Doctoral Degrees (General Internal Medicine)
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Browsing Doctoral Degrees (General Internal Medicine) by Subject "Dissertations -- Medicine"
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- ItemThe effect of highly active antiretroviral therapy on Human Papilloma Virus Infection and Cervical Dysplasia in women living with HIV(Stellenbosch : Stellenbosch University, 2014-04) Zeier, Michele D.; Nachega, Jean; Botha, Matthys Hendrik; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Medicine. General Internal Medicine.ENGLISH ABSTRACT: Title The Effect of Highly Active Antiretroviral Therapy on Human Papilloma Virus Infection and Cervical Cytological Abnormalities in Women Living With HIV Background Human Papillomavirus (HPV) infection causes cervical cancer. The prevalence of HPV-related dysplastic lesions is significantly higher in patients co-infected with the HI virus and thought to be linked to possible more persistent HPV infection. There is, however, conflicting evidence as to whether treatment of Human Immunodeficiency Virus (HIV) infection with antiretroviral agents may influence cervical HPV infection and the behaviour of Squamous Intraepithelial Lesions (SIL). Aims To examine the effect of the initiation of combination antiretroviral therapy (cART) on: 1) the persistence of cervical Low-grade SIL (LSIL); 2) The progression of cervical LSIL to High-Grade SIL (HSIL); 3) The effectiveness of excision treatment of HSIL 4) HPV genotypes detected, in HIVinfected and uninfected women at the Infectious Diseases Clinic and the Colposcopy Clinic, Tygerberg Teaching Hospital, Cape Town, South Africa. Design and Methods We conducted a retrospective cohort analysis of 1720 women with LSIL of the survival of progression-free-time or time-to-clearance. Time to progression or persistence was compared according to HIV status, antiretroviral treatment and CD4 count. In another retrospective cohort analysis, we investigated the effectiveness of excision treatment in 1848 women who underwent LLETZ or CKC biopsy was used. Logistic regression and survival analysis were used to compare excision treatment failure and recurrence-free time between groups according to HIV status, antiretroviral therapy and CD4 count. To investigate the effect of antiretroviral therapy on the cervical HPV infection, 300 HIV-infected women were prospectively enrolled and followed at 6-monthly interval. Cytological testing and cervical HPV sampling were done at each visit. Biopsy of suspicious lesions and excision treatment were done at colposcopy clinic according to standard a protocol. The Roche Linear array HPV genotyping test was used for HPV detection. Generalized Estimating Equation (GEE) multivariate analysis was applied to investigate the effect of cART on the detection of HPV infection, while adjusting for time-dependent covariates such as CD4 count, sexual activity and excision treatment. The effect on each HPV type was then also compared to the effect on HPV16. Results Overall, we found that there was no difference between the progression of LSIL to HSIL by HIV status. However, among HIV-infected patients, those who started ART before first LSIL had a significantly lower risk for progression (HR 0.66, 95% CI 0.54-0.81). CD4 count did not have an impact on the risk for progression. We also found lower persistence of SIL in the HIV uninfected group (HR 0.69, 95% CI 0.57-0.85) and that cART was independently associated with decreased persistence of LSIL. On the other hand, a higher CD4 count at the time of first LSIL was not associated with lower persistence of the lesion. HIV infected women with HSIL experienced much higher excision treatment failure than uninfected women (53.8% vs. 26.9%, p<0.001). Factors that improved outcome were higher CD4 count and complete excision. cART reduced the risk of detection of any HPV type by 47% (OR 0.53, 95% 0.49-0.58, p<001). When adjusted for covariates, time of exposure to cART and CD4 had a stronger effect. Every month of cART exposure reduced the risk detection of any HPV type with 7%. The effect was also significant on HPV16 alone (OR 0.93, 95% CI 0.90-0.95). All non-oncogenic subtypes were influenced similarly or more strongly than HPV16, as well as oncogenic HPV52. Only one oncogenic subtype HPV subtype, HPV39, was influenced marginally less (ratio of OR 0.95, CI 0.90-0.99, p=0.04). There was an increased risk for any HPV detection at CD4 count<200 (OR 1.63, 95% CI:1.50-1.77), but when adjusted, the time of cART exposure again remained the strongest predictor of risk (OR 0.94, 95% CI:0.93-0.95). Conclusion cART impact the outcome of cervical HPV infection by increasing clearance, decreasing progression of LSIL and recurrence after excision treatment. This effect is time dependent and also associated with CD4 count. Specifically, HPV16 detection risk is also reduced by cART, and all HPV types are influenced at least as much as HPV16, except possibly HPV39. It seems that increased cervical HIVproviral load is associated with HPV detection risk, and both are lowered by cART time.
- ItemThe effect of statins on bone and mineral metabolism(Stellenbosch : University of Stellenbosch, 2003-04) Maritz, Frans Jacobus; Hough, F. S.; Hulley, P. A.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Internal Medicine.ENGLISH ABSTRACT: The Effect of Statins on Bone and Mineral Metabolism Both statins and amino-bisphosphonates reduce the prenylation of proteins which are involved in cytoskeletal organization and activation of polarized and motile cells. Consequently statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1,5,10 and 20mg/Kg/day), administered orally over 12 weeks to intact female Sprague-Dawley rats, and the effect of simvastatin 20mg/Kg/day in sham and ovariectomised rats, on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH), compared to controls. Similarly, the affect of atorvastatin (2,5mg/Kg/day) and pravastatin (10mg/Kg/day) on BMD was investigated and compared to controls. BMD was decreased by simvastatin 1mg/Kg/day (p = 0.042), atorvastatin (p = 0,0002) and pravastatin (p = 0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA; p = 0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by simvastatin 20mg/Kg/day in two independent groups of intact rats, and reflected by a relatively unchanged BMD. At lower doses, simvastatin 1mg/Kg/day decreased bone formation while increasing bone resorption as reflected by a marked decrease in BMD. Ovariectomised animals receiving simvastatin 20mg/Kg/day showed no change in BMD relative to the untreated ovariectomised controls, their increase in bone formation was smaller than in sham-operated rats receiving simvastatin and there was no change in bone resorption. The dose response curves of simvastatin for bone formation and resorption differed from each other. From these studies it is concluded that:- a) low-dose simvastatin (1mg/Kg/day), atorvastatin 2.5mg/Kg/day) and pravastatin 10mg/Kg/day) decrease BMD in rodents;b) 1mg/Kg/day simvastatin decreases bone formation and increases bone resorption and is reflected by a reduced BMD; c) 20mg/Kg/day simvastatin increases bone formation and resorption and results in an unchanged BMD; d) the effects of simvastatin on QBH differ at different dosages; e) the dose-response curves for QBH parameters of bone resorption and bone formation differ from each other; f) the effects of simvastatin seen in intact rats are not observed in ovariectomised rats; g) simvastatin is unable to prevent the bone loss caused by ovariectomy.