Profile of mortality amongst women with gestational trophoblastic disease (GTD) infected with the human immunodeficiency virus (HIV) in relation to HIV non-infected women.

Thesis (MMed)-University of KwaZulu-Natal, Durban, 2008.OBJECTIVES: To determine if women with Human Immunodeficiency Virus infection with severe degrees of immunosuppression are more predisposed to mortality from Gestational Trophoblastic Disease compared with HIV-infected women with less severe degrees of immunosuppression and Human Immunodefiency Virus (HIV) non-infected women. DESIGN: Retrospective review of case records. METHOD: A retrospective review was performed on all patients with Gestational Trophoblastic from 2003 to July 2007. A chart review was conducted and information captured on a data sheet. This retrospective audit was performed at the combined gynaecology oncology clinic of Inkosi Albert Luthuli Central Hospital. All information was kept confidential and was strictly for the purposes of the audit. STATISTICS: Factors associated with mortality were tested using Fisher's exact test. Odds ratios were reported as a measure of the strength of association. Breslow-Day's test for homogeneity in odds ratios was used to compare mortality in HIV-infected and HIV non-infected women. The analysis was done using Stata 9. i RESULTS: A total of 78 patients with Gestational Trophoblastic Disease were reviewed. There were 53 patients with invasive molar pregnancy and 25 patients with choriocarcinoma. The HIV sero-prevalence was 31%. There were 15 deaths (19%). There were 8 HIV-infected (33%o) and 7 HIV non-infected (13%) women who demised. Of the 8 patients with CD4 counts less than 200 cells/ uL, 7 patients demised. There were no mortalities amongst patients with CD4 counts more than 200 cells/uL. Of the 15 deaths, 5 HIV-infected patients and 5 HIV non-infected patients received chemotherapy. There were 5 patients admitted in very poor general condition precluding the administration of chemotherapy. Amongst the 10 patients who received chemotherapy and demised, the causes of death included widespread disease, multiorgan failure and toxicity due to chemotherapy. CONCLUSION: The overall survival of all patients managed with Gestational Trophoblastic Disease was 82% in keeping with the expected high survival reported elsewhere. The majority of patients who demised were admitted in poor general condition and had abnormal blood profiles. Despite resuscitation, these patients failed to improve precluding the administration of chemotherapy which is the mainstay of treatment. Although the numbers are small, there is clear evidence that if patients are HIV-infected with CD4 counts 200 cells/uL despite transient grade 2 myelotoxicity

Brn-3b enhances the pro-apoptotic effects of p53 but not its induction of cell cycle arrest by cooperating in trans-activation of bax expression

The Brn-3a and Brn-3b transcription factor have opposite and antagonistic effects in neuroblastoma cells since Brn-3a is associated with differentiation whilst Brn-3b enhances proliferation in these cells. In this study, we demonstrate that like Brn-3a, Brn-3b physically interacts with p53. However, whereas Brn-3a repressed p53 mediated Bax expression but cooperated with p53 to increase p21(cip1/waf1), this study demonstrated that co-expression of Brn-3b with p53 increases trans-activation of Bax promoter but not p21(cip1/waf1). Consequently co-expression of Brn-3b with p53 resulted in enhanced apoptosis, which is in contrast to the increased survival and differentiation, when Brn-3a is co-expressed with p53. For Brn-3b to cooperate with p53 on the Bax promoter, it requires binding sites that flank p53 sites on this promoter. Furthermore, neurons from Brn-3b knock-out (KO) mice were resistant to apoptosis and this correlated with reduced Bax expression upon induction of p53 in neurons lacking Brn-3b compared with controls. Thus, the ability of Brn-3b to interact with p53 and modulate Bax expression may demonstrate an important mechanism that helps to determine the fate of cells when p53 is induced

A prospective study evaluating the association of specific risk factors with the development of preeclampsia

Thesis (MMed)--Stellenbosch University, 2015ENGLISH ABSTRACT: OBJECTIVE: To determine the association, if any, between certain risk factors for preeclampsia (PE) and the subsequent development of PE in a local cohort of South African women. DESIGN: A prospective study of women with any risk factor for PE for the duration of their pregnancy. METHOD: A prospective study was performed on selected women referred to Tygerberg Hospital, High-risk antenatal clinic, with specific risk factors for the development of PE. A history-based questionnaire was completed by participants at enrolment and biophysical parameters were recorded at each subsequent antenatal visit, admission and at confinement. All data was captured according to the attached data sheet. All information was kept confidential and was strictly for the purposes of this study. STATISTICS: Statistics were performed using the SPSS statistics software version 17.0. Pearson Chi-square test of independence was used for correlating maternal historical factors, mean arterial pressures (MAP) and cardio-metabolic risk with the development of PE in the index pregnancy. p values were considered significant at values < 0.05. RESULTS: The incidence of PE in the cohort was 11.4%. The age of the patient, parity, history of diabetes mellitus, MAP at booking and MAP at 24 weeks showed no significant association with the development of PE at any gestational age. There was a significant association between a history of PE in a previous pregnancy and the development of PE at any gestational age in the index pregnancy (p < 0.05). There were a significantly higher number of women with a history of chronic hypertension that developed PE in the index pregnancy (p < 0.0001). There were also a significantly greater number of obese women that developed PE at any gestational age in the index pregnancy (p < 0.05). The presence of any one or, a combination of cardio-metabolic risk factors was significantly associated with the development of PE at any gestational age (p < 0.005). CONCLUSION: The changing cardio-metabolic milieu, paralleling the pandemic in obesity, may be impacting on the development of PE. Screening for PE in South Africa may mean; validation of historical factors and MAP in prediction of PE in the local population, and if validated, incorporating it with the cardio-metabolic risk profile to triage women to appropriate levels of care. The pre-pregnancy, antenatal, postpartum and inter-pregnancy intervals can be used to optimise cardio-metabolic risk factors and these women, at the end of their reproductive careers, may benefit from life-long surveillance for cardiovascular disease.AFRIKAANSE OPSOMMING: Doel: Om die assosiasie, indien enige, te bepaal tussen sekere risikofaktore vir pre-eklampsie (PE)1 en die daaropvolgende ontwikkeling van PE in 'n lokale kohort Suid-Afrikaanse vroue. Ontwerp: 'n Prospektiewe studie van vroue met enige risikofaktor vir PE vir die duur van hul swangerskap. Metode: 'n Prospektiewe studie is uitgevoer op geselekteerde vroue wat na Tygerberg Hospitaal hoë risiko voorgeboortekliniek verwys is met spesifieke risikofaktore vir PE. 'n Geskiedenis gebaseerde vraelys is met werwing voltooi en biofisiese parameters is met elke daaropvolgende besoek, toelating en verlossing voltooi. Alle data is volgens die datablad vasgelê. Alle inligting is vertroulik hanteer en was spesifiek vir die doeleindes van die studie. Statistiek: Statistiese ontleding is met SPSS sagteware weergawe 17 uitgevoer. Pearson chi-kwadraat toets is gebruik om moederlike historiese faktore, gemiddelde arteriële druk (MAP) en kardio-metaboliese risiko met die ontwikkeling van PE in die indeks swangerskap te korrelleer. p-waardes < 0.05 is as betekenisvol beskou. Resultate: Die insidensie van PE in die kohort was 11.4%. Die ouderdom van die pasiënt, pariteit, geskiedenis van diabetes mellitus, MAP met bespreking en MAP teen 24 weke swangerskapsduurte had geen betekenisvolle assosiasie met PE op enige swangerskapsduurte nie. Daar was 'n betekenisvolle assosiasie tussen 'n geskiedenis van PE in 'n vorige swangerskap en die ontwikkeling van PE op enige swangerskapsduurte in die indeksswangerskap (p < 0.05). Daar was betekenisvol meer vroue met 'n geskiedenis van chroniese hipertensie wat PE ontwikkel het in die indeksswangerskap (p < 0.0001). Daar was ook betekenisvol meer obees vroue wat PE in die indeksswangerskap ontwikkel het (p < 0.05). Die teenwoordigheid van een, of 'n kombinasie van kardio-metaboliese risikofaktore was betekenisvol geassosieer met die ontwikkeling van PE op enige swangerskapsduurte. (p < 0.05). Gevolgtrekking: Die veranderende kardio-metaboliese milieu, met die pandemie van obesiteit, mag impak op die ontwikkeling van PE. Sifting vir PE in Suid-Afrika mag beteken: bevestiging van historiese faktore en MAP in die voorspelling van PE in die plaaslike bevolking en indien bevestig, die insluiting van kardio-metaboliese risikoprofiel om vroue na toepaslike vlakke van sorg te stuur. Die pre-swangerskap, voorgeboortelike, postpartum, en inter-swangerskap intervalle kan gebruik word om kardio-metaboliese risikofaktore te optimaliseer en hierdie vroue mag aan die einde van hul reproduktiewe lewe baat by lewenslange opvolg vir kardiovaskulêe siekte

Effect of SARS-CoV-2 infection in pregnancy on maternal and neonatal outcomes in research collaboration

In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health’s COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa

Perspective piece effect of SARS-CoV-2 infection in pregnancy on maternal and neonatal outcomes in Africa: An AFREhealth call for evidence through multicountry research collaboration

© 2021 by The American Society of Tropical Medicine and Hygiene In the African context, there is a paucity of data on SARS-CoV-2 infection and associated COVID-19 in pregnancy. Given the endemicity of infections such as malaria, HIV, and tuberculosis (TB) in sub-Saharan Africa (SSA), it is important to evaluate coinfections with SARS-CoV-2 and their impact on maternal/infant outcomes. Robust research is critically needed to evaluate the effects of the added burden of COVID-19 in pregnancy, to help develop evidence-based policies toward improving maternal and infant outcomes. In this perspective, we briefly review current knowledge on the clinical features of COVID-19 in pregnancy; the risks of preterm birth and cesarean delivery secondary to comorbid severity; the effects of maternal SARS-CoV-2 infection on the fetus/neonate; and in utero mother-to-child SARS-CoV-2 transmission. We further highlight the need to conduct multicountry surveillance as well as retrospective and prospective cohort studies across SSA. This will enable assessments of SARS-CoV-2 burden among pregnant African women and improve the understanding of the spectrum of COVID-19 manifestations in this population, which may be living with or without HIV, TB, and/or other coinfections/comorbidities. In addition, multicountry studies will allow a better understanding of risk factors and outcomes to be compared across countries and subregions. Such an approach will encourage and strengthen much-needed intra-African, south-to-south multidisciplinary and interprofessional research collaborations. The African Forum for Research and Education in Health\u27s COVID-19 Research Working Group has embarked upon such a collaboration across Western, Central, Eastern and Southern Africa