Thesis (B. Sc.(Hons.))--University of Queensland, 2002. / Includes bibliographical references.

Thesis (M Med.(Obstetrics and Gynaecology))--University of Limpopo, 2010. / STUDY RATIONALE: Cervical cancer is the most common cancer of women on the African continent and the second most common cancer of women worldwide and in South Africa ’. It has been estimated in 1997 that, among women who received no cervical screening in South Africa, 1 in 26 women were likely to develop cervical cancer . Screening will probably decrease the incidence of cervical cancer by 60% or more . There is a direct relationship between the number of women screened by Pap smears and the decreased incidence of cervical cancer. In Iceland, where more than 90% of women were screened in that time, the incidence decreased by 80%. In Norway, where only 5% of the women were screened, the incidence only decreased by 10% . In South Africa, it is estimated that Pap smears were taken in 18.8% of white women and only 2.6% of black women in 2002 . Real-world obstacles to successful cervical cancer prevention in develo- ping countries involve people more than technologies 3. This can be ma- naged by focusing on system quality management 3. The root causes of poor quality must be examined. Suba et al 3 found causes such as obso- 7 lete supplies, poorly maintained microscopes, insufficient training and suboptimal working conditions. Successful follow-up for screen-positive women has been achieved through the allocation of budgets for dedicated personnel to recontact women with positive test results 3. Human Papillomavirus (HPV) infection is known to cause cervical can- cer. Human Papillomavirus (HPV) infection is also regarded as the most common sexually transmitted infection worldwide, with an estimated life- time risk of 79% for women to contract at least one infection between the ages of 20 and 79 years . Although some men have anal or genital lesions associated with HPV 16 and 18, most men serve as vectors of oncogenic HPV. Male partners may be important contributors to their female partners’ risk of cervical cancer . The 15 HPV types, which are classified as high risk virus types, cause 95 % of all cervical cancer. The High Risk HPV Genotypes are: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73 and 82. HPV 16 and 18 together cause around 70 % of all cervical cancer ’. Squamous cell cervical cancer constitutes approximately 80% of cervical cancers . Adenocarcinoma is the second most common histological type and shows a rising incidence, even in developed countries . 8 There is geographical variation in type-specific HPV prevalence 9. HPV16 is the most common type associated with adenocarcinomas, except in Southeast-Asia, where the prevalence of HPV 18 exceeds that of HPV 16. HPV 16, 18, 35, 45and 59 are present in 96% of adenocarci- nomas of the cervix 10. A pooled analysis by Clifford et al 9 showed that the prevalence of high risk HPV types is around 18 % in sub-Saharan Africa, with HPV 16 and HPV 35 present in 8% of women. HPV 31 and HPV 33 were present in 7% of women and HPV 18 was present in 4% of women. Sub- Saharan Africa had the highest prevalence of all HPV types and Europe the lowest. The variation in prevalence of HPV 16 across regions was smaller for HPV 16 than for the other high-risk types. The next common high- risk types were HPV 33 and HPV 56 in Asia, HPV 58 in South America and HPV 31 in Europe 9. This study’s rationale was to ascertain the HPV types prevalent in pa- tients with abnormal Pap smears seen at the Gynaecological Outpatients Clinic at Dr. George Mukhari Hospital, the Gynaecological Oncology Clinic at Dr. George Mukhari Hospital, the Tshepang Clinic at Dr. George Mukhari Hospital and the Setshaba Research Centre of the University of Limpopo – Medunsa Campus in Soshanguve. 9 This study can also act as a pilot study for future studies to test the ef- fectiveness of using high risk HPV types screening as a primary screening method, instead of Pap smears, to identify patients who are at a higher risk to develop cervical cancer and who need further investigations such as Colposcopically directed biopsies.

Thesis (M. Med. Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 73-77).

Thesis (M.Med.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 73-77). Also available in print.

Abstract Introduction: "Pap smear" was first proposed in 1928 by Dr. Papanicolaou in USA as a screening test for cervical cancer. In most developed, higher-educated country,the majority of the female population receive regular Pap smear, and hence the incidence of invasive or late stage cervical cancer is relative low. In contrast, in those developing,or under-developed country ,the percentage of women receiving regular Pap smear is lower, and cervical neoplasm is more often diagnosed in the invasive or even later stage.General speaking,the incidence of invasive cervical cancer in a country may be recognized as a relative indicator for the quality of public health care. The higher the percentage of women receiving regular Pap smear is ,the lower the incidence of invasive cervical cancer. In Taiwan, the annual incidence of newly-diagnosed invasive cervical cancer remains high, and cervical cancer stand as the top one of the most lethal female cancer. In theory,since the incubation period from the pre-cancer stage(cervical intraepithelial neoplasm) to frank malignancy in cervix is rather long, allowing adequate opportunity and timing for Pap smear screening, more cervical neoplasm may be diagnosed and treated in the pre-cancer stage, and hence lower the incidence of cancer death from treatment failure. Disappointingly, even being a major program of public health care, and being supported by national institute, the Pap smear rate in Taiwan is far from ideal. We try to find out the causes of low Pap smear rate via analyzing the pattern and availability of health care, medical knowledge, and attitude of those cervical cancer patients. These factors may be of benefit to promote modifying public health program, and thus increase the receptivity and popularity of regular Pap smear in general population. Material and method: This is a retrospective study, focusing on the cervical cancer patients (including carcinoma in situ and invasive cancer of cervix), which were confirmed pathologically and treated successfully in a single hospital in the recent 3 years. Totally, 155 cases were enrolled. All these patients were interviewed face to face, and data were collected (focusing on basic data and the possible factors influencing Pap smear rate) according to a fixed form. SPSS for Windows Ver. 10.0 was used for data analysis. Percentage, distribution was used for descriptive statistics. Cross table analysis, chi-square test, and logistic regression analysis were used for comparing group difference. Results: The data analysis revealed: 1)Most cervical cancer patients didn¡¦t receive regular annual Pap smear 2)Most cervical cancer patients didn¡¦t realize the importance of regular Pap smear before 3)Though some of the cervical cancer patients did have the concept and importance of regular screening, they didn¡¦t receive regular annual Pap smear 4)Invasive cancer rate was higher than CIS rate in this study group 5)The government public health program ¡§¤»¤ÀÄÁÅ@ ¤@¥Í¡¨ (¡§only 6 min, and away from threat of cervical cancer¡¨) seemed to have no major effect in those Taiwanese-speaking, older, and less-educational subpopulation 6)The government public health program ¡§¤»¤ÀÄÁÅ@ ¤@¥Í¡¨ (¡§only 6 min, and away from threat of cervical cancer¡¨) seemed to be insufficient for promoting active participating of the Pap smear program in general population Conclusion: Despite the effort from government health institute, Pap smear rate remained far from ideal in Taiwan, leaving many cases of cervical neoplasm diagnosed and treated in the later and advanced stage. From the result of this study, we can see that some sub-population was prone to be missed in the health care program. The major lithotomy include poor knowledge (¡§language barrier¡¨), naive, wrong attitude (fear and shame of facing health provider under lithotomy position for Pap smear). There¡¦s still much to do to increase the Pap smear rate. The knowledge about cervical cancer and the importance of the Pap smear screening can never be over-emphasized. The education and the resource information should be provided via multiple pathways, including Internet source, regular seminars, or pronouncement in the TV, radio or magazines. The first-line health providers (local doctors, nurses, or even social workers) should be well-trained. The public education should be started right from lithotomy which is the important time point in cervical cancer carcinogen sis (HPV infection and integration). For those with lower socio-economic status, and those in urban area, the Pap smear may be promoted by way of free charge (financial support from national health institute), or packed with other general health examination program. The whole health-care system should be integrated well, and function well, to raise the Pap smear rate in our country. We hope that through the routine screening program, the incidence of invasive cervical cancer can be lowered, shifting most of the cases in the pre-cancer or in situ stage, and can be treated effectively

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

This study was undertaken to determine the clinical significance of detecting candida on Pap smear. Clinical information was obtained from a questionnaire sent to the health care provider whenever candida was identified during the study period. Candida was identified in 309 (3.0%) of the 10,370 Pap smears examined. Completed questionnaires were returned on 137 (44.3%) patients. All 137 smears were reviewed. Ninety-nine (72%) patients were asymptomatic, 29 (21%) had symptoms typical of candida infection, and nine (7%) had nonspecific symptoms. Forty-four (32%) patients had been treated for candida during the original clinic visit. After the Pap smear reported candida, 19 (20%) of the 93 nontreated patients were contacted and treated, while 10 (11%) were scheduled for further evaluation. No action was taken on the remaining 64 (69%) patients. There was a significant association between having initial symptoms and receiving immediate treatment (P < 0.001) and undergoing subsequent treatment or further evaluation after the Pap smear report (P < 0.001). Marked inflammation was statistically associated with symptoms (P = 0.014), but the form or number of candida organisms was not. In conclusion, the identification of Candida on Pap smear does not necessarily indicate a symptomatic infection, although the Pap smear results had a direct impact on the treatment of 21% of patients in this study and served as a confirmation for clinical treatment in another 32% who had received such treatment at the time of the original visit.

No description available.

Le facteur d'activation plaquettaire (PAF) est un puissant médiateur pro-inflammatoire impliqué dans des processus physiologiques et pathologiques.Le PAF exerce ses effets suite à la liaison à son récepteur, le récepteur du PAF (PAFR), qui est un récepteur à sept domaines transmembranaires et couplé aux protéines G (RCPG). La signalisation du PAFR est en partie médiée par les protéines G et implique principalement des sous-unités G[indice inférieur [alpha]i] et G[indice inférieur [alpha]q] dans plusieurs types cellulaires.Le PAFR peut également activer des effecteurs variés : des canaux ioniques, des phospholipases (PLA[indice inférieur 2], PLC, PLD), ainsi que plusieurs kinases (PKC, PI3K et MAPK). Nous avons récemment démontré que le PAFR peut activer de façon indépendante des protéines G la voie des Janus kinase (JAK) et des Signal Transducers and Activators of Transcription (STAT). JAK2, TYK2 et STAT1, 2, 3 et 5 sont ainsi activés dans la lignée cellulaire myéloïde humaine MonoMac1. Les SOCS sont une famille de protéines qui régulent négativement la signalisation des cytokines et qui ont récemment été démontrés comme impliqués dans la signalisation de certains RCPG dont le CXCR4 (récepteur de chimiokine 4 de la famille des C-X-C) et l'AT1 (récepteur de l'angiotensine II). Une stimulation au PAF induit de manière transcriptionnelle l'accumulation de l'ARNm de la protéine suppressors of cytokine signalling 3 (SOCS3) dans les monocytes humains et la lignée cellulaire MonoMac1, mais ne l'induit pas dans les cellules endothéliales de veines de cordons ombilicaux humain (HUVEC). En plus d'une augmentation de l'ARNm de SOCS3, une augmentation de la protéine SOCS3 est également observée suivant une stimulation au PAF. Premièrement, nous voulions déterminer l'importance de SOCS3 dans la signalisation du PAFR à l'aide de différentes lignées cellulaires (HEK293, COS7, MonoMac1) et diverses techniques de biologie cellulaire. Ensuite, nous désirions évaluer l'impact des différents domaines de SOCS3 dans ces fonctions par des approches de biologie moléculaire. Finalement, nous avons évalué le/s rôle/s de SOCS3 sur différents aspects fonctionnels pro-inflammatoires du PAF (Voies signalisation, adhésion cellulaires, etc.). Nous démontrons dans la présente thèse que SOCS3 module la signalisation du PAFR en plus de présenter certains aspects moléculaires entourant la relation entre le PAFR, TYK2 et SOCS3. Les présents travaux démontrent que SOCS3 peut être recruté de façon transitoire à la seconde boucle intracellulaire et la queue cytoplasmique du PAFR. Son domaine kinase inhibitory region (KIR) semble être requis pour le recrutement induit au PAFR, alors que son domaine SOCS box semble être impliqué dans le recrutement basal. Suivant une stimulation au PAF, SOCS3 est phosphorylé sur un/des résidus tyrosine. Cette modification est sous le contrôle essentiel de TYK2, alors que son mutant K930I (kinase inactive) ne le fait pas. SOCS3 joue un rôle très important dans la modulation des voies de signalisation du PAFR ainsi que sur certains effets biologiques de celui-ci. Ces actions se révèlent être également très spécifiques : SOCS3 ne module pas la voie de G[indice inférieur [alpha]q] (IP3 ), mais module la migration et également l'adhésion cellulaire induite par le PAF. SOCS3 ne module pas la phosphorylation des STAT 1, 3 et 5 induite par le PAF, mais module négativement la voie de TYK2 (activation du promoteur du PAFR) et la phosphorylation des STAT 1, 3 et 5 induite par l'OSM. SOCS3 ne module pas la voie des JNK MAPK, prolonge la voie des ERK MAPK et module négativement l'activation précoce de la voie de p38 MAPK. Enfin, SOCS3 joue un rôle de modulation négative dans la transcription induite par le PAF des promoteurs du PAFR, de l'IL-6 et de l'IL-8. En conclusion, cette thèse propose de nouveaux mécanismes par lesquels SOCS3 module certains aspects de la signalisation et effets biologiques du PAF et de son PAFR. Comme le PAF est impliqué dans plusieurs phénomènes à caractères inflammatoires, le travail présenté ici a porté son attention sur plusieurs aspects pro-inflammatoires du PAF plutôt que sur une pathologie en particulier, ce qui permettra de mieux comprendre divers aspects liant le PAFR, la kinase TYK2 et SOCS3.

MMed, Community Medicine, Faculty of Health Sciences, University of the Witwatersrand / INTRODUCTION: Cervical cancer continues to be a significant cause of morbidity and mortality, particularly in women in the developing world, due to the lack of effective population screening. It has proven difficult to implement and sustain cytological screening programmes as health systems in these settings are not functional. South Africa has adopted an organised cervical screening programme, and the goal is to screen 70% of women over 30 years nationally, within ten years of initiating the programme. However, it is also necessary to ensure that women with abnormal Pap smears are treated if we are to reduce cervical cancer incidence. Ensuring treatment of abnormal Pap smears is a challenge, and current data on this is needed to inform service delivery. AIM: The study aims to assess the current status of the cervical screening programme in the Johannesburg Metro District, specifically looking at screening coverage, and referral for treatment in women with abnormal Pap smears. METHODOLOGY: Secondary analysis of data in the District Health Information System was done; and registers at a sample of primary health care clinics and their referral colposcopy services were evaluated for the period April 2007 – March 2008. Descriptive statistics were employed to analyse the data. Multivariate analysis was also done to evaluate factors associated with colposcopy attendance. vi RESULTS: Screening coverage for the district was 6.3% for 2008 and the cumulative coverage from 2000 to 2008 was 35.8%, with significant variation between subdistricts. A high proportion (19%) of smears was done in women less than 30 years. Of 557 women with abnormal Pap smears requiring further treatment, 57% were informed of their results and referred, 38% had appointments for colposcopy, and only 28% attended these appointments. Women experienced long waiting times for appointments (up to 15 months), and there was inadequate record keeping and client tracing. HIV status and the sub-district and health authority where women were screened were associated with colposcopy attendance; the referral hospital was associated with length of waiting time between Pap smear and colposcopy. CONCLUSION: Cervical screening coverage is below target, and the referral for diagnosis and treatment remains a challenge. Unless referral and access to colposcopy services is improved, increasing screening coverage will not have an impact on decreasing cervical cancer incidence and mortality. It is hoped that this study will provide the data to target interventions to improve cervical screening coverage and effective referral and treatment in the district.