34 resultados para CONTRACTION STRESS


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Urinary incontinence is a common problem, affecting one third of the women at least at some time during their lives. The prevalence of urinary incontinence increases with advancing age, and the everyday impact of incontinence on women and on health services is enormous. Urinary incontinence is usually divided into three different subtypes, of which stress urinary incontinence (SUI) is the most common. Surgical treatment is often needed to cure SUI, and modern mid-urethral sling procedures give the possibility to cure this condition with a low risk of adverse events, a problem often associated with the so-called traditional incontinence operations. Life expectancy among women in Western countries has grown beyond 80 years of age. Long-term efficacy of treatment options for urinary incontinence therefore becomes an important issue in a world with limited eco-nomic resources. The purpose of the present study was to prospectively evaluate the long-term efficacy and safety of the first minimally invasive mid-urethral tape procedure, the Tension-free Vaginal Tape (TVT) procedure. The long-term (5-year) follow-up results of the TVT procedure as a repeat operation af-ter an unsuccessful mid-urethral tape operation were studied and the reasons for failure of the first operation were analyzed. Another purpose was to compare the original TVT procedure with a newer modification, the Tension-free Vaginal Tape Obturator (TVT-O) procedure within a multi-centre, randomized context in order to find out possible differences between these procedures re-garding efficacy and complications and the effects on symptoms of urgency. The first study of the present thesis is a prospective, Nordic, three-centre follow-up study of 90 women suffering from SUI, who were treated by means of the TVT procedure. The mean follow-up time was more than eleven years, and the study is the first to be published in connection with more than ten years of follow-up. The second study is a retrospective analysis of 26 women who were treated with a repeat TVT procedure after an unsuccessful primary mid-urethral tape procedure. The third and fourth studies concern 273 women in seven centres in Finland who were ran-domly assigned to the TVT and TVT-O procedures, the 3-year follow-up results of which are pre-sented in this thesis. After eleven years of follow-up, 90% of the women had a negative cough stress test result and a negative 24-h pad test result. The subjective cure rate measured as the women s global impression of cure was 77%, the rate of improvement 20%, and only 3% thought that the treatment had failed. No late-onset adverse effects were found. The repeat TVT procedure was successful in 75% of the cases when women who were cured and women who were significantly improved were included. The reasons for failure of the first operation could be separated into four different groups: tape material-related, operation technique-related, concomitant illness-related and a group with no identifiable reason. There were no intra-operative complications during the repeat operation. In the randomized trial comparing the TVT with the TVT-O procedure a cough stress test results were negative in 94.6% and 89.5% of the women in the two groups, respectively, after a 3-year follow-up period. There were no statistical differences in the cure rate or the rate of complications be-tween the two procedures. Symptoms of urgency were analyzed more closely and the main finding was that the prevalence of urgency symptoms decreased significantly after both mid-urethral sling procedures. The TVT operation was found to be an effective and safe procedure even after eleven years of follow-up. Long-term follow-up after a repeat TVT procedure revealed that the TVT procedure can well be considered after an unsuccessful mid-urethra tape procedure, because 75% of the patients showed significantly improvement of their incontinence. The TVT and TVT-O procedures showed no statistically significant differences in efficacy and rate of complications after three years of follow-up. In most cases these procedures alleviate preoperative symptoms of urgency and the risk of developing de novo urgency is low.

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Various intrinsic and external factors are constantly attacking the cells causing damage to DNA and to other cellular structures. Cells in turn have evolved with different kinds of mechanisms to protect against the attacks and to repair the damage. Ultraviolet radiation (UVR) is one of the major environmental genotoxic carcinogens that causes inflammation, mutations, immunosuppression, accelerated aging of the skin and skin cancers. Epidermis is the outermost layer of the skin consisting mostly of keratinocytes, whose primary function is to protect the skin against e.g. UV radiation. LIM domain proteins are a group of proteins involved in regulation of cell growth, damage signalling, cell fate determination and signal transduction. Despite their two zinc fingers, LIM domains do not bind to DNA, but rather mediate protein-protein interactions and function as modular protein binding interfaces. We initially identified CSRP1 as UVR-regulated transcript by using expression profiling. Here we have further studied the regulation and function of CRP1, a representative of cysteine rich protein- family consisting of two LIM domains. We find that CRP1 is increased by UVR in primary human keratinocytes and in normal human skin fibroblasts. Ectopic expression of CRP1 protected the cells against UVR and provided a survival advantage, whereas silencing of CRP1 rendered the cells more photosensitive. Actinic keratosis is a premalignant lesion of skin caused by excess exposure to sunlight and sunburn, which may lead to formation of squamous cell carcinoma. The expression of CRP1 was increased in basal keratinocytes of Actinic keratosis patient specimens suggesting that CRP1 may be increased by constant exposure to UVR and may provide survival advantage for the cells also in vivo. In squamous cell carcinoma, CRP1 was only expressed in the fibroblasts surrounding the tumour. Moreover, we found that ectopic expression of CRP1 suppresses cell proliferation. Transforming growth factor beta (TGFbeta) is a multifunctional cytokine that regulates several functions in cell including growth, apoptosis and differentiation, and plays important roles in pathological disorders like cancer and fibrosis. We found that TGFbeta-signalling pathway regulates CRP1 at protein, but not at transcriptional level. The increase was mediated both through Smad and non-Smad signalling pathways involving MAPK/p38. Furthermore, we found that TGFbeta-mediated increase in CRP1 was associated with myofibroblast differentiation, and that CRP1 was significantly more expressed in idiopathic pulmonary fibrosis as compared to normal lung specimens. Since cell contractility is a distinct feature of myofibroblasts, and CRP1 is associated with actin cytoskeleton, we studied the role of CRP1 in cell contractility. CRP1 was found to localize to stress fibres that mediate contractility and to mediate myofibroblast contraction. These studies identify CRP1 as a stress responsive and cytokine regulated cytoskeletal protein that participates in pathological processes involved in fibrotic diseases and cancer.

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Context. Turbulent fluxes of angular momentum and heat due to rotationally affected convection play a key role in determining differential rotation of stars. Aims. We compute turbulent angular momentum and heat transport as functions of the rotation rate from stratified convection. We compare results from spherical and Cartesian models in the same parameter regime in order to study whether restricted geometry introduces artefacts into the results. Methods. We employ direct numerical simulations of turbulent convection in spherical and Cartesian geometries. In order to alleviate the computational cost in the spherical runs and to reach as high spatial resolution as possible, we model only parts of the latitude and longitude. The rotational influence, measured by the Coriolis number or inverse Rossby number, is varied from zero to roughly seven, which is the regime that is likely to be realised in the solar convection zone. Cartesian simulations are performed in overlapping parameter regimes. Results. For slow rotation we find that the radial and latitudinal turbulent angular momentum fluxes are directed inward and equatorward, respectively. In the rapid rotation regime the radial flux changes sign in accordance with earlier numerical results, but in contradiction with theory. The latitudinal flux remains mostly equatorward and develops a maximum close to the equator. In Cartesian simulations this peak can be explained by the strong 'banana cells'. Their effect in the spherical case does not appear to be as large. The latitudinal heat flux is mostly equatorward for slow rotation but changes sign for rapid rotation. Longitudinal heat flux is always in the retrograde direction. The rotation profiles vary from anti-solar (slow equator) for slow and intermediate rotation to solar-like (fast equator) for rapid rotation. The solar-like profiles are dominated by the Taylor-Proudman balance.