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published_or_final_version / Community Medicine / Master / Master of Public Health

Orientador: Mauro Pedrine Santamaria / Coorientador: João Manoel Theotonio dos Santos / Banca: Maria Aparecida Neves Jardini / Banca: Germano Emilio Conceição Souza / Resumo: A doença arterial coronária (DAC), assim como a doença periodontal (PD) são patologias muito prevalentes e apresentam vias em comum na sua fisiopatologia que é a inflamação crônica. A angioplastia coronária percutânea com implante de stent se estabeleceu como a principal forma de revascularização miocárdica no tratamento da DAC porém cerca de 16% a 44% dos pacientes podem evoluir com reestenose do stent. Se a doença periodontal, pelo seu estado inflamatório sistêmico crônico estaria contribuindo para um aumento nas taxas de reestenose de stents convencionais não está definido e não é uma rotina na prática clínica a avaliação da cavidade oral antes de um procedimento de angioplastia coronária. O objetivo primário do estudo foi avaliar a correlação entre a doença periodontal com a incidência de reestenose do stent, enquanto os objetivos secundários foram avaliar a prevalência da doença periodontal, o número de dentes, o grau de perda óssea e finalmente a gravidade da doença periodontal na população do estudo. Para isto realizamos um estudo pioneiro, retrospectivo, caso controle e em um único centro no período de janeiro de 2016 a fevereiro de 2018. Foram analisados 1685 exames de cinecoronariografia dos quais 283 apresentavam imagem de stent com e sem reestenose sendo incluídos 49 pacientes separados entre o grupo caso, com reestenose (n=15) e o grupo controle, sem reestenose (n=34). Excluímos os pacientes portadores de Diabetes Mellitus (DM) não controlados, portadores de sten... (Resumo completo, clicar acesso eletrônico abaixo) / ABSTRACT: Coronary artery disease (CAD), as well as periodontal disease (PD) are very prevalent pathologies and present common pathways in their pathophysiology which is chronic inflammation. Percutaneous coronary angioplasty with stent implantation has been established as the main form of myocardial revascularization in the treatment of CAD but about 16% to 44% of patients may evolve with stent restenosis. If periodontal disease, because of its chronic systemic inflammatory state would be contributing to an increase in the rates of restenosis of conventional stents is not defined and it is not a routine in clinical practice to evaluate the oral cavity before a coronary angioplasty procedure. The primary objective of the study was to evaluate the correlation between periodontal disease and the incidence of stent restenosis, while the secondary objectives were to evaluate the prevalence of periodontal disease, number of teeth, degree of bone loss and finally severity of periodontal disease in the study population. For this, we conducted a pioneering, retrospective, case control and single-center study from January 2016 to February 2018. We analyzed 1685 coronary angiography exams, of which 283 presented stent imaging with and without restenosis and 49 patients were separated between the case group, with restenosis (n = 15) and the control group, without restenosis (n = 34). We excluded patients with uncontrolled diabetes mellitus (DM), those with stents of the pharmacological type or those with restenosis from stents implanted more than two years ago. For statistical analysis, the chi-square test in the qualitative variables, ANOVA test for quantitative variables, Odds Ratio calculation and Equality of Two Proportions test were used to compare the restenosis groups with the distribution of the type of periodontal disease. We found no statistically significant ...(Complete abstract click electronic access below) / Mestre

The aim of the thesis was to study cardiovascular side effects of radiotherapy (RT) in breast cancer (BC). In a study base of 25,171 women with BC diagnosed 1970-2000, we found a statistically significant 12% increase of stroke, compared to the stroke incidence in the background population. A case-control study of 282 cases with BC followed by a stroke and 1:1 matched controls with BC but not stroke was performed. In women irradiated to internal mammary chain (IMC) and supraclavicular lymph nodes (SCL) vs. a pooled group of women not irradiated or irradiated to targets other than IMC and SCL, a statistically significant increase of stroke with an odds ratio of 1.8 was observed. There were no associations between BC laterality, targets of RT, and hemisphere location of stroke. The radiation targets IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose. A study of 199 patients with BC, examined by coronary angiography, detected a four- to seven-fold increase of high grade coronary artery stenosis in mid and distal left anterior descending artery (LAD), including distal diagonal branch, when comparing women with irradiated left-sided BC to those with right-sided. An increase of clinically significant coronary artery stenosis was found in pre-specified hotspot areas for radiation among women irradiated to the left breast/chest wall or to the IMC. Thus, the coronary arteries should be regarded as organs at risk in RT of BC. In a study of 15 BC patients treated with 3D conformal RT, a marked difference in dose distribution in mid and distal LAD between left- and right-sided BC was demonstrated. Irradiated right-sided BC mainly received low doses of scattered and transmitted radiation to the coronary arteries. On the contrary, tangential RT to the left breast without regional lymph node irradiation yielded coronary artery max doses of approximately 50 Gray to distal LAD, probably not safe concerning late radiation vascular effects. To conclude, we found cardiovascular side effects in women irradiated for BC, resulting in stroke and coronary artery disease, and showed an association between the targets for RT and the anatomical location of these vascular events.

Made available in DSpace on 2016-08-12T18:48:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-04-28. Added 1 bitstream(s) on 2016-08-12T18:50:57Z : No. of bitstreams: 1 000866321.pdf: 1163995 bytes, checksum: fddc9784203913b96b1463e6003ad30d (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A doença cardiovascular compreende uma classe de patologias que envolvem o coração, e vasos sanguíneos, sendo a doença arterial coronária (DAC) a mais comum. O procedimento mais utilizado no tratamento das lesões coronarianas é a angioplastia com implante de stent. Entretanto, o sucesso desse procedimento tem sido comprometido por diversos eventos incluindo a injúria do endotélio, deposição de plaquetas, resposta inflamatória e reestenose. Os stents eluídos com as drogas sirolimus (rapamicina) e paclitaxel têm sido os mais utilizados, uma vez que podem efetivamente reduzir a incidência de reestenose. No entanto, a reestenose ainda permanece entre as causas do insucesso do tratamento coronariano. Considerando que tanto a lesão mecânica (estresse físico) causada pela colocação do stent, quanto o potencial tóxico das drogas utilizadas nos stents poderia ser responsável pela reestenose intra-stent, este estudo teve como objetivo investigar os mecanismos moleculares envolvidos na iniciação e desenvolvimento da reestenose. Citotoxicidade, genotoxicidade e alterações transcricionais (perfil de expressão gênica) possivelmente induzidas pelo sirolimus, paclitaxel, colchicina e estresse mecânico foram avaliados in vitro em células endoteliais (HCAEC) e musculares lisas de artéria coronária humana (HCASMC). Os dados mostraram diminuição da proliferação celular em ambas as linhagens celulares após o tratamento com as três drogas. O sirolimus inibiu o ciclo das HCAEC e HCASMC na fase G1; o paclitaxel apenas da HCASMC na fase G2 e a colchicina, tanto da HCAEC como da HCASMC, respectivamente, nas fases G1 e G2. O efeito citotóxico do paclitaxel e da colchicina foi também constado pelo aumento de células (HCAEC e HCASMC) em apoptose, ao passo que o sirolimus apresentou efeito genotóxico nas células musculares lisas. Os dados da análise de expressão gênica evidenciaram que os genes modulados pelo sirolimus e pelo... / Percutaneous transluminal revascularization of coronary arteries (angioplasty) with bare-metal stents is the most widely used and successful medical intervention for treatment of coronary artery disease (CAD). However, the success of this procedure can be compromised by several events including endothelium injury, platelet deposition, inflammatory response and restenosis. With the advent of drug-eluting stents (DES), incidence of in-stent restenosis has decreased, but is still about 5% to 10%. Thus, this study aimed to investigate the molecular mechanisms underlying the initiation and development of in-stent restenosis. Cytotoxicity, genotoxicity and transcriptional alterations (gene expression profile) possibly induced by sirolimus, paclitaxel, colchicine and also by mechanical stress (cell stretching) were evaluated in human coronary artery endothelial (HCAEC) and coronary artery smooth muscle (HCASMC) cell lines. Acting at different phase of the cell cycle, the three drugs were equally effective for reducing cell proliferation in both cell lines. Nevertheless, while paclitaxel and colchicine induced apoptosis, the main mechanism of cell death induced by sirolimus was necrosis. Similarly, while sirolimus was genotoxic (increase of oxidized pyrimidines) to only smooth muscle cells, colchicine mainly induced oxidative damage in endothelial cells. The transcriptome analyses revealed 82 differentially expressed genes (35 with known biological functions) in the treated groups compared to control. In HCAEC, three genes (TGM3, CTSF and MTSS1L) were differently expressed after sirolimus treatment; two (SLP1 and SLC4A1) after paclitaxel; one (PAQR8) 6 h after mechanical stretching; and 19 (WBE3A, ZBTB7A, CAMK1D, OR5AP2, EME1, C3AR1, VILL, RORC, MPV17L2, CEP350, RTEL1, ATG2A, SLC38A2, SLC25A25, FOXR2,SIGLEC8, CLIC4, ATP2A2 and VPRBP) after 12 h mechanical stretching. In HCASMC, two genes (NDST4 and FZD3) were differently expressed after ...

Orientador: Daisy Maria Fávero Salvadori / Coorientador: Glenda Nicioli da Silva / Banca: Ana Lucia dos Anjos Ferreira / Banca: Maria Aparecida Custódio Domingues / Banca: Daniel Araki Ribeiro / Banca: Verônica Elisa Pimenta Vicentini / Resumo: A doença cardiovascular compreende uma classe de patologias que envolvem o coração, e vasos sanguíneos, sendo a doença arterial coronária (DAC) a mais comum. O procedimento mais utilizado no tratamento das lesões coronarianas é a angioplastia com implante de stent. Entretanto, o sucesso desse procedimento tem sido comprometido por diversos eventos incluindo a injúria do endotélio, deposição de plaquetas, resposta inflamatória e reestenose. Os stents eluídos com as drogas sirolimus (rapamicina) e paclitaxel têm sido os mais utilizados, uma vez que podem efetivamente reduzir a incidência de reestenose. No entanto, a reestenose ainda permanece entre as causas do insucesso do tratamento coronariano. Considerando que tanto a lesão mecânica (estresse físico) causada pela colocação do stent, quanto o potencial tóxico das drogas utilizadas nos stents poderia ser responsável pela reestenose intra-stent, este estudo teve como objetivo investigar os mecanismos moleculares envolvidos na iniciação e desenvolvimento da reestenose. Citotoxicidade, genotoxicidade e alterações transcricionais (perfil de expressão gênica) possivelmente induzidas pelo sirolimus, paclitaxel, colchicina e estresse mecânico foram avaliados in vitro em células endoteliais (HCAEC) e musculares lisas de artéria coronária humana (HCASMC). Os dados mostraram diminuição da proliferação celular em ambas as linhagens celulares após o tratamento com as três drogas. O sirolimus inibiu o ciclo das HCAEC e HCASMC na fase G1; o paclitaxel apenas da HCASMC na fase G2 e a colchicina, tanto da HCAEC como da HCASMC, respectivamente, nas fases G1 e G2. O efeito citotóxico do paclitaxel e da colchicina foi também constado pelo aumento de células (HCAEC e HCASMC) em apoptose, ao passo que o sirolimus apresentou efeito genotóxico nas células musculares lisas. Os dados da análise de expressão gênica evidenciaram que os genes modulados pelo sirolimus e pelo... / Abstract: Percutaneous transluminal revascularization of coronary arteries (angioplasty) with bare-metal stents is the most widely used and successful medical intervention for treatment of coronary artery disease (CAD). However, the success of this procedure can be compromised by several events including endothelium injury, platelet deposition, inflammatory response and restenosis. With the advent of drug-eluting stents (DES), incidence of in-stent restenosis has decreased, but is still about 5% to 10%. Thus, this study aimed to investigate the molecular mechanisms underlying the initiation and development of in-stent restenosis. Cytotoxicity, genotoxicity and transcriptional alterations (gene expression profile) possibly induced by sirolimus, paclitaxel, colchicine and also by mechanical stress (cell stretching) were evaluated in human coronary artery endothelial (HCAEC) and coronary artery smooth muscle (HCASMC) cell lines. Acting at different phase of the cell cycle, the three drugs were equally effective for reducing cell proliferation in both cell lines. Nevertheless, while paclitaxel and colchicine induced apoptosis, the main mechanism of cell death induced by sirolimus was necrosis. Similarly, while sirolimus was genotoxic (increase of oxidized pyrimidines) to only smooth muscle cells, colchicine mainly induced oxidative damage in endothelial cells. The transcriptome analyses revealed 82 differentially expressed genes (35 with known biological functions) in the treated groups compared to control. In HCAEC, three genes (TGM3, CTSF and MTSS1L) were differently expressed after sirolimus treatment; two (SLP1 and SLC4A1) after paclitaxel; one (PAQR8) 6 h after mechanical stretching; and 19 (WBE3A, ZBTB7A, CAMK1D, OR5AP2, EME1, C3AR1, VILL, RORC, MPV17L2, CEP350, RTEL1, ATG2A, SLC38A2, SLC25A25, FOXR2,SIGLEC8, CLIC4, ATP2A2 and VPRBP) after 12 h mechanical stretching. In HCASMC, two genes (NDST4 and FZD3) were differently expressed after ... / Doutor

Coronary arteries stenosis causes ischemic heart disease which is the main fatality reason all over the world. For diagnosis arteries stenosis invasive and noninvasive methods are used. These methods are quite expensive and not all medical institutions can carry out such tests. Analysis of electrocardiogram could be one of the cheapest and current methods to diagnose arteries stenosis. Despite the fact, that in some cases such analysis is not very informative, medics look for the informative ECG parameters and their combinations in order to predict stenosis. The goal of this work is to create statistical methods and software for prognosis of coronary arteries stenosis using digital ECG parameters. Data was colecet and prepared for this reseach in Clinic of Cardiology of Kaunas Medical University. In this work are presented: 1.Statistical analysis models for prognosis of coronary arteries stenosis. 2.Software for uses. 3.Comparative analysis of statistical analysis models. 4.Results of real data analysis, which were obtained by using, developed statistical models and software. Obtained results will be used to improve methods of diagnosis ischemic heart disease and arteries stenosis in Clinic of Cardiology of Kaunas Medical University.

A Tomografia Computadorizada Dual-Source (TCDS) é uma tecnologia de imagem que permite a visualização da estenose coronária de uma maneira não-invasiva. Estudos recentes demonstraram uma alta acuracia deste teste diagnóstico, quando comparado ao padrão de referência, a angiografia coronária invasiva (ACI). O objetivo deste trabalho foi sintetizar as evidências de acurácia desta tecnologia por meio de uma revisão sistemática e uma síntese quantitativa (meta-análise) e avaliar possíveis diferenciais de acurácia relacionados aos seguintes subgrupos de pacientes: com frequência cardíaca elevada, arritmias cardíacas, escore de cálcio elevado e índice de massa corporal (IMC) elevado. Foi realizada uma busca bibliográfica nas bases de dados MEDLINE e LILACS no período de janeiro de 2000 a outubro de 2009. Foram selecionados estudos em inglês, espanhol e português que comparassem a TCDS com a ACI em pacientes com suspeita ou doença arterial coronariana (DAC) e que permitissem a extração de dados suficientes para a construção de uma tabela 2X2. Três avaliadores independentes extraíram as características dos estudos e resultados, com as divergências resolvidas por consenso. Foram incluídos 20 estudos na revisão sistemática, que utilizaram três unidades de análise: paciente, vaso e segmento arterial. Nas unidades de análises paciente, vaso e segmento arterial, os valores das sensibilidades sumárias foram respectivamente de 98% (IC de 95%, 96% a 99%), 94% (IC de 95%, 89-% a 97%) e 93% (IC de 95%, 89% a 95%) e das especificidades sumárias foram respectivamente 84% (IC de 95%, 76% a 89%), 92% (IC de 95%, 87% a 95%) e 96% (IC de 95%, 91% a 98%). Também foi avaliada a acurácia nos subgrupos de pacientes com frequência cardíaca elevada e escore de cálcio aumentado. Na análise por subgrupos de pacientes, a sensibilidade e especificidade se mantiveram altas em pacientes com frequência cardíaca elevada 93% (IC de 95%, 90% a 95%) e 98% (IC de 95%, 95% a 99%), respectivamente. Já em pacientes com elevada calcificação (> 400 unidades de agatston) a especificidade diminuiu bastante, caindo para 79% (IC de 95%, 25% a 98%). A evidência disponível aponta para uma elevada acurácia da TCDS para a detecção da estenose coronária. Entretanto, a população que mais se beneficiaria desta tecnologia população com dor torácica e risco intermediário de DAC geralmente não esteve incluída nos estudos. Foram incluídos pacientes com alta probabilidade pré-teste da doença, já que os estudos foram realizados usualmente em centros de referência, com indivíduos com indicação prévia de angiografia coronária invasiva / Dualsource computed tomography (DSCT) is an imaging technology that enables the visualization of coronary artery stenosis in a non-invasive way. Earlier studies showed high accuracy compared to conventional coronary angiography. The aims of this study were to evaluate the evidence of this technology using a meta-analytic process and its accuracy in different subgroups such as patients with high heart rates, arrhythmia, increased calcium score and high body mass index. A search of the literature in MEDLINE and LILACS was performed and articles published between January 2000 and October 2009. Studies in English, Spanish and Portuguese that compared DSCT with conventional coronary angiography performed for all patients and included sufficient data for compilation of 2 X 2 tables were included. Three investigators independently extracted the characteristics of the studies and differences were settled by consensus. Twenty studies were included in the systematic review, using three units of analysis: patient, vessels and segment. Analysis of patients, vessels and segments yielded a sensitivity of 98% (95% CI, 96% to 99%), 94% (95% CI, 89% to 97%) and 93% (95% CI, 89% to 95%) and a specificity of 84% (95% CI, 76% to 89%), 92% (95% CI, 87% to 95%) and 96% (95% CI, 91% to 98%), respectively. We also analyzed the accuracy of DSCT in subgroups of patients with high heart rate and increased calcium score. The analyses of patients subgroups demonstrated that sensitivity and specificity remained high in patients with high heart rate 93% (CI 95%, 90% to 95%) and 98% (CI 95%, 95% to 99%), respectively. In patients with increased calcium score (> 400 Agatston units) the specificity declined significantly, falling to 79% (95%, 25% to 98%). The available evidence points to a high accuracy of DSCT for the detection of coronary artery stenosis. However, the population who might benefit from this technology - individuals with chest pain and intermediate risk of coronary artery disease, CAD have not generally been included in the retrieved studies since the studies were usually conducted in reference centers where patients usually have an indication for invasive coronary angiography, and consequently a high pretest probability of CAD

A Tomografia Computadorizada Dual-Source (TCDS) é uma tecnologia de imagem que permite a visualização da estenose coronária de uma maneira não-invasiva. Estudos recentes demonstraram uma alta acuracia deste teste diagnóstico, quando comparado ao padrão de referência, a angiografia coronária invasiva (ACI). O objetivo deste trabalho foi sintetizar as evidências de acurácia desta tecnologia por meio de uma revisão sistemática e uma síntese quantitativa (meta-análise) e avaliar possíveis diferenciais de acurácia relacionados aos seguintes subgrupos de pacientes: com frequência cardíaca elevada, arritmias cardíacas, escore de cálcio elevado e índice de massa corporal (IMC) elevado. Foi realizada uma busca bibliográfica nas bases de dados MEDLINE e LILACS no período de janeiro de 2000 a outubro de 2009. Foram selecionados estudos em inglês, espanhol e português que comparassem a TCDS com a ACI em pacientes com suspeita ou doença arterial coronariana (DAC) e que permitissem a extração de dados suficientes para a construção de uma tabela 2X2. Três avaliadores independentes extraíram as características dos estudos e resultados, com as divergências resolvidas por consenso. Foram incluídos 20 estudos na revisão sistemática, que utilizaram três unidades de análise: paciente, vaso e segmento arterial. Nas unidades de análises paciente, vaso e segmento arterial, os valores das sensibilidades sumárias foram respectivamente de 98% (IC de 95%, 96% a 99%), 94% (IC de 95%, 89-% a 97%) e 93% (IC de 95%, 89% a 95%) e das especificidades sumárias foram respectivamente 84% (IC de 95%, 76% a 89%), 92% (IC de 95%, 87% a 95%) e 96% (IC de 95%, 91% a 98%). Também foi avaliada a acurácia nos subgrupos de pacientes com frequência cardíaca elevada e escore de cálcio aumentado. Na análise por subgrupos de pacientes, a sensibilidade e especificidade se mantiveram altas em pacientes com frequência cardíaca elevada 93% (IC de 95%, 90% a 95%) e 98% (IC de 95%, 95% a 99%), respectivamente. Já em pacientes com elevada calcificação (> 400 unidades de agatston) a especificidade diminuiu bastante, caindo para 79% (IC de 95%, 25% a 98%). A evidência disponível aponta para uma elevada acurácia da TCDS para a detecção da estenose coronária. Entretanto, a população que mais se beneficiaria desta tecnologia população com dor torácica e risco intermediário de DAC geralmente não esteve incluída nos estudos. Foram incluídos pacientes com alta probabilidade pré-teste da doença, já que os estudos foram realizados usualmente em centros de referência, com indivíduos com indicação prévia de angiografia coronária invasiva / Dualsource computed tomography (DSCT) is an imaging technology that enables the visualization of coronary artery stenosis in a non-invasive way. Earlier studies showed high accuracy compared to conventional coronary angiography. The aims of this study were to evaluate the evidence of this technology using a meta-analytic process and its accuracy in different subgroups such as patients with high heart rates, arrhythmia, increased calcium score and high body mass index. A search of the literature in MEDLINE and LILACS was performed and articles published between January 2000 and October 2009. Studies in English, Spanish and Portuguese that compared DSCT with conventional coronary angiography performed for all patients and included sufficient data for compilation of 2 X 2 tables were included. Three investigators independently extracted the characteristics of the studies and differences were settled by consensus. Twenty studies were included in the systematic review, using three units of analysis: patient, vessels and segment. Analysis of patients, vessels and segments yielded a sensitivity of 98% (95% CI, 96% to 99%), 94% (95% CI, 89% to 97%) and 93% (95% CI, 89% to 95%) and a specificity of 84% (95% CI, 76% to 89%), 92% (95% CI, 87% to 95%) and 96% (95% CI, 91% to 98%), respectively. We also analyzed the accuracy of DSCT in subgroups of patients with high heart rate and increased calcium score. The analyses of patients subgroups demonstrated that sensitivity and specificity remained high in patients with high heart rate 93% (CI 95%, 90% to 95%) and 98% (CI 95%, 95% to 99%), respectively. In patients with increased calcium score (> 400 Agatston units) the specificity declined significantly, falling to 79% (95%, 25% to 98%). The available evidence points to a high accuracy of DSCT for the detection of coronary artery stenosis. However, the population who might benefit from this technology - individuals with chest pain and intermediate risk of coronary artery disease, CAD have not generally been included in the retrieved studies since the studies were usually conducted in reference centers where patients usually have an indication for invasive coronary angiography, and consequently a high pretest probability of CAD