Les erreurs innées du métabolisme (EIM) constituent un large panel de désordres métaboliques héréditaires. Parmi les EIM, les anomalies de la neurotransmission peuvent affecter, entre autres, la synthèse ou le transport des neurotransmetteurs, notamment les amines biogènes (dopamine et sérotonine) et les folates. La reconnaissance de ces affections est d’une importance capitale pour le diagnostic et le traitement éventuel. L’analyse chimique du liquide céphalo-rachidien (LCR) est incontournable pour le diagnostic de ces pathologies. Or, les méthodes actuelles de dosage ne sont pas simples. Longues et fastidieuses, elles ont été, pendant longtemps, réservées aux laboratoires spécialisés. L’objectif de ce travail était de développer des méthodes simples et rapides de diagnostic des troubles de la neurotransmission et d’établir les valeurs normales fréquentes dans la population française. Le travail réalisé a permis, dans un premier temps, de développer une méthode de dosage directe, en une seule étape, de la tetrahydrobioptérine (BH4), cofacteur des hydroxylases intervenant dans la synthèse des amines biogènes, et des ptérines impliquées dans le cycle de synthèse et de dégradation de ce cofacteur, dans le LCR. Auparavant, le dosage de ces substances nécessitait au moins deux analyses chromatographiques précédées chacune d’une étape propre de préparation de l’échantillon. Par la suite, nous avons développé une méthode de diagnostic rapide, en moins de 10 minutes, par UHPLC (chromatographie liquide à ultra haute performance), couplée à une détection séquentielle par coulométrie et par fluorescence, des troubles dopaminergique et sérotoninergique. Cette méthode permet de doser simultanément, en une seule étape, tous les métabolites de la dopamine, de la sérotonine et de la noradrénaline, ainsi que les ptérines d’intérêt diagnostic, principalement la dihydroneoptérine (NH2) et la dihydrobioptérine (BH2). L’ensemble de ces explorations nécessitait, auparavant, la mise en œuvre d’au moins trois méthodes de dosage par HPLC (chromatographie liquide à haute performance), précédées chacune d’une étape propre de préparation de l’échantillon. Pour compléter l’exploration du métabolisme de la BH4 et du suivi thérapeutique des troubles de la neurotransmission, nous avons également proposé une méthode de dosage rapide, en une seule étape, par UHPLC, de tous les métabolites et de toutes les ptérines, incluant la BH4. Enfin, une méthode rapide de dosage (moins de 2 minutes), par UHPLC, du 5-méthyltetrahydrofolate dans le LCR a été développée, afin de compléter le diagnostic biologique de l’ensemble des troubles neurologiques visés. L’application des outils ainsi développés à plus de 1400 patients nous a permis d’établir des valeurs normales fréquentes dans la population française ainsi que de poser le diagnostic de quelques déficits enzymatiques. / Inborn errors of metabolism (IEM) consist of a wide range of hereditary metabolic disorders. Among IEM, neurotransmission anomaly can affect the synthesis or the transport of neurotransmitters, notably biogenic amines (dopamine and serotonin) and folates. Early diagnosis of such affections is of utmost importance especially as some of them can be treated effectively. Chemical analysis of cerebrospinal fluid (CSF) is essential for the diagnosis of neurotransmitter disorders; however, current quantitative methods are tedious and time consuming. For a long time the chemical diagnosis of neurotransmitter disorders has been available only in specialized laboratories. The purpose of this work was to develop simple and fast diagnosis methods of neurotransmitter disorders as well as to establish the reference values in French population. For this purpose, in a first step, we developed a single step direct method of simultaneous quantification of tetrahydrobiopterin (BH4), which is the main cofactor of the hydroxylases involved in biogenic amines syntheses, and the relevant reduced and oxidized forms of pterins involved in the cycle of synthesis – regeneration of BH4. Formerly, the quantification of those compounds required at least two chromatographic methods with two specific sample preparation procedures. Thereafter we developed a method of fast diagnosis in less than 10 minutes of dopaminergic and serotoninergic disorders using UHPLC (ultra high performance liquid chromatography) hyphenated to a sequential coulometric and fluorimetric detection. With only a simple filtration step as sample preparation procedure, this method enables the simultaneous quantification of all dopamine, serotonin and noradrenaline metabolites as well as dihydroneopterin (NH2) and dihydrobiopterin (BH2), the relevant pterin forms for the complete diagnosis. Formerly, at least three HPLC (high performance liquid chromatography) quantification methods preceeded by three tedious specific sample preparation procedures were required for such a diagnosis. To complete the investigation of BH4 metabolism and the follow up of neurotransmission disorders, we also developed a fast UHPLC method of simultaneous quantification of all the cited metabolites and pterins including BH4. In order to complete the rapid diagnosis of all targeted neurological disorders, we finally developed an UHPLC method of 5-methyltetrahydrofolate quantification in CSF. The application of these analytical tools in more than 1400 CSF samples, collected from patients followed in some Neurology centers located in several French areas covering nearly the entirety of the territory, allowed us to establish the reference values in French population as well as to diagnose several cases of enzymatic deficits.

Introdução: A diferenciação entre saúde e doença do sistema respiratório torna-se mais difícil devido à tendência de envelhecimento populacional e da necessidade de identificação das alterações próprias da senescência. Os testes de função pulmonar constituem ferramentas clínicas importantes para avaliação respiratória e sua interpretação está baseada em equações de referência derivadas de amostra de indivíduos saudáveis, que podem não expressar adequadamente o comportamento nesta faixa etária específica, dada a reduzida representatividade de indivíduos idosos nos estudos que postularam tais equações. Objetivo: Verificar a acurácia das equações de referência disponíveis para testes de função pulmonar e cardiopulmonar de esforço em relação aos valores obtidos em amostra de indivíduos idosos hígidos e o impacto clínico na interpretação funcional baseada nestas equações. Metodologia: Estudo prospectivo observacional transversal, com voluntários saudáveis, com idade igual ou superior a 65 anos, não tabagistas, urbanos. Em uma única visita, foram coletados dados demográficos, antropométricos e clínicos, seguidos da realização de provas de função pulmonar em repouso (espirometria, medidas de volumes pulmonares e difusão) e do teste cardiopulmonar de exercício máximo (TCPE). Os resultados obtidos foram comparados com os valores esperados de acordo com equações de referência rotineiramente utilizadas para a interpretação (teste-T pareado e avaliação de concordância pelo diagrama de Bland-Altman) e a frequência de casos fora das faixas previstas foi determinada. Novas equações de referência foram geradas por regressão linear múltipla. Resultados: Foram incluídos 95 indivíduos (55 mulheres), com idade (anos) 75 ± 6 (feminino) e 74±6 (masculino). Caracterizou-se diferença significativa entre as médias dos parâmetros de função pulmonar em repouso observados e previstos por pelo menos 2 das 3 equações testadas para CVF, VEF1, CPT, VR e difusão para ambos os sexos. O mesmo ocorreu para os parâmetros funcionais ao exercício (carga e VO2 no pico do esforço) para 3 de 4 equações testadas. Não houve homogeneidade de um autor específico em predizer com melhor acurácia os valores observados na amostra testada para todos os parâmetros funcionais em ambos os sexos. A frequência de classificação de parâmetros fora das faixas de referência foi elevada para todas as equações avaliadas. Novas equações de referência foram apresentadas a partir dos dados obtidos. Conclusões: A utilização das equações de referência existentes apresentou aplicabilidade limitada à amostra de idosos saudáveis estudada, gerando elevados índices de valores sub e superestimados, potencialmente comprometendo a sensibilidade e especificidade dos testes. Foram derivadas equações idade-específicas para uma amostra de idosos suadáveis brasileiros, visando contemplar as mudanças fisiológicas nesta faixa etária / Introduction: Differentiating between health and disease of the respiratory system becomes more challenging due to the tendency of population aging and the need to identify themselves senescence changes. Pulmonary function tests are important tools for respiratory evaluation. Its interpretation is based on reference equations derived from healthy people studies that possibly not accordingly express the behavior at this particular age group, due to the low representativity of elderly individuals in the studies that postulated such equations. Objective: To verify the accuracy of reference equations available for pulmonary function and cardiopulmonary exercise tests in comparison to values obtained in a sample of healthy elderly subjects and assess the clinical impact on functional interpretation based on these equations. Methodology: Cross-sectional observational prospective study in healthy volunteers, aged over 65 years, non-smokers, urban living. Demographic, anthropometric and clinical data, were collected and pulmonary function tests at rest (spirometry, lung volumes measures and diffusing capacity pulmonary), and the maximal cardiopulmonary exercise test (CPET) were performed. Results were compared to the expected values according to reference equations routinely used for interpretation (paired t-test and evaluation agreement by Bland-Altman plot) and the frequency of cases outside the reference ranges were determined. New reference equations elderly-specific were generated using multiple linear regression. Results: 95 subjects (55 women), age (years) 75 ± 6 (female) and 74 ± 6 (male) were included. Significant difference between the mean lung function parameters observed versus predicted by at least 2 of 3 tested equations for FVC, FEV1, TLC, RV for both sexes were identified. The same occured for exercise measurements (load and VO2 at peak exercise) for 3 of 4 tested equations. There was no homogeneity of a particular author to predict more accurately values observed in the sample tested for all functional parameters in both sexes. There was high rates of out of reference range classification for all evaluated equations. New elderly-specific reference equations were presented from the data obtained. Conclusions: The use of existing reference equations had limited applicability to the sample of healthy elderly studied, generating high rates of under and overestimated values, potentially compromising the sensitivity and specificity of the tests. Age-specific equations were derived from a sample of Brazilian healthy elderly, aiming to represent the physiological changes in this age group

O nível sérico do Fator de crescimento semelhante à insulina tipo I (IGF-I) é fundamental para auxiliar no dignóstico e controle terapêutico dos transtornos relacionados à secreção do Hormônio de Crescimento (GH), bem como no diagnóstico e seguimento de outras doenças. Estabelecer valores de referência para as dosagens séricas de IGF-I por um ensaio imunoquimioluminométrico (ICMA), utilizando o sistema automatizado Immulite 2000/Diagnostic Products Corporation (DPC), e por um ensaio imunoradiométrico (IRMA), utilizando o kit comercial ACTIVE IGF-I/Diagnostic System Laboratories (DSL)-5600, numa população brasileira adulta da cidade do Rio de Janeiro. Este estudo, aprovado pelo Comitê de Ética do Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brasil, incluiu amostras de 484 indivíduos saudáveis (251 homens e 233 mulheres) com idades entre 18 e 70 anos. As amostras foram estudadas por ICMA- Immulite 2000/DPC and IRMA- ACTIVE IGF-I/DSL-5600. Para análise dos dados foram utilizados modelos específicos para idade e sexo, após transformação dos dados de IGF-I. Foi observada uma lenta diminuição dos níveis de IGF-I com a idade usando ambos os ensaios. Os níveis de IGF-I foram signicativamente (p=0,0181) mais elevados em mulheres do que em homens, quando as amostras foram analisadas usando ICMA. Não houve diferença significativa dos níveis de IGF-I entre homens e mulheres quando as amostras foram analisadas usando IRMA. Este estudo estabeleceu valores de referência de IGF-I específicos para idade e sexo, determinados com o sistema automatizado ICMA-Immulite 2000/DPC, e valores de referência de IGF-I específicos para idade, determinados com o kit comercial IRMA- ACTIVE IGF-I/DSL-5600, em uma população adulta brasileira, da cidade do Rio de Janeiro. / Serum level of insulin-like growth factor I (IGF-I) is fundamental in order to aid in the diagnosis and follow-up of growth hormone (GH)-related disorders, as well as in the diagnosis and follow-up of other diseases. The aim of this investigation was to determine reference values for IGF-I using an automated immunochemiluminometric assay (ICMA) system Immulite 2000/Diagnostic Products Corporation (DPC); and an immunoradiometric assay (IRMA), using the commercial kit ACTIVE IGF-I/Diagnostic System Laboratories (DSL)-5600, in an adult Brazilian population of Rio de Janeiro city. The study, approved by the Ethical Committee of the Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, Brazil, included samples of blood taken from 484 healthy subjects (251men, 233 women) aged from 18 up to 70. The samples were analyzed by ICMA- Immulite 2000/DPC and IRMA- ACTIVE IGF-I/DSL-5600. For statistical analysis, age and sex-specific models were fitted after transformation of IGF-I values. In adulthood, a slow age-dependent decrease was found, using both assays. IGF-I in women were significantly (p=0,0181) higher than in men when samples were analayzed using ICMA.There was no significant difference between men and women IGF-I values when samples were analayzed using IRMA. The present study established age- and sex specific IGF-I reference values, determined with the automated system: ICMA-Immulite 2000/DPC and age-specific IGF-I reference values determined with the IRMA- ACTIVE IGF-I/DSL-5600, in an adult Brazilian population of Rio de Janeiro city.

Introdução: A diferenciação entre saúde e doença do sistema respiratório torna-se mais difícil devido à tendência de envelhecimento populacional e da necessidade de identificação das alterações próprias da senescência. Os testes de função pulmonar constituem ferramentas clínicas importantes para avaliação respiratória e sua interpretação está baseada em equações de referência derivadas de amostra de indivíduos saudáveis, que podem não expressar adequadamente o comportamento nesta faixa etária específica, dada a reduzida representatividade de indivíduos idosos nos estudos que postularam tais equações. Objetivo: Verificar a acurácia das equações de referência disponíveis para testes de função pulmonar e cardiopulmonar de esforço em relação aos valores obtidos em amostra de indivíduos idosos hígidos e o impacto clínico na interpretação funcional baseada nestas equações. Metodologia: Estudo prospectivo observacional transversal, com voluntários saudáveis, com idade igual ou superior a 65 anos, não tabagistas, urbanos. Em uma única visita, foram coletados dados demográficos, antropométricos e clínicos, seguidos da realização de provas de função pulmonar em repouso (espirometria, medidas de volumes pulmonares e difusão) e do teste cardiopulmonar de exercício máximo (TCPE). Os resultados obtidos foram comparados com os valores esperados de acordo com equações de referência rotineiramente utilizadas para a interpretação (teste-T pareado e avaliação de concordância pelo diagrama de Bland-Altman) e a frequência de casos fora das faixas previstas foi determinada. Novas equações de referência foram geradas por regressão linear múltipla. Resultados: Foram incluídos 95 indivíduos (55 mulheres), com idade (anos) 75 ± 6 (feminino) e 74±6 (masculino). Caracterizou-se diferença significativa entre as médias dos parâmetros de função pulmonar em repouso observados e previstos por pelo menos 2 das 3 equações testadas para CVF, VEF1, CPT, VR e difusão para ambos os sexos. O mesmo ocorreu para os parâmetros funcionais ao exercício (carga e VO2 no pico do esforço) para 3 de 4 equações testadas. Não houve homogeneidade de um autor específico em predizer com melhor acurácia os valores observados na amostra testada para todos os parâmetros funcionais em ambos os sexos. A frequência de classificação de parâmetros fora das faixas de referência foi elevada para todas as equações avaliadas. Novas equações de referência foram apresentadas a partir dos dados obtidos. Conclusões: A utilização das equações de referência existentes apresentou aplicabilidade limitada à amostra de idosos saudáveis estudada, gerando elevados índices de valores sub e superestimados, potencialmente comprometendo a sensibilidade e especificidade dos testes. Foram derivadas equações idade-específicas para uma amostra de idosos suadáveis brasileiros, visando contemplar as mudanças fisiológicas nesta faixa etária / Introduction: Differentiating between health and disease of the respiratory system becomes more challenging due to the tendency of population aging and the need to identify themselves senescence changes. Pulmonary function tests are important tools for respiratory evaluation. Its interpretation is based on reference equations derived from healthy people studies that possibly not accordingly express the behavior at this particular age group, due to the low representativity of elderly individuals in the studies that postulated such equations. Objective: To verify the accuracy of reference equations available for pulmonary function and cardiopulmonary exercise tests in comparison to values obtained in a sample of healthy elderly subjects and assess the clinical impact on functional interpretation based on these equations. Methodology: Cross-sectional observational prospective study in healthy volunteers, aged over 65 years, non-smokers, urban living. Demographic, anthropometric and clinical data, were collected and pulmonary function tests at rest (spirometry, lung volumes measures and diffusing capacity pulmonary), and the maximal cardiopulmonary exercise test (CPET) were performed. Results were compared to the expected values according to reference equations routinely used for interpretation (paired t-test and evaluation agreement by Bland-Altman plot) and the frequency of cases outside the reference ranges were determined. New reference equations elderly-specific were generated using multiple linear regression. Results: 95 subjects (55 women), age (years) 75 ± 6 (female) and 74 ± 6 (male) were included. Significant difference between the mean lung function parameters observed versus predicted by at least 2 of 3 tested equations for FVC, FEV1, TLC, RV for both sexes were identified. The same occured for exercise measurements (load and VO2 at peak exercise) for 3 of 4 tested equations. There was no homogeneity of a particular author to predict more accurately values observed in the sample tested for all functional parameters in both sexes. There was high rates of out of reference range classification for all evaluated equations. New elderly-specific reference equations were presented from the data obtained. Conclusions: The use of existing reference equations had limited applicability to the sample of healthy elderly studied, generating high rates of under and overestimated values, potentially compromising the sensitivity and specificity of the tests. Age-specific equations were derived from a sample of Brazilian healthy elderly, aiming to represent the physiological changes in this age group

Neste trabalho a determinação de elementos químicos em tecidos biológicos (sangue total, ossos e orgãos) de camundongos distróficos, usados como modelo animal da Distrofia Mucular de Duchenne (DMD), foi realizada utilizando técnica analítica nuclear. O objetivo do presente trabalho foi a determinação dos valores de referência para elementos de relevância em bioquímica clínica (Ca, Cl, K, Mg e Na) e nutricional (Br e S) em sangue total, tíbia, quadríceps anterior e coração de camundongos da linhagem distrófica Dmdmdx/J (10 machos e 10 fêmeas) e grupo controle C57BL/6J (10 machos), utilizando a técnica de Análise por Ativação com Nêutrons AAN. Para obter mais detalhes das alterações que esta disfunção pode causar nesses tecidos biológicos, foram calculadas matrizes de correlação entre as espécies Dmdmdx/J e comparadas ao grupo controle C57BL/6J. Para a realização deste estudo 119 amostras de tecidos biológicos foram irradiadas no reator nuclear IEA-R1 no IPEN (São Paulo, Brasil). Os resultados de análise, por AAN, constituem as primeiras estimativas para os valores de referência nesses tecidos biológicos dos camundongos Dmdmdx/J e C57BL/6J. Além disso, as alterações em alguns dos coeficientes de correlações entre os animais saudáveis e com disfunção indicam uma conexão entre esses elementos no sangue, tíbia, quadríceps e coração. Esses dados poderão auxiliar pesquisadores avaliar e comparar as vantagens e desvantagens dos diferentes tratamentos, realizados na distrofia muscular, quando estes modelos animais forem empregados, auxiliando os pesquisadores a avaliar a eficácia de novos procedimentos terapêuticos antes de serem empregados em paciente com DMD. / In this work the determination of chemistry elements in biological tissues (whole blood, bones and organs) of dystrophic mice, used as animal model of Duchenne Muscular Dystrophy (DMD), was performed using analytical nuclear technique. The aim of this work was to determine reference values of elements of clinical (Ca, Cl, K, Mg, Na) and nutritional (Br and S) relevance in whole blood, tibia, quadriceps and hearts from Dmdmdx/J (10 males and 10 females) dystrophic mice and C57BL/6J (10 males) control group mice, using Neutron Activation Analysis technique (NAA). To show in more details the alterations that this disease may cause in these biological tissues, correlations matrixes of the DMDmdx/J mouse strain were generated and compared with C57BL/6J control group. For this study 119 samples of biological tissue were irradiated in the IEA-R1 nuclear reactor at IPEN (São Paulo, Brazil). The concentrations of these elements in biological tissues of Dmdmdx/J and C57B/6J mice are the first indicative interval for reference values. Moreover, the alteration in some correlation coefficients data among the elements in the health status and in the diseased status indicates a connection between these elements in whole blood, tibia, quadriceps and heart. These results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy.

Devido às dificuldades encontradas excessivas variabilidades de água no organismo do lactente, considera-se a análise vetorial de impedância bioelétrica (BIVA) um método propício para avaliação da composição corporal. Trata-se de um método que não faz nenhuma pressuposição sobre valores da composição corporal, podendo ser controlado por seus próprios valores, independente de equações ou modelos. Os objetivos deste estudo foram descrever valores de referência e criar curvas de BIVA para lactentes saudáveis de 30 a 90 dias de vida e descrever valores de normalidade de ângulo de fase em lactentes a termo, sadios e adequados para a idade gestacional de 30 a 90 dias de idade, além de comparar os dados de BIVA entre os sexos e entre os existentes na literatura para neonatos e lactentes jovens, com os obtidos neste estudo. Este estudo descritivo transversal avaliou 150 lactentes do Centro Médico Social Comunitário Vila Lobato de Ribeirão Preto - SP - Brasil. Foram coletados dos lactentes os dados antropométricos e a impedância bioelétrica (aparelho de monofrequência RJL System ® modelo Quantum II - 800 ?A e 50 KHz). Usando distribuição bivariável normal de resistência e reactância por comprimento (R/H e Xc/H) do lactente, respectivamente, foram calculados e assim confeccionados os gráficos RXc com os intervalos de tolerância de 95, 75, 50% do valor vetorial da impedância por meio do BIVA Software 2002. Foram avaliados 150 lactentes (48,6% do sexo feminino), nascidos a termo, adequados para idade gestacional e em aleitamento materno exclusivo. A idade média foi 56,4 (± 23,1) dias. O peso médio encontrado foi de 5038,5g (± 902,4), sendo maior no sexo masculino (p = 0,001). Quanto ao comprimento corporal, a média foi 56,0 cm (± 0,03), sendo maior no sexo masculino (p = 0,001). As médias de R (±DP) foram 521,2 (± 52,1); 519,4 (± 53,4) e 523,0 (± 51,1) ?, e para Xc foram 39,2 (± 5,3); 38,6 (± 5,5) e 39,7 (± 4,9) ?, respectivamente para todos os lactentes, e separados por sexo (meninos e meninas), não havendo diferença entre os sexos (p = 0,6) e (p = 0,1). Em relação ao ângulo de fase, encontrou-se o valor de normalidade de 4,3° (± 0,7°) para todos os lactentes, 4,3° (± 0,6°) para os do sexo masculino e 4,4° (± 0,5°) para os do sexo feminino, não havendo diferença estatisticamente significativa (p = 0,3). Para a análise vetorial de lactentes de 30 a 90 dias de idade, devem ser utilizados os valores de referência específicos para esta faixa etária e sexo, pois estes se apresentaram diferentes dos descritos na literatura. Com o modelo de estudo BIVA torna-se possível a comparação direta do vetor medido na criança pequena ou com necessidade de cuidados especiais com os intervalos de tolerância de referência de lactentes saudáveis, permitindo uma avaliação qualitativa da composição corporal e sem erro de predição das fórmulas. Com os valores de ângulo de fase caracterizados no presente estudo para lactentes brasileiros saudáveis, de 30 a 90 dias de idade, dados de pacientes críticos podem ser comparados, sendo útil durante a internação e acompanhamento de pacientes graves. / Bioelectrical impedance vectorial analysis (BIVA) can be considered a favorable method for evaluation of the body composition, due to the difficulties in the early life and excessive variability of the amount of water in the organism of the infants. It is a method that doesn\'t make any presumption on values of the body composition, which can be controlled by their own values, with no need for validation based on gold standards, not depending on equations or models. The aims of the study are to establish reference values creating BIVA curves, and to establish reference values for phase angle in term infants, healthy and appropriate-forgestational age (AGA), from 30 to 90 days of life. This study still intend to compare the data of BIVA between genders, among newborns and young infants, presented in the literature, and the ones obtained in this study. This transversal cohort study assessed healthy infants of a Community Centre for Social Medicine Vila Lobato, located in Ribeirão Preto, São Paulo, Brazil. Data of infants, anthropometry and bioelectrical impedance were collected (singlefrequency - RJL System ® model Quantum II - 800 ?A and 50 KHz). Using bivariate normal distribution of R/H and Xc/H (resistance and reactance for infants length, respectively), graphs RXc with the 95, 75 and 50% tolerance intervals of the vectorial value of the impedance, were made through BIVA Software 2002. 150 infants were studied (48,6% girls), term, AGA, exclusively breastfed. The average age was 56,4 (± 23,1) days, average weight was 5038,5g, higher in girls (p = 0,001), and the average length was 56,0 cm (± 0,03), higher in girls (p = 0,001). The values of R (± SD) were 521,2 (± 52,1); 519,4 (± 53,4) and 523,0 (± 51,1) ? and for Xc were 39,2 (± 5,3); 38,6 (± 5,5) e 39,7 (± 4,9) ?, respectively for all the infants, and boys and girls, with no difference between the genders (p = 0,6) and (p = 0,1). Regarding to the phase angle, we found normal value of 4,3° (± 0,7°) for all the infants, 4,3° (± 0,6°) for male and 4,4° (± 0,5°) for female, without statistical difference (p = 0,36). For Bioelectrical Impedance Vector analysis of infants from 30 to 90 days of life, it would be interesting to use specific reference values for this age group and gender. BIVA model makes possible the direct comparison of the measured vector of the small children; still makes it possible for children needing special care, using the tolerance reference values of healthy infants. This comparison allows us a qualitative assessment of the body composition, with no need of equations. With the values of phase angle characterized in the present study for healthy Brazilian infants, from 30 to 90 days of life, critical patients data can be compared, being useful during the hospitalization due to severe illness.

Auditory filters were derived in 20 normal-hearing human listeners at center frequencies (CFs) of 913, 1095, 3651, and 4382 Hz using the roex (p,r) method. Comparisons were made between slopes of the filters' skirts at the neighboring CFs with filter output levels of 45 and 70 dB. The same comparisons were made with regard to filter equivalent rectangular bandwidth (ERB). In the 1000-Hz region, the low-frequency slopes (Pl) of filters centered at 913 and 1095 Hz were significantly correlated at both stimulus levels, while the high-frequency slopes (Pu) were similar only at the high test level. In the 4000-Hz region, for sinusoids of 3651 and 4382 Hz, the level effect was clearer as both Pu and Pl values diverged at the low level but were related at high levels. The ERBs centered at the same CFs displayed a similar level dependence. At the stimulus level most likely to be affected by an active feedback mechanism, auditory filters centered at nearly the same frequency displayed quite distinct frequency selectivity, and this trend was stronger in the 4000-Hz region than the 1000-Hz region. The findings suggest that a saturating, active cochlear mechanism may not be distributed evenly, or contribute to peripheral tuning with equal effectiveness throughout the length of the partition.

The very old, aged 80 years and over, is the fastest growing age group today, and the demands for healthcare and services will be even higher in the future. It is, therefore, of great importance to advance our knowledge about this group. The main purpose of this thesis was to describe living conditions and health, with a special focus on physical ability, falls and morale, in women and men in three different age groups of very old people in northern Sweden. Half the population aged 85, and the total population aged 90 and ≥95 (-103) in the municipality of Umeå were selected for participation (n=348) in this population-based cross-sectional study, entitled the Umeå 85+ Study. Structured interviews and assessments were performed with the participants in their homes, and data were also collected from next-of-kins, caregivers and medical charts. Cognition was screened for using the Mini-Mental State Examination (MMSE), depressive symptoms using the Geriatric Depression Scale-15 (GDS-15), and nutritional status using the Mini Nutritional Assessment (MNA). Activities of Daily Living (ADL) were assessed using the Staircase of ADL (including the Katz Index of ADL) and morale using the Philadelphia Geriatric Center Morale Scale (PGCMS). Participants also rated their own health and answered a questionnaire about symptoms. Physical ability was assessed using a gait speed test over 2.4 meters (8 feet), three consecutive chair stands, and the Berg Balance Scale (BBS). A follow-up study for falls was performed during a period of six months with fall calendars and telephone calls. The very old people in this northern population have more depression, hypertension and hip fractures, as well as a higher consumption of drugs than comparable, more southern populations. In general, younger participants had lower rates of diagnoses and prescribed drugs, were less dependent in ADL and other functional variables than older participants, and men had lower rates of diagnoses and reported symptoms than women. However, there were no age or sex differences in self-rated health or morale, which were both rated as good by the majority of the participants. There was a wide range of physical ability among these very old people, especially in women, where an age-related decline was seen. The results also demonstrate that men had greater physical ability than women. The BBS had no floor or ceiling effects in the present sample. In contrast, a large proportion was unable to perform the gait speed and chair stands test, resulting in a floor effect for the timed performances, especially in women. Falling is a major public health problem in very old people. From the results of the present study, it could be predicted that every seventh participant and every third of the people who did fall would suffer a fracture over a period of one year. The independent explanatory risk factors for time to first fall in this sample of very old people were dependency in personal (P-) ADL but not bedridden, thyroid disorders, treatment with Selective Serotonin Reuptake Inhibitors (SSRIs) and occurrence of fall/s in the preceding year. These factors should all be considered in fall prevention programmes. The morale of very old people was found in this study to be rather high, with similar scores among age groups and sexes. The most important factors for high morale were the absence of depressive symptoms, living in ordinary housing, having previously had a stroke and yet still living in ordinary housing, not feeling lonely and having few symptoms. The PGCMS seems applicable in the evaluation of morale in very old people. In conclusion, there were wide variations in health status and physical ability in this northern population of very old people. Women had poorer health and physical ability than men. Falls and fractures were common and serious health problems. Morale seemed to be high, despite the fact that a large proportion of the participants suffered from many diseases and functional decline.

Kohlenmonoxid (CO) wird nach Einatmung weitgehend an Hämoglobin gebunden, eine minimale Bindung findet auch an Myoglobin statt. Die Kohlenmonoxid-Hämoglobinkonzentration (COHb) im Blut steigt nach Inhalation proportional zur inhalierten CO-Menge und zur Hämoglobinmasse an. Dieser Anstieg wird über die CO-Hämoxymetrie ermittelt und resultierend aus der CO-Verdünnung die Hämoglobinmenge berechnet. Über die Hämoglobinkonzentration und den Hämatokrit kann im Anschluss das Blutvolumen berechnet werden. Grundsätzlich ist dieses Verfahren seit über 100 Jahren bekannt und wird seit ca. 1995 als Routinemethode zur Blutvolumenbestimmung in der Sportmedizin verwendet. Es existieren darüber hinaus methodische Probleme durch die CO-Abatmung und die Evaluierung in großen Kollektiven. Die hier vorgestellte Methodik beinhaltet die Weiterentwicklung der CO-Methode zur Direktmessung im geschlossenen System. Die Probanden atmen dabei ein exakt definiertes Bolus-Volumen in einem geschlossenen Atmungssystem über 15 Minuten ein. Die maximale Arbeitsplatzkonzentration (MAK: COHb 5%), also die resultierende COHb-Konzentration im Blut bei einer CO-Langzeitexposition von 35 ppm, wird in der Regel nur leicht überschritten. Dazu wurden an 104 Probanden zwei Vergleichsmessungen in definiertem Abstand und an 20 Probanden Wiederholungsmessungen nach Blutspende zum Nachweis der Reliabilität und Validität durchgeführt. Zusätzlich ist die Abfallkinetik von COHb an 20 Probanden bestimmt worden. Im Ergebnis stellt sich methodenbedingt ein COHb-Steady-State nach 9 Minuten Rückatmung im geschlossenen System ein. Der Typical-Error der Messwiederholung der Methodik liegt bei 1,9% bzw. nach weiterer Modifizierung der Methodik bei 1,3%. Der Nachweis eines Blutverlustes von 490 ml im Rahmen einer Blutspende zeigt nur eine minimale Abweichung von 10 g Hämoglobinmasse zwischen gemessenem und kalkuliertem Verlust. Die Halbwertszeit von COHb wurde mit 135 min bestimmt. Die verwendete Methodik zeigt aufgrund der induzierten COHb-Steady-State-Kinetik Vorteile bei der Anwendung und Genauigkeit. Der Nachweis der Wiederholbarkeit und Messgenauigkeit konnte an einem hinreichend großen Kollektiv gezeigt werden. Bei Mehrfachanwendung bietet die Sensitivität der Methodik die Möglichkeit der Aufdeckung von Manipulationen des Blutes über Erythropoetin (EPO) oder Eigenbluttransfusion. Dabei bewegt sich die eingesetzte CO-Belastung während der Methode im Bereich des Konsums von wenigen Zigaretten.

Made available in DSpace on 2015-07-22T20:49:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-06-30. Added 1 bitstream(s) on 2015-08-11T03:26:07Z : No. of bitstreams: 1 Publico-12636.pdf: 1313292 bytes, checksum: 9dc5695df095889d7733e20c113824b4 (MD5) / Objetivo: Comparar os valores absolutos da CVF e VEF1 de uma amostra randomizada da populacao de Sao Paulo com mais de 40 anos de idade com os valores previstos das equacoes mais utilizadas no Brasil. Comparar os valores em percentuais do previstos da CVF e VEF1 das equacoes selecionadas com os da equacao PLATINO. Avaliar a mudanca de estadio da DPOC ao se utilizar as diferentes equacoes de referencia. Material e Metodos: Estudo retrospectivo, com 178 pessoas normais da amostra de moradores da regiao metropolitana de Sao Paulo, com idade .40 anos, proveniente do estudo PLATINO. Para a comparacao da CVF e do VEF1, foram subtraidos dos valores previstos a partir de cada equacao os valores absolutos obtidos de cada individuo, considerando uma diferenca de ate 0,15L, como definida pela ATS. Tambem foi realizada a diferenca entre os valores do percentual do previsto da CVF e VEF1 das equacoes com os da equacao PLATINO, com diferenca . 3% (ATS). O diagnostico de DPOC foi definido pela relacao VEF1/CVF < 0,70 pos-broncodilatador e a comparacao do estadiamento foi realizada utilizando a variavel VEF1 em porcentagem do previsto de cada equacao, tendo como referencia o percentual previsto da equacao PLATINO. As equacoes foram aplicadas de acordo com os seus limites de idade e altura. Teste t-student, Qui-quadrado e coeficiente de correlacao intraclasse foram utilizados para avaliar o comportamento da CVF e VEF1 nas diferentes equacoes e os dados foram apresentados em media, desvio padrao, erro padrao e intervalo de confianca de 95%. Resultados: Observamos que as equacoes que apresentam menor diferenca entre o valor previsto e o valor absoluto para CVF e VEF1, em ambos os sexos, foram Roca et al. (n=151), Pereira et al. 2007 (n=176), Enright et al (n=43) e PLATINO (n=178). A equacao Knudson et al (n=177). subestimou os valores absolutos para CVF e VEF1. Na comparacao com a equacao PLATINO, em percentual do previsto para CVF e VEF1, a equacao que apresentou menor diferenca foi a NHANES III (n=172), exceto para CVF masculina, que apresentou grande variabilidade. Foram avaliados 152 pacientes com DPOC, estadiados pelo VEF1, segundo a equacao PLATINO, observando-se mudanca no estadiamento em 29,6% dos pacientes em relacao as equacoes, tendo a equacao Knudson et al. apresentado o maior numero de alteracoes. Conclusao: Existe uma grande variabilidade nos valores previstos entre as equacoes de referencia. As equacoes que apresentaram menor variabilidade e melhor coeficiente de correlacao intraclasse foram Roca et al., NHANES III caucasiano et al., Enright et al. e PLATINO, recomendando-se o seu uso para a populacao brasileira. Existe mudanca no estadio da DPOC quando diferentes equacoes sao aplicadas, sugerindo-se o uso de uma unica equacao durante o tratamento do mesmo paciente para evitar eventuais alteracoes no tratamento. / Objective: To compare the absolute values of FVC and FEV1 found in a random sample of a Brazilian population over 40 years of age with values of equations most used in Brazil. To compare the values in percentage of predicted of FVC and FEV1 of the selected equations with the PLATINO equation ones. To evaluate the change in COPD staying when using different reference equations. Material and Methods: We conducted a retrospective study from a representative sample of residents in the metropolitan region of Sao Paulo, aged .40 years, from the PLATINO study. For comparison of the FVC and FEV1, were subtracted from the predicted values of each equation the absolute values obtained from each individual, considering the equation inadequate wherever there was a difference of up to 0.15 L as defined by ATS. We also evaluated the difference between the values of FVC and VEF1 in percentage of predicted of the equations with the PLATINO equation, considering as a limit a difference .3% (ATS). The diagnosis of COPD was defined as FEV1/FVC <0.70 after bronchodilator, and the comparison of staging was performed using the FEB1 in percentage of predicted in each equation, with reference to the percentage expected from the PLATINO equation. T-student test, chi-squared and the intraclass correlation coefficient were used to evaluate the performance of FVC and FEV1 in different equations and data are presented as mean, standard deviation, standard error and confidence interval of 95%. Results: After evaluating 178 healthy subjects, we observed that the equations that show less difference between the predicted value and the absolute value for both FEV1 and FVC in both sexes were Roca et al., Pereira et al. 2006, Enright et al. and PLATINO. The Knudson et al. equation underestimated the absolute values for both FVC and FEV1. In comparison with PLATINO equation, the percentage of predicted for FVC and FEV1, the equation showing the lowest difference was NHANES III, except for FVC male, who showed a wide variability. We evaluated 152 patients with COPD, observing staging changes in 29.6% in relation to the difference equations, being Knudson et al. the equation that showed the greatest number of changes. Conclusion: There is a great variability among the reference equations. The equations showing less variability and better intraclass correlation coefficient were Roca et al., Caucasian NHANES III et al., Enright et al. and PLATINO, which are the ones that should be recommended to be used for the Brazilian population. There is a change in the COPD staging when different equations are applied, suggesting that the use of a single equation for the treatment of the patient would avoid possible alterations in treatment. / TEDE / BV UNIFESP: Teses e dissertações