We undertook a prospective randomised controlled trial to investigate the efficacy of autologous retransfusion drains in reducing the need for allogenic blood requirement after unilateral total knee replacement. We also monitored the incidence of post-operative complications. There were 86 patients in the control group, receiving standard care with a vacuum drain, and 92 who received an autologous drain and were retransfused postoperatively. Following serial haemoglobin measurements at 24, 48 and 72 hours, we found no difference in the need for allogenic blood between the two groups (control group 15.1%, retransfusion group 13% (p = 0.439)). The incidence of post-operative complications, such as wound infection, deep-vein thrombosis and chest infection, was also comparable between the groups. There were no adverse reactions associated with the retransfusion of autologous blood. Based on this study, the cost-effectiveness and continued use of autologous drains in total knee replacement should be questioned.
We studied 33 third generation, alumina ceramic-on-ceramic bearings retrieved from cementless total hip replacements after more than six months in situ. Wear volume was measured with a Roundtest machine, and acetabular orientation from the anteroposterior pelvic radiograph. The overall median early wear rate was 0.1 mm3/yr for the femoral heads, and 0.04 mm3/yr for the acetabular liners. We then excluded hips where the components had migrated. In this stable subgroup of 22 bearings, those with an acetabular anteversion of <
15° (seven femoral heads) had a median femoral head wear rate of 1.2 mm3/yr, compared with 0 mm3/yr for those with an anteversion of ≥15° (15 femoral heads, p <
0.001). Even under edge loading, wear volumes with ceramic-on-ceramic bearings are small in comparison to other bearing materials. Low acetabular anteversion is associated with greater wear.
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) 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.
We compared peri-prosthetic bone mineral density between identical cemented and cementless LCS rotating platform total knee arthroplasties. Two matched cohorts had dual energy x-ray absorptiometry scans two years post-operatively using a modified validated densitometric analysis protocol, to assess peri-prosthetic bone mineral density. The knee that was not operated on was also scanned to enable the calculation of a relative bone mineral density difference. Oxford Knee and American Knee Society scores were comparable in the two cohorts. Statistical analysis revealed no significant difference in absolute, or relative peri-prosthetic bone mineral density with respect to the method of fixation. However, the femoral peri-prosthetic bone mineral density and relative bone mineral density difference were significantly decreased, irrespective of the method of fixation, particularly in the anterior distal portion of the femur, with a mean reduction in relative bone mineral density difference of 27%. There was no difference in clinical outcome between the cemented and cementless LCS total knee arthroplasty. However, both produce stress-shielding around the femoral implants. This leads us to question the use of more expensive cementless total knee components.
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.
Injuries to the spinal cord may be associated with increased healing of fractures. This can be of benefit, but excessive bone growth can also cause considerable adverse effects. We evaluated two groups of patients with fractures of the spinal column, those with neurological compromise (n = 10) and those without (n = 15), and also a control group with an isolated fracture of a long bone (n = 12). The level of transforming growth factor-beta (TGF-β), was measured at five time points after injury (days 1, 5, 10, 42 and 84). The peak level of 142.79 ng/ml was found at day 84 in the neurology group (p <
0.001 Our findings suggest that TGF-β may have a role in the increased bone turnover and attendant complications seen in patients with acute injuries to the spinal cord.
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.
Following review of data regarding the preoperative distribution of pain in 2000 patients attending for hip replacement, it was noted that 40% of these patients had complained of pain at or below the knee. We proposed to prospectively investigate the severity and location of pain in patients attending for THR and assessed how this distribution of pain altered following surgery. We also proposed to examine the distribution of radiological wear preoperatively and assess if there is any relationship between localisation of pain, and the severity or distribution of the radiological wear pattern.
All patients underwent a standardised preoperative AP and Lateral x-ray. The AP film was divided into three areas, and the lateral film was divided into 5 areas. Each zone was assessed as to the severity of wear pattern and graded from 1–3 (no change in joint space, decreased joint space, femoral or acetabular destruction).
With regard to the frequencies and severity of x-ray changes, zone-1 (34%) was most commonly severely damaged with femoral and/or acetabular destruction in the AP film, with the anterior and anterolateral areas being most commonly affected areas in the lateral film (20% and 19% respectively). When the distributions and severities of x-ray changes were correlated with the distribution of pain localised pre and postoperatively we were unable to show any association between the degree of radiological wear in any one zone and the locatin of pain identified by the patient. In fact, there was a normal distribution to the severity of radiological damage between each of the zones and localisation of pain in any of the 9 areas.
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-ß) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration. Results show TGF-ß 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 non 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-ß levels seen between the clinically more severely injured patients, ie complete neurological deficit and the less severely injured patients, ie 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-ß in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.
self complete proforma video recording.
ii) A check-list of treatment modalities was constructed from this proforma. Twelve sessions were recorded on video (one new and one review patient for each therapist). The recordings were rated by 3 blinded, independent observers using the checklist. These were compared with the self-report audit forms relating to the same physiotherapy session.
In shallow or deficient sockets, we describe a simple technique by 180° rotation of the Cormet 2000 metal-on-metal resurfacing pegged acetabular prosthesis. This works by utilising ischio-pubic splines for superolateral socket engagement. We have used this technique in three patients with successful outcome avoiding the need of structural graft augmentation. In one patient, this technique was supplemented with cadaveric allograft.
The intended early contact (within first week) of workers absent with musculoskeletal disorders only occurred at one experimental site; the control sites had no procedure for early contact. Absence rates improved over the four years at the intervention sites compared with the control sites: a decrease of 2.0 v an increase of 0.9 days/1000 working hours. The median return-to-work time for early intervention compared with controls was 4 days v 5 days (P=NS). Considering return-to-work time irrespective of whether the intervention was delivered early or late, the median durations were also 4 days v 5 days (P<
0.05). When looking at work retention over 12 months, the median duration of subsequent absence for early intervention was 5 days compared with 11 days for controls (P=NS). For the larger number of workers receiving a late intervention, the median duration of subsequent absence was median 4 days v 11 days for controls (P<
0.05).
Previously defined cut-off scores were used to categorise hypothesised risk; scores beyond the cut-off point were considered detrimental, and the ‘flag’ was considered to be ‘flying’. Odds ratios (OR) were calculated to explore the association between the flags and taking sick leave; a statistically significant association was found with ORs between 1.5 and 2.9. The cut-off scores were then used to compare the length of absence between workers who had zero flags flying and those who had one or more flags flying. Absence over the ensuing 15 months was significantly longer for those people who had one or more flags flying (mean 10.6 days compared with 6.1 days, P<
0.05). There was a trend for longer absence with more flags flying.
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.
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.
This basic science study attempts to explain why patients with spinal cord injuries have been seen to display increased healing of attendant fractures. For the main part, this 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 group 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 (24hrs, 120hrs, 10 days, 6 weeks and 12 weeks). The time period most closely related to the end of the acute inflammatory reaction and the laying down of callus was the 10-day post injury time period. Serum samples taken at this time period were analysed for IGF-1 and TGF-ß levels, both known to initiate osteoblastic activity, using ELISA kits. They were also exposed to an osteoblast cell culture line and cell proliferation was measured. Results show that the group with neurology has increased levels of IGF-1 compared to the other groups (p<
0.14, p<
0.18 respectively, Student’s t-test) but had lower TGF-ß (p<
0.05, p<
0.006) and osteoblast proliferation levels (p<
0.002, p<
0.0001). When the neurology group is subdivided into complete (n=5) and incomplete (n=5), it was shown that the complete group had higher levels of both IGF-1 and TGF-ß. This trend is reversed in the osteoblast proliferation assay. This work, for the first time in human subjects, identifies a factor which may be regulating this complication of acute spinal cord injuries, namely IGF-1. Furthermore, the observed trend in the two cytokines seen in the complete neurology group may suggest a role for TGF-ß. However, the results do show that a direct mediation of this unwanted side effect of spinal cord injuries is unlikely as seen in the proliferation assay. Further work remains to be done to fully understand the complexities of the excessive bone growth recognised in this patient group.
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.
Total knee arthroplasty has evolved considerably over the last thirty years. Early implant design achieved the short-term goals of pain relief and mobility, however loosening and polyethylene wear associated with over constraint was problematic. The Low Contact Stress total knee arthroplasty was developed in an attempt to address the problems of loosening and polyethylene wear. The highly congruent interface between the femoral component and the mobile insert minimises stress within the polyethylene and reduces the potential of wear and damage. Furthermore, the mobile bearing phenomenon minimises both torsional and shear stresses at the component bone interface. In our unit the impact of choice is the LCS rotating platform prosthesis, which is inserted with cruciate-sacrifice. We reviewed 219 patients (272 knees) with an average follow-up of 6 years (5–8 years). In almost all cases the components were inserted with cement fixation. The patella was primarily resurfaced in 20 patients (21 knees). All operations were performed or supervised by the senior author. Female to male ratio was 2:1. Average age at surgery was 68 years (40–86) with osteoarthritis being the commonest primary diagnosis (89%). Postoperative range of motion ranges from 30–130° (average 103°). Average Oxford Knee, American Knee Society Score and Patellar Score was 19 (12–53), 160 (42–199) and 25 (4–30) respectively. Six patients (1.7%) required MUA at six weeks. Two patients (0.6%) required secondary patellar resurfacing. Three patients (0.8%) had revision of their components for persistent pain. At operation all components were noted to be well fixed. Spinout of the rotating platform occurred in one patient (0.3%). This was treated by exchange of the insert. In conclusion, our early results of the LCS rotating platform prosthesis are encouraging with no cases of component loosening to date. This supports the continued use of the implant.
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.
Rapidly progressive cases of primary idiopathic hip osteoarthrosis are well known and recognised. The prevalence reported in the literature varies from 4–18%. Three types have been identified- type 1 (rapid), type 2 (moderate) and type 3 (delayed) depending on the duration of chondrolysis and the subsequent rate of bone loss per year. We reviewed the charts of all patients deemed to be RPO type 1 who had underwent hip arthroplasty under the care of the senior author (DEB) over a two-year period in an attempt to identify risk factors, which may have contributed to the rapid progression of their disease. All patients were treated using a custom femoral stem and a spiked Duraloc cementless socket following careful preparation of the acetabulum. We identified 34 patients (40 hips) with type 1 rapidly progressive osteoarthrosis. Over the same time period 991 patients had underwent primary total hip arthroplasty, giving a prevalence of 4%. Of the 34 patients, 29 were female of average age 70.6 years (range, 51–83 years). All of the bilateral cases (6 patients) were female. Body mass index (BMI) for the female group ranged from 20.6 to 41.1Kg/m2 (average, 28.2kg/m2) whilst that for the males was on average 25.8Kg/m2 (range, 23.4–29.7Kg/m2). Preoperative erythrocyte sedimentation rate (ESR) was 18mm/hr on average for the female group (range, 2–65mm/hr) and ranged from 3–52mm/hr (average, 20mm/hr) for the male patients. The preoperative Oxford Hip Score averaged 51 points for the female group and 48 points for the male group. A detailed review of occupational history did not reveal any common occupational hazard. The majority of patients were non-smokers and denied any regular alcohol intake. Twenty-two patients (65%) had a history of hypertension. Twenty-seven patients (79%) had a history of non-steroidal anti-inflammatory use (most common preparation-diclofenac). Twenty-four patients (71%) resided in a rural area. When compared to a cohort of patients undergoing primary total hip arthroplasty over the same time period, the only statistically significant risk factor identified was female gender. We conclude, that patients who develop rapidly progressive osteoarthrosis of the hip are difficult to identify due to the absence of specific clinical features. We also outline our experience in the management of these technically challenging cases.
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 (24hrs, 120hrs, 10 days, 6 weeks and 12 weeks). The time period most closely related to the end of the acute inflammatory reaction and the laying down of callus was the 10-day post injury time period. Serum samples taken at this time period were analysed for IGF-1 and TGF-β levels, both known to initiate osteoblastic activity, using ELISA kits. They were also exposed to an osteoblast cell culture line and cell proliferation was measured. Results show that the group with neurology has increased levels of IGF-1 compared to the other groups (p<
0.14, p<
0.18 respectively, Student’s t-test) but had lower TGF- (p<
0.05, p<
0.006) and osteoblast proliferation levels (p<
0.002, p<
0.001), despite having a significantly higher cell proliferation than a control group (p<
0.0001). When the neurology group is subdivided into complete (n=5) and incomplete (n=5), it was shown that the complete group had higher levels of both IGF-1 and TGF-. This trend is reversed in the osteoblast proliferation assay. This work, for the first time in human subjects, identifies a factor which may be regulating this complication of acute spinal cord injuries, namely IGF-1. Furthermore, the observed trend in the two cytokines seen in the complete neurology group may suggest a role for TGF-β. However, the results do show that a direct mediation of this unwanted side effect of spinal cord injuries is unlikely as seen in the proliferation assay. Further work remains to be done to fully understand the complexities of the excessive bone growth recognised in this patient group.
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).
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.
Dupuytren’s disease is a benign fibroproliferative disease of unknown aetiology. It is often familial and commonly affects Northern European Caucasian men, but genetic studies have yet to identify the relevant genes. Transforming growth factor beta one (TGF-β1) is a multifunctional cytokine which plays a central role in wound healing and fibrosis. It stimulates the proliferation of fibroblasts and the deposition of extracellular matrix. Previous studies have implicated TGF-β1 in Dupuytren’s disease, suggesting that it may represent a candidate susceptibility gene for this condition. We have investigated the association of four common single nucleotide polymorphisms in TGF-β1 with the risk of developing Dupuytren’s disease. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping TGF-β1 polymorphisms. DNA samples from 135 patients with Dupuytren’s disease and 200 control subjects were examined. There was no statistically significant difference in TGF-β1 genotype or allele frequency distributions between the patients and controls for the codons 10, 25, −509 and −800 polymorphisms. Our observations suggest that common TGF-β1 polymorphisms are not associated with a risk of developing Dupuytren’s disease. These data should be interpreted with caution since the lack of association was shown in only one series of patients with only known, common polymorphisms of TGF-β1. To our knowledge, this is the first report of a case-control association study in Dupuytren’s disease using single nucleotide polymorphisms in TGF-β1.
Traditional biomedical/ergonomic occupational interventions to reduce work loss show limited success. Attention is now focussing on tackling the psychosocial factors that influence occupational back pain. A workforce survey of Glaxo Smith Kline (reported to the Society last year) established that clinical and occupational psychosocial factors (yellow &
blue flags) act independently and may represent obstacles to recovery. Consequently, a nurse-led intervention was devised. Occupational nurses at two manufacturing sites were trained to identify both clinical and occupational psychosocial factors, and address them using a basic ‘counselling’ technique that reinforces evidence-based messages and advice, along with availability of modified work. The program should ideally be implemented within the first days of absence, with ‘case-management’ by the nurse for a further 4 weeks. Control sites simply offer ‘usual management’. Outcomes at 12-month follow-up are rates for work loss/work retention. The target for contacting the worker (3 days) was achieved at one site, but not the other (mean 12 days), thus exerting a differential delay in delivering the intervention. The lack of early identification at the second site was due to local reporting/recording mechanisms. This study reveals a third class of obstacles to recovery – black flags – company policies/procedures that can impede occupational rehabilitation programs.
Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain. We have compared the 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 (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay. There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p <
0.006 and p <
0.003, respectively). The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.
A bipolar spacer was inserted for severe arthritic destruction of the shoulder in 14 patients, and followed up for a mean of 5.9 years. In one patient the operation failed because of infection. Two others required revision for loss of low-friction properties which caused loosening of the humeral component. At the end of the follow-up all the patients showed improvement. The Hospital for Special Surgery pain score had increased from 5.3 to 18.9 and the movement score from 7.5 to 20.1.
We dissected 105 cadaveric shoulders to study the origin of the tendon of the long head of biceps, and examined histologically the interrelationship between the tendon, the supraglenoid tubercle and the superior labrum of the glenoid. In all specimens approximately 50% of the biceps tendon arose directly from the superior glenoid labrum with the remainder attached to the supraglenoid tubercle. The main labral origin was from the posterior labrum in more than half of the specimens, and in a quarter this was the only labral attachment. On the basis of the biceps attachment to the anterior or posterior labrum, we distinguished four types of origin. These normal anatomical variations are significant for arthroscopic diagnosis and may help to explain the various patterns of injury seen in partial or complete detachment of the tendon, the labrum or both.
The long-term functional result of exposed total knee arthroplasty, treated by flap cover, is presented and the results compared with those of a randomly selected control group. The wound was successfully covered and the prosthesis was preserved in 76% of cases, but the final functional score was not as good as in those with primary wound healing.
Augmentation of the acetabular component of total hip replacements is a method of increasing stability and preventing recurrent dislocation. We report a series of mechanical experiments designed to evaluate the turning moments and angles required to dislocate standard, long posterior wall and two different augmented prostheses.
Thirty-three patients with impingement syndrome of the rotator cuff were studied before and at operation. It was shown that the rotator cuff lengthens and twists during elevation of the arm. Elevation is achieved by early glenohumeral abduction and continuous flexion and external rotation. The range of free rotation at the glenohumeral joint diminishes progressively during elevation. Rotator cuff impingement occurs towards the end of the early glenohumeral abduction. Excision arthroplasty of the acromioclavicular joint and anterior acromioplasty is highly effective for impingement under the acromion, but only moderately effective where impingement is under the acromioclavicular joint.
Major ruptures of the rotator cuff were repaired in 89 patients over a six-year period, using an approach through the split deltoid muscle and the bed of the excised outer centimetre of the clavicle. Review of these patients showed that poor results were associated with larger cuff defects, with more pre-operative steroid injections and with pre-operative weakness of the deltoid muscle. A randomised prospective study showed that repair followed by splinting in abduction gave no better results than repair followed by resting the arm at the side. Excision of the coraco-acromial ligament was associated with worse results than leaving its divided halves in situ. Follow-up showed that the results continued to improve for two years after operation; their quality was maintained in patients less than 60 years old, but in those over 60 there was deterioration with time.
Non-operative management has frequently been adopted for closed injuries of the infraclavicular brachial plexus and its branches in the belief that spontaneous recovery is likely to occur, and surgical exploration is performed only if recovery has not occurred in the expected time. This paper correlates the clinical and electrophysiological features with the operative findings in six patients with such injuries. The axillary nerve was ruptured in all six patients, the musculocutaneous nerve in two and the radial nerve in two. When the muscles supplied by a branch of the plexus were denervated, the differentiation between rupture of that branch and a lesion in continuity could only be made by surgical exploration, which should be performed as soon as other injuries permit.