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OBJECTIVE: To investigate pelvic floor dysfunction (PFD; urinary incontinence (UI), faecal incontinence (FI) and prolapse) ≥20 years after childbirth and their association with delivery mode history and demographic characteristics. DESIGN: Cohort study with long-term follow-up. SETTING: Maternity units in Aberdeen and Birmingham (UK) and Dunedin (NZ). POPULATION: Women giving birth in 1993/1994. METHODS: Postal questionnaires at 20 (New Zealand) or 26 (United Kingdom) years after index birth (n = 6195). Regression analyses investigated associations between risk factors and UI, FI and prolapse symptoms. MAIN OUTCOME MEASURES: Prevalence of self-reported UI, FI, 'something coming down' from or in the vagina (SCD), and the Pelvic Organ Prolapse-Symptom Score, and relationships with delivery method. RESULTS: Thirty-seven per cent (n = 2270) responded at 20/26 years, of whom 61% reported UI (59% of whom reported more severe UI), 22% FI and 17% prolapse symptoms. Having only caesarean section (CS) was associated with a significantly lower risk of UI (OR 0.63, 95% CI 0.46-0.85), FI (OR 0.63, 95% CI 0.42-0.96) and SCD (OR 0.44, 95% CI 0.27-0.74) compared to only spontaneous vaginal deliveries (SVDs). Having any forceps delivery was associated with reporting FI compared to only SVDs (OR 1.29, 95% CI 1.00-1.66), but there was no association for UI (OR 0.95, 95% CI 0.76-1.19) or SCD (OR 1.05, 95% CI 0.80-1.38). Higher current BMI was associated with all PFD outcomes. CONCLUSIONS: Prevalence of PFD continues to increase up to 26 years following index birth, and differences were observed according to delivery mode history. Exclusive CS was associated with less risk of UI, FI and any prolapse symptoms.
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Objectives: Farnesyltransferase inhibitors (FTI), which inhibit the prenylation of Ras GTPases, were developed as anti-cancer drugs. As additional target proteins for prenylation were identified in the past, it is likely that FTI have potential value for therapeutic purposes beyond cancer. The effect of FTI on B-cells remains unclear. To address this issue, we investigated the effects of in vitro FTI treatment on effector and regulatory B-cells in healthy controls and renal transplant patients. Methods: For this purpose, B-cells were isolated from the peripheral blood of healthy controls and renal transplant patients. Purified B-cells were stimulated via Toll-like-receptor 9 (TLR-9) in the presence or absence of FTI. Regulatory functions, such as IL-10 and Granzyme B (GrB) secretion, were assessed by flow cytometry. In addition, effector B-cell functions, such as plasma cell formation and IgG secretion, were studied. Results: The two FTI Lonafarnib and tipifarnib both suppressed TLR-9-induced B-cell proliferation. Maturation of IL-10 producing B-cells was suppressed by FTI at high concentrations as well as induction of GrB-secreting B-cells. Plasma blast formation and IgG secretion were potently suppressed by FTI. Moreover, purified B-cells from immunosuppressed renal transplant patients were also susceptible to FTI-induced suppression of effector functions, evidenced by diminished IgG secretion. Conclusion: FTI suppress in vitro B-cell proliferation and plasma cell formation while partially preserving IL-10 as well as GrB production of B-cells. Thus, FTI may have immunosuppressive capacity encouraging further studies to investigate the potential immunomodulatory value of this agent.