Thesis(MSc(Med)Pharmacy)) -- University of Limpopo, 2011. / ABSTRACT Introduction: Non-invasive detection of tumour hypoxia theoretically adds value to the. outcome of treatment; however the practical aspect of using 99mTc-EC-MN in cervical cancer remains un-attempted. 99mTc-EC-MN has been used to indirectly detect hypoxia in many tumours (head and neck) and other hypoxic states such as strokes and MI. This study aims to determine the value of using this tracer in early stage cervical cancer. Objectives: This study aimed to investigate the use of 99mTc-EC-MN to determine the degree of hypoxia in cervical cancer. The original study design was to determine whether SPECT with 99mTc-EC-MN would detect ~l'poxi~cervicalc;ancer 'lesions and compare the results with the histological report. The practice of safe handling of radiopharmaceuticals and gaining knowledge in conducting research formed part of the secondary objective of the study. Due to circumstances beyond the control of the researcher, the focus of the study changed from a clinical to a chemistry-based project. Method development: Safety of EC-MN was tested through determination of the labelling efficiency with pertechnetate initially by ITLC-SG. Ethyl acetate, ethanol, saline and ac;etone were selected to develop 99mTc-EC-MN chromatograms to identify the system which best displays separation. Radio-ITLC displayed multiple peaks due to high residual activity in ethyl acetate- and acetone-developed scans. Saline- and ethanol-developed scans showed better separation of 99mTc-EC-MN but separation from free pertechnetate was difficult. Radio HPLC coupled with a diode array detector was used to successfully separate the labelled product, 99mTc-EC-MN from free pertechnetate, thereby achieving good radiolabelling. Clinical application: After the relative safety of the product was established, it was injected IV in the selected patient who had early stage cervical carcinoma. Clinical examinations which included pre-operative WBC, ultrasonography of the kidneys and bladder, and chest x-rays were performed. Histological analysis was performed after surgery and gave results that were insufficient to conclude the absence or the presence of tumour hypoxia. Detection of 99mTc-EC-MN was analysed from blood-flow and -pool images, thyroid and pelvic static, SPECT, and WBS images obtained from a gamma scintillation camera. Faint hot spots consistent with low levels of free pertechnetate were detected in the salivary glands. Hot areas which paralleled the bio-distribution of the 99mTc-EC-MN were also detected in the thyroid, liver, intestines, kidneys, and bladder. There was no tracer detection in the pelvic area. Conclusions: Experience was gained in QC procedures and aseptic preparation of radiopharmaceuticals, and in conducting and co-managing a chemical and clinical based research. Radiochemically related findings demonstrated that tin (II) chloride can be solubilised in water; 99mTc-EC-MN migrates with the solvent front in saline and ethanol developed ITLSG scans; and ITLC cannot sufficiently separate 99mTc-EC-MN from free pertechnetate. Successful labelling of EC-MN was confirmed by scintigraphy and showed tracer distribution that parallels those previously described. Successful labelling of EC-MN with 99mTc can be achieved up to two years after kit manufacture given appropriate storage conditions for the EC-MN. The hypoxic status of the tumour remained inconclusive; therefore the prognostic impact of 99mTc-EC-MN in cervical cancer remains unknown. Recommendations: Product stability and potential expiry should be available for all products, even in the developmental stages and particularly for clinical trials. A simple QC method to separate 99mTc-EC-MN from free pertechnetate should be developed. Further studies are required in order to confirm the efficacy of 99mTc-EC-NM in determining tumour hypoxia in cervical cancer. If a suitable animal model is not available, patients with known cancer tissue hypoxia should be evaluated and compared with those who are non-hypoxic

Cervical cancer is the second most common malignancy worldwide. Infection with HPV is a necessary cause of cervical. Hispanic women in the U.S. experience significantly higher rates of invasive disease than non-Hispanic Whites. In this population, HPV vaccines hold significant potential to eliminate further disparities in cervical cancer morbidity and mortality. The purpose of this study was to examine factors associated with Human Papillomavirus (HPV) vaccine acceptability among a national sample of Spanish speaking callers to the National Cancer Institute's (NCI) Cancer Information Service (CIS). Specifically this research aimed to identify the sociodemographic, sociocultural and attitudinal determinants of HPV vaccine acceptability. This research involved a cross-sectional study with phone-based interviews conducted in Spanish (n = 836). All female Spanish callers to the CIS were asked to respond to a three-part questionnaire that included items relating to ethnic identity and acculturation, knowledge of cervical cancer and related risk factors, and HPV vaccine acceptability. Descriptive, univariate and multivariate logistic regression were used to characterize the study population and to determine the effect of each of the demographic/sociocultural variables on vaccine acceptance. Independent predictors of HPV vaccine acceptability were determined using multivariate linear regression models. Results showed that HPV vaccine acceptance was high among this group of Hispanic women (78%) and that attitudes about vaccines in general and the HPV vaccine specifically were positive. Factors associated with vaccine acceptance included physician recommendation, awareness and accurate knowledge about HPV, and speaking only or mostly Spanish. Other important predictors included influence of peers, positive attitudes about vaccines in general, higher education and being a mother of a female adolescent. The primary reason cited by those who did not favor vaccination was concern over vaccine safety. This research was the first study looking at vaccine acceptability in a large, national sample of Hispanic women. HPV vaccination can lead to important public health benefits for Hispanic women. Targeted educational interventions must take into account the important sociocultural and attitudinal influences on the decision to vaccinate, such as those identified in the present study. Future educational efforts must involve the physician and take into the account the cultural context of attitudes and beliefs regarding vaccine safety and disease susceptibility. Further studies elucidating the interplay between culture specific beliefs and practices regarding vaccination and the decision to participate in HPV vaccination are needed.

Cervical Spine injuries are a common occurrence during motor vehicle accidents, and they represent a significant economic cost to society. Numerical Finite Element (FE) models have been formulated to investigate the response of the neck under various loading scenarios and to improve vehicle safety. The Global Human Body Models Consortium (GHBMC) was formed to develop a detailed FE model capable of simulating occupant response and predicting subsequent soft tissue injuries in the cervical spine. The objective of this thesis was to validate the neck region of the GHBMC model at the segment level in flexion and extension, and at rotation rates observed during car crash scenarios. Nine cervical spines, under the age of 50, were procured from post mortem human subjects and they were dissected into segments. A segment consisted of two vertebrae with the ligaments and the intervertebral disc intact, and the muscle, nervous, and cardiovascular tissues removed. A custom built fixture was built to test each specimen three times in flexion and extension at two rotation rates: a low rate (one degree per second) and a high rate (500 degrees per second). To avoid damaging the specimens after the first test, the segments were only rotated up to ten degrees for the segments at the C2-C3 through C5-C6 level, and up to eight degrees for the C6-C7 and C7-T1 level. The segment response was represented by plots of the moment against the angle of rotation in the sagittal plane. The segment models were simulated at the same low and high rotation rates, and the model results were evaluated against the experimental response. The low speed experimental results were compared to existing quasi-static studies, but there was not an elevated rotation rate study at each segment level to compare with the high rate response. The segment response from the existing data was generally weaker than the results of this thesis because the earlier studies tested older specimens, and the exiting studies applied a step-wise loading protocol instead of a continuous one. A statistical analysis was conducted to determine the significance of the difference between the low and high rate experimental response. At the maximum angle of rotation, the analysis found moderate evidence (p < 0.05) of increased segment stiffness at the high rotation rate for the C5-C6 and C6-C7 segments in flexion and extension, and weak evidence of increased stiffness for the C3-C4 and C4-C5 segments in flexion and extension, and for the C2-C3 and C7-T1 segments in extension. Below six degrees of rotation, there was no statistical evidence that the low and high speed responses were significantly different for any segment. In flexion, the model response was within one standard deviation of the experimental mean at the C6-C7 and C7-T1 segment level. For the C2-C3 through C5-C6 segment levels, the model was stiffer than the experimental mean. In extension, the model was within one standard deviation at every segment level except at the C2-C3 and C7-T1 segment levels where the model response was weaker than the experimental response. For the high rate model analysis, the model predicted that the high rate simulations were stiffer than the low rate simulation at every segment level; however the difference was much greater in flexion than in extension. Recommendations for further research included studying the high rate behaviour of the intervertebral discs under compressive and bending loading, and investigating the translational and rotational displacement of the spine during flexion and extension and compare the results with the model. The procurement of more post mortem human subjects would increase the sample size and it could improve the significance of the statistical analysis, and additional spines would permit the analysis of other effects, such as the influence of gender.

Epithelial adhesion molecule, E-cadherin plays important role in maintaining structural integrity of epithelial tissue. Altered expression of E-cadherin might result in the loss of contact inhibition growth property, abnormal cell growth and differentiation, hence the oncogenic transformation. To explore the role of E-cadherin in the tumor progression, we have investigate the expression pattern of E-cadherin in invasive cervical carcinomas. 77 paraffin embedded specimen with FIGO staging Ia¡]N=15¡^, Ib¡]N=19¡^, Ib meta¡]N=13¡^ IIa¡]N=17¡^, IIb¡]N=13¡^were included in immunohistochemical study, 18 surgical removed tumor tissues of Ib stage and its normal counter parts were used for semi-quantitative RT-PCR analysis. The results indicated that no significant correlation between E-cadherin expression level and tumor metasis, patient prognosis. However, E-cadherin immunostainimg intensity was significanty inverse correlated with tumor size¡]p < 0.001¡^. Notably, loss of membranes E-cadherin expression might be a significant factor that correlated with tumor metasis¡]p = 0.001,< 0.005¡^.

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

Thesis (B.S.) Magna Cum Laude --Butler University, 2009. / Includes bibliographical references (leaf 26).

Human papillomavirus (HPV), a major sexually-transmitted disease, causes cervical cancer, in addition to numerous other cancers in females and males. This thesis uses mathematical modeling, theory and simulations to study the transmission dynamics of HPV, and associated dysplasia, in a community. A new deterministic model is designed and used to assess the population-level impact of Pap cytology screening on the transmission dynamics of the disease in a community. The model is rigorously analyzed for its dynamical features, vis-a-vis determining the conditions for the effective control (or elimination) and persistence of the disease. Furthermore, the effect of uncertainties in the estimates of the parameter values used in the numerical simulations of the model is accounted for via uncertainty and sensitivity analysis. Simulations of the model show that Pap screening dramatically reduces the incidence of cervical cancer in the community.

No description available.

Cervical Spine injuries are a common occurrence during motor vehicle accidents, and they represent a significant economic cost to society. Numerical Finite Element (FE) models have been formulated to investigate the response of the neck under various loading scenarios and to improve vehicle safety. The Global Human Body Models Consortium (GHBMC) was formed to develop a detailed FE model capable of simulating occupant response and predicting subsequent soft tissue injuries in the cervical spine. The objective of this thesis was to validate the neck region of the GHBMC model at the segment level in flexion and extension, and at rotation rates observed during car crash scenarios. Nine cervical spines, under the age of 50, were procured from post mortem human subjects and they were dissected into segments. A segment consisted of two vertebrae with the ligaments and the intervertebral disc intact, and the muscle, nervous, and cardiovascular tissues removed. A custom built fixture was built to test each specimen three times in flexion and extension at two rotation rates: a low rate (one degree per second) and a high rate (500 degrees per second). To avoid damaging the specimens after the first test, the segments were only rotated up to ten degrees for the segments at the C2-C3 through C5-C6 level, and up to eight degrees for the C6-C7 and C7-T1 level. The segment response was represented by plots of the moment against the angle of rotation in the sagittal plane. The segment models were simulated at the same low and high rotation rates, and the model results were evaluated against the experimental response. The low speed experimental results were compared to existing quasi-static studies, but there was not an elevated rotation rate study at each segment level to compare with the high rate response. The segment response from the existing data was generally weaker than the results of this thesis because the earlier studies tested older specimens, and the exiting studies applied a step-wise loading protocol instead of a continuous one. A statistical analysis was conducted to determine the significance of the difference between the low and high rate experimental response. At the maximum angle of rotation, the analysis found moderate evidence (p < 0.05) of increased segment stiffness at the high rotation rate for the C5-C6 and C6-C7 segments in flexion and extension, and weak evidence of increased stiffness for the C3-C4 and C4-C5 segments in flexion and extension, and for the C2-C3 and C7-T1 segments in extension. Below six degrees of rotation, there was no statistical evidence that the low and high speed responses were significantly different for any segment. In flexion, the model response was within one standard deviation of the experimental mean at the C6-C7 and C7-T1 segment level. For the C2-C3 through C5-C6 segment levels, the model was stiffer than the experimental mean. In extension, the model was within one standard deviation at every segment level except at the C2-C3 and C7-T1 segment levels where the model response was weaker than the experimental response. For the high rate model analysis, the model predicted that the high rate simulations were stiffer than the low rate simulation at every segment level; however the difference was much greater in flexion than in extension. Recommendations for further research included studying the high rate behaviour of the intervertebral discs under compressive and bending loading, and investigating the translational and rotational displacement of the spine during flexion and extension and compare the results with the model. The procurement of more post mortem human subjects would increase the sample size and it could improve the significance of the statistical analysis, and additional spines would permit the analysis of other effects, such as the influence of gender.

Thesis (MAppSc in Physiotherapy) -- University of South Australia, 1998