Preterm birth (PTB), defined as birth before 37 weeks of gestation, is the leading cause of neonatal morbidity, and survivors can face lifelong medical difficulties. PTB remains a clinical challenge worldwide, with rates of PTB rising in all countries with reliable data. A lack in understanding of the mechanisms that lead to PTB has made developing diagnostics and therapeutics challenging, and existing ones are often ineffective. For a successful pregnancy, the major reproductive organs and surrounding tissues must sustain the growing loads of pregnancy. The cervix is one of these major reproductive organs. The cervix sits at the base of the uterus and has a versatile mechanical function in pregnancy. First, it must stay closed during gestation while the fetus develops; second, the cervix must remodel sufficiently and timely to dilate and allow delivery. The proper timing and extent of remodeling are critical for a healthy pregnancy. Improper cervical remodeling is a final common pathway to PTB and is the tissue of focus in this thesis. To improve our ability to identify when a PTB birth will occur and ultimately be able to treat those at risk, this thesis will identify the mechanical role of three extracellular matrix (ECM) components at various gestational ages and evaluate the ability of two major hormones to alter cervix function. Using experimental techniques (large-deformation tensile testing, digital-image correlation, imaging, biochemical) and theoretical and computational techniques (constitutive modeling, finite element analysis), the mechanical behavior of whole mouse cervices will be characterized in wild type, genetic knockout, and hormone-treated animals. First, the loss of both Class-I small leucine rich proteoglycans (SLRPs), decorin and biglycan, is detrimental to cervix function in late gestation. When the cervix should be most compliant and extensible, cervices without decorin and biglycan cannot stretch and are as stiff as the nonpregnant cervix. The loss of these proteoglycans also slows the cervix’s stress dissipation mechanism in late gestation, which could put the cervix at increased risk for damage. The mechanism of stiffening and lost viscoelasticity indicates the fibril crosslinking associated with SLRPs is a structural mechanism of the ECM contributing to cervical remodeling. Second, the loss of hyaluronic acid diminishes the cervix’s mechanical function at every gestational age tested. For nonpregnant to mid-gestational age, the cervix is softer than normal. Though by late gestation, the loss of hyaluronic acid stiffens the cervix; this is at a point when the cervix should be at its softest. The loss of hyaluronic acid also decreases the cervix’s protective stress dissipation mechanism in late gestation. There is limited knowledge of the interaction of collagen, elastic fibers, and hyaluronic acid in the cervix. The significant mechanical role of hyaluronic acid in the cervix warrants exploration of the structural mechanisms of these functional changes. Third, the loss of endogenous hormones stiffens the tissue and increases extensibility compared to the nonpregnant cervix. The administration of estrogen recovers large amounts of extensibility (beyond the stretch level of a late gestation cervix), stiffens the tissue (such that it is stiffer than a nonpregnant cervix), and recovers a significant amount of cervix strength. Fourth, relaxin increases cervix extensibility in mid-gestation and endows the cervix with viscoelastic ability in late gestation. Altogether, understanding the correlation between these extracellular matrix components, hormones, and functional changes of the cervix is fundamental to teasing out mechanisms of cervical remodeling and developing improved PTB diagnostics and therapeutics.

Submitted in fulfillment of the requirements of the degree of the Master of Technology : Radiography, Durban University of Technology, 2014. / Research Aims The purpose of this study is to compare 2D HDR Brachytherapy planning and 3D HDR Brachytherapy planning in terms of dose distribution in order to accurately determine bladder and rectal doses. Further research questions were explored to determine whether relationships existed between Computer Tomography volumes and bladder and rectum dose. Methodology The 30 female patients that volunteered for the study were conveniently selected. Their age and ethnic group did not contribute to their selection. All participants were prepared for cervical HDR Brachytherapy. The Brachytherapy templates were computer generated and treatments were given based on the templates. They then had a Computer Tomography (CT) scan (3D data set) of the pelvis. The computer generated templates for 2D Brachytherapy planning were applied to the CT data set i.e. 2DBP. The plans were optimised to take into consideration the dose to the bladder and the rectum i.e. 3DBP. The 2DBP and the 3DBP were then evaluated in order to determine which method of planning yielded more acceptable dose distributions to the bladder and rectum. Results Significant differences in dose distribution were noted on comparison of 2DBP and 3DBP. A significant relationship was noted in respect of bladder mean dose and rectum mean dose. 3DBP proved to be more efficient in yielding lower mean dose to the bladder and the rectum. Whilst a significant relationship was noted in respect of bladder maximum dose, an insignificant relationship was noted for rectum maximum dose. Therefore, the efficiency of 3DBP to yield lower bladder maximum dose was established but its efficiency to yield lower rectum maximum dose is questionable. This has implications for the management of patients’ with cervical cancer who require cervical Brachytherapy. Recommendations It is imperative that imaging modalities be used for the accurate planning of cervical Brachytherapy. This study recommends that CT be used for HDR Brachytherapy planning by proving its greater efficiency compared to template planning.

Thesis (MCur)--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Title: Awareness, knowledge and experiences of women regarding cervical cancer in rural Kwa- Zulu-Natal, South Africa. Background: Cervical cancer has been identified as the second most common cancer in women and contributes to the high mortality rate in women. Among all cancers in women, cervical cancer is rated the second most common cancer in women worldwide. In poorly resourced settings, access to services offering cervical screening is still a challenge and it is estimated that more than 50% of women in developing countries have never had a single screening test for cervical abnormalities. Purpose: The purpose of this study was to assess women’s awareness, attitudes and experiences regarding cervical smear testing and for cervical cancer in rural KwaZulu-Natal and to better understand factors influencing access to and utilization of cervical cancer screening services by rural women. Methods: The method employed was a descriptive study using a questionnaire to collect quantitative data. The sample consisted of 69 women aged 30 years and above, was taken from women who were enrolled in the on-going Microbicide Clinical Trial and attending follow-up clinic visits between July and August 2009. The primary outcome measure for the analyses was who has been screened for cervical cancer and this was assessed from the previous history reports of the women. The secondary outcome measure was to investigate knowledge and perceptions regarding cervical cancer and screening. Socio-demographic factors associated with having been screened were also explored. Results: Out of 69 women, only N=13 (18.8%) reported ever screening for cervical cancer. More than half of women who had never screened reported lack of information as a barrier to screening N=50 (71.4%). Older women aged 35-45, 45 and above were less likely to screen compared to women aged 30 to 34 years of age (OR: 0.06). Having an educational background seemed to increase the likelihood to screen, twice if a woman had primary education (OR 2.0) and almost three times (OR 2.67) if a woman had a secondary or a higher education. More than half of the respondents considered themselves at risk for cervical cancer N=42 (60.8%) and almost all showed a willingness to screen in the future N=64 (93%). Conclusion: Most of the women in this study had never been screened for cervical cancer in their lifetime as reflected by n=55 (82%) while only n=14 (18%) ever screened for cervical cancer. The results of this study cannot be generalised to the population due to the small sample size. However, there is need to facilitate comprehensive health education and the implementation of cervical screening programmes to target women in rural communities to contribute to the success of the cervical screening programme. The results of this study showed that 60% of respondents were informed by health care professionals on cervical cancer screening. Health care workers also should play a vital role in educating communities on cervical cancer and on the benefits for cervical cancer screening, through reaching all patients who utilise health care services with cervical cancer information and also communities through outreach programmes. / AFRIKAANSE OPSOMMING: Titel: Vrouens se bewustheid, houding en ervarings van smeertoetse en servikale karsinoom in die landelike gebiede van KwaZulu-Natal Agtergrond: Servikale kanker is geïdentifiseer as die tweede mees algemene karsinoom in vrouens en dra by tot die hoë sterftesyfer in vrouens. Van al die tipes karsinoom wat by vrouens voorkom, is servikale karsinoom die tweede mees algemene karsinoom onder vrouens wêreldwyd. Die beskikbaarheid van dienste wat servikale smeer toetsing bied, is nog steeds ’n uitdaging in arm gebiede en daar word geskat dat meer as 50 % van vrouens in ontwikkelende lande nog nooit ’n toets vir enige servikale abnormaliteite gehad het nie. Doel: Die doel van hierdie studie was om vrouens se bewustheid, houding en ervarings van servikale smeer toetsing en van servikale karsinoom in die plattelandse gebiede van KwaZulu-Natal te toets en om ’n beter begrip te kry van faktore wat ’n invloed het op toegang tot en gebruik van servikalesmeer toetsing by vrouens in landelike areas. Metode: Die metode wat gebruik is, is ’n beskrywende studie waarin gebruik gemaak is van vraelyste om kwantitatiewe data te versamel. Die monster het bestaand uit 69 vrouens, ouderdom 30 jaar en ouer, wat deelnemers was aan die “Microbicide Kliniese Navorsingsprojek” en wat opvolgbesoeke by klinieke gehad het tussen Julie en Augustus 2008. Die primêre bevinding, wie al ooit vir servikale karsinoom getoets is, is bereik deur die inligting in die laboratorium verslae van die vroue na te gaan. Die sekondêre bevinding was om die deelnemers se kennis en persepsies aangaande servikale karsinoom te toets. Sosio-demografiese faktore wat verband hou met of deelnemers ooit getoets is, is ook ondersoek. Resultate: Van die 69 vrouens, het slegs N=13 (18.8 %) gerapporteer dat hulle ooit getoets is vir servikale kasinoom. Meer as die helfte van die vrouens wat ooit getoets is vir servikale karsinoom het gerapporteer dat ’n gebrek aan inligting ’n weerhoudende faktor was tot die toetse, N=50 (71.4%). Ouer vrouens tussen die ouderdom van 35 – 45, 45 en ouer was minder bereid om te toets in vergelyking met vrouens tussen die ouderdom van 30 tot 34 (OR: 0.06). Dit blyk asof skoolonderrig die kanse op toetsing verhoog, vrouens met primêre skoolopleiding se kanse dat hulle getoets is, is twee keer groter (OR 2.0) en amper drie keer meer (OR 2.67) as ’n vrou sekondêre onderrig of hoër onderrig ontvang het. Meer as die helfte van die respondente dink hulle loop ’n risiko om servikale kanker te kry N=42 (60.8%) en feitlik almal was bereid om hulle te laat toets in die toekoms N=64 (93 %). Bevinding: Die meeste vroue in hierdie studie n=55 (82%) was nog nooit in hul leeftyd getoets vir servikale karsinoom nie terwyl slegs n=14 (18%) ooit getoets was vir servikale karsinoom. Die resultate van hierdie studie kan nie veralgemeen word nie, aangesien die navorsingspopulasie as gevolg van die klein steekproef te klein was. Nietemin is daar ‘n behoefte vir die fasilitering van omvattende gesondheidsopvoeding en die implementering van servikalesmeer toetsing programme. Die resultate van hierdie studie het aangedui dat 60% van die respondente deur professionele gesondheids werkers ingelig is met betrekking tot servikalesmeer toetsing. Gesondheidswerkers behoort ‘n vitale rol te speel in die opvoeding van gemeenskappe in verband met servikale karsinoom en die voordele van hiervan deur alle pasiente wat gesondheidsdienste benut in te lig omtrent servikale karsinoom en ook deur middel van gemeenskaps-uitreikings programme.

Thesis (PhD)--Stellenbosch University, 2014. / 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. / AFRIKAANSE OPSOMMING: Titel Die Effek van Kombinasie Antiretrovirale Terapie op Menslike Papilloomvirusinfeksie en Servikale Sitologiese Abnormaliteite in Menslike Immuniteitsgebrekvirus-geïnfekteerde Vroue Agtergrond Menslike Papilloomvirusinfeksie (MPV) veroorsaak servikale kanker. Die prevalensie van MPVverwante displastiese letsels is betekenisvol hoër in pasiënte wie ook met Menslike Immuniteitsgebrekvirus (MIV) geïnfekteer is en dit word gereken dat dit te wyte is aan meer persisterende MPV infeksie. Daar is egter teenstrydige bewyse oor of die behandeling van MIV infeksie met antiretrovirale (ART) middels die infeksie met MPV en die gedrag van Plaveisel Intraepiletiële letsels (PIL) kan beïnvloed. Doelwitte Om die effek van die inisiasie van kombinasie ART op: 1) die persistering van Laegraadse PIL (LPIL); 2) die progressie van servikale LPIL na hoëgraadse PIL (HPIL) 3) die sukses van eksisiebehandeling van HPIL; 4) MPV genotypies waarneembaar, in MIV-geïnfekteerde vroue by die Infeksiesiektekliniek en die Kolposkopiekliniek,Tygerberghospitaal, Kaapstad, Suid-Afrika, te ondersoek. Studie-ontwerp en Metodes `n Retrospektiewe kohort-analise op 1720 vroue met LPIL van die oorlewing van progressive-vrye tyd en tyd tot opklaring van PIL is gedoen. Tyd tot progressie of opklaring is vergelyk na aanleiding van die pasiënt se MIV status, behandeling met antiretrovirale terapie en CD4-telling. In nog `n retrospektiewe kohort-analise is die effektiwiteit van eksisiebehandeling in 1848 vroue wie LLETZ or Kouemeskonus eksisie ondergaan het, ondersoek. Logistiese regressie en oorlewingsanalise is toegepas om die voorkoms van onsuksesvolle uitkoms en tyd sonder herhaling van letsels tussen groepe te vergelyk na aanleiding van MIV status, ART en CD4-telling. Om die effek van antiretroviral therapie op servikale MPV infeksie te ondersoek, is 300 MIVgeïnfekteerde vroue opgeneem in `n prospektiewe studie en sesmaandeliks opgevolg. Sitologiese en MPV servikale smere is met elke besoek geneem. Biopsies van verdagte letsels en eksisiebehandeling is by die Kolposkopiekliniek gedoen volgens die standaardpraktyk. Die Roche Linear Array HPV Genotyping toets is gebruik vir MPV deteksie. Algemeen-beraamde vergelyking (GEE) meerveranderlike analise is toegepas om die effek van die anti-MIV terapie op die teenwoordigheid van MPV op die serviks te ondersoek. Die aangepaste effek is ook getoets deur die CD4-telling, die seksuele aktiwiteits- en eksisiebehandelingstatus by elke besoek in ag te neem. Die effek op elke MPV genotipe is laastens dan ook vergelyk met die effek op ‘n spesifieke basislyn genotype; in hierdie geval was MPV16 gekies. Resultate Daar was geen statisties beduidende verskil tussen die progressie van LPIL na HPIL na aanleding van HIV status nie, maar pasiënte wie met ART begin het voordat hulle vir die eerste keer met LPIL gediagnoseer was, het ‘n laer risiko gehad vir progressie (HR 0.66, 95% VI 0.54-0.81). Daar is ook gevind dat dit onafhanklik van die CD4 telling was. Die persistering van PIL was laer in die MIV negatiewe groep (HR 0.69, 95% VI 0.57-0.85), maar ook hier was antiretrovirale behandeling geassosieer met verminderde persistering. Weer eens was daar nie ‘n verband met die CD4 telling nie. MIV-geinfekteerde vroue met HPILwas baie meer geneig tot gefaalde eksisiebehandeling (53.8% teenoor 26.9%, p<0.001). Verbeterde uitkoms was geassosieer met ‘n hoër CD4-telling en ‘n eksisie wat as volledig beskryf was. ART wat reeds voor die eksisiebehandeling begin was, het nie die risiko vir onsuskesvolle uitkoms statisties beduidend verminder nie, maar het egter die risiko vir herhaling van letsels na die eksisie sterk verlaag. ART het die kans dat enige MPV tipe waargeneem sou word, met 47% verlaag (OR 0.53, 95% VI 0.49-0.58, p<001). Wanneer aangepas vir ander faktore, was die tyd wat verloop het sedert ART begin was, sowel as vir die CD4 telling, sterker. Vir elke maand sedert ART begin was, het die kans dat enige MPV tipe waargeneem word, met 7% verminder. `n Soortgelyke effek is op HPV16 alleen gevind (OR 0.93, 95%, VI 0.90-0.95). Die effek was net so sterk of sterker op alle subtipes. Slegs een onkogeniese subtipe, MPV39, was gering minder beïnvloed (ratio van OR 0.95, VI 0.90-0.99, p=0.04). Die kans vir waarneming van enige MPV subtype is hoër wanneer die CD4 telling laer as 200 selle/ɥl is (OR 1.63, 95% VI: 1.50-1.77), maar wanneer aangepas, was die tyd van ART weer eens die sterkste voorspeller van MPV infeksie (OR 0.94, 95% VI:0.93-0.95). Gevolgtrekkings ART verbeter die uitkoms van servikale infeksie met MPV deur progressie en persistering van LPIL en herhaling van PIL na eksisie te verminder. Die effek is tydsafhanklik en word ook deur die CD4 telling beïnvloed. Die kanse dat MPV16 spesifiek waargeneem word, word ook deur ART verminder, en all MPV tipes ondervind dieselfde of groter verlaging van waarnemingsrisiko as MPV16, behalwe miskien MPV39. Ons kon aandui dat verhoogde teenwoordigheid van servikale MIV verband hou met die risiko vir die waarneming van MPV infeksie, en beide word verminer deur die tyd waarmee die pasiënt met ARV terapie behandel is.

This study is a secondary analysis of survey data collected in fall 2000 from patients of a safety-net hospital and its eight community health outreach clinics in Fort Worth, Texas. The study examined three objectives. These include explaining the utilization of Pap smear tests among the sample who were low-income women, by ascertaining the determinants of using these services. Using binary logistic regressions analyses primarily, the study tested 10 hypotheses. The main hypothesis tested the race/ethnicity/immigration status effect on Pap smear screening. The remaining hypotheses examined the effects of other independent/control variables on having a Pap smear. Results from the data provide support for the existence of a race/ethnicity/immigration status effect. Anglos were more likely to have had a Pap smear, followed by African Americans, Hispanic immigrants, and finally, by Hispanic Americans. The persistence of the race/ethnicity/immigration status effect, even when the effects of other independent/control variables are taken into account, may be explained by several factors. These include cultural differences between the different groups studied. The race/ethnicity/immigration status effect on Pap smear screening changed with the introduction of age, usual source of care, check-up for current pregnancy, and having multiple competing needs for food, clothing and housing into the models studied. Other variables, such as marital status, employment status and health insurance coverage had no statistically significant effects on Pap smear screening. The findings of this study are unique, probably due to the hospital-based sample who has regular access to subsidized health insurance from a publicly funded safety-net healthcare network and its healthcare providers. Given the importance of race/ethnicity/immigration status for preventive Pap smear screening, public education efforts to promote appropriate Pap smear tests among vulnerable populations should target specific race/ethnicity/immigration status groups in the U.S. within the cultural context of each group. Furthermore, publicly funded health programs for underserved populations such as the John Peter Smith Connections and Medicaid should be maintained and strengthened.

M.Cur. (Nursing Management) / Transformational leadership involves the creation of a motivating climate that enhances growth, development, commitment, goal achievement and enjoyment which encourages behaviour based on a set of shared values (Price, 2006:124). In this study transformational leadership referred to concepts of motivation, and change management with regard to the implementation of the Cervical Cancer Screening Programme in a PRe setting. During support visits in Ekurhuleni Health District, the researcher observed a lack of transformational leadership among facility managers in Primary Health Care Clinics to transform the Cervical Cancer Screening Program in line with relevant health care legislation. It was apparent that the problems in implementing the Cervical Cancer Screening Programme were related to poor motivation and lack of implementation of change management principles in the PHC clinics. From the problem statement the following research questions emerged: To what extent is the facility manager perceived as a transformational leader to implement the Cervical Cancer Screening Programme in a PHC clinic? Which actions should the facility manager take to implement the Cervical Cancer Screening Programme in PHe? From the findings guidelines for the facility managers were described to enable them to implement a Cervical Cancer Screening Programme in a Primary Health Care clinic within legal requirements...

A dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Masters in Science. December 2015 / Cervical cancer remains a global health related issue among females of Sub-Saharan Africa, with over half a million new cases reported each year. Different therapeutic regimens have been suggested in various regions of Africa, however, over a quarter of a million women die of cervical cancer, annually. This makes it the most lethal cancer amongst black women in this area, and makes it important to search for new effective therapeutic drugs through screening of medicinal plant extracts used by many in Sub-Saharan Africa as potential anti-cervical cancer agents. The aim of this study was to evaluate the anti-proliferative effects of Cannabis sativa extracts and its isolate, cannabidiol on cervical cancer cell lines HeLa, SiHa, and ME-180. To achieve our aim, phytochemical screening, MTT assay, cell growth analysis, flow cytometry, morphology analysis, Western blot, caspase 3/7 assay, and ATP measurement assay were conducted were conducted. Results obtained indicate that both plant extracts induced cell death at an IC50 of 50 – 100μg/ml and the Inhibition of cell growth was cell line dependent. Flow cytometry confirmed that, with or without cell cycle arrest, the type of induced cell death was apoptosis. Cannabis sativa extracts led to the up-regulation of apoptosis proteins (p53, Bax, caspase-3, and caspase-9) and the down regulation of anti-apoptosis proteins (Bcl-2 and RBBP6), signalling the execution of apoptosis. Apoptosis induction was further confirmed by morphological changes, an increase in Caspase 3/7 and a decrease in the ATP levels. In conclusion, this data implies Cannabis sativa crude extracts has the potential to inhibit growth and induce apoptosis in cervical cancer cell lines, which may be due to the presence of cannabidiol. Key words: Apoptosis, cervical cancer cells, cannabidiol, and Cannabis sativa extracts

INTRODUÇÃO: A lesão intraepitelial cervical de alto grau causada pelo HPV, precursora do câncer cervical, é facilmente diagnosticada e seu tratamento pode ser realizado de maneira ambulatorial, sem muitas complicações. Mesmo assim, o seguimento das pacientes tratadas deve ser feito de maneira criteriosa e sistemática para que a recorrência ou persistência da doença não passe despercebida. Conseguir identificar o grupo de pacientes com maior probabilidade de recorrência ou persistência da doença facilitaria sobremaneira esse seguimento, diminuindo o ônus econômico e psicológico que o seguimento generalizado produz. O objetivo deste trabalho é identificar marcadores que possam indicar o grupo de pacientes com maior possibilidade de recorrência da lesão intraepitelial cervical de alto grau. MÉTODOS: Neste estudo 114 mulheres com diagnóstico de lesão intraepitelial cervical de alto grau foram submetidas à conização cervical por cirurgia de alta frequência (CAF) no Setor de Patologia do Trato Genital Inferior (PTGI) da Divisão da Clínica Ginecológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) no período entre março de 2006 e maio de 2009. O seguimento foi realizado a cada seis meses durante o período de 24 meses. No seguimento foi coletada a citologia cervical, captura híbrida para HPV e realizada a colposcopia. Foram avaliados os testes de captura híbrida para HPV coletadas durante o seguimento, imuno-histoquímicos para oncoproteína viral E6 e proteína p16 na peça cirúrgica como possíveis marcadores de recorrência. RESULTADOS: A avaliação anatomopatológica da peça cirúrgica diagnosticou 85 (74,6%) casos de lesão intraepitelial cervical de alto grau e 29 (25,4%) casos de lesão intraepitelial de baixo grau. Nessas peças, 45 (39,5%) apresentaram expressão positiva para oncoproteína E6 e 69 (60,5%) apresentaram expressão negativa para E6; 74 (64,9%) apresentaram expressão positiva para p16 e 40 (35,1%) apresentaram expressão negativa para p16. A oncoproteína E6 não se associou com a apresentação mais grave da doença. Já a proteína p16 esteve positiva em 68 (80%) casos diagnosticados como lesão intraepitelial de alto grau e negativa em 23 (79,3%) casos com diagnóstico anatomopatológico de lesão intraepitelial de baixo grau ou cervicite crônica. A CH coletada no primeiro retorno apresentou sensibilidade de 83,3%, especificidade de 87,8%, VPP de 50% e VPN de 97,3%. Comparando a CH coletada no primeiro retorno com a citologia coletada após os 24 meses de seguimento, a CH apresentou sensibilidade de 75%, especificidade de 83,1%, VPP de 20% e VPN de 98,3%. CONCLUSÕES: A expressão das oncoproteína E6 e proteína p16 na peça cirúrgica não demonstraram ter valor para predizer recorrência no seguimento de pacientes tratadas por lesão intraepitelial cervical de alto grau, mesmo a p16 estando associada à presença de lesões mais graves. A CH pode ser usada como um teste preditivo de recorrência durante o seguimento de pacientes tratadas por lesão intraepitelial de alto grau. O VPN do teste é bastante alto e seu resultado negativo, seis meses após o tratamento indica uma taxa baixíssima de recorrência da doença / INTRODUCTION: The high grade cervical intraepithelial lesion caused by HPV, a pre-malignant condition, is easily diagnosed and its treatment can be done in outpatients without many complications. Nevertheless the patients follow-up must be done in a very systematic way to avoid any recurrence or persistence of the disease. To be able to identify the group of patients with higher rate of recurrence or persistence of the disease would make this follow-up much easier and decrease the economic and psychological burden of stressed outcome. The goal of our study is to identify markers that could indicate the group of patients more likely to recur. METHODS: In this study, 114 women diagnosed with high grade cervical intraepithelial lesion were treated with LLETZ at the Discipline of Gynecology, Faculty of Medicine, São Paulo University from March 2006 and May 2009. The follow-up visits after the treatment included Pap smear, HPV DNA test and colposcopy and occurred every 6 months for 24 months. The markers evaluated were the HPV DNA test collected during the follow-up and immunohistochemical tests performed on the surgical specimen: E6 oncoprotein and protein p16. RESULTS: We found 85 cases (74,6%) of HSIL and 29 cases (25,4%) of LSIL in the surgical specimen obtained with the LLETZ. The E6 oncoprotein was expressed in 45 (39,5%) and not expressed in 69 (60,5%) of the specimen; 74 (64,9%) expressed p16 and 40 (35,1%) didnt express p16. The E6 oncoprotein was not associated with severe presentation of the disease. The protein p16 was positive in 68 (80%) cases of diagnosed HSIL and negative in 23 (79,3%) cases with diagnosed LSIL or chronic cervicitis. The HPV DNA test collected at the first follow-up consult at 6 months presented a sensitivity of 83,3% specificity of 87,8%, positive predictive value (PPV) of 50% and negative predictive value (NPV) of 97,3%. Comparing the HPV DNA test collected at the first follow-up visit and the cervical cytology collected at the fourth and last follow-up visit at 24 months, the HPV DNA test presented a sensitivity of 75%, specificity of 83,1%, PPV of 20% and NPV of 98,3%. CONCLUSIONS: The E6 oncoprotein and protein p16 expression on the surgical specimen were not able to predict recurrence of the disease during the follow-up of the patients. The HPV DNA test can be used as a marker of the recurrence on the follow-up of patients treated for HSIL with LLETZ. The HPV DNA test negative result at the 6 month follow-up visit represents an extremely low recurrence rate

INTRODUÇÃO: Pouco se sabe sobre parâmetros ultrassonográficos transvaginais possíveis de serem avaliados durante a gestação além do comprimento do colo uterino. A escassa literatura sugere que o volume calculado através da ultrassonografia tridimensional, a quantificação de sinal power Doppler em todo o órgão e o Doppler das artérias uterinas possam sofrer alterações de acordo com o comprimento cervical, e até mesmo anteceder seu encurtamento no processo que leva ao parto. OBJETIVOS: agregar novos parâmetros bi e tridimensionais ultrassonográficos à avaliação do colo uterino em gestações únicas. MÉTODO: Estudo transversal desenvolvido com dados de 2014 a janeiro de 2018 do projeto PROPE, no qual foi realizada ultrassonografia transvaginal em pacientes entre 20 e 23 semanas e 6 dias de gestação. Foram compilados e submetidos à análise secundária os dados de 162 gestantes com comprimento do colo uterino >= 25 mm (grupo Controle), 68 gestantes com comprimento do colo >= 15 mm e < 25 mm (grupo Colo Curto) e 18 gestantes com comprimento do colo < 15 mm (grupo Colo Muito Curto). Foram analisadas as características demográficas e antecedentes obstétricos das gestantes, e foram comparados entre os grupos os parâmetros cervicais de comprimento, volume e vascularização, além do Doppler de artérias uterinas bilateralmente. RESULTADOS: O comprimento médio (± DP) dos colos uterinos de cada grupo foi 35,28 ± 5,12 mm para o grupo Controle, 20,51 ± 2,47 mm para o grupo Colo Curto, e 10,72 ± 2,51 mm para o grupo Colo Muito Curto. Houve diferença entre os grupos quanto à idade materna, cor (etnia) e idade gestacional de inclusão. Quanto aos antecedentes obstétricos, houve associação somente entre a presença de colo curto na gestação atual e pelo menos um parto prematuro anterior em gestantes não nulíparas (p = 0,021). Em relação aos parâmetros ultrassonográficos, verificou-se correlação linear positiva moderada entre volume e comprimento do colo (coeficiente de Pearson=0.587, valor p < 0.0001). Os grupos Controle, Colo Curto e Colo Muito Curto foram estatisticamente diferentes em relação às médias (± DP) de volume (46,38 ± 13,60 cm vs. 32,15 ± 13,14 cm vs. 22,08 ± 11,10 cm, respectivamente)(p <= 0,001), e em relação às médias (± DP) de índice de fluxo (IF) (39,81 ± 6,42 cm vs. 38,73 ± 4,99 cm vs. 36,02 ± 5,34 cm, respectivamente) (p = 0,027), em que a diferença estatística ocorre entre os grupos Controle e Colo Muito Curto. Porém, na presença da informação do volume, após regressão linear, a associação entre os grupos e IF deixa de ser significativa. Também não houve relação entre os grupos estudados e o Doppler de artérias uterinas. CONCLUSÃO: Existe correlação linear positiva entre o volume e o comprimento do colo uterino. Na ausência de informações sobre o volume, comprimento cervical e índices de vascularização não se correlacionam. O comprimento cervical também não está relacionado a alterações no Doppler de artérias uterinas. Apesar das limitações de uma amostra pequena e escassez de dados comparativos na literatura, este estudo foi realizado com uma amostra homogênea da população e abre caminho para maiores pesquisas sobre o assunto / INTRODUCTION: Little is known about transvaginal ultrasound parameters other than cervical length that can be assessed during gestation. The literature suggests that changes in volume on three-dimensional ultrasound, quantification of power Doppler signal in the entire organ, and Doppler sonography of uterine arteries may be related to cervical length, and even precede its shortening during spontaneous delivery. OBJECTIVES: To include new two- and three-dimensional ultrasonographic parameters for evaluation of the uterine cervix in single pregnancies. METHODS: A crosssectional study of data from Project PROPE on transvaginal ultrasonography performed in patients between 20 and 23 weeks and 6 days of gestation from May 2014 to January 2018 was conducted. Secondary analysis of data from 162 pregnant women with uterine cervical length >= 25 mm (Control group), 68 pregnant women with cervical length >= 15 mm and < 25 mm (Short Cervix group), and 18 pregnant women with cervical length < 15 mm (Very Short Cervix group) was performed. The demographic characteristics and obstetric history of the pregnant women were analyzed, and the cervical length, volume, and vascularization were compared between the groups. In addition, Doppler velocimetry of the uterine arteries was performed bilaterally. RESULTS: The mean cervical length (± SD) was 35.28 ± 5.12 mm for the Control group, 20.51 ± 2.47 mm for the Short Cervix group, and 10.72 ± 2, 51 mm for the Very Short Cervix group. The groups differed in maternal age, ethnicity, and gestational age. When analyzing the obstetric history of only non-nulliparous patients we observed a significant association between the presence of a short cervix in the current pregnancy and at least one previous preterm birth (p = 0.021). With regard to the ultrasonographic parameters, we observed a moderate positive linear correlation between the volume and length of the cervix (Pearson coefficient = 0.587, p < 0.0001). The Control, Short Cervix, and Very Short Cervix groups showed differences in the mean (± SD) volume (46.38 ± 13.60 cm vs. 32.15 ± 13.14 cm vs. 22.08 ± 11.10 cm, respectively) (p <= 0.001) and mean (± SD) flow index (FI) parameter of cervical vascularization (39.81 ± 6.42 cm vs. 38.73 ± 4.99 cm vs. 36.02 ± 5.34 cm, respectively) (p = 0.027), and the difference between the Control and Very Short Cervix groups was statistically significant. However, after linear regression, in the presence of volume information, we found no association between the groups and FI. CONCLUSION: Cervical length and volume are positively correlated. When information about the volume is not provided, there\'s no association between cervical length and vascularization. Uterine artery Doppler is not related to cervical length. Despite the limitations of a small sample size and less comparative data in the literature, this study was performed with a homogeneous sample population and paves the way toward further research on the subject

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2016-07-07T17:27:31Z No. of bitstreams: 1 gustavohenriquedeoliveira_dissert.pdf: 920807 bytes, checksum: dd35cbbf5e85078e466e6f5bcd2d444e (MD5) / Made available in DSpace on 2016-07-07T17:27:31Z (GMT). No. of bitstreams: 1 gustavohenriquedeoliveira_dissert.pdf: 920807 bytes, checksum: dd35cbbf5e85078e466e6f5bcd2d444e (MD5) Previous issue date: 2010-12-09 / Aim: To evaluate the importance of cervical gland area (CGA) to predict spontaneous preterm birth (SPB). Method: A prospective study was performed from October 2008 to September 2009 of 102 singleton pregnancies at 20 and 24 weeks. A transvaginal ultrasound during the routine morphological scan investigated: the cervical length, CGA, its thickness and signs of cervical funneling. A preterm birth is defined as one that occurs at less than 37 weeks gestation. Ultrasound and clinical variables were submitted to univariate analysis by calculations of descriptive statistics, the Student t-test, percentages, and two-dimensional associative arrays evaluated using the Fisher exact test and odds ratio. The level of significance was set at 5%. Results: Of the 102 patients, four were lost in the follow up and seven were excluded as delivery was induced prematurely; ten patients presented spontaneous preterm births and 81 at term. The mean maternal age was 28.8 years old (18-41 years) without significant difference between the spontaneous preterm birth and term groups. There were statistical differences in the mean (33.9 vs. 36.1 cm), median (33.5 vs. 37.0 cm) and spread (standard deviation: 9.6 vs. 7.0) of the cervical length between the two groups. Risk factors for SPB gave an odds ratio of 15.06. All patients presented a CGA with a mean thickness of 8.4 mm (5.1 to 15 mm – SD: 3.1) for SPB and 8.9 mm (3.0 to 13.9 mm – SD: 2.3) for term individuals. Conclusion: The results suggest that the presence or absence and thickness of CGA are not correlated to SPB even in clinically or ultrasonographically high-risk patients. Further studies are necessary to reevaluate the parameters used to predict SPB. / Objetivo: Avaliar a importância do eco glandular endocervical (EGE) na predição de parto prematuro espontâneo (PPE). Método: Estudo prospectivo de 102 gestações únicas, entre 20-24 semanas, de outubro/2008 a setembro/2009. Na ecografia morfológica, o exame transvaginal avaliou: comprimento do colo uterino, EGE, espessura e sinal do afunilamento. Foi considerado PPE interrupção antes de 37 semanas de gestação. As avaliações ultrassonográfica e clínica foram submetidas à análise univariada pelos cálculos de estatísticas descritivas, teste t de Student, distribuições percentuais, tabelas associativas para análises bidimensionais, teste exato de Fisher e odds ratio no nível de significância de 5%. Resultados: Das 102 pacientes, quatro perderam seguimento, sete foram excluídas por parto prematuro induzido, dez pacientes apresentaram PPE e 81 parto a termo (PT). A idade materna média foi de 28,8 anos (18-41 anos), sem diferença nos dois grupos (PPE e PT). No comprimento do colo observaram-se diferenças na média (33,9 x 36,1 cm), mediana (33,5 x 37,0 cm) e na dispersão (desvio–padrão 9,6 x 7,0). Fatores de risco para PPE mostraram odds ratio de 15,06. Todas as pacientes apresentaram EGE, com espessura média de 8,4 mm (5,1 a 15 mm - desvio padrão 3,1) para PPE, e de 8,9 mm (3,0 a 13,9 mm - desvio padrão de 2,3) para PT. Conclusão: Os resultados indicam que a presença, ausência ou espessura do EGE não se correlacionou com PPE, mesmo naquelas pacientes com alto risco clínico e/ou ultrassonográfico de PPE. São necessárias novas pesquisas para reavaliação dos parâmetros indicadores de PPE.