Female pelvic floor disorders – outcome after mesh-augmented procedures and studies on vaginal connective tissue

Pelvic floor disorders, such as urinary incontinence (UI) and pelvic organ prolapse (POP), are common disorders in women. Because of the prolonged life expectancy the prevalence of UI and POP and the probability of ending up in surgery are increasing. However, the pathophysiology behind these disorders is still unsolved. The aim of this thesis is to study possible alterations in the connective tissue in the vaginal wall in patients with and without POP. The long-term outcome and complications of mid-urethral slings (MUS) and mesh-augmented POP surgery were studied in heterogenic patient populations. More elastin and a slight increase in immunostaining of type III and V collagens in tissue samples were obtained from patients with POP compared to controls in whom type I collagen was more prominent. The studies assessing the mesh-augmented procedures revealed good efficacy and high patient satisfaction after a long-term follow-up. Patients operated on because of mixed incontinence and with BMI >30 kg/m² reported significantly more urinary symptoms and a lower quality of life than the patients operated on because of stress urinary incontinence and the ones with BMI ≤30 kg/m². The objective outcome was equal between the groups. Mesh exposure through vaginal mucosa occurred in 23 % of the patients after POP surgery, most of these being asymptomatic. There are alterations in connective tissues in patients with POP. Mid-urethral sling procedures produced good long-term cure rates and patient satisfaction. As to the prolapse surgery, in spite of relatively high exposure rate, mesh-augmented procedure proved to be safe and effective method for the correction of POP.

The little organ book

Ennen jokaista preludia esitetään koraali johon kyseinen preludi perustuu.

Transcriptional Profiling of Organ‐Specific Autoimmunity in Human

Our understanding of the pathogenesis of organ‐specific autoinflammation has been restricted by limited access to the target organs. Peripheral blood, however, as a preferred transportation route for immune cells, provides a window to assess the entire immune system throughout the body. Transcriptional profiling with RNA stabilizing blood collection tubes reflects in vivo expression profiles at the time the blood is drawn, allowing detection of the disease activity in different samples or within the same sample over time. The main objective of this Ph.D. study was to apply gene‐expression microarrays in the characterization of peripheral blood transcriptional profiles in patients with autoimmune diseases. To achieve this goal a custom cDNA microarray targeted for gene‐expression profiling of human immune system was designed and produced. Sample collection and preparation was then optimized to allow gene‐expression profiling from whole‐blood samples. To overcome challenges resulting from minute amounts of sample material, RNA amplification was successfully applied to study pregnancy related immunosuppression in patients with multiple sclerosis (MS). Furthermore, similar sample preparation was applied to characterize longitudinal genome‐wide expression profiles in children with type 1 diabetes (T1D) associated autoantibodies and eventually clinical T1D. Blood transcriptome analyses, using both the ImmunoChip cDNA microarray with targeted probe selection and genome‐wide Affymetrix U133 Plus 2.0 oligonucleotide array, enabled monitoring of autoimmune activity. Novel disease related genes and general autoimmune signatures were identified. Notably, down‐regulation of the HLA class Ib molecules in peripheral blood was associated with disease activity in both MS and T1D. Taken together, these studies demonstrate the potential of peripheral blood transcriptional profiling in biomedical research and diagnostics. Imbalances in peripheral blood transcriptional activity may reveal dynamic changes that are relevant for the disease but might be completely missed in conventional cross‐sectional studies.