INTRODUÇÃO: O hipotireoidismo congênito (HC) é uma doença, de acometimento neonatal, caracterizada por diminuição nos níveis de hormônios tireoidianos. As causas mais comuns de HC primário permanente são as alterações no desenvolvimento da glândula tireóide (disgenesia) e os defeitos de síntese dos hormônios tireóideos (disormonogênese). A determinação da etiologia do HC tem papel importante na determinação da gravidade da doença, evolução e tratamento. Essa investigação é feita através de exames como ultrassonografia e cintilografia (CINT) da tireóide. Além disso, com o conhecimento do genoma humano, diversas mutações foram descritas, sendo a investigação molecular importante para a determinação da etiologia da doença. OBJETIVOS: 1. Determinar o diagnóstico etiológico dos pacientes com HC a partir de dosagens hormonais, tireoglobulina e exames de imagem; 2. Estabelecer a importância do uso da ultrassonografia com Doppler colorido (USDC) no diagnóstico etiológico; 3. Estabelecer a importância do uso do teste do perclorato de sódio intravenoso (PSIV) no diagnóstico diferencial de HC por disormonogênese; 4. Estudar os genes PAX8 e receptor do TSH (TSHR) em pacientes com HC causado por disgenesia tireoidiana MÉTODOS: Avaliamos 40 pacientes acompanhados na APAE - São Caetano com diagnóstico de HC primário e permanente acima de 3 anos de idade. Os pacientes realizaram dosagens de T3, T4, T4 livre, TSH, tireoglobulina (TG) e anticorpo anti-TG pelo método imunofluorimétrico, além de USDC e CINT. Os pacientes com suspeita de disormonogênese foram submetidos ao teste PSIV e avaliação com otorrinolaringologista e audiometria tonal, se necessário. Os pacientes que apresentavam disgenesia tireoidiana tiveram o DNA extraído a partir de leucócitos periféricos para o estudo dos genes PAX8 e TSHR através de PCR e sequenciamento automático. RESULTADOS: Avaliamos 28 pacientes do sexo feminino e 12 do sexo masculino, após suspensão do tratamento com levotiroxina por 4 semanas. A idade média foi de 6,5 anos. O TSH médio foi 129,9 UI/mL (normal: 0,7-6,0). Os valores de T3, T4 e T4 livre variaram de 14 217 ng/dL (normal: 105-269), <1,6 15,8 g/dL (normal: 1,5-15) e < 0,3 2,7 ng/dL (normal: 0,7-1,5), respectivamente. A TG variou de <1 287 ng/dL (normal: 1,7-35). A USDC mostrou 21 pacientes com tireóide tópica (53%), 8 pacientes com tireóide ectópica (20%) e 11 pacientes com atireose (27%). Na CINT, o mapeamento identificou tireóide tópica em 20 pacientes (51%), tireóide ectópica em 13 pacientes (32%), e atireose em 7 pacientes (17%). A captação mostrou-se aumentada em 2 horas em 10 pacientes. O teste PSIV foi realizado em 9 pacientes com bócio ou glândula de tamanho normal ao USDC, cuja captação foi aumentada. Apenas um paciente apresentou vômito ao início do teste. Seis pacientes apresentaram teste positivo, considerando uma queda maior que 20%. Nenhum desses pacientes apresentava surdez neurossensorial. Encontramos discrepância entre USDC e CINT em 9 pacientes, principalmente nos casos de ectopia. A dosagem de TG auxiliou na confirmação de atireose. Os níveis mais altos de TG encontrados foram nos casos de disormonogênese causados por defeito na organificação. Assim, determinamos o diagnóstico de ectopia em 32,5% dos pacientes, hipoplasia em 20%, defeito na organificação (defeito de TPO ou THOX2) em 17,5%, atireose em 15%, defeito na TG em 7,5% e 3 casos a esclarecer (7,5%). Vinte e sete pacientes foram diagnosticados como portadores de disgenesia tireoidiana e não apresentaram mutações nos genes PAX8 e TSHR. CONCLUSÃO: Estabelecemos o diagnóstico etiológico em 37 dos 40 pacientes estudados. A USDC mostrou-se importante no diagnóstico etiológico do HC, especialmente associada à dosagem de TG. O teste PSIV mostrou-se seguro no diagnóstico diferencial do HC por disormonogênese. Não identificamos nenhuma mutação nos genes PAX8 e TSHR nos casos estudados de disgenesia / INTRODUCTION: Congenital hypothyroidism (CH) is a disease at neonatal period characterized by low thyroid hormones levels. Most common causes of primary CH are alterations at thyroid gland development (dysgenesis) and thyroid hormone synthesis defects (dyshormonogenesis). The establishment of CH etiology has important role to define the severity, evolution and treatment of the disease. This investigation is based on thyroid ultrasound and radiouptake and radionuclide imaging (RAIU). With human genome knowledge, several mutations were described, becoming molecular investigation so important to etiology definition. OBJECTIVES: 1. Establish the etiologic diagnosis of CH patients using hormonal measurements, thyroglobulin and imaging exams. 2. Establish the importance of color Doppler ultrasound (CDUS) in etiologic diagnosis. 3. Establish the importance of intravenous perchlorate sodium test in differential diagnosis of CH due to dyshormonogenesis. 4. Study PAX8 and TSH receptor (TSHR) genes in patients with CH due to thyroid dysgenesis. METHODS: We evaluated forty patients followed-up at APAE - São Caetano with primary and permanent CH diagnosis above 3 years-old. Patients performed T3, T4, free T4, TSH, thyroglobulin (TG) and anti-TG antibody using immunofluorimetric assays, besides thyroid CDUS and RAIU. Patients with thyroid dysgenesis had their DNA extracted from peripheral leukocytes to study PAX8 and TSHR genes using PCR and automatic sequencing. Patients with dyshormonogenesis suspected were submitted to intravenous perchlorate sodium test and otorhinolaryngologist and tonal audiometric evaluation, if necessary. RESULTS: We evaluated 28 female and 12 male after levothyroxine treatment off for 4 weeks. Mean age of studied patients was 6.5 years-old. Mean TSH was 129.9 UI/mL (normal: 0.7-6.0). T3, T4 and freeT4 ranged from 14 217 ng/dL (normal 105-269) , <1.6 15.8 g/dL (normal: 1.5- 15) and < 0.3 2.7 ng/dL (normal: 0.7-1.5) respectively. TG level ranged from < 1 287 ng/dL (normal 1.7-35). CDUS showed normally located thyroid in 21 patients (53%), ectopy in 8 patients (20%), and athyrosis in 11 patients (27%). At RAIU, thyroid scan identified normal located gland in 20 patients (51%), ectopy in 13 patients (32%) e athyrosis in 7 patients (17%). Two-hours uptake was elevated in ten patients. Intravenous perchlorate sodium test was performed in 9 patients with goiter or normal volume at CDUS, with normal or elevated uptake. Only one patient presented vomit. Six patients had positive test, considering more than 20% of decline. None from these patients had neurosensorial deafness. We found discrepancy between CDUS and RAIU in 9 patients, especially in ectopic cases. Thyroglobulin measurement helped to confirm athyrosis. Highest TG levels were found in dyshormonogenesis patients due to organification defects. Therefore we determined etiologic diagnosis of ectopic gland in 32,5% of patients, hypoplasia in 20%, organification defect (TPO or THOX2 defects) in 17,5%, athyrosis in 15%, thyroglobulin defect in 7,5% and three cases were undefined (7,5%). Twenty seven patients were diagnosed with thyroid dysgenesis and had no mutation in PAX8 and TSHR genes. CONCLUSION: We established the etiologic diagnosis in 37 from 40 patients here studied. CDUS was useful on etiologic diagnosis of CH, especially associated to thyroglobulin level. Intravenous perchlorate sodium test was safe and efficient in CH differential diagnosis of dyshormonogenesis. We identified no mutation in PAX8 and TSHR genes in dysgenesis cases

Wong Wai Lun. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 119-125). / Abstract also in Chinese. / Acknowledgments --- p.i / Legend for Figures --- p.ii / Legend for Tables --- p.iv / Abstract --- p.v / Abstract in Chinese --- p.ix / Chapter Chapter I --- Introduction --- p.1 / Objective --- p.5 / Chapter Chapter II --- Literature Review / Chapter II.1. --- Anatomy of the urinary system --- p.6 / Chapter II.2. --- Physiology of the urinary system --- p.10 / Chapter II.3. --- Methods for investigating the urinary system --- p.12 / Chapter II.3.1. --- Plain film radiography --- p.12 / Chapter II.3.2. --- Excretory Urogram --- p.12 / Chapter II.3.3. --- Ultrasound --- p.13 / Chapter II.3.4. --- Computed Tomography --- p.15 / Chapter II.3.5. --- Renal Angiography --- p.16 / Chapter II.3.6. --- Magnetic Resonance Imaging (MRI) --- p.16 / Chapter II.3.7. --- Radionuclide Imaging --- p.17 / Chapter II.4. --- Radiopharmaceuticals for renal parenchyma imaging --- p.17 / Chapter II.4.1. --- Tc-99m GHA --- p.18 / Chapter II.4.1.1. --- Chemistry of Tc-99m GHA --- p.18 / Chapter II.4.1.2. --- Preparation --- p.18 / Chapter II.4.1.3. --- Doses --- p.18 / Chapter II.4.1.4. --- Biological behavior --- p.19 / Chapter II.4.2. --- Tc-99m DMSA / Chapter II.4.2.1. --- Chemistry of Technetium-99m Dimercaptosuccinic Acid (Tc-99m DMSA) --- p.20 / Chapter II.4.2.2. --- Chemical property of Tc-99m DMSA --- p.21 / Chapter II.4.2.3. --- Preparation --- p.22 / Chapter II.4.2.4. --- Radiochemical purity measurement --- p.22 / Chapter II.4.2.5. --- Doses --- p.23 / Chapter II.4.2.6. --- Pharmacokinetic of Tc-99m DMSA --- p.23 / Chapter II.4.2.7. --- Renal handling of injected Tc-99m DMSA --- p.25 / Chapter II.5. --- General consideration for quantitative uptake measurement in organs --- p.26 / Chapter II.5.1. --- Clinical significance of renal Tc-99m DMSA uptake --- p.28 / Chapter II.5.2. --- Special consideration and problems for quantitative renal Tc-99m uptake measurement --- p.29 / Chapter II.5.3. --- Suggestions and solutions for quantitative renal Tc-99m uptake measurement --- p.29 / Chapter II.5.3.1. --- Planar images Vs SPECT images for quantification --- p.29 / Chapter II.5.3.2. --- Background subtraction --- p.31 / Chapter II.5.3.3. --- Choice of location for background ROI --- p.32 / Chapter II.5.3.4. --- Attenuation --- p.35 / Chapter II.5.3.5. --- Principle of the conjugate view method --- p.36 / Chapter II.5.3.6. --- Body thickness and kidney depth measurement --- p.37 / Chapter II.6. --- Glomerular Filtration / Chapter II.6.1. --- Introduction --- p.39 / Chapter II.6.2. --- Gold standard for GFR measurement --- p.40 / Chapter II.6.3. --- Laboratory studies for the measurement of glomerular filtration : Serum Creatinine and Blood Urea Nitrogen (BUN) levels --- p.41 / Chapter II.6.3.1. --- Calculation of Creatinine Clearance Rate --- p.43 / Chapter II.6.3.2. --- Critique for using creatinine clearance as a measurement of renal function --- p.44 / Chapter II.6.3.3. --- Limitation of the serum creatinine concentration used alone as a measurement of renal function --- p.46 / Chapter II.6.4. --- Radionuclide technique for the assessment of the glomerular function --- p.48 / Chapter II.6.4.1. --- Diethylene Triamine Penta Acetic acid (DTPA) --- p.49 / Chapter II.6.4.2. --- Methods / Chapter II.6.4.2.1. --- Measurement of Glomerular Filtration Rate using Tc-99m DTPA with single injection techniques --- p.51 / Chapter II.6.4.2.2. --- Compartment model --- p.52 / Chapter II.6.4.2.2a. --- Two-compartment model --- p.52 / Chapter II.6.4.2.2b. --- Single-compartment model --- p.54 / Chapter II.6.4.2.3. --- Single blood sample technique: a modification of Tauxe's OIH method in which counts in a single plasma sample correlated with a GFR nomogram --- p.56 / Chapter II.6.4.2.4. --- Gamma camera based method --- p.58 / Chapter II.6.4.2.4a. --- Gates-modification of Schlegel's OIH technique --- p.58 / Chapter II.6.4.2.4b. --- Critique for the Gamma camera technique for measuring GFR --- p.62 / Chapter II.7. --- The relationship between the Tc-99m DMSA uptake and GFR --- p.67 / Chapter Chapter III --- Material and Methods --- p.69 / Chapter III.1. --- Subjects and Sampling Methods --- p.69 / Chapter III.2. --- Quantitation of Absolute DMSA uptake --- p.70 / Chapter III.2.1. --- Parameters for Tc-99m DMSA uptake study --- p.70 / Chapter III.2.1.1. --- Materials and methods --- p.70 / Chapter III.2.1.1.1. --- Instrumentation --- p.70 / Chapter III.2.1.1.2. --- Dosage --- p.70 / Chapter III.2.1.1.3. --- Optimum acquisition start time --- p.70 / Chapter III.2.1.1.4. --- Length of acquisition time --- p.71 / Chapter III.2.1.1.5. --- Acquisition parameter --- p.71 / Chapter III.3. --- Calculation of absolute renal DMSA uptake --- p.72 / Chapter III.3.1. --- Attenuation Coefficient factor(μ) --- p.73 / Chapter III.3.2. --- Table attenuation --- p.75 / Chapter III.3.3. --- Body thickness measurement --- p.77 / Chapter III.3.4. --- Decay correction --- p.78 / Chapter III.3.5. --- Calculation of DMSA uptake --- p.78 / Chapter III.3.6. --- Counting dose injected --- p.80 / Chapter III.3.7. --- Calculation of absolute quantitation of Tc-99m DMSA uptake --- p.80 / Chapter III.3.8. --- Dose infiltration --- p.81 / Chapter III.4. --- GFR measurement --- p.82 / Chapter III.4.1. --- Instrumentation --- p.82 / Chapter III.4.2. --- Methods --- p.82 / Chapter III.5. --- Statistical and analytical methods --- p.84 / Chapter Chapter IV --- Results --- p.87 / Chapter IV. 1. --- Characteristics of experimental subjects and their serum creatinine profile --- p.88 / Chapter IV.2. --- Absolute Tc-99m DMSA uptake / Chapter IV.2.1. --- The change of absolute Tc-99m uptake with time --- p.89 / Chapter IV.2.2. --- Absolute Tc-99m DMSA uptake measurement at 6 and 24 hours --- p.90 / Chapter IV.2.3. --- Gender difference in absolute Tc-99m uptake measurement at 6 hour --- p.92 / Chapter IV.3. --- GFR measurement --- p.93 / Chapter IV.3.1. --- GFR measurement by single (3hr) and double (1&3 hrs) plasma sampling --- p.93 / Chapter IV.3.2. --- Gender difference in GFR measurement using single plasma sampling --- p.96 / Chapter IV.4. --- Univariate Correlation --- p.97 / Chapter IV.4.1. --- Correlation between GFR using single plasma sampling and absolute Tc-99m uptake --- p.97 / Chapter IV.4.2. --- Correlation between GFR using single plasma sampling and plasma creatinine levels --- p.98 / Chapter IV.4.3. --- Correlation between anthropometric variables on GFR(3 hr) --- p.99 / Chapter IV.4.4. --- Correlation between anthropometric variables and serum creatinine plasma level on absolute Tc-99m DMSA uptake measurement at 6 hour --- p.101 / Chapter IV.4.5. --- Multiple linear stepwise regression --- p.103 / Chapter Chapter V. --- Discussion / Chapter V. 1 --- . Review of the study --- p.104 / Chapter V.1.1. --- Experimental subjects and their absolute Tc-99m DMSA uptake (%) at 6 hr --- p.104 / Chapter V.1.2. --- Experimental subjects and their GFR(3 hr) --- p.105 / Chapter V.2. --- Discussion on subject --- p.105 / Chapter V.2.1. --- Subject preparation --- p.106 / Chapter V.3. --- Discussion of method --- p.106 / Chapter V.3.1. --- Equipment --- p.106 / Chapter (a) --- Dose calibrator --- p.106 / Chapter (b) --- The sensitivity of the head 1 and 2 of the gamma camera --- p.106 / Chapter (c) --- Validation of quantification of injected activity by gamma camera method--------constancy of performance for gamma camera --- p.110 / Chapter (d) --- LEHR Collimator --- p.112 / Chapter (f) --- Dead time loss --- p.112 / Chapter V.4. --- Discussion on measurement --- p.113 / Chapter (a) --- Length of acquisition time --- p.113 / Chapter (b) --- Attenuation Coefficient factor (\x) --- p.113 / Chapter (c) --- "Body thickness, L, measurement" --- p.113 / Chapter (d) --- Optimum acquisition time for data collection --- p.115 / Chapter v.5. --- Discussion on overall error estimation --- p.115 / Chapter (a) --- Tc-99m DMSA uptake measurement at 6 hr --- p.115 / Chapter (b) --- GFR measurement by single (3 hr) sample --- p.116 / Chapter Chapter VI --- Conclusion --- p.117 / Reference --- p.119 / Appendix I --- p.126 / Appendix II --- p.128 / Appendix III --- p.134

Submitted by Fabíola Silva (fabiola.silva@famerp.br) on 2018-01-17T11:04:30Z No. of bitstreams: 1 kleberrobertosantanna_dissert.pdf: 2567533 bytes, checksum: eae324ad76ed0dfd667eaf47bad5c5ea (MD5) / Made available in DSpace on 2018-01-17T11:04:30Z (GMT). No. of bitstreams: 1 kleberrobertosantanna_dissert.pdf: 2567533 bytes, checksum: eae324ad76ed0dfd667eaf47bad5c5ea (MD5) Previous issue date: 2017-03-08 / Introduction: Lymphedema is a clinical condition in which there is an accumulation of macromolecules in the interstitial space. As a result, it promotes water retention, consequently a failure in the formation or lymph drainage. Objectives: To access the images obtained from Computed Scintigraphy Chamber through a specific protocol of Lymphoscintigraphy and associate them to epidemiological data such as gender, age, educational level, socioeconomic status and prevalence of Lymphedema. Method: Epidemiological data were evaluated in a quantitative cross-sectional study comparing the diagnostic results for Lymphedema of the lower limbs using the Lymphoscintigraphy. They were correlated with gender, age, education level, family income and prevalence among the lower limbs at Hospital de Base in the last 10 years, 2006 to 2016. All patients clinically suspected of Lymphedema of the lower limbs were included and lymphoscintigraphic examinations of the upper limbs were excluded. Descriptive data were considered, and Fisher's exact test was used to correlate these variables considering alpha error of 5%. Results: A total of 430 patients were analyzed, 320(74.42%) were female and 110 (25.58%) male patients. Their age ranged from 10 to 90 years (mean = 48 years). A total 199 (46.27%) were positive findings and 231 (53.73%) negative. Among the images analyzed as positive; female patients were the majority, 183 (91.95%); Fisher's exact test p-value <0.001. When comparing patients with the first grade of high school with patients with complete college education, it was clear that Lymphedema was more prevalent in the first grade of high school, according to Fisher's exact test, p<0.0001. Comparing the second grade of high school with the ones with college education, it was observed that Lymphedema was more prevalent in those with high school; Fisher's exact test, p<0.0001. When comparing the wage gain from one to three minimum wages per month with three to five gains, five to seven and over seven salaries, a higher prevalence of Lymphedema was observed in the group of one to three salaries in relation to the others by Fisher's exact test, p<0.0001 in all evaluations. Comparing the salary range of three to five salaries with the salary range of five to seven and over seven monthly minimum wages, greater prevalence was observed in the range of three to five minimum wages; Fisher's exact test, p<0, 0.001 in both comparisons. The right lower limb presented 65 patients (32.66%), and 87(43.71%) unilateral left limb and 7 patients (23.63%), bilaterally were found. The left side was more prevalent than the right side; Fisher's exact test, p<0.01. Conclusions: Lymphedema is a public health issue that affects mostly women from lower cultural-educational socioeconomic status. One-sided onset can occur in the limb, but bilateral occurrence is frequent and Lymphoscintigraphy is useful in defining the diagnosis in cases of doubt. / Introdução: O Linfedema é uma condição clínica na qual ocorre um acúmulo de macromoléculas no espaço intersticial. Como consequência, promove retenção hídrica tendo como causa uma falha na formação ou na drenagem da linfa. Objetivos: Avaliar as imagens obtidas em Câmara de Cintilação Computadorizada por meio do protocolo de Linfocintilografia específico e relacioná-las com dados epidemiológicos como sexo, idade, grau de escolaridade, nível socioeconômico e prevalência de Linfedema. Método: Foram avaliados em estudo transversal quantitativo, dados epidemiológicos comparando-se os resultados diagnósticos para Linfedema de membros inferiores, utilizando a Linfocintilografia. Foram correlacionados com o sexo, idade, grau de escolaridade, renda familiar e predominância entre os membros inferiores no Hospital de Base nos últimos 10 anos, 2006 a 2016. Foram inclusos todos os pacientes com suspeita clínica de Linfedema de membros inferiores e excluídos os exames Linfocintilográficos de membros superiores. Foram considerados dados descritivos e utilizado o teste exato de Fisher para correlacionar essas variáveis, considerando-se erro alfa de 5%. Resultados: Foram analisados 430 pacientes sendo que 320(74,42%) eram pacientes do sexo feminino e 110(25,58%) pacientes do sexo masculino. A idade dos pacientes variava de 10 a 90 anos (média=48 anos). Os achados positivos somavam 199(46,27%) e negativos 231(53,73%); dentre as imagens analisadas como positivas, predominavam pacientes do sexo feminino; 183(91,95%); no teste exato de Fisher valor p<0,001. Quando se comparou o primeiro grau de escolaridade do ensino médio com o segundo grau do ensino médio, ficou evidenciado que o Linfedema é mais prevalente no primeiro grau do ensino médio, de acordo com o teste exato de Fisher, valor p<0,0001. Comparando-se o primeiro grau do ensino médio com os pacientes que possuíam grau do ensino superior, detectou-se que a prevalência do Linfedema é maior no primeiro ano do ensino médio de escolaridade; teste exato de Fisher, valor p<0,0001. Comparando-se segundo grau do ensino médio de escolaridade com os do ensino superior, detectou-se que o Linfedema é mais prevalente no segundo grau do ensino médio; teste exato de Fisher, valor p<0,0001.Quando se comparou o ganho salarial de um a três salários mínimos por mês com ganhos de três a cinco, cinco a sete e acima de sete salários detectou-se uma maior prevalência do Linfedema no grupo de um a três salários em relação aos demais com teste exato de Fisher, valor p<0,0001 em todas as avaliações. Comparando-se a faixa salarial de três a cinco salários com a faixa salarial de cinco a sete e maior que sete salários mínimos mensais detectou-se maior prevalência na faixa de três a cinco salários mínimos, teste exato de Fisher, valor p<0,0001 nas duas comparações. O membro inferior direito apresentou 65 pacientes (32,66%), e 87(43,71%) achados unilaterais de membro inferior esquerdo e bilateralmente em 47 pacientes (23,63%). O lado esquerdo é mais prevalente que o lado direito; teste exato de Fisher, valor p<0,01. Conclusões: O Linfedema é um problema de saúde pública que acomete na sua maioria, as mulheres de classe socioeconômica cultural e educacional mais baixa. Ocorre uma unilateralização no acometimento do membro, porém a ocorrência bilateral é frequente e a Linfocintilografia é útil na definição do diagnóstico nos casos de dúvida.

O objetivo deste estudo foi avaliar o uso da cintilografia de perfusão miocárdica planar de repouso para o diagnóstico de insuficiência coronariana aguda em pacientes com dor torácica e eletrocardiograma sem alterações sugestivas de isquemia. Foram estudados 71 pacientes com idades entre 34 e 87 (média 58, desvio-padrão 12) anos; 44 (62%) eram do sexo masculino e 27 (38%) do feminino. Os pacientes com dor torácica foram avaliados na unidade de emergência com anamnese, exame físico e eletrocardroqrarna de 12 derivações. Pacientes com dor torácica de duração superior a 20 minutos, em vigência da dor ou sem dor, mas que sofreram dor torácica até seis horas anies do atendimento e com eletrocardioqrarna sem alterações sugestivas de isquemia miocárdica, foram submetidos à cintilografia planar de perfusão miocárdica de repouso quando solicitada pelo médico assistente. O tempo médio entre o início da dor toràcica e a Injeção do radiotraçador foi de três horas e seis minutos. Treze pacientes apresentavam dor torácica no momento da injeção. Foram colhidas amostras sanguineas para dosagens de atividade da creatinoquinase-MB (CK-MB), CK-MB massa, troponina I e mioglobina, seis horas após o início da dor torácica. O diagnóstico de insuficiência coronariana aguda foi feito em pacientes com angina de repouso, infarto agudo do miocárdio, pacientes submetidos à revascularização miocárdica, presença de lesões coronarianas significativas na angiografia (>- 70% estenose em artérias coronárias ou seus ramos ou .- 50% em tronco de artéria coronária esquerda) realizada durante a inernação e morte cardíaca foram considerados eventos cardíacos maiores. As cintilografias com defeito de captação foram consideradas sugestivas de isquemia miocárdica e foram comparadas com o diagnóstico clínico e com a ocorrência de eventos cardíacos maiores até três meses após a alta.Pacientes sem insuficiência coronariana aguda, dispensados da unidade de emergência, foram encaminhados para realização ambulatorial de cintilografia de perfusão miocárdica tomográfica de esforço ou com dipiridamol. Vinte e um pacientes (29,6%) tiveram o diagnóstico de insuficiência coronariana aguda e em 15 (21,1%) ocorreram eventos cardíacos maiores (oito com infarto agudo do miocárdio e sete foram submetidos à revascularização miocárdica). A cintilografia planar de perfusão miocárdica demonstrou defeitos de captação em 21 (29,6%) pacientes, dos quais 16 (76,2%) tiveram o diagnóstico de insuficiência coronariana aguda, 12 (80%) apresentaram eventos cardíacos maiores e 7 (87,5%) infarto agudo do miocárdio. O valor preditivo negativo da cintilografia planar de perfusão miocárdica foi de 90% para o diagnóstico de insuficiência coronariana aguda e de 94% para detecção de eventos cardíacos maiores. Portanto a cintilografia planar de perfusão miocárdica foi eficaz para o diagnóstico de insuficiência coronariana aguda em pacientes com dor torácica e electrocardiograma sem alterações sugestivas de isquemia / The objective of the study was to evaluate the usefulness of rest scintigraphic planar myocardial perfusion imaging in patients with acute chest pain suspected of myocardial ischemia and nondiagnostic ECG in the diagnosis of acute coronary syndromes and to predict adverse cardiac outcomes. Patients within 6 hours of chest pain onset and nondiagnostic ECGs underwent planar myocardial perfusion imaging with Technetium-99m sestamibi and measurements of serum creatine kinase-MB, creatine kinase-MB mass. troponin and myoglobin 6 hours after the onset of symptoms. Studies showing perfusion defects were considered suggestive of acute coronary syndromes and were compared to the diagnosis made by the attending cardiologist. Clinical diagnosis of acute coronary syndromes was made In patients with rest angina admitted to the hospital, acute myocardial Infarction, myocardial revascularization, demonstration of significant coronary artery disease on angiography or cardiac death. Acute myocardial revascularization and cardiac death were considered major cardiac events. Patients discharged without acute coronary syndromes were scheduled for outpatient stress myocardial perfusion imaging. A total of 71 patients underwent planar myocardial perfusion imaging. The mean age was 58 +- 12 years, 44 (62%) were male and 27 (38%) female. The mean time between chest pain onset and radiotracer injection was 3 hours and 6 minutes, thirteen patients had chest pain at the moment of iniection. Twenty-one (29,6%) patients had acute coronary syndromes, 15 (21,1 %) had major cardiac events (8 myocardial infarction and 7 underwent myocardial revascularization). Planar perfusion imaging demonstrated perfusion defects in 21 patients, 16 (76,2%) patients with acute coronary syndromes, 12 (80%) patients who had major cardiac events and in 7 (87,5%) patients with myocardial infarction. The negative predictive value of planar perfusion image was 90% for diagnosis of acute coronary syndromes and 94% for detecting major cardiac events. In conclusion, early planar perfusion imaging allowed for a rapid and accurate risk stratification of emergency departments patients with possible myocardial ischemia and nondiagnostic ECGs

Bibliography: leaves 94-106. / v, 106, [33] leaves, [2] leaves of plates : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Assessment of myocardial metabolism with radiolabelled substrates and positron emission tomography provides a potentially sensitive technique to investigate physiological and pathological cardiac states "in vitro". Prior studies have indicated that overall metabolic activity cannot be estimated from rates of utilization of any one particular substrate. It was hypothesized that acetate labelled with carbon-11 would provide an index of oxidative metabolism, based on fundamental biochemical principles. The hypothesis is confirmed in studies using isolated perfused rabbit hearts and closed chest canine studies. / Thesis (M.D.)--University of Adelaide, Dept. of Medicine, 1995

<p>The two purposes of this thesis were to evaluate new diagnostic techniques of lymphnode staging in invasive bladder cancer and to evaluate the results of neoadjuvant chemotherapy in invasive bladder cancer.</p><p>Sentinel node detection was performed in 13 patients in preparation for radical cystectomy. The method showed to be feasible, and the results displayed the occurrence of metastatic nodes outside the traditional area of diagnostic dissection in a majority of patients. Four patients were metastasized, each one with one metastatic node detected with the help of the sentinel node procedure.</p><p>Four randomly selected sentinel nodes from four different unmetastasized patients were compared to the four metastatic sentinel nodes from the first series. After microdissection, p53 genomic structure, immunohistochemical expression and MVD (microvessel density) were assessed in the primary tumors and corresponding sentinel nodes. The results suggested that invasive bladder cancer mainly involved monoclonal proliferation with predominantly homogenous biomarker profile, but there were also signs of clonal evolution.</p><p>The Nordic Cystectomy Trial 2 (NCT2), is a randomized prospective trial investigating the possible benefit of neoadjuvant chemotherapy versus cystectomy only, in 311 eligible patients with urinary bladder cancer T2-T4aNXM0.Evaluation of overall survival did not show any statistically significant benefit in the experimental arm. This probably due to lack of statistical power.</p><p>To increase the statistical power we performed a combined analysis of randomized patients from both the Nordic Cystectomy Trial 1 (NCT1) and NCT2, n = 620. Eligible patients from NCT1 had T1G3, T2-T4a NXM0 urinary bladder cancer. Standard meta-analysis methods were used. The only end-point analysed was overall survival. Neoadjuvant platinum based combination therapy was associated with a 20 % reduction in the relative hazard in probability of death.</p>

The two purposes of this thesis were to evaluate new diagnostic techniques of lymphnode staging in invasive bladder cancer and to evaluate the results of neoadjuvant chemotherapy in invasive bladder cancer. Sentinel node detection was performed in 13 patients in preparation for radical cystectomy. The method showed to be feasible, and the results displayed the occurrence of metastatic nodes outside the traditional area of diagnostic dissection in a majority of patients. Four patients were metastasized, each one with one metastatic node detected with the help of the sentinel node procedure. Four randomly selected sentinel nodes from four different unmetastasized patients were compared to the four metastatic sentinel nodes from the first series. After microdissection, p53 genomic structure, immunohistochemical expression and MVD (microvessel density) were assessed in the primary tumors and corresponding sentinel nodes. The results suggested that invasive bladder cancer mainly involved monoclonal proliferation with predominantly homogenous biomarker profile, but there were also signs of clonal evolution. The Nordic Cystectomy Trial 2 (NCT2), is a randomized prospective trial investigating the possible benefit of neoadjuvant chemotherapy versus cystectomy only, in 311 eligible patients with urinary bladder cancer T2-T4aNXM0.Evaluation of overall survival did not show any statistically significant benefit in the experimental arm. This probably due to lack of statistical power. To increase the statistical power we performed a combined analysis of randomized patients from both the Nordic Cystectomy Trial 1 (NCT1) and NCT2, n = 620. Eligible patients from NCT1 had T1G3, T2-T4a NXM0 urinary bladder cancer. Standard meta-analysis methods were used. The only end-point analysed was overall survival. Neoadjuvant platinum based combination therapy was associated with a 20 % reduction in the relative hazard in probability of death.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 6 uppsatser.

Orientador: Sonia Marta Moriguchi / Resumo: O câncer de mama é o tipo mais comum entre as mulheres no Brasil e no mundo, com 28% de novos casos a cada ano. O diagnóstico tardio pode identificar carcinoma de mama localmente avançado (CMLA) que necessita tratamento sistêmico quimioterápico pré-operatório que visam reduzir o tamanho do tumor e da carga tumoral. A quimiorresistência pode estar relacionada à expressão de glicoproteína P (GpP), que promove o efluxo celular da droga, diminuindo o tempo de permanência da droga na célula e, consequentemente a apoptose celular. O sestamibi-99mTc utilizado na realização da cintilografia de mamas (CM) é um substrato dessas proteínas, similar às drogas quimioterápicas, sendo o único método de imagem a representar o tempo de permanência dessa droga. O índice preditor da resposta quimioterápica por cintilografia tem sido utilizado para prever o tempo de permanência dessas drogas nessas células. O objetivo desse estudo foi verificar se o índice preditor de resposta quimioterápica neoadjuvante obtido por cintilografia de mamas com sestamibi-99mTc proposto por Alonso e cols. relacionou-se com resposta quimioterápica do estudo anatomopatológico da mama pós-cirurgia (AP), considerado padrão ouro, analisando-se os índices isolados: índice precoce (IP) e índice tardio (IT) e associados (IP+IT). Tratou-se de estudo transversal, observacional e descritivo, com coleta retrospectiva de dados de prontuários de portadores de CMLA atendidas nessa Instituição no período de 2012-2017, que foram subm... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Breast cancer is the most common cancer among women, both in Brazil and globally, with 28% of cases each year being new. Delayed diagnosis can identify locally advanced breast carcinoma (LABC), which requires preoperative systemic chemotherapy that aims to reduce the size and load of the tumor. The chemo-resistance may be related to expression of glycoprotein P (GpP) that promotes cellular efflux of the drug, diminishing not only its time within the cell but consequently cellular apoptosis. Sestamibi99mTc, utilized in performing scintimammography (SMM), is a substrate of these proteins, similar to chemotherapeutic drugs, being the only imaging method to represent the permanence time of this drug. The predictive index of chemotherapeutic response by SMM has been utilized to predict the permanence time of chemotherapeutic drugs into these cells. This study aimed to verify whether the predictive index of neoadjuvant chemotherapeutic response, obtained by SMM with sestamibi99mTc proposed by Alonso and colleagues, is related to the chemotherapeutic response, as shown by postoperative anatomopathological study of the breasts (AP), considered the gold standard, analyzing the isolated indices, early index (EI) and late index (LI), and associated index (EI+LI). This was a transversal, observational and descriptive study, with retrospective data collected from charts of patients who were carriers of LABC attended at this Institution in the period from 2012 to 2017, that were submitted ... (Complete abstract click electronic access below) / Mestre