Introdução: A rinossinusite crônica com polipose nasal constitui um subgrupo particular da rinossinusite crônica, caracterizado por uma inflamação da mucosa que leva a um espessamento da mesma e à formação de pólipos, podendo ser especialmente difícil de tratar. A Doxiciclina é um antibiótico bacteriostático, de largo espectro, que também tem uma ação antiinflamatória, e tem se mostrado útil no controle dos sintomas das recidivas desta doença, promovendo inclusive uma diminuição do pólipo. Objetivo: avaliar se o uso de baixas doses de Doxiciclina, por períodos prolongados, pode melhorar o controle clínico da rinossinusite crônica com polipose nasal, de difícil tratamento. Métodos: este é um estudo prospectivo, aberto, realizado em 60 pacientes com rinossinusite crônica de difícil tratamento que se submeteram a cirurgia endoscópica nasal. Os pacientes foram divididos em 2 grupos: 28 pacientes receberam corticóide nasal, lavagem nasal com soro fisiológico, e Doxiciclina (200mg no primeiro dia, seguido por 100mg uma vez ao dia) por 12 semanas, enquanto 30 pacientes receberam apenas corticóide nasal e lavagem nasal com soro fisiológico. O principal resultado avaliado foi a existência de uma melhora, dose efeito, clinicamente significativa do SNOT-20 após o tratamento com a Doxiciclina. Outros resultados avaliados foram os valores do SNOT-20, NOSE e do Lund-Kennedy. Os seguintes parâmetros também foram analisados: asma, rinite, doença respiratória exacerbada pela Aspirina (DREA), níveis séricos de IgG, IgA, IgE, IgM, ANCA e contagem de eosinófilos. Resultados: oy tratamento com a Doxiciclina promoveu uma melhora, dose efeito, clinicamente significativa do SNOT-20. Pacientes que receberam a Doxiciclina também tiveram resultados significativamente melhores do SNOT-20, NOSE e Lund-Kennedy. Houve uma associação negativa entre a melhora clinicamente significativa do SNOT-20 e a presença de asma, DREA e níveis séricos elevados de IgE pré-tratamento. Conclusão: os achados sugerem que a doxiciclina pode ter uma ação benéfica nos pacientes com rinossinusite crônica com polipose nasal, especialmente naqueles pacientes sem asma, DREA ou níveis séricos elevados de IgE prétratamento / Introduction: Chronic rhinosinusitis with nasal polyps is a particular subset of chronic rhinosinusitis characterized by a mucosal inflammation that leads to mucosal thickening and polyp formation, and can be especially difficult to treat. Doxycycline is an oral, available, broad-spectrum bacteriostatic antibiotic which also has anti-inflammatory action, that has been used to treat this disease and has shown a successful control of symptoms even reducing the volume of polyps. Objective: Evaluate if long-term low-dose doxycycline is effective in controlling clinical symptoms of difficult-to-treat chronic rhinosinusitis with nasal polyps. Methods: This was a prospective, open-label study of 60 patients with difficultto- treat chronic rhinosinusitis with nasal polyps who had undergone endoscopic sinus surgery. Patients were divided into two groups: 28 received nasal steroids, saline irrigation, and doxycycline (200 mg on the first day, followed by 100 mg daily) for 12 weeks, while 30 received only nasal steroids and saline irrigation. The main outcome measure was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Other outcome measures were the SNOT-20, NOSE, and Lund-Kennedy scores. The following parameters were also analyzed: asthma, rhinitis, non-steroidal-exacerbated respiratory disease (NERD), and baseline serum IgG, IgA, IgE, IgM, ANCA, and eosinophil count. Results: There was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Patients who received doxycycline also had significantly better outcomes regarding SNOT-20, NOSE, and Lund-Kennedy scores. There was a negative association among a clinically significant improvement of SNOT-20 and presence of asthma, NERD, and elevated serum IgE levels before treatment. Conclusion: These findings suggest that doxycycline may have a beneficial role for chronic rhinosinusitis with nasal polyps patients, especially for those without asthma, NERD or high levels of serum IgE before treatment

Orientadores: Sophie Françoise Mauricette Derchain, Luiz Claudio Santos Thuler / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T13:10:42Z (GMT). No. of bitstreams: 1 Ishikawa_NeliMuraki_D.pdf: 1821196 bytes, checksum: 275765cd47c5e7b5eb453f3a8a771525 (MD5) Previous issue date: 2009 / Resumo: Objetivos: Validar a versão em português do questionário Functional Assessment of Cancer Therapy-Fatigue (FACT-F) em pacientes com câncer e avaliar a fadiga e a qualidade de vida em mulheres com câncer de mama em quimioterapia. Sujeitos e métodos: Para este estudo de validação do questionário FACT-F foram incluídos 270 pacientes, sendo 85 para avaliar a reprodutibilidade do questionário com diferentes tipos de câncer. Para avaliar a fadiga e qualidade de vida em mulheres com câncer de mama em quimioterapia foi realizado um estudo longitudinal e incluídas 188 mulheres. O período de realização dos estudos foi de setembro de 2005 a março de 2007. Inicialmente foi avaliada a reprodutibilidade do FACT-F através do teste-reteste para a língua portuguesa em pacientes com câncer; em seguida a versão para língua portuguesa foi submetida à validação, a fim de estabelecer propriedades incluindo a validade e confiabilidade em uma amostra de pacientes brasileiros com câncer; finalmente foi avaliada a relação entre fadiga e qualidade de vida relacionada à saúde em pacientes com câncer de mama antes do início da quimioterapia, e após 3º e 6º ciclo de quimioterapia. Resultados: O FACT-F apresentou uma boa correlação intraclasse para os domínios que foram de 0,72 para bem-estar físico; 0,91 para bem-estar social e familiar; 0,90 para bem-estar emocional; 0,86 para bem-estar funcional; 0,88 para subescala fadiga e 0,91 para FACT-F. O coeficiente a de Cronbach foi de 0,78 para bemestar físico; 0,68 para bem-estar social e familiar; 0,75 para bem-estar emocional; 0,74 para bem-estar funcional; 0,91 para subescala fadigas e 0,92 para o FACTF. A correlação de Pearson foi excelente entre domínio vitalidade do SF-36 e FACTF total (r=0,76), e subscala fadiga (r=0,77); sendo boa entre o FACT-F e na maioria dos domínios do SF-36, variando de r =0,51 a 0,76, exceto para domínio físico (r =0,31). Houve uma diminuição significante dos escores do FACT-F (p<0,001), FACT-G (p=0,029), subescala fadiga (p<0,001) e bem-estar físico (p<0,001) entre antes da quimioterapia e após o terceiro ciclo de quimioterapia e permanecendo um platô até após o sexto ciclo (p<0,001) refletindo uma manutenção da fadiga e baixa qualidade de vida em mulheres com câncer de mama. O escore do bem-estar emocional teve um pequeno aumento após o terceiro ciclo (p<0,001), permanecendo após o sexto ciclo (p<0,001) enquanto os escores do bem-estar funcional e do bem-estar social e familiar não mostraram diferença entre antes e durante a quimioterapia. A fadiga está relacionada à baixa qualidade de vida relacionada à saúde. Conclusões: O instrumento FACT-F apresentou uma boa reprodutibilidade teste-reteste em uma série heterogênea de pacientes, com diferentes tipos de câncer, performance status e estadiamento. A versão portuguesa do FACT-F é um instrumento válido e confiável para avaliar a fadiga e qualidade de vida em pacientes com câncer. A fadiga aumentou e piorou a qualidade de vida em pacientes com câncer de mama submetidas à quimioterapia. / Abstract: Objectives: Validate the Portuguese version of the FACT-F questionnaire in cancer patients and fatigue and quality of life in breast cancer patients in chemotherapy. Subjects and methods: This study of FACT-F validation included 270 patients, 85 were to evaluate the questionnaire reproducibility in patients with different types of cancer. The study to evaluate fatigue and quality of life in breast cancer during chemotherapy was prospective and 188 women were included. The study was conducted from September 2005 to March 2007. It was initially assessed the reproducibility of the FACT-F through the test-retest for the Portuguese language in patients with cancer, following the Portuguese language version was submitted to validation in order to establish properties including the validity and reliability in a sample of Brazilian cancer patients, finally, it was assessed the relation between fatigue and quality of life related to health in patients with breast cancer before the start of chemotherapy, and after 3 and 6 cycle of chemotherapy. Results: FACT-F had a Intraclass Correlation Coefficient to the domains that were 0.72 for physical well-being, 0.91 for social/family well-being; 0.90 for emotional well-being, 0.86 for functional well-being, 0.88 fatigue subscale and 0.91 for total FACT-F. Cronbach a coefficient was 0.78 for physical well-being, 0.68 for social/family well-being, 0.75 for emotional well-being, 0.74 for functional wellbeing, 0.91 for fatigue, and 0.92 for total FACT-F. The Pearson correlation was excellent between SF-36 vitality scale and total FACT-F (r=0.76) and fatigue subscale (r=0.77); and good correlation in most dimensions ranging from r=0.51 to r=0.76, except to SF-36 physical (r=0.31). There were a significant decrease in mean FACT-F (p<0.001), FACT-G (p=0.029), Fatigue subscale (p<0.001), Physical well being (p<0,001) scores between the start of the treatment and after cycle 3 and than appeared to plateau at cycle 6 (p<0.001) reflecting maintenance in fatigue symptoms and lower quality of life in breast cancer patients. The Emotional well being scores increased a little between the start of chemotherapy and after cycle 3 (p<0.001) and remained a plateau at cycle 6 (p<0.001) while social/family well-being scores showed no differences before and during chemotherapy. Fatigue is related to lower health related quality of life. Conclusion: FACT-F questionnaire in Portuguese has good test-retest reproducibility in patients with different types of cancer, performance status and stages. The Portuguese version of FACT-F is a reliable and valid instrument to assess QOL and fatigue to screen cancer-related fatigue in Brazilian cancer patients. Fatigue increased and worsened in health related HRQOL in breast cancer submitted to chemotherapy. / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-09-04T15:18:51Z No. of bitstreams: 0 / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-09-04T15:53:06Z (GMT) No. of bitstreams: 0 / Made available in DSpace on 2018-09-04T15:53:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-07-31 / A colite ulcerativa (CU) é uma doença inflamatória crônica cujas manifestações podem afetar drasticamente a qualidade de vida do indivíduo sendo por isso importante a adesão ao tratamento a fim de mantê-la em fase de remissão. Fatores individuais podem interferir na continuidade do tratamento do paciente em remissão. Assim, o objetivo deste estudo foi avaliar a prevalência de não adesão e a possível influência das características sóciodemográficas, clínicas e farmacoterapêuticas associadas com a não adesão ao tratamento da CU em remissão. Trata-se de estudo transversal com adultos portadores de CU em remissão acompanhados no Centro de Doenças Inflamatórias Intestinais do Hospital Universitário da Universidade Federal de Juiz de Fora, Minas Gerais, conduzido entre agosto de 2017 e janeiro de 2018. Os fatores associados à não adesão ao tratamento foram investigados por meio da aplicação de questionário padronizado contendo dados sociodemográficas, clínicos e farmacoterapêuticos dos pacientes, além da Escala de Adesão Terapêutica de Morisky (MMAS-8), Inventario de Depressão de Beck (IDB) e Subescala de Ansiedade de sete itens da Escala Hopitalar de Ansiedade e Depressão. O total de 90 pacientes foi incluído neste estudo com média de idade de 50,4±12,9. A prevalência de não adesão foi de 77,8% e não foram encontradas dentre as 21 variáveis analisadas, nenhuma relacionada com o comportamento de não adesão. A prevalência de não adesão em pacientes com CU em remissão foi elevada. Nenhuma das características sociodemográficos, clínicas e farmacoterapêuticas analisadas foram associadas com este comportamento, alertando para a necessidade de maior atenção dos profissionais de saúde a esse importante aspecto do tratamento. / Ulcerative colitis (UC) is a chronic inflammatory disease whose manifestations can drastically affect the quality of life of patients. Therefore, treatment adherence is important in order to keep it in remission. Individual factors may interfere with the continuity of the patient's treatment in remission. To verify the prevalence of non-adherence and the influence of the sociodemographic, clinical and pharmacotherapeutic characteristics associated with non-adherence to the treatment of UC in remission. A cross-sectional study was conducted with adults presenting UC in remission followed at the Clinical Gastroenterology outpatient clinic of the Clinical Gastroenterology Ambulatory of Universitary Hospital, in Juiz de Fora, Minas Gerais, Brazil, between August 2017 and January 2018. Factors of risk for non-adherence to treatment were investigated by applying a questionnaire on sociodemographic, clinical and pharmacotherapeutic characteristics of the patient. The Morisky Therapeutic Adhesion Scale (MMAS-8), Beck Depression Inventory (BDI) and Subscale of Anxiety of seven items of the Hopitalar Anxiety and Depression Scale were also applied. A total of 90 patients were included, with a mean age of 50.41±12.94 years. The prevalence of non-adherence to therapy was 77.8% and we did not identified among 21 variables analyzed anyone associated with non-adherence prevalence. High proportions of patients with UC in remission presented non-adherents to therapy; however, we did not found characteristics among sociodemographic, clinical and pharmacotherapeutic data that would be able to explain this behavior, alerting the need for greater attention of health professionals to this important aspect of treatment.

African Potato (Hypoxis hemerocallidea), (AP) is an African traditional medicine (TM) that is commonly used for various nutritional/medicinal purposes and also by people infected with the human immuno deficiency virus HIV and AIDS patients as an immune booster. The use of AP has also been recommended by the former Minister of Health of South Africa for use by HIV positive people. The main phytochemical component of AP is a norlignan glucoside, hypoxoside, and other relatively minor components have also been reported. A recent in vitro study reported the effects of AP extracts, hypoxoside and rooperol (the metabolite of hypoxoside) on human metabolic enzymes such as the cytochrome P450 (CYP450) group of enzymes and also on the transporter protein, p-glycoprotein (P-gp). This research focussed on investigating the clinical significance of those in vitro effects on the pharmacokinetics of efavirenz (EFV) in humans. EFV was chosen as the substrate drug because it is in first-line regimen of treatment of HIV/AIDS in South Africa, and also has been reported to be a substrate for the specific CYP isozymes, 3A4 and 2B6, in common with APs metabolic involvement with 3A4. A high performance liquid chromatography method with ultra-violet detection (HPLC-UV) for the quantitative determination of EFV in plasma was developed and successfully validated according to international standards with good reproducibility, accuracy, recovery, linear response and requisite sensitivity. The preparation of the plasma samples for analysis was effected by using a simple and rapid precipitation method, and the mobile phase consisted of readily available solvents. EFV in plasma samples was found to be stable under the relevant storage conditions studied. The oral dose of AP, administered as a freshly prepared traditional decoction, was standardised based on the hypoxoside content, and the quality of all the AP decoctions was analysed immediately prior to administration, using a validated HPLC-UV method. A single dose, two-phase sequential study was conducted over a period of 31 days in 10 healthy volunteers. The clinical study was approved by the Rhodes University Ethical Standards Committee, and all the participants agreed to the conditions of the study by giving their informed consent. On day 1 of the study, human subjects were administered a 600 mg EFV tablet and blood samples were collected before dosing and at various intervals over a period of 48 hr post dosing. From day 16, a traditionally prepared AP decoction was administered daily at a standardized dose of 15 mg/kg/day per subject until day 30. On day 29, volunteers were administered a single 600 mg dose of EFV as was done on day 1. Plasma samples were harvested immediately after blood sample collection and frozen at -80 ºC until assayed. Geometric mean ratios of relevant pharmacokinetic parameters, Cmax (maximum plasma concentration achieved following dosing) and AUC0-48 (area under the curve of a plot of drug plasma concentrations versus time representing the extent of absorption) of EFV before and after co-administration of 14 successive daily doses of AP were compared and evaluated to determine whether an interaction had occurred. All subjects completed the study and the geometric mean ratios of Cmax and AUC0-48 were 97.30 and 102.82 with corresponding 90% confidence intervals (CIs) of 78.81-120.14% and 89.04-118.80%, respectively. Whereas the acceptance criteria for the ratios of the AUCs fell within the preset 90% CIs indicating no interaction, the Cmax ratios fell outside the limits. Although the protocol was developed in accordance with the United States of America Food & Drug Administration’s Guidance for Drug Interactions, a priori stating that both criteria need to fall within the acceptance limits to indicate no interaction, an argument is presented to waive the Cmax requirement for the declaration of an interaction. As a result, the pharmacokinetic data generated during this study indicated that the effect of AP on the pharmacokinetics of EFV is not clinically significant. Hence, co-administration of AP is unlikely to affect the clinical use of EFV. In summary the objectives of this project were: 1. To develop and validate a suitable HPLC-UV method for the quantitative determination of EFV in plasma. 2. To perform a mini-validation of the determination of hypoxoside for use as a marker in the quality control and standardisation of AP decoctions. 3. To conduct a clinical interaction study in order to determine whether AP affects the pharmacokinetics of EFV following concurrent administration. 4. To apply the validated HPLC-UV method to determine plasma concentrations of EFV in plasma of human subjects. 5. To use appropriate statistical methods and treatments such as a non-compartmental pharmacokinetic analysis to determine the occurrence of an interaction.

Estudo de fase III, prospectivo, aleatorizado e duplo-cego de prevenção de mucosite oral com laser de baixa potência. Foram incluídos pacientes portadores de câncer de cabeça e pescoço, tratados com radioquimioterapia. Grupo A laser 2,5 J/cm2 diariamente durante o tratamento e grupo B laser placebo. Inclusão de 75 pacientes (A/B 37/38). Grau III /IV mucosite: A/B 2a semana (4/5) P=1.0, 4a semana (4/12) P=0.04 e 6a semana (8/9) P=1.0. Interrupções da RT devido à mucosite A/B 0/6 P=0.02. Dor severa A/B 2a semana (5/5), 4a semana (8/8) e 6a semana (8/8) P=1.0. O tratamento com laser foi efetivo, tendo adiado o aparecimento da mucosite severa e reduzido as interrupções da radioterapia. / Phase III, prospective, randomized, double-blind study of oral mucositis prophylaxis by low energy laser. Patients included had a diagnosis of head and neck cancer and were managed with radiochemotherapy. Arm A laser 2.5 J/cm2 daily throughout treatment and B sham laser. Inclusion of 75 patients (A/B 37/38). Grade III /IV mucositis A/B: week 2 (4/5) P=1.0, week 4 (4/12) P=0.04 and week 6 (8/9) P=1.0. Treatment breaks due to mucositis A/B 0/6 P=0.02. Severe pain A/B week 2 (5/5), week 4 (8/8) and week 6 (8/8) P=1.0. Low laser therapy was effective, delaying severe mucositis and reducing radiotherapy breaks.

The description and interpretation of Latinas’ experience with chemotherapyinduced premature menopause from breast cancer treatment were explored in this study, which utilized an interpretive descriptive method from a feminist lens, and Knobf’s (1998, 2002) “Carrying on” theory. The specific aims of the study and the interview questions were guided by the state of the science literature. Overall, the impact of physiological effects, psychosocial effects, barriers, influencing factors that made their experience easier or harder, and how participants adjusted to a cancer diagnosis, treatment course, and menopause transition were described as bigger than the menopause experience alone. Participants also described a period of uncertainty or “ever-changing landscape” that began at the time of diagnosis and continued through survivorship. The impact of information, access to healthcare, acculturation levels, support, and a sense of control were elucidated as important factors in “working through” the experience. A range of collateral data sources were employed. Study limitations and future implications for practice, research, and health policy were demarcated.

No description available.

My thesis research began with a project in which we were trying to determine the function of embryonic stem cell (ESC)-specific miRNAs. Using luciferase constructs containing miRNA binding sites, luciferase expression was inhibited by endogenous miRNAs in ESCs, and by exogenous miRNAs in HeLa cells. Inhibition of luciferase expression by miRNAs was inhibited in HeLa cells using 2’O-methyl-oligonucleotides. In ESCs, 2’O-methyl-oligonucleotides were only effective in partially inhibiting miR290 function. Partial inhibition of miR290 did not result in any obvious phenotypic changes in mESCs. Later studies using 2’O-methyl-oligonucleotides in ESCs were also unsuccessful. The function of ESC-specific miRNAs has since been studied by re-introducing miRNAs into Dicer -/- cells which cannot make miRNAs. These studies have shown that ESC-specific miRNAs are involved in de novo DNA methylation, self-renewal, and cell-cycle regulation. Newly diagnosed glioblastoma (GBM) patients rarely survive more than two years even after surgery, radiotherapy, and chemotherapy using temozolomide (TMZ) or 1,3-bis(2-chloroethy)-1-nitrosourea (BCNU). Eventual regrowth of the tumor indicates that some tumor cells are resistant to therapy. GBM neurosphere-initiating cells (NICs) are thought to be similar to tumor-initiating cells in vivo, and will form invasive tumors in mice, making neurosphere cultures a good model system for studying GBMs. To test whether GBM NICs were resistant to chemotherapy, we used a neurosphere formation assay to measure the number of proliferating NICs in the presence of TMZ or BCNU. The concentrations of chemotherapy drugs required to inhibit neurosphere formation were much less than those required to inhibit bulk cell proliferation or to induce cell death in our neurosphere cultures. For some cultures, there was a robust recovery of neurosphere formation after chemotherapy treatment which appeared to be DNA damage independent. Some of the cultures that showed significant recovery of neurosphere formation underwent reversible cell cycle arrest, possibly reducing chemotoxicity in these cultures. Collectively, these results indicate that GBM neurosphere cultures can regrow after being treated with clinically relevant doses of chemotherapy drugs. Chemotherapy-treated neurosphere cultures remained viable, and formed tumors when injected into mice. Our experiments show that these in vitro assays may be useful in predicting in vivo responses to chemotherapeutic agents.

No description available.

No description available.