No description available.

No description available.

Background: Animal studies have shown that the commonly used arthroscopic irrigation fluid, 0.9% normal saline, can be toxic to articular cartilage. There have been several reports of chondrolysis following arthroscopy especially with the use of local anaesthetic pain pumps post operatively. In vitro studies have shown severe toxicity of local anaesthetics to articular cartilage but there are currently no published studies looking at methods to prevent this toxicity. Aims: To study the effect of different irrigation fluids and local anaesthetics on human articular cartilage and the ability of Glucosamine or Corticosteroids to protect against or recover from any potential toxicity. Materials and Methods: Chondral explants obtained from human femoral heads were exposed to different irrigation fluids, local anaesthetics, Glucosamine, Methylprednisolone or culture medium (control) for one hour. After exposure, explants were incubated with radio-labelled[superscript 35]SO[subscript 4] and uptake was measured after 16 hours as an indicator of proteoglycan synthesis. Results: The inhibition of [superscript 35]SO[subscript 4] uptake was 10% by Ringer's solution, 24% by 1.5% Glycine, 31% by 5% Mannitol (p=0.03)and 35% by Normal saline (p=0.04). Lidocaine 1 and 2%, Bupivacaine 0.25 and 0.5% and Levobupivacaine 0.5% were all toxic causing inhibition ranging from 61% to 85% (p<0.001). The addition of Glucosamine or Methylprednisolone at the same time as 0.5% Bupivacaine protected articular cartilage and reduced the inhibition by approximately 50% (p<0.001). Conclusions: Ringer's solution was the least toxic arthroscopic irrigation fluid and should replace normal saline in clinical practice. Intra-articular local anaesthetic injections should only be used with careful consideration of risks and benefits. Further clinical studies are required to assess the potential damage to cartilage from local anaesthetics or normal saline and to investigate the protective effect of Glucosamine or Corticosteroids.

No description available.

Following an introductory chapter on the geographical framework and historical outline of the region, problems and the details of sampling and geographical analysis are contained in Chapters 2 and 3 respectively. Chapter 4 comprises a detailed review of dermal nomenclatures to supplement recommendations for methodological consistency given in Dyn 1977 4, 1-60. Necessary rulings have been amended, especially for the mainlines, to improve interrater accuracy in the scoring of attributes. Chapter 5 concerns details of data management specific to the survey. Chapter 6 deals with the genetics of digital and palmar dermatoglyphics. In Chapters 7 and 8 interrelationships between 152 dermal variables are investigated using bivariate and multivariate procedures. Other matters considered are measurement levels, frequency distributions and transformations, bilateral asymmetry and sex differences. Observations are made on the behaviour of different correlation coefficients. In Chapter 8, factoring of the unilateral digital and unilateral maximal digital ridge counts has been effected and preliminary results reported for the palmar variables. Multiple regression analysis has been carried out on the palmar ridge couits and on the palmar mainlines, in the latter case, in an attempt to demonstrate the possible redundancy of those attributes. Results of the spatial study are contained in Chapters 9 and 10. In Chapter 9, the multiplicity of ways for presenting univariate results has been disclosed, the importance of mapping procedures emphasized and a choropleth design described to locate class intervals for a limited number of regions. In Chapter 10 different distance coefficients, variable subsets and display procedures have been used to disclose population relationships and order in rectangular migration matrices. Multiple regression analyses have been effected between the interregional biological distances and various predictors, and a method described to reveal the effects of sampling error. Concluding matters are dealt with in Chapter 11.

Articular cartilage is a resilient and load bearing material that provides diarthrodial joints with excellent friction, lubrication and wear characteristics required for continuous motion. However, articular cartilage has a poor regenerative capacity and its degeneration is a common cause of morbidity in terms of loss of joint function and osteoarthritis, frequently resulting in the need for total knee replacement. Articular cartilage has a distinct zonal architecture with biochemical and cellular variations existing from the surface zone to the deeper calcified layers. Thus, the development of the tissue must be stringently controlled, both spatially and temporally in order for the complex structure to be established. Importantly, the surface zone is believed to be responsible for the appositional growth of articular cartilage during development and this growth is believed to be driven by a population of slow cycling progenitor cells within the surface zone itself. The focus of this thesis is the isolation and characterisation of articular cartilage progenitor cells together with an exploration of the cells capabilities in potential cartilage repair therapies. The cells were identified on the basis of differential adhesion assays and colony forming ability. Subsequent experiments were carried out to show the differential expression of various cell surface markers eg Notch 1 receptors and the role of the onco-foetal form of fibronectin, known as fibronectin-EDA on the modulation of cell behaviour. In terms of the potential of the cells for use in tissue engineering, a promising feature of the cells is the discovery that enriched populations of the cells can undergo extensive expansion in simple monolayer cultures and yet retain their ability to undergo chondrogenic differentiation. This property may enable the use of the cells in commercial cartilage repair and/or tissue engineering strategies.

No description available.

Monitoring of gait in daily living allows a quantitative analysis of walking in unrestricted conditions, with many potential clinical applications. This thesis aims at addressing the limitations that still hinder the wider adoption of this approach in clinical practice, providing healthcare professionals and researchers new tools which may impact on current gait assessment procedures and improve the treatment of many diseases leading to – or generated by – mobility impairments. The thesis comprises four experimental sections: Accuracy of commercially-available devices. Step detection accuracy in currently available physical activity monitors was assessed in healthy individuals. The best performing device was then tested in multiple sclerosis patients, showing reliability but highly speed-dependent accuracy. These findings suggest that a short set of tests performed in controlled conditions could inform researchers before starting unsupervised monitoring of gait in patients. Differences between laboratory and free-living gait parameters. The study assessed the accuracy of two algorithms for gait event detection, and provided normative values of gait temporal parameters for healthy subjects in different environments and types of walking. A pilot study toward clinical application. This pilot study compared laboratory based tests with daily living assessment of gait features in multiple sclerosis patients. Results provided clear evidence that in this population clinical gait tests might not represent typical gait patterns of daily living. Analysis of free-living walking in patients with Diabetes. A systematic review is presented looking for evidence of the effectiveness of walking as physical activity to reduce inflammation. Then, cadence and step duration variability are examined during free-living walking in a group of patients with diabetes. This thesis systematically highlighted potential and actual limitations in the use of wearable sensors for gait monitoring in daily life, providing clear practical indications and normative values which are essential for the widespread informed and effective clinical adoption of this technology.

Introduction: The role of microRNAs (miRs) in articular cartilage is still not well established, however many studies have reported the differential expression of a number of miRs between healthy and osteoarthritic (OA) articular cartilage. These studies have focused on the OA pathology itself without considering the impact of mechanical load, which is one of the major risk factors implicated in the loss of cartilage integrity and the onset of OA development. Previous studies have already identified a number of mechanically-regulated miRs, therefore I hypothesised that (i) physiological and non-physiological magnitudes of compressive load differentially regulate the expression of mechano-sensitive miRs, and (ii) mechanically-regulated miRs differentially expressed in response to a non-physiological magnitude of load are implicated in the regulation of mechano-sensitive matrix molecule turnover and are involved in OA development. Results: Transcriptional assessment of selected mechanically-regulated matrix molecules demonstrated that loading regimes of 2.5MPa and 7MPa (1Hz, 15 minutes) induced homeostatic and catabolic responses at the gene level respectively, therefore they were selected to represent ‘physiological’ and ‘non-physiological’ magnitudes of loads which have the potential to induce biosynthetic and degradative protein responses if applied for prolonged periods of time. Next generation sequencing (NGS) of articular cartilage miRs libraries demonstrated that the alteration in expression of specific miRs occurs in a magnitude- and time-dependent manner. However, 24h post-load, according to the NGS data, seems to be the most appropriate to observe significant changes in miRs levels. Validation of a few miRs, important for cartilage integrity, at 24h post-load indicated up-regulation of miR-21-5p, miR-27a-5p, miR-221 and miR-222 and down-regulation of miR-483 in response to the ‘non-physiological’ 7MPa magnitude (1Hz, 15 minutes) whereas in explants subjected to a ‘physiological’ 2.5MPa magnitude (1Hz, 15 minutes) the level of these miRs remained unchanged. Identification of target genes of miR-21-5p, miR-221 and miR-222 performed by NGS of RNA extracted from primary articular chondrocytes transfected with specific miR inhibitors demonstrated a number of differentially expressed genes. qPCR validation of these potential miR target genes on RNA collected from cells transfected with functional miR-21-5p, miR-221 and miR-222 inhibitors or mimics identified TIMP-3 as a direct target of miR-21-5p, miR-221 and miR-222, whereas CPEB was targeted by miR-21-5p. Conclusion: This current study confirms the reported mechano-regulation of miR-221 and miR-222, and furthermore demonstrates the novel mechano-regulation of miR-21-5p, miR-27a-5p and miR-483 in cartilage explants. This work is the first to identify TIMP-3 as a target of miR-21-5p and miR-221/-222, and CPEB3 as a direct target of miR-21-5p in primary chondrocytes. An association between the identified differentially-regulated miRs in response to a non-physiological magnitude of load, with those that are expressed in OA cartilage and their regulatory effect on molecules important for cartilage integrity, described in this thesis may pioneer future studies aimed at identifying cartilage biomarkers of load-induced OA and provide therapeutic potential for OA treatment.

A musculoskeletal model of the lower limb has been implemented and assessed in order to be used as a predictive tool to quantify the hip contact force (HCF) vector acting between the femoral head and the pelvic acetabulum. The model is based on a published anatomical dataset, which has been critically revised and extended. The HCFs obtained through the model have been assessed at multiple levels of detail against measurements from instrumented prostheses from a publicly available dataset. In the first instance, a direct comparison has been undertaken in order to verify predicted HCF magnitudes close to the measured and muscle recruitment consistent with electromyographic activation profiles reported in the literature. Secondly, a trend validation was performed to ensure the correct behaviour of the model when the same daily living task (level walking) was performed with different modalities. Finally, a falsification of the model was performed by challenging it to predict the exact components of the measured hip contact forces for both level walking and stair climbing. The closest achievable predictions were also calculated, together with the accuracy of a conventional use of the model not exploiting a priori knowledge of the joint contact forces. Once the assessment of the model was completed, a dataset of anthropometric, kinematic and kinetic data was collected on eight young healthy subjects performing daily living activities. As a demonstration of the potential use of the dataset, a subject specific model was generated and used to estimate HCF direction and magnitude for level walking and stair climbing, the same activities investigated during model validation. The model was further extended in order to include the upper part of the body and potentially analyze full body kinematics and kinetics. A further modified version of the model was finally developed in order to be used in finite elements analyses or more generally in applications requiring equilibrated sets of muscle and joint forces acting on a bone structure, as the highly discretized representation of the muscles makes the model particularly suitable for this kind of use. The developed model has been implemented in the open source software OpenSim and is freely available for download and use in research.