Background: Axis fractures are a common injury in the elderly population. Treatment is often complicated due to osteoporosis and patient comorbidity. Knowledge of the incidence of these fractures, as well as their treatment, outcome and mortality rate, will improve knowledge and decision-making processes for this fragile group of patients. Objectives: This thesis aims (1) to review the literature on the non-surgical and surgical treatment of odontoid fractures type 2 in the elderly population, (2) to provide an updated overview of axis fracture subtypes, their incidence and their treatment in a cohort in two university cities, (3) to map the incidence of fractures and the treatment of these patients in Sweden, (4) to investigate the effect on mortality of both the surgical and non-surgical treatment of axis fractures and (5) to present the protocol for a randomized controlled trial (RCT) on the treatment of odontoid fractures type 2 in the elderly population. Methods: A systematic review was performed using the MeSH keywords “odontoid AND fracture AND elderly”. The data for the cohort study were extracted from the regional hospital information system. The radiographs were reviewed retrospectively. Data were extracted from the Swedish National Patient Registry (NPR) and the mortality registry for the national registry studies. Finally, the RCT protocol was carried out according to the SPIRIT and CONSORT statements for clinical trial reporting. Results and conclusions: So far, there has been a scarcity of existing evidence on treatment of odontoid fractures type 2 in the elderly population. In this thesis, we found in two university cities an increased incidence, and a trend towards more surgical treatment of type 2 and 3 odontoid fractures 2002-2014. Between 1997 and 2014 in Sweden, there was an increasing incidence of C2 fractures, but the treatment trend went towards more non-surgical treatment. Surgically treated patients had a greater survival rate than non-surgically treated patients. Among those over 88 years of age, surgical treatment lost its effect on survival. In the RCT we will study the function of patients with odontoid fractures type 2 and by comparing non-surgical treatment with posterior C1-C2 fusion, the cost-effectiveness of the treatment options.

Human papillomavirus (HPV) related cervical cancer is still the most common gynaecological malignancy in developing countries and, as yet, there is no alternative to surgery for the treatment of HPV-associated pre-malignant lesions. HPV 'hijacks' the host-cell ubiquitin-proteasome system to degrade the p53 and Rb tumour suppressor proteins which in turn, leads to the development of cancer. Previous studies have shown that the HIV protease inhibitor lopinavir selectively inhibits the chymotryptic-like activity of the 26S proteasome which stabilises p53 and induces the apoptosis of HPV positive cervical carcinoma cells. Based on this it was hypothesised that lopinavir treatment of HPV positive cervical carcinoma cells would produce changes in the levels of a wide range of cellular proteins that are dis-regulated by HPV-related activation of the proteasome. In order to address this, antibody microarray screening was carried out on lopinavir treated and control untreated HPV positive SiHa cervical carcinoma cells. This showed lopinavir induced alterations in 51 proteins including the cellular antiviral defence protein RNase L. Lopinavir induced both a dose and time dependent increase in RNase L which was subsequently confirmed by western blotting. Transient siRNA silencing of RNase L expression reduced the lopinavir-dependent toxicity in SiHa cells, suggesting an important role for this protein in the toxicity of lopinavir in HPV infected cells. SiHa cells were much more sensitive to lopinavir than CaSKi cervical carcinoma cells which had much higher levels of the E6 protein and did not up regulate RNase L. Furthermore, lopinavir treated HPV16 E6/E7 immortalised keratinocytes were also shown to up regulate RNase L protein expression and these cells were much more sensitive to lopinavir induced apoptosis than mortal control keratinocytes. In addition, transient expression of RNase L in RNase L-deficient C33A cells and the same cells stably transfected with HPV16 E6 (C33AE6) demonstrated that E6 protected these cells from RNaseL-induced cell death. Surprisingly, analysis of RNase L protein levels in these cells demonstrated that E6 did not induce the degradation of the RNase L protein. Instead it was found that E6 stabilised the interaction between RNase L and its endogenous inhibitor protein, ABCE1, and that lopinavir de-stabilised this interaction. Given that C33A tumour cells, E6/E7 immortalised keratinocytes and hTert immortalised keratinocytes are all sensitive to lopinavir, this implies that this compound does not specifically target HPV immortalised cells but rather targets immortalised cells in general, regardless of how this was achieved. The optimum concentration of lopinavir for all these effects was 25 μM, which is 15-fold higher than is observed in cervico-vaginal secretions following oral dosing with the drug Kaletra. In conclusion these results have confirmed the potential of lopinavir to treat HPV related pre-cancerous cervical lesions and provided at least part of the mode-of-action. Indeed they strongly support the use of lopinavir as a low-cost, self-applied topical alternative to surgery for this disease which will be of particular benefit in low-resource countries. Finally, the ability of lopinavir to induce apoptosis of non-HPV related immortalised cells merits further investigation since this indicates this drug may be useful for the treatment of other non HPV related pre-malignant conditions.

M.Tech. / Purpose: The aim of this study was to compare the effects of Chiropractic adjustments to Muscle Energy Technique (MET) with regards to pain, disability and range of motion in the cervical spine. Method: Thirty participants, male or female between the ages of 18 and 55 years, diagnosed with cervical facet syndrome were used in the study. The thirty participants were randomly divided into two groups consisting of fifteen individuals each, ensuring equal male to female and age ratios. Group A received Chiropractic adjustment/s over the restricted joint/s to the cervical spine. Group B received MET to the cervical spine.The trial consisted of seven visits over a treatment period of three weeks, of which the first six visits the participants received treatment and the seventh visit served the purpose of obtaining the final data. The data was gathered on the first, fourth and seventh visits. The data was always gathered before the treatment was performed. Objective data consisted of measuring cervical spine range of motion with a CROM instrument. Subjective data was obtained by using the Numerical Pain Rating Scale (NPRS) and the Vernon-Mior Neck Pain and Disability Index. Results: The results indicated that Group A (Chiropractic adjustments) proved to be the most effective treatment protocol. Although the other treatment protocol, Group B (Muscle Energy Technique), also showed good results. Both subjective and objective results showed that although Group B produced statistically significant results, Group A showed the best results overall. Thus it was noted that in order to achieve a potentially lasting increase in range of motion and a decrease in pain and disability, the treatment protocol used for Group A should be the treatment of choice. Conclusion: It was concluded, based on the results, that Chiropractic adjustments was more effective than MET in the treatment of cervical facet syndrome. This conclusion is based on the results that Chiropractic adjustments was more effective in all the objective and all the subjective measurements. However, this does not rule out MET as a treatment for neck pain, because MET treatment did show improvements in cervical spine ROM and a decrease in pain, although not as efficiently as Chiropractic treatment.

Since the introduction of Auranofin in 1985 there has been no new clinically approved gold containing drugs introduced. Although promising results were achieved with a gold(I) phosphine complex [Au(dppe) 2]Cl (Hoke et al., 1991; Mckeage et al., 2002), this compound was never entered into clinical trials due to its toxicity to normal tissue such as the liver and heart (Smith et al.,1989). Six novel derivatives of [Au(dppe) 2]Cl were developed and synthesized to identify possible new candidates with improved tumour specificity compared to [Au(dppe) 2]Cl and cisplatin. Human cervical carcinoma cells (HeLa) were used for an initial toxicity screening. IC50’s obtained for [Au(dppe) 2]Cl and cisplatin were 0.661 and 0.710 µM respectively. Three mixed novel derivatives (MM4, MM5 and MM6) displayed IC50’s ranging between 0.026 and 0.103 µM. These compounds were then selected to be tested further for selectivity and cytotoxicity on various malignant and normal cell lines. MM4 showed selectivity for ovarian, prostate, cervical and breast cancer cells, while MM5 was the most effective against ovarian, colon, prostate, cervical and breast cancer cells. MM6 was most active against ovarian, colon, prostate, cervical and breast cancer cells. The experimental compounds had much higher IC50’s when tested on the normal cells, which indicates selectivity for cancer cells. The octanol/water partition coefficient (lipophilicity) of all the experimental compounds was measured to determine the lipophilicity of the compounds. [Au(dppe) 2]Cl was found to be strongly lipophilic; while the novel compounds had varying degrees of lipo- and hydrophilicity. The octanol/water partition coefficient (lipophilicity) was also used to establish whether there is a correlation between the lipophilicity, IC50 and tumour specificity. In this study no correlation was found between these parameters. [Au(dppe) 2]Cl is known to have an effect on the mitochondrial membrane potential of cells. MM4, MM5, MM6 and cisplatin were compared to [Au(dppe) 2]Cl for effects on mitochondrial membrane potential. PHA stimulated human lymphocytes and a human undifferentiated leukemia T-cell line (Jurkat cells) were used in these experiments. [Au(dppe) 2]Cl, MM4, MM5 and MM6 depolarized the mitochondrial membranes of PHA stimulated lymphocytes significantly, while only [Au(dppe) 2]Cl depolarized the mitochondrial membranes of the Jurkat cells significantly, indicating that a different mechanism of action might be operational. MM4, MM5, MM6 and cisplatin were compared to [Au(dppe) 2]Cl for effects on plasma membrane potential. PHA stimulated human lymphocytes and Jurkat cells were used in these experiments. [Au(dppe) 2]Cl and MM6 depolarized the plasma membranes of both PHA stimulated lymphocytes and the Jurkat cells significantly. In order to determine whether the depolarization of mitochondrial and plasma membranes was a precursor for apoptosis, experiments were done to determine whether MM4, MM5 and MM6 induce apoptosis in Jurkat cells. [Au(dppe) 2]Cl and cisplatin were added for comparison. [Au(dppe) 2]Cl, cisplatin, MM4 and MM6 did induce apoptosis in Jurkat cells, but MM5 did not. The effect of [Au(dppe) 2]Cl, cisplatin, MM4, MM5 and MM6 on the cell cycle of Jurkat cells was determined to establish whether the experimental compounds altered this process. [Au(dppe) 2]Cl, MM4, MM5 and MM6 arrested the cell cycle in the G1 phase and cisplatin did so in the S phase. In order to determine whether the inhibition of cell growth and partition coefficient of the experimental compounds is related to the uptake of the drug, radio labeled drug uptake experiments were carried out with 198Au labeled [Au(dppe) 2]Cl, MM5 and MM6. Two different types of ovarian cancer cells were used for these studies. One cell line was sensitive to cisplatin (A2780) and the other was resistant to cisplatin (A2780 cis). Results obtained from these experiments showed that the uptake of these experimental compounds was dependent on their octanol/water partition coefficient. However, the inhibition of cell growth did not correlate with the uptake of these compounds by the cells that were tested. To confirm the octanol/water partition coefficient and drug uptake results, 198Au labelled [Au(dppe) 2]Cl, MM5 and MM6 were testedin vivo for bio distribution in rats. [Au(dppe) 2]Cl (lipophilic) had higher bio distribution compared to MM5 and MM6 (hydrophilic). Conclusion The experimental compounds show low IC50’s combined with increased tumour specificity. This indicates that these compounds have great potential to target tumour cells selectively and should be investigated further as anti-cancer agents. / Dissertation (MSc)--University of Pretoria, 2008. / Pharmacology / unrestricted

Orientador: Carlos Frazatto Jr / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-18T19:19:22Z (GMT). No. of bitstreams: 1 Carvalho_MarcosBrasilinode_D.pdf: 3538369 bytes, checksum: 44e9e476ecd55e600fe5e5d0397aad13 (MD5) Previous issue date: 1993 / Resumo: Estudo prospectivo de 115 pacientes consecutivos portadores de carcinoma epidermóide da laringe ou da hipofaringe, atendidos no período de maio de 1981 a janeiro de 1988, no Serviço de Cirurgia de Cabeça e Pescoço do Complexo Hospitalar Heliópolis, São Paulo, Brasil. Todos os pacientes foram submetidos a tralamento cirúrgico que compreendia um esvaziamento cervical completo e laringectomia ou faringolaringectomia. Os casos foram dirigidos alealóriamente para um dos dois tipos de esvaziamento: com ou sem conservação da veia jugular interna, do músculo esternocleidomaslóideo e do nervo espinal acessório. O principal pré-requisito para a inclusão do caso neste estudo era que, no linfonodo metastático, a neoplasia deveria estar confinada ao seu interior e não deveria apresentar transposição macroscópica da cápsula. O objetivo deste trabalho foi avaliar: 1. a importância da recidiva cervical homolateral; 2. a influência da conservação da veia jugular interna, do músculo esternoclei domastóideo e do nervo espinal acessório sobre os índices de recidivas e de sobrevida; 3. quais os fatores que devem ser considerados na escolha de uma cirurgia mais conservadora. Os cálculos da sobrevida atuarial foram feitos através da técnica de KAPLAN & MEIER (1958) e as comparações entre as distribuições de sobrevida para categorias de urna mesma variável foram feitas através do teste de Mantel-Cox (MANTEL, 1966; COX, 1972). Os resultados observados mostraram que o esvaziamento cervical oferece uma taxa de controle das metástases cervicais homolaterais em 95.1 % dos casos. A conservação de estruturas não linfáticas (veia músculo e nervo) não compromete a radicalidade oncológica da cirurgia mas deve-se estar a tento à cadeia da veia jugular interna que é preferencial para o desenvolvimento de metástases homo ou contralateral. A idade do paciente, a sede da lesão primária, o grau de diferenciação histológica do tumor, o estadiamento clínico, o diâmetro e o número dos linfonodos comprometidos e o estado microscópico da cápsula linfonodal não estiveram correlacionadas aos resultados observados para os dois lipos de esvaziamento. / Abstract: A prospective study of 115 consecutive patients with epidermoid carcinoma of the larynx or hypopharynx aclmitted to the Head and Neck Service of the Heliópolis Hospital Complex, São Paulo, Brasil, from May 1981 through January 1988. All patients underwent surgical treatment which consisted of comprehensive neck dissection and laryngectomy or pharyngolaryngectomy. The cases were chosen at random to undergo one of two types of neck dissection: with or without internal jugular vein, sternocleidomastoid muscle and spinal accessory nerve preservation. The main condition to be included in this protocol was: no patient with macroscopic extracapsular spread of carcinoma in cervical lymph nodes should be admitted. The purpose of this study was to analyze: 1. the importance of homolateral cervical relapse; 2. the influence of preservation of the interna I jugular vein, sternocleidomastoid muscle and spinal accessory nerve on the rates of reccurences and survival; 3. which factors should be considered in order to indicate a more conservative surgery. The actuarial survival was determined by the KAPLAN & MEIER (1958) method and the Mantel-Cox test was used to compare the .distribution of survival for categoJi'ies of the same variable (MANTEL, 1966; COX, 1972). The rates of homolateral cervical metastasis control were 95.1%. The preselvation of nonlymphatic structures (vein, muscle and nerve) do not compromise the oncologycal radicality and we should be careful with the dissection of jugular nodes that are regularly involved with homolateral or contralateral metastatic carcinoma. This study showed no statistically significant differences for the patients treated by one of the two types of neck dissection as the rates were adjusted for age, primary site, histologic differentiation, stage, size and number of metastatic nodes and degree of microscopic capsular involvement. / Doutorado / Doutor em Cirurgia

Thesis (M. Sc. (Biochemistry)) -- University of Limpopo, 2019 / Cervical cancer is the fourth most common cancer in females, and the seventh of all cancer types in both genders, with an estimated 500,000 new cases each year. As with liver cancer, a large majority (around 85%) of the global burden occurs in the less developed regions, where it accounts for almost 12% of all female cancers. About 90% of cervical cases are associated with human papillomavirus (HPV) as a causative agent and this virus is frequently transmitted through sexual contact involving exchange of fluids (Walboomers et al., 1997). Due to the ineffectiveness, undesirable side effects and costly treatment for the disease the current study was aimed at determining the anti-proliferative effects of extracts of selected medicinal plants for their anticancer activity on HeLa cell line invitro. In order to accomplish the outcome of this research study, medicinal plants (Toona cilliata, Seriphium plumosum and Schkuhria pinnata) from Limpopo Province (South Africa) with history of traditional use on cervical cancer-associated patients were selected. The Toona cilliata plant leaves were collected from Tzaneen, area while Seriphium plumosum and Schkuhria pinnata leaves were collected from Mankweng area. The dried leaves were grounded into powder and extracted using acetone. Thereafter, extracted leaf materials of selected plants were subjected to fingerprint profiling using TLC silicon coated plates immersed in tanks with different mobile phases (TEA, CEF and EMW) of various increasing polarities since. The plates were sprayed with vanillin/H2SO4, dried and visualised under UV light. Scavenging ability of the plant extracts was determined through investigating the presence of antioxidant activities using 0.2% of the 2,2- diphenyl-1- picrylhydrazyl (DPPH) indicator. The quantitative presence of total phenolic and flavonoids contents was also determined using garlic and quercetin as standards, respectively. Quantitative antioxidant scavenging activities were also determined and ascorbic acid was used as a positive control. This was followed by quantitative determination of ferric reducing power and thereafter the EC50 values of the extracts were determined by linear regression. Cell proliferation or viability was determined using the 3[4, 5 dimethylthiazol-2-yl]-2-5 diphenyltetrazolium (MTT) assay with actinomycin as a xv positive control and untreated cells as the negative control. Apoptotic effects of the extracts were determined using the Annexin V Fluos staining kit. This was followed by determining whether apoptosis was calcium dependent or independent using a calorimetric assay. In comparing the acetone extract yield per 10 g leaves of plants, Toona cilliata leaves exhibited the highest yield followed by Seriphium plumosum and with the least yield from Schkuhria pinnata. The finger print profile showed the prominent separation and was achieved from all the plants when using the non-polar TEA solvent. All plants were shown to contain extracts with varying levels of antioxidant activity especially when using CEF and EMW mobile phases. When evaluating the total phenolic and flavonoids contents all plant extracts exhibited presence of phenolic compounds with high presence observed in Seriphium plumosum and Toona cilliata. Extracts from Seriphium plumosum and Toona cilliata showed to have higher concentrations of phytochemicals that may be of a benefit in antioxidant activities as compared to Schkuhria pinnata in relation to the positive control and a similar trend were observed in the ferric reducing power assay. Extracts from Seriphium plumosum were shown to have the best IC50 scavenging values followed by Toona cilliata and Schkuhria pinnata respectively. All the plants exhibited free radical scavenging abilities with Seriphium plumosum shown to possess higher activities in comparison with the positive control. All the plants exhibited a dose-dependent cytotoxicity activity against the HeLa cervical cell line. Evidence of induced apoptotic activity was observed in HeLa cells when using extracts from Seriphium plumosum and Toona cilliata. Induction of apoptosis by plant extracts was shown to be calcium dependent as there was a decrease in calcium concentration with a decrease in the number of viable cells. In conclusion, the leaf extracts from Toona cilliata, Seriphium plumosum and Schkuhria pinnata contain compounds of various polarities with freeradical, antioxidant and anti-cancerous activities that may be beneficial if further studies are conducted to identify chemical compounds that may inhibit anticervical cancer activities.

Thesis (MPH.) -- University of Limpopo, 2015 / Background Cervical cancer is the 2nd most common cancer in women globally representing 13% of female cancers and accounting for 11% of the total cancer deaths (Ahmedin et al.2011). Several studies demonstrated the association between HIV and HPV. In Zimbabwe the prevalence of HIV/AIDS is high and cervical cancer is the leading cause of cancer deaths among women of all age groups. The aim of the study was to determine the knowledge, attitude and practices of HIV infected women on cervical cancer and cervical cancer screening at Musiso Hospital, Masvingo Province, Zimbabwe. Methods 208 self administered questionnaires were used with a 100 per cent response rate. Quantitative data were analysed using STATA statistical package version 12 for descriptive and inferential statistics. Chi-squared tests were done for hypothesis testing at 5 per cent level of significance and 95 per cent confidence level. Multiple variable logistic regressions models were also used to assess association between outcomes of interest and socio-demographic characteristics. All open ended questions were analysed using qualitative methods. Results Out of the 208 participants, 45 (21.6 per cent) respondents claimed to know what cervical cancer is. About 55.3 per cent said cervical cancer is preventable. The majority (92.8 per cent) did not know any screening tests. Just above three quarters (77.3 per cent) of the respondents believed they were at risk of having cervical cancer. About 9 per cent (18) of all participants had screened for cervical cancer before and 95.8 per cent respondents reported would like to screen for cervical cancer in the future. Conclusion HIV infected women at Musiso mission hospital were found to be having inadequate knowledge, positive attitude and inadequate practices on cervical cancer and cervical cancer screening. There is need to equip these women with knowledge on cervical cancer and cervical cancer screening to increase cervical cancer screening uptake. Key Concepts: knowledge, attitude, practice, screening, cervical cancer

Though vaccine uptake and public support have risen since the release of the first HPV vaccines, the United States has far lower initiation and completion rates for the HPV vaccine series in comparison to other vaccines indicated for youth. Disparities are even greater in the Appalachian regions. Understanding factors contributing to these discrepancies is vital to improving raise vaccine rates in Appalachia. A comprehensive literature search identified all articles pertaining to HPV vaccination in children and adolescents living in Appalachia. The final 15 articles were included in a systematic review of the topic. Findings: HPV disease and HPV vaccine-related knowledge and communication were low in Appalachian communities, and vaccine uptake was lower in all areas of Appalachia as compared to non-Appalachian U.S. Moreover, large variations in uptake existed among Appalachian subregions. Many variables appear to contribute to this variation, including vaccine acceptance for younger adolescents, local and press-driven critical reports of the vaccine, physician communication, and views of the family matriarchs. Targeting the Appalachian subregions, specific campaigns or intervention may be more impactful than viewing the region as a homogenous whole.

Background: External Beam Radiotherapy is essential in the management of locally advanced cervical cancer (LACC). Generally, VMAT is thought to achieve higher conformity to the Planned Target Volume (PTV) and better sparing of organs at risk (OAR) when compared to 3D-CRT. This study focused on these principles as it applied to treatment and potential toxicity in the management of LACC. Aim: To compare dosimetric parameters between VMAT and 3D-CRT in the management of LACC. Setting: The study analysed patients treated at Groote Schuur Hospital between May and December 2017. Method: A non-randomized comparative retrospective study. EBRT plans for 3D-CRT and VMAT were generated and data on treatment parameters for PTV D50%, Dmax, Dmean, Conformity Index (CI), Homogeneity Index, Treated Volume (TV), Irradiated Volume (IV) and OAR constraints; femoral heads, bladder, bowel bag, rectum and bone marrow were collected. Results: Of the 45 patients assessed, VMAT showed significantly lower treatment parameter values for CI (1.09 vs 1.49; p< .001) whereas, 3D-CRT showed lower Dmax (48.1Gy vs 49.2Gy; p< .001) and rectum (88.5% vs 96%). A reduced 3D-CRT dose was noted for bladder Dmax (47.4Gy vs 48.3Gy; p< .001). Conclusion: VMAT offered a superior dosimetric option, with better OAR dose sparing and optimal tumour dosimetry.

Objetivo: Describir la prevalencia de genotipos del VPH con PCR y secuenciación del ADN en 397 mujeres que acudieron a consulta externa del Hospital Regional Docente de Cajamarca desde Marzo hasta Septiembre del 2017. Materiales y métodos: las muestras del endocérvix y ectocérvix fueron almacenadas y luego se procedió a la detección de tipos del alto y bajo riesgo con PCR. Resultados: un PCR positivo para VPH se observó en 121 muestras cervicales. Se encontró 63.6% (77/121) de genotipos de alto riesgo, 23.1% (28/121) genotipos probablemente oncogénicos y 7.4% genotipos de bajo riesgo. De los genotipos de alto riesgo, VPH-31 fue el más común en un 20% (21/77), seguido de VPH-16 en un 11.4% (12/77). Coinfección entre dos o más genotipos se observó en 12 casos. / Objective: Describe the prevalence of HPV genotypes via PCR and DNA sequencing in 397 women who attended to the gynecological outpatient clinic in the Hospital Regional Docente de Cajamarca from March to September 2017. Methods and materials: The samples from the endocervix and ectocervix were stored and then we proceeded to do detection with genotyping, high and low risk types, by PCR. Results: A positive PCR result for HPV was observed in 121 cervical samples. A high-risk genotype was found in 63.6% (77/121) of patients, a probably oncogenic type in 23.1% (28/121) and a low-risk type in 7.4%. Among the high-risk genotypes, HPV-31 was the most common one present in 20% (21/77), followed by HPV-16 in 11.4% (12/77). Coinfections between two or more genotypes were observed in 12 cases. / Tesis