Interstitial supraspinatus tears can cause persistent subacromial impingement symptoms despite non operative treatment. Autologous tendon cell injection (ATI) is a non-surgical treatment for tendinopathies and tear. We report a randomised controlled study of ATI compared to corticosteroid injection (CS) as treatment for interstitial supraspinatus tears and tendinopathy.

Inclusion criteria were patients with symptom duration > 6 months, MRI confirmed intrasubstance supraspinatus tear, and prior treatment with physiotherapy and ≥ one CS or PRP injection. Participants were randomised to receive ATI to the interstitial tear or corticosteroid injection to the subacromial bursa in a 2:1 ratio, under ultrasound guidance. Assessments of pain (VAS) and function (ASES) were performed at baseline, and 1, 3, 6 and 12 months post treatment.

30 participants (19 randomised to ATI) with a mean age of 50.5 years (10 females) and a mean duration of symptoms of 23.5 months. Baseline VAS pain and ASES scores were comparable between groups. While mean VAS pain scores improved in both groups at 3 months after treatment, pain scores were superior with ATI at 6 months (p=0.01). Mean ASES scores in the ATI group were superior to the CS group at 3 months (p=0.026) and 6 months (p=0.012). Seven participants in the CS group withdrew prior to 12 months due to lack of improvement. At 12 months, mean VAS pain in the ATI group was 1.6 ± 1.3. The improvements in mean ASES scores in the ATI group at 6 and 12 months were greater than the MCID (12.0 points). At 12 months, 95% of ATI participants had an ASES score > the PASS (patient acceptable symptom state).

This is the first level one study using ATI to treat interstitial supraspinatus tear. ATI results in a significant reduction in pain and improvement in shoulder function.

Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear.

This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=15), and compares them with a control group with isolated long bone fractures (n=12). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days (12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-β using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-β levels of 142.79+/-29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (p=0.009 vs. all other time points, ANOVA). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51+/-36.81 ng/ml) and long bone (102.28=/-47.58 ng/ml) groups at 84 days post-injury (p=0.009 and p=0.04 respectively, ANOVA).

In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-β in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.

Purpose: Since 1966 silicone implant arthroplasty has been used to treat arthritis of the PIP joint as an alternative to fusion. The volar approach to expose this joint spares the extensor mechanism at the cost of increased risk to neurovascular structures. In the dorsal approach, the extensor mechanism must be carefully handled, reattached and then protected during rehabilitation. Several surgical techniques have been used to handle the extensor mechanism. Swanson et al. recommended midline incision of the central tendon followed by release of the lateral insertion on the middle phalanx and then reattachment to the base of the middle phalanx. Our clinical experience led us to a new surgical technique; splitting then repairing the extensor mechanism without bone reattachment as recommended by Swanson. The purpose of this study was to biomechanically compare the strength and function of this proposed technique with that of Swanson.

Method: Four pairs of fresh-frozen cadaveric hands were used. The index, long and ring finger were harvested for testing. Twelve digits (3 digits × 4 hands) were designated as control and were used to measure the fixation strength of Swanson’s procedure. The other 12 digits of the paired hands were designated as experimental and were used to measure the fixation strength of the proposed new technique.

Results: The fixation strength mean ± SD were, respectively, 4.74 ± 0.46 N/mm for the control group and 4.62 ± 0.30 for the experimental group. The results were not statistically different, p=0.45.

Conclusion: The simple repair of the central slip without the bone reattachment preserves the function of the extensor mechanism on the PIP joint. In our clinical cases we haven’t noticed any increase in the incidence of extensor lag or boutonnière deformity as a result of that. This technique can also be applied for fracture fixation in the area.

Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. While the benefits are obvious, this excessive bone growth also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear.

This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=15), and compares them with a control group with isolated long bone fractures (n=12). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days(12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-.) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-.; levels of 142.79±29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (.0.009 vs. all other time points, ANOVA). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51±36.81 ng/ml) and long bone (102.28±47.58 ng/ml) groups at 84 days post injury (p=0.009 and p=0.04 respectively, ANOVA).

In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-.; in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.

Introduction: The use of a trans-physeal, trans-articular suture anchor across a joint as a means of internal stabilisation has not previously been described. This study assesses the damage caused by the procedure to the immature porcine hip.

Methods: Six twelve week old pigs underwent unilateral hip surgery. Anteroposterior pelvic radiographs were taken preoperatively and six weeks post-operatively. The acetabular index and diameter of the femoral head ossific nucleus of both hips were measured and compared. Specimens were analysed macroscopically for femoral head diameter, acetabular dimensions and for evidence of gross chondrolysis. Histological analysis was performed to assess the presence of articular chondrolysis and proximal femoral physeal arrest.

Results: In four out of six specimens the rate of change of the acetabular index slowed as compared to the unoperated side, though none worsened. The diameter of the femoral ossific nucleus continued to increase in size at a similar rate to the unoperated side on radiological examination. Similar findings were seen with the macroscopic analysis. Gross and histological analysis of the articular cartilage showed only local areas of chondrolysis, related to the drilling. Metaphyseal growth at the proximal femoral physis was unaffected by the procedure.

Discussion: The use of a trans-articular suture-anchor across the hip appears to cause marginal retardation of acetabular development in the normal hip. The trans-physeal approach to the hip does not appear to affect proximal femoral physeal or epiphyseal growth in the short-term, and the presence of a bioabsorbable suture within the joint did not result in chondrolysis.

The aim of this study is to evaluate the effectiveness of the application of vibration, during the femoral cementation, as a cementing technique.

It has been demonstrated that when vibration of a constant frequency was utilised, flow of low viscosity cement increased with vibration of increasing amplitude up to a particular acceleration. Above this acceleration there was little additional benefit. It has also been shown that when constant amplitude was used the flow increase was uniform over a wide frequency range, eventually falling off over a particular frequency. These results prove that the flow of orthopaedic bone cement is significantly affected by mechanical vibration of the receiving structure. It is our hypothesis that vibration promotes the ingress of bone cement into cancellous bone.

The effect of mechanical vibration in the frequency range 0–500 Hz on the cadaveric human femur has been assessed in the past. It was found that when the bone was fixed at both ends, its resonant frequency was markedly affected by end loading and damping. If the conditions of the experiment were designed to simulate the condition of the femur when prepared for a total hip replacement, it was found that the bone did not resonate but behaved in a mass-like mode. The significance of this observation is that in the event of vibration being applied to enhance the penetration of orthopaedic bone cement, the movement induced in the bone will be proportional to the force applied regardless of frequency.

Aseptic loosening is the single most important long-term complication of total joint arthroplasty. Wear debris induced inflammation stimulates osteoclastic resorption of bone. Cellular mechanisms involved in osteoblast viability in PWD induced inflammation is poorly understood.

Wear induced inflammation increases osteoblast necrosis and susceptibility to death by apoptosis. PMMA cement has a detrimental effect on osteoblast resistance to apoptosis, and that this is via an receptor mediated pathway. Osteoblast cell cultures (Human and MG63) were grown with and without PMMA cement and assessed for apoptosis and necrosis. TNF-α or Fas antibody simulated inflammation. Viability and apoptosis with PI exclusion, flow cytometry and western blotting assessed response.

Cement induced osteoblast necrosis up to 1 hour. This effect was negated after 24 hours. Culture of osteob1asts on cement had no direct effect on spontaneous apoptosis but susceptibility to inflammation was increased.

Polymerised cement has no direct effect on osteoblast cell death. Effects are mediated by inhibiting expression of anti-apoptotic protein (Bcl-2), and increasing susceptibility to inflammatory. Osteoblast resistance to death may represent a novel and important factor in aseptic loosening. The role of gene therapy is explored.

Increased bone turnover and fracture healing is associated with acute spinal cord injuries. Experimental work to date has been confined to animal models. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi.

This paper evaluates two groups of patients with spinal column fractures – those with neurological compromise and those without, and compares them with a control group with isolated long bone fractures. Serum was taken from these patients at 10 days post injury and was analysed for the known osteogenic cytokines Insulin-like Growth Factor-1 (IGF-1) and Transforming Growth Factor-b1 (TGF-b1) as well as being added to an osteoblast cell culture line to analyse cell proliferation.

The results for the IGF-1 show a higher level in the neurology group compared to the no neurology group (p=0.038). In the TGF-B1 assay, the neurology group has a lower level than the other two groups (p< 0.0001 and p=0.002 respectively). However, when this group is subdivided into patients with complete and incomplete neurology, it can be seen that the levels of the complete group are elevated, although not significantly so (p=0.228).

All three groups stimulated markedly increased osteoblast cell proliferation versus a control group (p=0.086, p=0.005 and p=0.002 respectively). However, the neurology group is significantly lower than the other two groups (p=0.007 and p=0.001 respectively). Furthermore the complete group causes a lower proliferation rate than the incomplete group (p=0.539).

In conclusion, at 10 days post injury when the acute inflammatory reaction is subsiding and new bone is being laid down, patients with acute spinal cord injuries have increased bone turnover. This increase is being indirectly mediated by IGF-1, and more elevated levels with more severe neurological compromise suggest a contributory role of TGF-b1. Direct stimulation of osteoblasts does not appear to have any role to play in this accelerated bone healing.

Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear.

This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=11), and compares them with a control group with isolated long bone fractures (n=10). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days(12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-b) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-b levels of 142.79+/−29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (p< 0.001 vs. day 1, day 5 and day 10 and p=0.005 vs. 42 days, ANOVA univariate analysis). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51+/−36.81 ng/ml) and long bone (102.28=/−47.58 ng/ml) groups at 84 days post injury (p=0.011 and p=0.021 respectively, ANOVA univariate analysis). There was statistically significant difference in TGF-b levels seen between the clinically more severely injured patients i.e. complete neurological deficit and the less severely injured patients i.e. incomplete neurological deficit.

In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-b in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.

Aims: The aim of this study was to investigate the ability of control and degenerate human nucleus pulposis to respond to an exogenous proinßammatory stimulus. Methods: Disc material from patients undergoing surgery for scoliosis, sciatica and low back pain was cultured under basal and lipopolysaccharride (LPS) stimulated conditions using a serumless technique. Levels of IL-1β, TNFα, LTB4, GM-CSF, IL-6, IL-8, MCP-1, PGE2, bFGF and TGFβ-1 in the media were estimated using commercially available enzyme linked immunoabsorbent assay kits. Results: Neither basal nor LPS stimulated control nucleus pulposis (NP) produced detectable levels of IL-1β, TNFα, LTB4 or GM-CSF. LPS induced a significant increase in scoliotic disc IL-8 production, p< .02. LPS induced signiþcant increases in degenerate disc IL-6, IL-8 and PGE2 production, p< .01, p< .001 and p< .005 respectively. LPS signiþcantly increased degenerate disc IL-6, IL-8 and PGE2 production compared to LPS stimulated scoliotic disc, p< .05, p< .02 and p< .003 respectively. Conclusions: Human nucleus pulposus can react to a pro-inßammatory stimulus by secreting IL-6, IL-8 and PGE2, suggesting that the NP may actively participate in the genesis of chemical radiculitis and dis-cogenic back pain.

Recently there has been considerable interest in the role of inflammatory mediator production by herniated degenerate discs. Modic has described MR endplate changes which have an inflammatory appearance and have been linked with discogenic back pain. To date there has been no biomechanical investigation of discs with associated Modic changes.

The aim of this study is to determine if degenerate discs with associated Modic changes have higher levels of pro-inflammatory mediator production than those without Modic changes.

Intervertebral disc tissue was obtained from 52 patients undergoing spinal surgery for sciatica [40] and discogram proven discogenic low back pain [12]. The tissue was cultured and the medium analysed for interleukin-6, interleukin-8 and prostaglandin E2 using an enzyme linked immunoabsorbetn assay method. Preoperative MR images of the patients were examined by a double blinded radiologist to determine the Modic status of the cultured disc level.

Forty percent of patients undergoing surgery for discogenic low back pain had a Modic 1 change compared to only 12.5% of patients undergoing surgery for sciatica [p< .05] There was a statistically significant difference between levels of IL-6, IL-8 and PGE2 production by both the Modic1 [M1] and Modic2 [M2] groups compared to the Modic negative [NEG] group. IL-6:NEGvM1 p< .001, NEG v M2 p< .05, IL-8: NEG v M1 p< .01, NEG v M2 p> .05, PGE2: NEG v M1 p< 01, NEG v M2 p< .05.

Modic changes have been associated with positive provocative discography by a number of authors. Pain generation requires the presence of nerves and hyperalgsia inducing mediators. Both IL-8 and PGE2 are known to induce hyperalgesia. The fact that Modic changes are associated with high levels of production of these mediators supports their role as an objective marker of discogenic low back pain.

Introduction: Increased levels of IL-6 and IL-8 have been found in intervertebral disc (IVD) tissue from patients undergoing fusion for discogenic low back pain. The stimuli that induce these mediators in degenerate discs remain unknown. Impaired diffusion of nutrients and wastes to and from the nucleus pulposus (NP) is believed to be an important factor in the degenerative process. The oxygen tension and pH in the NP of degenerating discs are significantly decreased.

Aims: The aims of this study were to (1) demonstrate the ability of porcine NP to respond to a proinflamma-tory stimulus (lipopolysaccharride) in vitro, (2) investigate the effects of pH, pO₂ and glucose concentration on NP proinflammatory mediator secretion and (3) determine if methylprednisolone or indomethacin can block NP proinflammatory mediator secretion.

Methods: IVDs were harvested from 6-month old pigs and dissected under sterile conditions in the laboratory. 200mg samples of NP were cultured under optimal conditions (control), in a 1% O₂ environment, at pH6 and in culture medium without glucose for 72 hours. Blocking experiments were performed by culturing LPS-stimulated samples with either methylprednisolone or indomethacin for 24 hours. IL-6 and IL-8 levels were estimated by ELISA.

Results: Time and dose-response curves were generated for each experiment (results not shown). Results for the optimum dose and at 72 hours incubation were note.

Data = mean ± standard deviation. Statistical analysis was by students t test. A significant result between control and stimulated groups is indicated by: * p=0.024m, † p=0.0007 or ‡ p=0.012.

Methylprednisolone (2mg/ml) caused a significant (p=0.044) 30-fold reduction in IL-6 production and a significant (p=0.00004) 500-fold reduction in IL-8 levels as compared with nucleus pulposus cultured with 5 μg/ml LPS alone for 24 hours.

Addition of 500 μM indomethacin significantly (p=0.04) decreased IL-6 production by a factor of 120 and IL-8 levels by a factor of 50 (p=0.00004).

Necrotic cell death, as measured by lactate dehydrogenase (LDH) concentration, was not significant in any of the experiments.

Degenerate disc disease is a major cause of low back pain, yet its aetiology is still poorly understood. The intervertebral disc is the largest avascular structure in the body. Cells of the nucleus pulposus, therefore, rely on diffusion of oxygen & nutrients down concentration gradients from peripheral vessels in the cartilage end-plates. Thus, there is a low oxygen tension and cellular respiration is largely anaerobic.

The purpose of this study was to examine the effects of inflammation, hypoxia and acidosis on degeneration and pro-inflammatory mediator production in virgin porcine nucleus pulposus cultures.

Intervertebral discs were harvested from normal 6-month old agricultural pigs slaughtered for other purposes. Nucleus pulposus was contained within the annulus until further dissection under sterile conditions in the laboratory was performed. Nucleus pulposus was harvested, diced and divided into 200mg samples. Samples were incubated under optimal conditions.

Discs were cultured in 5μg/ml E. coli lipopolysaccharide, in a hypoxic environment or at low pH. IL-6, IL-8 and LDH assays were performed by ELISA, in accordance with manufacturer’s instructions.

Time and dose-response curves were generated for each experiment (results not shown). Results at 72 hours incubation are tabulated below:

These results confirm that nucleus pulposus is a biochemically active tissue capable of producing pro-inflammatory mediators in response to environmental stresses. IL-6 and IL-8 are both involved in the inflammatory cascade, causing chemotaxis of neutrophils and macrophages to the area. IL-8 itself causes hyperalgesia. Acidotic and inflammatory conditions, but not hypoxia, stimulated cytokine release. This may indicate a protective reduction in cellular activity in reduced oxygen environments. Necrosis, as measured by LDH production, was negligible.

The role of nucleus pulposus (NP) biology in the genesis of sciatica is being increasingly investigated.

The aim of this study was to examine the ability of control and degenerate human nucleus pulposus to respond to an exogenous pro-inflammatory stimulus.

Control disc material was obtained from surgical procedures for scoliosis and degenerate disc tissue from surgical procedures for sciatica and low back pain. Disc specimens were cultured using a serumless technique under basal and lipopolysaccharride (LPS) stimulated conditions and the media harvested, aliquoted and stored at –80°C for subsequent analysis. Levels of IL-1β,TNFα, LTB4, GM-CSF, IL-6, IL-8, MCP-1, PGE2, bFGF and TGFβ-1 in the media were estimated using commercially available enzyme linked immunoabsorbent assay kits.

Neither basal nor LPS stimulated control or degenerate NP produced detectable levels of IL-1β, TNFα, LTB4 or GM-CSF. Control disc IL-8 secretion increased significantly with LPS stimulation, p< .018. Degenerate disc IL-6, IL-8 and PGE2 production increased significantly with LPS stimulation, p< .01, p< .001 and p< .005 respectively. LPS stimulated degenerate NP secreted significantly more IL-6, IL-8 and PGE2 than LPS stimulated control NP, p < 0.05, 0.02 and 0.003 respectively.

LPS induces an increase in both control and degenerate NP mediator production demonstrating the ability of human NP to react to a noxious stimulus by producing pro-inflammatory mediators. The difference in levels of basal and LPS stimulated mediator production between control and degenerate discs show that as a disc degenerates it increases both its level of inflammatory mediator production and its ability to react to a pro-inflammatory stimulus. The increased sensitivity of degenerating human NP to noxious stimuli and increased ability to respond with inflammatory mediator production support the role of NP as an active participant in the genesis of lumbar radiculopathy and discogenic back pain.

Metallic implants are used frequently in the operative repair of joints and fractures in orthopaedic surgery. Metal infection is a catastrophic complication of the surgery with patients loosing their newfound mobility and independence, associated morbidity and mortality is high. Orthopaedic implant infection is chronic and biofilm based. Present treatment focuses on removing the infective substratum and implant surgically as well as prolonged anti-microbial therapy. Biofilms are 500 times more resistant than planktonic strains of bacterial flora to antibiotics, and with evolving resistant strains this form of therapy is loosing ground. Silver coatings on polymers and nylon (catheters, heart valve cuffs, burn dressings) have shown inhibition of this biofilm formation in its adhesion stage. Our aim was to deposit effective, minute, biocompatible, anti-bacterial layers of silver on orthopaedic stainless steel K-wires.

Combining magnetron sputtering with a neutral atom beam (Saddle Field) plasma source at 10⁻⁴ mbar in argon gas at temperatures of 60°C, a silver coating of 99.9% purity was deposited onto stainless steel orthopaedic K-wires. Coating thickness measurements were obtained using glancing angle x-ray diffraction of glass slides coated adjacent to wires. Magnetron parameters were modified to produce varying thickness of silver. Adhesiveness was examined using Rockwell punch tests and tape tests. Silver leaching experiments were carried out in phosphate buffered saline at 37°C for 48hrs and using inductive coupled plasma spectrometry to assess leached silver ions. Surface microscopy visualised physical changes in the coatings. Biofilm adhesion was determined by exposing wires to Staphylococcus aureus ATCC 29213 -NCTC 12973 for 15 min to allow biofilm adhesion and initiation. Wires were then cultured for 24h at 37°C in RPMI. Subsequently wires were sonicated at 50Hz in ringer’s solution and gently vortexed to dislodge biofilm. Sonicate was plated by the log dilution method on blood agar plates. Bacterial colonies were then counted and changes expressed in log factors. Surface biofilms were visualised using scanning electron microscopy. Cytotoxicity was assessed using fibroblast cell cultures lines.

K-wires were coated with 5 to 50 nm of silver by running the magnetron sputtering at low currents. These coatings showed excellent adhesive properties within the 48hr exposed with only 5% of silver leaching in buffered saline. The silver coated wires showed a log 3–4 fold reduction in biofilm formation as compared to control wires. The coatings showed no cytotoxic effects.

Silver coating of medical implants has been shown in urological catheters to reduce biofilm infection. We have perfected a method of depositing thin layers of anti-bacterial silver onto stainless steel, which is both anti-infective and biocompatible. This coating could potentially add to the armourary of anti-infective agents in the elimination of infection related orthopaedic implant failure.

Dupuytren’s contracture is characterised by abnormal fibroblast proliferation and extracellular matrix deposition in the palmar fascia. Fibroblast proliferation and matrix deposition in connective tissues are regulated by cytokines. A number of cytokines including transforming growth factor beta (TGFβ), basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF) and epidermal growth factor (EGF) are known to have potent anabolic effects on connective tissue. The aim of this study was to investigate the role played by anabolic cytokines in the pathogenesis of Dupuytren’s disease.

Twelve specimens of Dupuytren’s contracture and six control specimens of palmar fascia obtained from patients undergoing carpal tunnel release were cultured using a serumless method under standard conditions for 72 h. Levels of TGFβ-1, bFGF, PDGF and EGF in the medium were estimated using an enzyme linked immunoabsorbent assay technique.

Neither Dupuytren’s tissue nor control palmar fascia produced any EGF. The mean (±S.D.)levels of bFGF, PDGF and TGFβ-1 produced by cultured palmar fascia were: 1270 ± 832, 74 ± 24, < 7, and for Dupuytren’s tissue were 722 ± 237, 139 ± 76.6, 645 ± 332, respectively. The levels of PDGF and TGFβ-1 were significantly higher in Dupuytren’s tissue.

PDGF is produced in increased amounts by Dupuytren’s tissue. This may contribute to the fibroblast proliferation and increased ECM deposition observed in this condition. TGFβ-1 is not produced by normal palmar fascia but is produced in large amounts by Dupuytren’s tissue. The major physiologic role of TGFβ-1 is to stimulate formation of fibrous tissue. It plays a major role in wound healing and also in pathological conditions where fibrosis is a prominent feature. Inappropriate production of TGFβ-1 in the palmar fascia in Dupuytren’s disease may play a central role in initiating and stimulating the abnormal fibroblast proliferation and collagen synthesis seen in this condition.

The pathophysiology of discogenic low back pain is poorly understood. The morphological changes occurring in disc degeneration are well documented but unhelpful in determining if a particular degenerate disc will be painful or not.

Herniated intervertebral disc tisssue has been shown to produce a number of pro-inflammatory mediators and cytokines. No similar studies have to date been done utilising disc material from patients with discogenic low back pain.

The aim of this study was to compare levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and Prostaglandin E2 (PGE2) in disc tissue from patients undergoing discectomy for sciatica with that from patients undergoing fusion for discogenic low back pain.

Tissue from 50 patients undergoing discectomy for sciatica and 20 patients undergoing fusion for discogenic low back pain was cultured and the medium harvested for subsequent analysis using an enzyme linked immunoabsorbent assay method. Statistical analysis of the results was performed using the Mann-Whitney test.

Disc specimens from both experimental groups produced measurable levels of all three mediators. Mean production of IL-6, IL-8 and PGE2 in the sciatica group was 26.2±75.7, 247±573 and 2255±3974 respectively. Mean production of IL-6, IL-8 and PGE2 in the low back pain group was 92±154, 776±987 and 3221±3350 respectively (data = mean production pg/ml ± 1 standard deviation).

There was a statistically significant difference between the levels of IL-6 and IL-8 production in the sciatica and low back pain groups (p< 0.006 and p< 0.003 respectively).

The high levels of pro-inflammatory mediator production found in disc tissue from patients undergoing fusion for discogenic LBP may indicate that nucleus pulposis pro-inflammatory mediator production is a major factor in the genesis of a painful lumbar disc. This could explain why some degenerate discs cause LBP while other morphologically similar discs do not.

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 Staph. aureus and Staph. Epidermidis to stainless steel and titanium implants in vitro and in vivo was quantified by sonication and log dilution technique. The response to this surface manipulation of charge varied for both the bacterial species and the type of metallic implant. In vitro studies produced an 88% reduction in Staph. aureus adhesion to stainless steel and a 36% reduction in adhesion to titanium. However Staph. epidermidis showed an increased adhesion to stainless steel (Log 1.81 ± 1.12 in vitro) and to titanium (log 1.80 ± 0.12). Staph aureus demonstrated a log increase of 1.56± 0.09 in adhesion to titanium in vivo while Staph. epidermidis generated a log increase of 3.97± 0.10 in adherent bacteria.

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

Aseptic loosening has become the single most important long-term complication of total joint replacements. The pathophysiology of this loosening is multifactorial in origin ranging from mechanical wear, poor surgical technique, thermal damage and the inflammatory response to particulate wear debris. Cytokines are released in response to macrophage activation by particulate wear debris (PWD), the resultant inflammatory cascade stimulates osteoclastic resorption of bone. The failure of remodelling and repair mechanisms may be as a result of Osteonecrosis from cement (PMMA).

Hypothesis: That PMMA increases Osteoblast susceptibility to necrosis and apoptosis following inflammatory challenge.

Materials and Methods: Osteoblast cell cultures were grown on PMMA cement plates and assessed for apoptosis and necrosis by PI exclusion staining, morphological changes on light and electron microscopy and flow cytometry.

Results: PMMA induced osteonecrosis is highest at 1 hour (34.45) in comparison to control levels (4.55). There is no significant change in Apoptosis at 24 hours. Culture of the Osteoblasts on cement and delayed stimulation with TNF-α causes increased Apoptosis and Necrosis.

Conclusion: PMMA cement causes Osteoblast necrosis in the early stages of polymerisation, after 24 hours there is little increase in apoptosis/necrosis. However Osteoblasts that grow in contact with cement are more susceptible to apoptosis and necrosis following TNFα challenge. This may prove to be an important step in the pathogenesis of Aseptic loosening.

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.