published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

No description available.

Colposuspension is an effective treatment for genuine stress incontinence. Continence is restored by positioning the bladder neck in a fixed and elevated retro-pubic position. Despite a high success rate of up to 90%, post-operative complications occur which may have an adverse effect on quality of life. Voiding difficulties develop in 0-43% of patients and detrusor instability in 2- 25%. This considerable variability is due to differences in definition, the timing of assessment, patient selection, and probably also in surgical technique. The natural history of these complications is not clearly known due to the lack of prospective follow-up studies. There is also general uncertainty with regards to their causes. While retrospective studies have attempted to identify pre-operative risk factors, there are no prospective studies which attempt to correlate the anatomical and functional changes caused by surgery with the development of voiding dysfunction and detrusor instability. This study has investigated prospectively 77 women undergoing the operation of colposuspension in relation to the incidence, natural history and causes of post-operative voiding dysfunction and detrusor instability. The complications were identified and followed-up objectively by means of serial urodynamic studies. Patients were also assessed clinically and using quality of life measures. The development of complications were correlated to a number of anatomical and functional changes caused by surgery. Anatomical changes were identified mainly by imaging the bladder neck with Magnetic Resonance Imaging (MRI). Functional changes were identified using urodynamic studies. Voiding dysfunction after colposuspension was common, with 69% of women requiring a catheter for more than seven days, and 28% for longer than 14 days. Improvement occurred gradually in most cases, with only 7. 7% and 2.5% of them needing catheterization at three months and one year respectively. De novo detrusor instability occurred in 21% of women at three months follow-up, and was symptomatic in 66% of these cases. Objective and subjective resolution was seen in 50% of these at one year follow-up. Quality of life after colposuspension improved in most cases despite the development of these complications, probably due to the resolution of their incontinence. Voiding dysfunction and detrusor instability after colposuspension were found to be multifactorial, due to patient related factors (age and detrusor contractility for voiding dysfunction, and age and a past history of bladder neck surgery for detrusor instability), and to operative factors (amount of bladder neck elevation and urethral compression). These findings might lead to the development of preventative measures.

Bladder cancer (BICa) is the second most common genitourinary cancer, affecting both men and women. Most (70%) cases present at the superficial stage; 20% of these recur with muscle-invasive disease. Major genetic alterations associated with BICa include: loss/gain in expression or mutations in Retinoblastoma (RB) gene, human epidermal growth factor receptors (HERs), H-ras, p53 and FGFR3. Only p53 mutations are well correlated with invasive BICa; other changes show variable correlations with disease status. To understand the progression of BICa, a model of nine human BICa cell sublines derived from a single parent but differing in in vivo characteristics, has been developed previously. These cells represent a heterogenous population from a single tumour and a model of different stages of BICa progression, from non-tumourigenic to invasive. Two sublines were selected for further investigation: C3 (non-tumourigenic) and B8 (invasive). These were transfected with green (C3-GSP-2) and red fluorescent reporters (B8-RSP-gck) respectively to investigate the effects of their co-injection in vivo, specifically, promotion of C3 tumour growth by B8 cells. Surprisingly, B8 tumour growth was inhibited by C3 cells in vivo at different cell numbers and proportions of cells injected. Microarray analysis of C3 and B8 cells revealed differential expression of 1367 genes with dramatic differences in the transforming growth factor- ?? and integrin-mediated pathways. Gene expression of BMP2,INHBB, FST, NOG, ID4 and TGF- ??1, in the TGF- ?? pathway was further analysed with qRT-PCR in all nine sublines. Expression of BMP2 was significantly related to tumourigenic potential (p=0.0238, Mann-Whitney) and INHBB to invasive ability (p=0.0476, Mann-Whitney). The BICa model did not include a metastatic component. To broaden the model, cell lines were established from an invaded lymph-node (B8-RSP-LN) and a bonemetastasis (B8-RSP-BN) after subcutaneous and intra-cardiac injection of B8- RSP-gck cells. No significant differences were observed in the migratory capability and anchorage-independent colony formation of these metastatic cells compared with B8 cells. Evaluation of expression of the panel of TGF-beta genes (BMP2, INHBB, FST, NOG, /04 and TGF- (31) and metastasis-related genes (MMP9, MMP2 and KAI1) indicated that expression of BMP2, FST, /04 and MMP9 was decreased or lost in the metastatic sublines.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 8 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Diss. (sammanfattning) Göteborg : Göteborgs universitet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 4 uppsatser.