type of fracture and its treatment and follow up was evaluated. All results were recorded on standard excel spreadsheets and statistical analysis was performed using Instat statistics (Graphpad USA 2002). The Male to female ratio in street injuries was 1:1, whereas in ramp injuries 4:1. 60 injuries occurred on the street whereas 40 occurred whilst using the ramps. The mean age was 11.4yrs. The mean length of time using rollerblades/skateboards was 20 and 19 months for street and ramps respectively. The number of children wearing some form of protective gear shows only 20 children out of the 100 studied wore gear, of these 15 wore helmets only. The treatment initiated shows almost 80% of ramp related injuries required formal manipulation under general anaesthesia or open reduction and internal fixation, where as only 25% of street fractures required this form of treatment, The usage of ramps demonstrates an increased relative risk of 4.26 (95% CI 3.5–5.1) This study shows that skateboards and rollerblades still constitute a major component of childhood fracture admissions. Only 20% of children use some form of protective gear whilst skating, this needs to be addressed on a national level. The wearing of helmets whilst protecting the child against head injury do not prevent serious orthopaedic injuries. Wrist guards should be worn by all children skating as the fall onto outstretched hand still remains a childs defensive mechanism when thrown off balance. Almost 75% of all fractures involve the wrist or the forearm. We urge better education and a tighter supervision of children whilst skating. Dedicated skateparks should only be used by experienced and older children and they should at least be supervised during their first attempts at using the parks, 85% of ramp injuries occurred during first or second time users. A child using a skatepark particularily for the first time is three times more likely to sustain a fracture, and almost 4 and a half times more likely to require definitive surgical treatment of this fracture. This constitutes a huge orthopaedic burden as well as it’s associated morbidity and financial costs to the health service. Children should be encouraged to use limb protectors as well as helmets whilst skating and should be supervised more closely during their initial attempts.
A retrospective study was undertaken in our unit to investigate any change in osteomyelitis trends in the last ten years (1991-2001). These results were then compared to 3 previous studies conducted by our unit on childhood osteomyelitis, 1977-1979 45 cases(O’Brien et al)1, 1980-87 (84 cases) and 1988-1991 (54 cases). 149 patients were identified from hospital discharge database with a diagnosis of osteomyelitis between 1991 and 2001. 136 fully completed charts were discovered and included in the study. 22 children did not fulfil the criterion for the diagnosis of acute or subacute osteomyelitis and were excluded. Cellulitis was the actual diagnosis 18/22 cases, leukaemia or other neoplasm in 4/22 cases. 28% of the children 32/114 had acute haematog-enous osteomyelitis with classical signs and symptoms the remaining 72% fell into the subacute osteomyelitis category as described by Gledhill. Table 1 shows the comparison between the 4 studies. 89% of patients underwent 3 phase bone scanning, and 90% of these were positive. Blood cultures were performed in 87% of patients and were positive in 8.5%, 2 patients being positive and symptomatic of Nesseria meningitis, 4 Staph aureus, 2 Strep Pneumonia, 1 staph epidermidis and 1 E.Coli. As compared to previous 3 studies no case of haemophilus influenza type B was encountered. Aspiration was performed in 22 patients and 18 demonstrated bacteria, the two commonest pathogens were Staphylococcus aureus 66% and epider-midis 16%. 8 patients underwent surgical debridement or drilling if clinically septic or because of failure to improve despite medical treatment. Initial antibiotic treatment comprised of i.v. penicillins and oral fucidin in 92% of patients, the remainder receiving cephalosporins as favoured by physicians or erythromycin if history of hypersensitivity. Antibiotics arethen tailored to clinical picture or culture results. Table 2 shows the changing duration pattern of antibiotic administration. There were four cases of complications, 2 cases of chronic osteomyelitis and 2 cases of limb shortening both around the knee joint. Our results correlate well with other authors. Surgery has an ever-decreasing role in the management of osteomyelitis, with conservative antibiotic management and splintage being the treatment of choice. Subacute osteomyelitis is an ever-increasing entity as reflected in other studies. The incidence of osteomyelitis presenting to our unit has fallen to 2.34 per 10000 per yea. A possible explanation may lie in altered host pathogen interactions, increased host resistance, the frequent administration of broad-spectrum antibiotics in general practice. Increased population wealth as experienced in Ireland in the last 8 years may also have a role.
Introduction: Subject to recent literature citing a reduction in ankle range of motion predisposing to ankle fractures in children, we decided prospectively to analyse the passive range of motion in children presenting to our fracture clinic with simple distal radial metaphyseal fractures treated conservatively in cast. The range of motion was assessed by two observers, and measured using a goniometer in 80 patients. (42 radial fractures and 38 controls) The controls were recruited from children presenting with lower limb injuries and with no prior history of an upper limb injury or neuromuscular condition. The fractures were as a result of simple falls onto the outstretched hand with definite radiological and clinical findings. The range of motion in the contralateral limb was assessed. Both groups showed an equal distribution of dominant and non-dominant limbs. Results: Both groups were well matched with an average age of 10 and 10.3 years fracture group and control group respectively, and gender 55% male fracture group and 52.5% control group. The m injured group showed a passive range of motion of 1680, whereas the control group showed a higher range of motion of 1820, a difference of 140 (p<
. 005 student t-test). A third blinded independent observer of 20 children assessed Intra and interobserver error, and no observer was noted to have higher or lower readings. Conclusion: Children with radial fractures have a lower passive range of motion of their wrists than Controls. This may contribute to the aetiology of wrist fractures in a paediatric population. An possible explanation may be as cited in original work that children who sustain fractures have less mobility around their joints due to reduced elasticity in their musculoskeletal framework. Simple passive stretching of fracture prone joints should therefore be advised.
Infection around implanted biomaterials in humans is a major healthcare issue and current ability to effectively prevent and treat such infections using antibiotics is limited. The hypothesis of the study was that surface charge could be manipulated to a positive state and thus moderate bacterial adhesion to the implant. The surface charge was manipulated by creating a galvanic cell using a zinc strip in a standard suction drain. Adhesion of In this experiment we have shown that alteration of the electrochemical environment around an implant influences bacterial adhesion. While our technique is not therapeutically viable, further manipulation of surface charge of an implant is possible using other electroactive materials. This may be explored in the prophylactic treatment of implant infection
The authors wished to determine if macrophage activation and the release of osteolytic cytokines in response to orthopaedic wear debris could be suppressed pharmacologically with the use of anti-inflammatory and anti-oxidant agents. The current long-term results of total joint arthroplasty are limited by mechanical wear of the implants with an associated immune mediated bone lysis with subsequent loosening and eventual failure. It has been demonstrated that the osteolysis seen in cases of aseptic loosening is mediated by the immune system both directly and indirectly by activated macrophages. Macrophages indirectly cause osteolysis through release of the osteoclast activating cytokines TNFα, IL-1 and PGE2. They also directly resorb bone in small amounts when activated by wear particles. We utilised established cell culture models of both peripherally derived monocyte/macrophages and lymphocyte enriched co-cultures and examined the effects of polymethylmethacrylate particles alone on the cells in culture. The effect of anti-inflammatory and anti-oxidant agents (dexamethasone, diclofenac and n-acetyl cysteine) in varying concentrations was then examined using ELISA of cytokine release and electron microscopy to examine ultra structural responses. Cell viability was also measured in cultures over 24 hour periods (at 6, 12 and 24 hours) using Trypan blue exclusion and Coulter counter, while cell type and morphology were determined cytologically, including-naphthyl acetate esterase cytochemical identification and electron microscopy. The use of N-acetyl cysteine was associated with very significant suppression of TNF, IL-1 and PGE2 in both macrophage and lymphocyte enriched co-culture with no effect on cell viability. While diclofenac was also associated with significant decreases in cytokine expression, it was associated with a decrease in cell viability that approached significance. Dexamethasone did not have a reliable effect on these cytokines. Ultra-structural electron microscopic examination of the cells also demonstrated signs of definite down-regulation of cytoplasmic and nuclear activation. Novel anti-oxidant therapies and possibly other immune modulating drugs can eliminate the activation of macrophages in response to periprosthetic wear particles without any associated decrease in cell viability and thus may provide a means of reducing the incidence of loosening and failure of total joint arthroplasty.
Polyethylene wear in total hip arthroplasty Is associated with generation of particulate wear debris and component failure. Wear has both mechanical and biological consequences with one of the most important of these being the stimulation of immune medicated periprosthetic osteolysis in response to polyethylene particles. It has been shown that the amouont of wear debris generated correlates with the degree of osteolysis encountered. Unfortunately, the assessment of wear of components remains difficult and we wished to apply a new digitised technique of measuring wear using engineering computer softwear on a population of uncemented total hip replacement (THR) patients. Forty patients having primary uncemented THR (ABG 1 prosthesis) for osteoarthritis were enrolled in the study. Seventeen had a 28mm femoral head implanted and 23 had a 32mm head. There were 28 females and 12 males concerned, all having standardised (120 cm hip to x-ray tube) ;weight bearing antero-posterior plain radiographs of the hip performed in the immediate post-operative period and again at a mean of 6 years post-operatively (range 54 – 96 months). The x-rays were then scanned to computer and analysed using Autocad software. The analysis essentially involved 4 steps, namely assessing sphericity of the cup, sphericity of the head, superimposition of the post-operative and 6 year radiographs an.d obtaining computer generated analysis of both the amount and direction of wear. The results of our analysis demonstrated that there was an overall mean wear of 0.157mm per year (range 0.08 – 0.27mm). Of the 17 patients with a 28mm head the mean wear was 0.143mm per year, whereas the 32mm heads were associated with a mean wear rate of 0.188mm per year, with the difference reaching statistical significance (p=0.004). Analysis of the direction of wear demonstrated that as expected wear typically occurred in a superolateral direction with a mean vector of 9° lateral to the vertical axis of the hip. These results primarily demonstrate the usefulness of appropriate computer software in determining wear of components in THR. This allows for assessment of rate and degree of wear which may be important in identifying patients at particular risk of developing significant osteolysis, loosening and ultimately component failure. The results are also consistent with previous reports of increased volumetric wear with large diameter heads and direction of wear in retrieval studies. It is therefore promising as an investigative tool for the in vivo assessment of inovations in THR design in the future.
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.
The current long term results of total joint arthroplasty are limited by mechanical wear of the implants with an associated immune mediated bone lysis with subsequent loosening and eventual failure. It has been demonstrated that the osteolysis seen in cases of aseptic loosening is mediated by the immune system, particularly, both directly and indirectly, by activated macrophages. Macrophages indirectly cause osteolysis through release of the osteoclast activating cytokines: TNFα, IL-1 and PGE2 and also directly resorb bone in small amounts when activated by wear particles. We wished to determine if macrophage activation and the release of osteolytic cytokines in response to orthopaedic wear debris could be suppressed pharmacologically, with the use of anti-inflammatory and anti oxidant agents. We utilised established cell culture models of both peripherally derived monocyte/macrophages and lymphocyte enriched co-cultures and examined the effects of polymethylmethacrylate particles alone on the cells in culture. The effects of anti-inflammatory and anti-oxidant agents (dexamethasone, diclofenac and n-acetyl cysteine) in varying concentrations were then examined using ELISA of cytokine release and electron microscopy to examine ultra structural responses. Cell viability was also measured in cultures over 24 hour periods (at 6, 12 and 24 hours) using Trypan blue exclusion and Coulter counter, while cell type and morphology were determined cytologically, including α-naphthyl acetate esterase cytochemical identification and electron microscopy. The use of N-acetyl cysteine was associated with very significant suppression of TNFα, IL-1β and PGE2 in both macrophage and lymphocyte enriched co-culture with no effect on cell viability. While diclofenac was also associated with significant decreases in cytokine expression it was associated with a decrease in cell viability that approached significance. Dexamethasone did not have a reliable effect on these cytokines. Ultra-structural electron microscopic examination of the cells also demonstrated signs of definite down-regulation of cytoplasmic and nuclear activation. We have demonstrated, therefore, that novel anti-oxidant therapies and possibly other immune modulating drugs can eliminate the activation of macrophages in response to peri-prosthetic wear particles without any associated decrease in cell viability and thus may provide a means of reducing the incidence of loosening and failure of total joint arthroplasty.
The intermetatarsal angle is widely used to determine whether a basal or distal metatarsal osteotomy should be used to correct a hallux valgus deformity. We have noticed that the point of intersection of the long axes of the first and second metatarsals on standard pre-operative weight-bearing AP radiographs consistently predicts the type of osteotomy required. A basal osteotomy is generally recommended if the inter-metatarsal angle is ≥14°, whereas a distal osteotomy is usually sufficient if the angle is less than 14°. Sixty standardised pre-operative AP weight bearing in-patients undergoing hallux valgus correction were included in our study. The intermetatarsal angle was measured in a standard fashion. The point of intersection in the foot was recorded in terms of the distance from the talonavicular joint. Using a Pearson’s Correlation coefficient, our study revealed that an intermetatarsal angle of 14° or more consistently intersected either within the talar head or distal to thetalonavicular joint. We propose that this as an accurate and simple method of pre-operatively determining the choice of metatarsal osteotomy.
Although there have been many studies of the epidemiology of hip fractures in the older population, including the assessment of bone density and the predictive value of a Cole’s fracture in particular for later hip fracture, there has not previously been an analysis of combined presentation of hip and upper limb fractures. We performed this study to examine the incidence and risk factors of such combined injuries and to assess the impact these have on rehabilitation and subsequent treatment in order to formulate a possible clinical pathway or treatment protocol for such patients. The study was performed retrospectively, with all patients admitted over 3 years with fractured neck of femur being reviewed. Of the 681 patients admitted over this period of time (324 intracapsular and 357 extracapsular fractured necks of femur), 22 were found to have a contemporaneous fracture of the upper limb. The associated upper limb fractures were distal radius (n=11), olecranon (n=5) and neck of humerus (n=6), with the same ratio of intracapsular to extra-capsular fractures as the whole group. The female to male ratio in both isolated hip and combined fracture groups was the same at 3:1. The mean patient age was 77.6 years for isolated hip fractures and 78.4 for the combined group. The usual mechanism of injury in both groups was a fall onto the side, but patients in the combined group also typically described having the arm outstretched for protection. The mean total length of stay in hospital for isolated hip fracture was 10.9 days and for combined fractures was 23.2 days (p<
0.05, ANOVA). Exact details were not retrievable from the nursing homes taking some of these patients, but from the data obtained there was a trend apparent for more of the combined group to require such care and for longer. In summary, it is obvious that patients sustaining combined upper limb and hip fractures can become a significant burden on already busy hospital services. These patients therefore require an even more concerted effort at rehabilitation than those patients with isolated hip fractures. We therefore now recommend the use of a specific clinical pathway or protocol including early fixation, immediate co-ordinated multidisciplinary team involvement and rehabilitation, with everyone involved with the treatment of these patients, doctors, physiotherapists, occupational therapists and others, being aware of these extra requirements. Issues for further analysis in these patients include assessing the contribution of bone density to such double fractures, the associated risk of further fractures and therefore whether such patients require further treatment or protective measures.