No description available.

No description available.

Abstract Background: Myofascial trigger points (MTrPs) have been cited as a cause of musculoskeletal pain and dysfunction. There is a paucity of evidence in the lower limb and specifically the triceps surae for the prevalence of MTrPs and efficacy of targeted interventions. Aims: To investigate the prevalence of active and latent MtrPs and associated pressure pain threshold (PPT) of the triceps surae in a healthy university population. To inform future phase 11 investigations on the efficacy of trigger point (TrP) pressure release on triceps surae dysfunction in a patient population. Methods: The first phase of this thesis established a new clinical probe adaptation to algometry. This new adaptation was used in a cross sectional study (n=220) to establish normative data on active and latent MTrP prevalence and PPT in the triceps surae. The results informed a case series on a patient population (n=10) with triceps surae dysfunction. Results: In the preliminary algometer probe study, the majority of participants indicated that PPT measurements using the 2cm2 probe with open cell polyurethane (Poron®) most clinically replicated the palpating thumb. The prevalence study identified no active MTrPs in the triceps surae muscles whereas latent MTrPs were identified in all triceps surae sites with prevalence varying from 13% (right soleus) to 30% (left gastrocnemius). An overall significant difference in PPT values (p<0.001) confirmed latent MTrP prevalence for all sites. The case series demonstrated a prevalence of active and latent MTrPs and myofascial pain syndrome (MPS) for all participants. On discharge the overall prevalence of active MTrPs had decreased in the triceps surae muscles, with individual improvements on outcome measures. The treatment used and appropriate outcomes have informed a future phase II investigation. Conclusion: The original findings of this thesis have enhanced the present MTrP knowledge base and informed clinical practice and future research. (Word count=298)

No description available.

No description available.

No description available.

Collagen is the major protein of bone, and an intronic polymorphism of the COLIA1 gene is associated with low bone mineral density (BMD) and with osteoporotic vertebral fracture. This polymorphism has not been extensively studied in hip fracture. We screened a cohort of 661 females with osteoporotic hip fracture in comparison with 483 controls, and carried out a similar analysis in 169 males. Genotyping was carried out for the COLIA1 <I>sp1</I> and VDR <I>Bsm1</I> polymorphisms. The COLIA 1 <I>Sp1</I> polymorphism was found to be an independent risk factor for hip fracture among females, with 'ss' homozygotes being at increased risk (OR=2.772; 95% CI: 1.11-693; p=0.031). No such difference was seen in relation to VDR genotype. Hip geometry is a risk factor for hip fracture. We investigated the relationship between COLIA1 <I>Sp1 </I> alleles and femoral neck geometry by carrying out measurements in pelvic radiographs from 153 patients with hip fracture, and in DXA scan printouts from 183 normal subjects. While no difference was seen between hip axis length and femoral neck width between COLIA1 genotypes, a wider femoral neck angle (approx. 2°) was seen in individuals expressing the 's' allele (p=0.001; GLM ANOVA). Such an increase in angle may have unfavourable biomechanical consequences in the event of a fall. We also investigated the effect of etidronate therapy on BMD in relation to COLIA1 genotype in a cohort of 108 post-menopausal women using a randomised-controlled trial. Individuals expressing the 's' allele had a heterogeneous BMD response at the hip as compared with 'SS' homozygotes. In general 'Ss' heterozygotes responded poorly to etidronate at the hip, but this differential response was not seen at the lumbar spine. The COLIA1 <I>Sp1</I> polymorphism thus has complex effects on the structure and function of bones as studied at the femoral neck.

The Charcot-Marie-Tooth (CMT) syndrome comprises a heterogeneous group of disorders affecting the peripheral nerves and anterior horn cells of the spinal cord. They constitute a significant proportion of the burden of disability due to the single gene neurological disorders, with a prevalence of 18.1 per 100000 of the South Wales population. The clinical manifestations of these disorders have been documented and their severity assessed using a standard protocol. The commonest disorder in the group is type I hereditary motor and sensory neuropathy (type I HMSN) (prevalence 11.0 per 100000 population) which has been mapped using genetic linkage analysis to chromosome 17, band p11.2 (the CMT1a locus). There was no evidence of genetic heterogeneity (ie any locus other than that at 17p11.2) within the type I HMSN group in the study population. Families with type V HMSN and the spinal form of the Charcot-Marie-Tooth syndrome have been shown not to be linked to this locus in this study. A number of families gave inconclusive results due either to small family size or to lack of informativeness for the polymorphisms studied. It has been possible to document in 91% of affected individuals with type I HMSN, heterozygous for the Msp1 polymorphisms of locus D17S122, trisomy (using the cDNA probe pVAW409R3a) within band 17p11.2. This was not seen in any normal individuals nor in any case of the spinal form of the Charcot-Marie-Tooth syndrome nor in HMSN types II or V. The demonstration of this trisomy in individual cases and families not suitable for conventional linkage analysis provides a rapid means of determining affection status for the CMT1a mutation. Presymptomatic and prenatal testing for this disorder is now feasible for individuals who request it.

No description available.

Development of the synovial joint is complex involving a sequence of precisely controlled events. Separation of the cartilage anlagen involves differential matrix turnover and requires mechanical stimuli, the loss of mechanical stimuli results in joint fusion. Synthesis of hyaluronan at the developing joint line occurs and its continued synthesis is necessary for maintenance of frictionless movement in the adult joint. Hyaluronan is synthesised by synovial fibroblasts and as a component of the synovial fluid and synovium, helps maintain a consistent volume and viscosity of synovial fluid when the joint is flexed. Reduction in hyaluronan concentration within the synovial fluid is associated with osteoarthritis and rheumatoid arthritis. Joints become painful to move and nihility is lost. The study aimed to investigate whether synovial cells from osteoarthritic knees were able to respond to mechanical stimuli and if so, were cells able to modulate hyaluronan synthesis. Results at the cellular level would be the first step in considering exercise based therapies as a treatment for osteoarthritis. A four point bending mechanical loading jig was used to apply mechanical strain to synovial cells. Results indicate that synovial cells from osteoarthritic knees are capable of responding to a brief period of mechanical stimuli and modulate hyaluronan release. Differential expression of the three HAS genes was also observed upon mechanical strain. It was clear however, that the response to strain varied depending on cell passage. As a result, the development of an immortalised synovial cell line was investigated. Data obtained however, showed that ectopic hTERT expression alone was not sufficient to immortalise synovial cells. Development of exercise based therapies for the treatment of osteoarthritis will require a considerable amount of further work. This study however, has demonstrated that alterations in hyaluronan synthase expression and subsequent hyaluronan synthesis by synovial cells occurs upon mechanical stimuli and thus provides a foundation for future studies.