Gluteal Tendinopathy is a poorly understood condition that predominantly affects post-menopausal women. It causes lateral hip pain, worse when lying on the affected side or when walking up a hill or stairs. It has been labelled ˜Greater Trochanteric Pain Syndrome” a name that recognises the lack of understanding of the condition.

Surgical reconstruction of the gluteal cuff is well established and has been undertaken numerous times over the last 16 years by the senior author (AJL). However, the quality of collagen in the tendons can be very poor and this leads to compromised results. We present the results of gluteal cuff reconstruction combined with augmentation using a bioinductive implant.

14 patients (11 female, 3 male; mean age 74.2 ± 6.3 years) with significant symptoms secondary to gluteal tendinopathy that had failed conservative treatment (ultrasound guided injection and structured physiotherapy) underwent surgical reconstruction by the senior author using an open approach. In all cases the iliotibial band was lengthened and the trochanteric bursa excised. The gluteal cuff was reattached using Healicoil anchors (3–5×4.75mm anchors; single anchors but double row repair) and then augmented using a Regeneten patch. Patients were mobilised fully weight bearing post-operatively but were asked to use crutches until they were no longer limping. All had structured post-surgery rehabilitation courtesy of trained physiotherapists.

There were no post-operative complications and all patients reported an improvement in pain levels (Visual Analogue Scale 7.8 pre-op; 2.6 post-op) and functional levels (UCLA Activity Score 3.5 pre-op; 7.1 post-op) at 6 months post surgery.

Surgery for gluteal tendinopathy produces good outcomes and the use of Regeneten as an augment for poor quality collagen is seemingly a safe, helpful addition. Further comparative studies would help clarify this.

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.

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.

The mechanism by which cells die is important in an immune response and its resolution. The role of apoptosis in sepsis and trauma, and its regulation by cytokines is unclear. During the systemic inflammatory response, rates of human neutrophil apoptosis are decreased. Peritoneal macrophage apoptosis has been induced by nitric oxide and Lipopolysaccharide (LPS) in vitro but this has not as yet been demonstrated in vivo.

We examined the induction and effects of macrophage apoptosis in a model of trauma and sepsis.

One hundred female CD-I mice were randomised into four groups: Control, Septic model, challenged with intraperitoneal LPS (1.Img/200ul/mouse), Traumatic model, received hind limb amputation (HLA) and a Combined trauma/septic model. After 24 hrs mice were sacrificed and peritoneal macrophages were assessed for apoptosis by morphology and DNA fragmentation by flow cytometry and DNA gel electrophoresis

Peritoneal lavage from septic models had a decreased percentage of macrophages in comparison to control and trauma groups. The septic model also had a significantly increased incidence of apoptosis in comparison to control and trauma levels. There was no significant difference between control and traumatic groups.

These findings demonstrate that in a murine model of sepsis, lipopolysaccharide induces macrophages apoptosis. Modulation of this immune response may have important roles in the management of trauma patients.

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.

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.

1. Telemetering electromyography has been used to investigate the pattern of activity of certain muscles of the lower limb and back while the subjects walked up and down stairs.

2. During walking up and down stairs each limb has a supporting and swinging phase in each complete step.

3. Walking up stairs revealed the following facts. Firstly, raising the body on to the stair above is brought about by the contraction of the soleus, quadriceps femoris, hamstrings and gluteus maximus; the gluteus medius at the same time prevents the body falling on to the unsupported side. Secondly, the tibialis anterior dorsiflexes the foot during the swinging phase and helps the limb to clear the stair on which the supporting limb is placed. Thirdly, the hamstrings flex the leg at the knee in the early part of the swinging phase and control the terminal part of extension at the knee at the end of this phase. Fourthly, both erectores spinae contract twice in each step and control the forward bending of the body at the vertebral column.

4. Walking down stairs revealed the following. Firstly, the body is lowered on to the stair below by the controlled lengthening of the soleus and quadriceps femoris; the gluteus medius at the same time prevents the body from falling on to the unsupported side. Secondly, the tibialis anterior inverts the foot at the beginning of the supporting phase as the toe is placed on the stair below and dorsiflexes the foot in the middle of the swinging phase. Thirdly, the hamstrings control the extension of the leg at the knee during the middle of the swinging phase. Fourthly, both erectores spinae contract twice in each step and prevent forward bending of the trunk at the vertebral column.