Aims

Hip arthroplasty aims to accurately recreate joint biomechanics. Considerable attention has been paid to vertical and horizontal offset, but femoral head centre in the anteroposterior (AP) plane has received little attention. This study investigates the accuracy of restoration of joint centre of rotation in the AP plane.

Introduction

Cross linked polyethylene (XLPE) has gained popularity as a bearing surface of choice for younger patients despite only medium term results being available for wear rates. Concern remains regarding the long-term stability and durability of these materials. In order to address these issues we present the longest radiological and clinical follow-up of XLPE.

Introduction

There are over 110 special tests described in the literature for clinical examination of the shoulder, but there is no general consensus as to which of these are the most appropriate to use. Individual opinion appears to dictate clinical practice. Rationalising which tests and clinical signs are the most useful would not only be helpful for trainees, but would also improve day to day practice and promote better communication and understanding between clinicians.

Introduction

Four weeks after the earthquake in Kashmir, multidisciplinary surgical teams were organised within the UK (MiST). The aim was to help with disaster victims who had been transferred to Rawalipindi. We reviewed the work carried by one such team from the 5-18 November 2005.

Background: Current treatments for Low back pain (LBP) are often empirical and few directed at the underlying disorder, altered discal cell metabolism, which precipitates the problem. The use of gene therapy to manipulate discal metabolism to treat LBP is an interesting possibility. The Intervertebral disc (IVD) is a therapeutic target in LBP, and one approach to gene therapy would be to isolate IVD chondrocytes (IVDC) and transfer genes Ex Vivo into these cells. Subsequent reinjection of these genetically altered cells into the lumbar IVD, would permit the expression of the trans-gene in vivo, generating the therapeutic protein within the IVD.

Methods: To test the viability of this approach, we isolated human IVDC from patients undergoing surgery, grew them Ex vivo and transfected them with the marker gene LacZ, using an adenovirus vector and the CMV promoter. Expression of the gene was then measured using X-gal staining for the gene product ~-galactosidase.

Results: IVDC infected with adenovirus/CMV-LacZ showed maximal LacZ expression 2 days post infection, with almost 50% of cells displaying X-gal positivity within monolayer cultures and 100% infection within alginate culture, gene expression was maintained up to 4 weeks and control cultures showed no LacZ expression.

Conclusion: This study shows that human IVDC can be transfected with a foreign gene using the adenovirus vector. The gene transduction of a therapeutic gene into IVDC, could provide long lasting effect. In addition the use of inducible promoters could allow for the autoregulation of gene expression.

Background: Low back pain (LBP) is a major cause of disability. However, current treatments are often empirical and few are directed at the underlying disorder, altered discal cell metabolism, which precipitates the problem. The use of gene therapy to manipulate discal metabolism to treat LBP is an interesting possibility. The Intervertebral disc (IVD) is a therapeutic target in LBP, and one approach to gene therapy would be to isolate IVD chondrocytes (IVDC) and transfer genes ex vivo into these cells. Subsequent reinjection of these genetically altered cells into the lumbar IVD, would permit the expression of the transgene in vivo, generating the therapeutic protein within the IVD.

Methods: To test the viability of this approach, we isolated human IVDC from patients undergoing surgery, grew them ex vivo and transfected them with the marker gene LacZ, using an adenovirus vector and the CMV promoter. Expression of the gene was then measured using X-gal staining for the gene product _-galactosidase. Post infection, some cells were treated with forskolin for 24 hours to assess whether expression of the transgene could be manipulated.

Results: IVDC infected with adenovirus/CMV-LacZ showed maximal LacZ expression 2 days post infection, with almost 50% of cells displaying X-gal positivity. Cells maintained a low level of expression for the remaining 12 days of the study. Control cultures showed no LacZ expression. Cells treated with forskolin after infection with adenovirus/CMV-LacZ exhibited 4 times the level of _-galactosidase activity seen in unstimulated cultures.

Conclusion: This study shows that human IVDC can be transfected with a foreign gene using the adenovirus vector. The gene transduction of a therapeutic gene into IVDC could provide a long lasting effect. In addition, the use of inducible promoters could allow for the autoregulation of gene expression.

Purpose and Background: There is increasing evidence that events within the diseased intervertebral disc (IVD) are mediated by locally synthesised cytokines. A prominent histological, imaging and surgical feature of IVD disease is degradation of the cartilaginous discal matrix. Whilst the mechanism by which this is mediated is unknown, in other situations where connective tissues are degraded degradation is the result of production of matrix-degrading enzymes by local connective tissue cells stimulated by cytokines, particularly the beta isoform of interleukin-1 (IL-1β). Included amongst these disorders is osteoarthritis (OA) of diarthrodial joints. OA has many similarities to the discal “degeneration” seen in mechanical back pain syndromes. In the current study, we have used a combination of in-situ techniques to establish if IL-1β is responsible for stimulating matrix degradation in the IVD.

Methods: Using a combination of radioactive in-situ hybridisation (ISH) and competitive in situ zymography (ISZ) we have studied expression of IL-1β and IL-1R – its type 1 receptor (ISH) and matrix degradation (ISZ) in five diseased lumbar IVD taken at spinal fusion surgery and 10 cadaveric IVD (five normal and five diseased). The nucleus pulposus (NP) was separated from the annulus fibrosus and diced into 0.5cm cubes. Half the cubes (typically three) were fixed in formalin and processed into paraffin wax for ISH, and half were used for ISZ. For ISH, 5 μm sections of paraffin-embedded tissue were reacted with cDNA probes radiolabelled with 35S to 580 and 530 base segments of the IL-1β and IL-1R molecules. Hybridisation was disclosed using autoradiography. For ISZ, 50 μm vibratome sections were placed into wells on microscope slides precoated with gelatin. Sections were incubated for 10 days, half in culture medium and half in medium supplemented with human recombinant IL-1 receptor antagonist (IL-1Ra – an inhibitor of IL-1). Sections were photographed at daily intervals to detect evidence of gel degradation.

Results: Chondrocytes within patient and cadaveric diseased but not normal discs expressed mRNA for both IL-1β and IL-1R. By ISZ, the same cells degraded gelatin. Degradation was inhibited by recombinant IL-1Ra.

Conclusion: This study shows that chondrocytes of diseased discs express IL-1 and its receptor. The same cells produced matrix-degrading enzymes by a mechanism that can be inhibited by the IL-1 inhibitor IL-1Ra. IL-1 is a potential therapeutic target for the management of IV disc disease.