Background: With usual supplementation practices, most children are Vitamin D Deficient (VDD) following Congenital Heart Disease (CHD) surgery and alternative regimens need consideration. Methods/Results: i) A systematic review identified 88 pediatric trials of high dose vitamin D. Studies evaluating the Institute of Medicine (IOM) Tolerable Upper Intake Level (UL) did not rapidly normalize levels, while loading therapy (≥ 40000 IU) did so within 3 days. Hypercalcemia occurred more often with doses above 400000 IU. ii) A double blind RCT was designed to determine whether pre-operative administration of the IOM UL can prevent post-operative VDD. Results after the first 30 participants completed study procedures demonstrated it was possible to recruit (1.8 patients per month) and complete study procedures (i.e. blood collection). Unfortunately few participants (45%) received more than 30 doses of study drug. Conclusion: Prevention of post-operative VDD in the majority of CHD patients will require alternatives to the IOM recommendations.

Orientadores: Maria Francisca Colella dos Santos, Maria Cecília Marconi Pinheiro Lima / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-29T00:17:12Z (GMT). No. of bitstreams: 1 Rogerio_AmandaFerreiraHernandez_M.pdf: 1768414 bytes, checksum: dd625ff1370108694748a76f0e50882f (MD5) Previous issue date: 2015 / Resumo: Os Hormônios Tireoidianos são fundamentais para o crescimento e desenvolvimento de vários órgãos e tecidos de vertebrados e, embora os mecanismos fisiopatológicos da perda auditiva no hipotireoidismo não estejam totalmente estabelecidos, estudos indicam que alterações auditivas podem ocorrer em 20% das crianças com Hipotireoidismo Congênito (HC) e as anormalidades da audição permanecem mesmo quando são tratadas. Objetivo: Analisar a audição de lactentes com Hipotireoidismo Congênito por meio de avaliação eletrofisiológica e comportamental, considerando a idade, sexo, orelha direita e esquerda e níveis de hormônios de TSH e T4 livre. Metodologia: A amostra foi constituída por 22 crianças do grupo Hipotireoidismo Congênito (GHC) e 16 crianças do grupo controle (GC) sem doença tireoidea, ambos os grupos com idade de 0 a 24 meses. A avaliação audiológica foi constituída por testes eletrofisiológicos, eletroacústicos e comportamentais, como os Potenciais Evocados Auditivos de Tronco Encefálico (PEATE), Emissões Otoacústicas Transientes (EOAT), supressão das EOAT, timpanometria, observação das respostas comportamentais com sons calibrados e não calibrados. Resultados: O GHC apresentou menor amplitude das EOAT e supressões das emissões quando comparado ao GC. Houve correlação negativa para os níveis de hormônios do TSH e T4 livre com os resultados do PEATE para a latência da onda V a 60 dB e interlatência I-III a 80 dB. O GHC apresentou desempenho estatisticamente inferior para as observações das respostas comportamentais com sons calibrados e não calibrados. Conclusão: A partir da análise dos resultados obtidos na avaliação audiológica pode-se concluir que as crianças com hipotireoidismo congênito do nosso estudo apresentaram amplitude diminuída nas Emissões Otoacústicas Evocadas Transientes, o que pode revelar alterações cocleares com funcionamento prejudicado das células ciliadas externas. Além disso, apresentaram desenvolvimento auditivo prejudicado / Abstract: The Thyroid hormones are essential for the growth and development of various organs and tissues of vertebrates and, although the pathophysiological mechanisms of hearing loss in hypothyroidism is not fully established, studies indicate that auditory alterations may occur in 20% of children with Congenital hypothyroidism (CH) and the abnormalities of hearing remain even when they are treated.Objective: To analyze the hearing of infants with Congenital Hypothyroidism through electrophysiological evaluation and behavioral, considering the age, sex, right and left ears and hormone levels of free T4 and TSH. Methodology: The sample was composed of 22 children of group Congenital Hypothyroidism (GHC) and 16 children in the control group (CG) without thyroid disease, both groups with age from 0 to 24 months. The audiological evaluation was composed of electrophysiological tests and behavioral, such as the Brainstem Evoked Response Audiometry (BERA), Transient Evoked Otoacoustic Emissions (TEOAE), TEOAE suppression, tympanometry, Minimum Response Levels (MRL) and instrumental evaluation. Results: The GHC showed lower TEOAE amplitude when compared to the CG. Negative correlation was observed for the hormone levels of TSH and free T4 with the ABR results for latency of wave V 60 dB and interpeak interval latencies I-III to 80 dB. GHC presented performance statistically inferior to the behavioral tests. Conclusion: based on the analysis of the results obtained in the audiological evaluation it can be concluded that children with congenital hypothyroidism in our study showed decreased amplitude of Transient Evoked Otoacoustic Emissions, which can reveal changes with cochlear functioning impaired external ciliated cells. Furthermore, presented auditory development suffers / Mestrado / Interdisciplinaridade e Reabilitação / Mestra em Saúde, Interdisciplinaridade e Reabilitação

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Congenital heart disease (CHD) is characterized by structural defects of the heart and great vessels. It is the most common birth defect, affecting an estimated 1% of live births, and is the leading cause of mortality among birth defects. Despite recent progress in genetic research, more than 50% of CHD cases remain unexplained. An estimated 23% are due to aneuploidies and copy number variants and up to 30% has been attributed to de novo variation, though that number ranges between 3-30% depending on CHD complexity. The contribution of somatic mosaicism, or de novo genetic mutations arising after oocyte fertilization, to congenital heart disease (CHD) is not well understood due to limitations in sample size, detection method, and validation rate. Further, the relationship between mosaicism in blood and cardiovascular tissue has not been determined. We developed a computational method, Expectation-Maximization-based detection of Mosaicism (EM-mosaic), to analyze mosaicism in exome sequences of 2530 CHD proband-parent trios. EM-mosaic accurately detected 309 mosaic mutations in blood, with 85 of 94 (90%) candidates tested independently confirmed. We found twenty-five likely damaging mosaics in plausible CHD-risk genes, affecting 1% of our cohort. Variants in these genes predicted as damaging had higher variant allele fraction than benign variants, suggesting a role in CHD. The frequency of protein-coding mosaic variants detectable in blood was 0.122 or roughly 1 in 8 individuals. Analysis of 66 individuals with matched cardiac tissue available revealed both tissue-specific and shared mosaicism, with shared mosaics generally having higher allele fraction. CHD patients often present with comorbid cardiac and extracardiac anomalies that further their impact quality of life. Neurodevelopmental disorders (NDDs) are especially prevalent in CHD cases compared to the general population, yet the underlying genetic causes remain poorly explained. Further, patients with single ventricle defects undergoing surgery often later develop arrhythmias and experience worsening ventricular function. We used a statistical approach to dissect the association between de novo variation and these clinical outcomes and found that pleiotropic mutations contribute a large fraction of the risk of acquiring NDD and abnormal ventricular function phenotypes in CHD patients. We developed a proof-of-concept rare variant risk score that combines information from de novo, rare transmitted, and copy- number variants and show that prediction of outcomes such as NDD can be improved, especially in complex CHD cases.

The incidences of maternal opioid use and neonatal opioid withdrawal syndrome (NOWS) have increased by nearly 400% over the past decade. Isemann and colleagues (2017) developed prediction tools (TiTE/TiTE2) to differentiate, within the first two days of life, between infants who will require pharmacotherapy for NOWS from those infants who will not require pharmacotherapy for NOWS. The goal of the current experiment was to replicate and extend their prediction model. The present experiments successfully replicated Isemann et al., (2017) results and also established alternative cutoff values for requiring treatment that provide better balance between all four metrics. Moreover, new prediction models (TEN/TEN2) were proposed based on a factor analysis of modified Finnegan scores across the first 48 hours of life. Area Under the Curve-Receiver Operating Characteristic curve analyses indicated that the TEN2 was the best prediction model compared to the TiTE2 and the TEN.

A 36-year-old woman was seen with complaints of exertional chest pain and shortness of breath. Her medical history included atrial fibrillation and diabetes. Physical examination was unremarkable except for an irregular cardiac rhythm. Myocardial perfusion imaging revealed the presence of a large area of infarction involving the entire anterior and apical walls and part of the anteroseptal wall with minimal periinfarct ischemia. Computed tomography coronary angiogram revealed an anomalous left main coronary artery arising from the main pulmonary artery. Right and left heart catheterizations demonstrated moderate pulmonary hypertension with a slight step-up in oxygen saturation between the right ventricle and main pulmonary artery. Coronary angiography showed a large tortuous right coronary artery with collaterals to the left anterior descending artery that drained into the main pulmonary artery. She was referred for surgery. This case demonstrates a rare coronary artery anomaly in an adult where survival is dependent on collateral circulation.

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京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18142号 / 医博第3862号 / 新制||医||1002(附属図書館) / 31000 / 京都大学大学院医学研究科医学専攻 / (主査)教授 山田 亮, 教授 小杉 眞司, 教授 松田 文彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18178号 / 医博第3898号 / 新制||医||1004(附属図書館) / 31036 / 京都大学大学院医学研究科医学専攻 / (主査)教授 宮地 良樹, 教授 羽賀 博典, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DGAM

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