Influence of respiratory biofeedback associated to re-expansive ventilation patterns in individuals with functional mouth breathing

Objectives: Assess the effect of re-expansive respiratory patterns associated to respiratory biofeedback (RBF) on pulmonary function, respiratory muscle strength and habits in individuals with functional mouth breathing (FMB). Methods: Sixty children with FMB were divided into experimental and control groups. The experimental group was submitted to 15 sessions of re-expansive respiratory patterns associated to RBF (biofeedback pletsmovent; MICROHARD (R) V1.0), which provided biofeedback of the thoracic and abdominal movements. The control group was submitted to 15 sessions using biofeedback alone. Spirometry, maximum static respiratory pressure measurements and questions regarding habits (answered by parents/guardians) were carried out before and after therapy. The Student`s t-test for paired data and non-parametric tests were employed for statistical analysis at a 5% Level of significance. Results: Significant changes were found in forced vital. capacity, Tiffeneau index scores, maximum expiratory pressure, maximum inspiratory pressure and habits assessed in FMB with the use of RBF associated to the re-expansive patterns. No significant differences were found comparing the experimental and control groups. Conclusions: The results allow the conclusion that RBF associated to re-expansive patterns improves forced vital capacity, Tiffeneau index scores, respiratory muscle strength and habits in FMB and can therefore be used as a form of therapy for such individuals. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Allergic asthma in patients with common variable immunodeficiency

P>Background: Many patients with common variable immunodeficiency (CVID) have a clinical history suggestive of allergic respiratory disease. However, in such individuals, the prevalence of asthma and the role of atopy have not been well established. The objective of this study was to evaluate pulmonary function and identify asthma in patients with CVID. We also investigated the role of IgE as a trigger of asthma in these patients. Methods: Sixty-two patients diagnosed with CVID underwent spirometry, as well as skin prick testing and in vitro determination of serum-specific IgE levels for aeroallergens, together with bronchial provocation with histamine and allergen. Results: The most common alteration identified through spirometry was obstructive lung disease, which was observed in 29 (47.5%) of the 62 patients evaluated. Eighteen (29.0%) of the 62 patients had a clinical history suggestive of allergic asthma. By the end of the study, asthma had been diagnosed in nine (14.5%) patients and atopy had been identified in six (9.7%). In addition, allergic asthma had been diagnosed in four patients (6.5% of the sample as a whole; 22.2% of the 18 patients with a clinical history suggestive of the diagnosis). Conclusion: In this study, CVID patients testing negative for specific IgE antibodies and suspected of having allergic asthma presented a positive response to bronchial provocation tests with allergens. To our knowledge, this is the first such study. When CVID patients with a history suggestive of allergic asthma test negative on traditional tests, additional tests designed to identify allergic asthma might be conducted.

Relationship between induced sputum cytology and inflammatory status with lung structural and functional abnormalities in asbestosis

Background Asbestosis is associated with lung cellular and immunological abnormalities. Induced sputum cytology and local and systemic markers of inflammation may be helpful to characterize disease status and progression in these patients. Methods Thirty-nine ex-workers with asbestosis on high-resolution CT (HRCT) and 21 non-exposed controls were evaluated. Sputum cytology and IL-8 in serum and sputum were related to lung function impairment. Results Subjects with asbestosis had reduced sputum cellularity but higher macrophagel neutrophil ratio and % macrophage as compared with controls. Sputum and serum IL-8 were also higher in patients with asbestosis (P < 0.05). In addition, evidence of lung architectural distorption on HRCT was associated with increased levels of serum IL-8. Interestingly, absolute macrophage number was negatively correlated with total lung capacity (r = -0.40; P = 0.04) and serum IL-8 to lung diffiusing capacity (r = -0.45; P = 0.01). Conclusions Occupationally exposed subjects with asbestosis on HRCT have cytologic abnormalities in induced sputum and increased local and systemic pro-inflammatory status which are correlated to functional impairment.

Effects of Somatosensory Stimulation on Motor Function After Subacute Stroke

Background. Previous works showed potentially beneficial effects of a single session of peripheral nerve sensory stimulation (PSS) on motor function of a paretic hand in patients with subacute and chronic stroke. Objective. To investigate the influence of the use of different stimulus intensities over multiple sessions (repetitive PSS [RPSS]) paired with motor training. Methods. To address this question, 22 patients were randomized within the second month after a single hemispheric stroke in a parallel design to application of 2-hour RPSS at 1 of 2 stimulus intensities immediately preceding motor training, 3 times a week, for 1 month. Jebsen-Taylor test (JTT, primary endpoint measure), pinch force, Functional Independence Measure (FIM), and corticomotor excitability to transcranial magnetic stimulation were measured before and after the end of the treatment month. JTT, FIM scores, and pinch force were reevaluated 2 to 3 months after the end of the treatment. Results. Baseline motor function tests were comparable across the 2 RPSS intensity groups. JTT improved significantly in the lower intensity RPSS group but not in the higher intensity RPSS group at month 1. This difference between the 2 groups reduced by months 2 to 3. Conclusions. These results indicate that multiple sessions of RPSS could facilitate training effects on motor function after subacute stroke depending on the intensity of stimulation. It is proposed that careful dose-response studies are needed to optimize parameters of RPSS stimulation before designing costly, larger, double-blind, multicenter clinical trials.

POLYETHYLENE GLYCOL ADDITION DOES NOT IMPROVE EXOGENOUS SURFACTANT FUNCTION IN AN EXPERIMENTAL MODEL OF MECONIUM ASPIRATION SYNDROME

Meconium (MEC) is a potent inactivator of pulmonary surfactant. The authors studied the effects of polyethylene glycol addition to the exogenous surfactant over the lung mechanics and volumes. Human meconium was administrated to newborn rabbits. Animals were ventilated for 20 minutes and dynamic compliance, ventilatory pressure, and tidal volume were recorded. Animals were randomized into 3 study groups: MEC group (without surfactant therapy); S100 group (100 mg/kg surfactant); and PEG group (100 mg/kg porcine surfactant plus 5% PEG). After ventilation, a pulmonary pressure-volume curve was built. Histological analysis was carried out to calculate the mean alveolar size (Lm) and the distortion index (DI). Both groups treated with surfactant showed higher values of dynamic pulmonary compliance and lower ventilatory pressure, compared with the MEC group (P .05). S100 group had a larger maximum lung volume, V30, compared with the MEC group (P .05). Lm and DI values were smaller in the groups treated with surfactant than in the MEC group (P .05). No differences were observed between the S100 and PEG groups. Animals treated with surfactant showed significant improvement in pulmonary function as compared to nontreated animals. PEG added to exogenous surfactant did not improve lung mechanics or volumes.

Cholinergic Hyperresponsiveness of Peripheral Lung Parenchyma in Chronic Obstructive Pulmonary Disease

Background: Up to 60% of chronic obstructive pulmonary disease ( COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. Objectives: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. Methods: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of alpha-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. Results: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p <= 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = -0.451, p < 0.05). Conclusions: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test. Copyright (C) 2011 S. Karger AG, Basel

Short-Term Effects of Hydroxyethylstarch Resuscitation on Systemic and Regional Hemodynamics and Metabolism in a Brain-Dead Canine Model

Background. Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. Methods. Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33mL/kg), and HES (6% HES 450/0.7, 17mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. Results. Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. Conclusion. Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions. (C) 2011 Elsevier Inc. All rights reserved.

Efeitos de um programa de educação para a saúde no doente portador de DPOC

Objectivo: Verificar o efeito de um programa de educação para a saúde em doentes portadores de DPOC. Metodologia: Estudo experimental (ensaio clínico) com 18 doentes portadores de DPOC seleccionados aleatoriamente através da consulta de Medicina Geral e Familiar. Depois de informar os objectivos do estudo e os aspectos éticos, os participantes realizaram uma avaliação da função pulmonar, capacidade de tolerância ao exercício, qualidade de vida, actividades de vida diária (AVD), dispneia e ansiedade e depressão. Posteriormente os indivíduos do grupo controlo receberam um manual informativo e os incluídos no grupo experimental além de receber o manual foram submetidos a 6 sessões de educação. Após 8 semanas todos os doentes foram reavaliados. O nível de significância utilizado nos testes estatísticos foi α=0.05 (intervalo de confiança de 95%). Resultados: A análise da diferença dos ganhos entre os grupos revelou-se estatisticamente significativa nas variáveis qualidade de vida (p<0,001), AVD (p<0,001) e depressão (p<0,001). Na capacidade de tolerância ao exercício ambos os grupos melhoraram significativamente mas a diferença de ganhos não foi estatisticamente significativa (p=0,289), tal como na variável ansiedade (p=0,960). Conclusão: Este estudo parece demonstrar que o programa de educação foi eficaz nas variáveis qualidade de vida, AVD e depressão.

Analysis of the respiratory dynamics during normal breathing by means of pseudo phase plots and pressure-volume loops

This paper reports on the analysis of tidal breathing patterns measured during noninvasive forced oscillation lung function tests in six individual groups. The three adult groups were healthy, with prediagnosed chronic obstructive pulmonary disease, and with prediagnosed kyphoscoliosis, respectively. The three children groups were healthy, with prediagnosed asthma, and with prediagnosed cystic fibrosis, respectively. The analysis is applied to the pressure–volume curves and the pseudophaseplane loop by means of the box-counting method, which gives a measure of the area within each loop. The objective was to verify if there exists a link between the area of the loops, power-law patterns, and alterations in the respiratory structure with disease. We obtained statistically significant variations between the data sets corresponding to the six groups of patients, showing also the existence of power-law patterns. Our findings support the idea that the respiratory system changes with disease in terms of airway geometry and tissue parameters, leading, in turn, to variations in the fractal dimension of the respiratory tree and its dynamics.

Is multidimensional scaling suitable for mapping the input respiratory impedance in subjects and patients?

This paper presents the application of multidimensional scaling (MDS) analysis to data emerging from noninvasive lung function tests, namely the input respiratory impedance. The aim is to obtain a geometrical mapping of the diseases in a 3D space representation, allowing analysis of (dis)similarities between subjects within the same pathology groups, as well as between the various groups. The adult patient groups investigated were healthy, diagnosed chronic obstructive pulmonary disease (COPD) and diagnosed kyphoscoliosis, respectively. The children patient groups were healthy, asthma and cystic fibrosis. The results suggest that MDS can be successfully employed for mapping purposes of restrictive (kyphoscoliosis) and obstructive (COPD) pathologies. Hence, MDS tools can be further examined to define clear limits between pools of patients for clinical classification, and used as a training aid for medical traineeship.

Avaliação do débito máximo da tosse (peak cough flow) na doença pulmonar obstrutiva crónica

Resumo Objectivos: Avaliação da Tosse em doentes com Doença Pulmonar Obstrutiva Crónica (DPOC). Identificar e determinar a relação dos factores preditivos que contribuem para a deterioração da capacidade de tosse nestes indivíduos. Tipo de estudo: Estudo observacional descritivo de natureza transversal. Definição dos casos: Os critérios de diagnóstico da DPOC são o quadro clínico e o Gold standard para diagnóstico da DPOC – a espirometria. População-alvo: Todos os utentes com patologia primária de DPOC diagnosticada que se desloquem ao serviço de função respiratória do Hospital de Viseu, para realizar provas. Método de Amostragem: Foi utilizada uma amostra aleatória constituída por todos os indivíduos, que cumpriram os critérios de inclusão, conscientes e colaborantes, que aceitaram participar neste estudo. Dimensão da amostra: Uma amostra de 55 indivíduos que se deslocaram ao serviço de função respiratória, entre Janeiro e Junho de 2009, para realizar provas de função respiratória. Condução do estudo: Os utentes que aceitaram participar neste estudo foram sujeitos a um questionário de dados clínicos e realizaram 5 testes: índice de massa corporal (IMC), estudo funcional respiratório e gasometria arterial, avaliação da força dos músculos respiratórios (PImax e PEmax) e avaliação do débito máximo da tosse (Peak Cough Flow). Análise estatística: Foram obtidos dados caracterizadores da amostra em estudo, sendo posteriormente correlacionado o valor de débito máximo da tosse (Peak Cough Flow) com os resultados obtidos para as avaliações do IMC, estudo funcional respiratório, PImax e PEmax, gasometria, avaliação da capacidade de Tosse e número de internamentos no último ano por agudização da DPOC. Tendo sido encontrados os valores de correlação entre o Peak Cough Flow e os restantes parâmetros. Resultados: Após análise dos resultados, foram obtidos os valores de Peak Cough Flow para a população com DPOC e verificou-se valores diminuídos em comparação com os valores normais da população, tendo-se verificado maiores valores de PCF em indivíduos do sexo masculino, em comparação aos valores do sexo feminino. Foi analisada a relação entre o PCF e a idade, peso, altura e IMC, não tendo sido encontrada relação, dado que a tosse não apresenta uma variação segundo os valores antropométricos, tal como a relação com os valores espirométricos. Quanto aos parâmetros funcionais respiratórios foram analisadas as relações com o PCF. Verificou-se relações significativas entre o PCF e o FEV1, a FVC, o PEF, apresentando uma relação positiva, onde maiores valores destes parâmetros estão correlacionados com maiores picos de tosse. Quanto a RAW e RV, o PCF apresenta uma relação negativa, onde uma maior resistência da via aérea ou doentes mais hiperinsuflados leva a menores valores de PCF. Por outro lado não foi encontrada relação entre o PCF e a FRC e o TLC. Quanto à força dos músculos respiratórios, verificou-se relação significativa com o PImax e a PEmax em que a fraqueza ao nível dos músculos respiratórios contribuem para um menor valor de PCF. Relativamente aos valores da gasometria arterial, verificou-se relação entre o PCF e a PaO2 de forma positiva, em que doentes hipoxémicos apresentam menores valores de tosse, e a PaCO2, de forma negativa, em que os doentes hipercápnicos apresentam menores valores de PCF tendo sido verificada relação entre o PCF e o pH e sO2. Quanto à relação entre o número de internamentos por agudização da DPOC no último ano e o PCF verificou-se uma relação significativa, onde um menor valor de PCF contribui para uma maior taxa de internamento por agudização da DPOC. Conclusão: Este conjunto de conclusões corrobora a hipótese inicialmente formulada, de que o Peak Cough Flow se encontra diminuído nos indivíduos com Doença Pulmonar Obstrutiva Crónica onde a variação do PCF se encontra directamente relacionada com os parâmetros funcionais respiratórios, com a força dos músculos respiratórios e com os valores de gasometria arterial. ABSTRACT: Aims: Cough evaluation in Chronic Obstructive Pulmonary Disease (COPD) patients. Identify and determine the relation of the predictive factors that contribute to the cough capacity degradation in this type of patients. Type of study: Descriptive observational study of transversal nature. Case definition: The COPD diagnosis criteria are the clinical presentation and the gold standard to the COPD diagnosis- the Spirometry. Target Population: Every patients, with primary pathology of COPD diagnosed, who went to the respiratory function service of Viseu hospital to perform tests. Sampling Method: It was used a random sample constituted by all the, conscious and cooperating individuals, who complied with the inclusion criteria and who accepted to make part of this study. Sample size: A sample of 55 individuals that went to the respiratory function service between January and June 2009 to perform respiratory function tests. Study: The patients who accepted to make part of this study were submitted to a clinical data questionary and performed 5 tests: body mass index (BMI), respiratory functional study, arterial blood gas level, evaluation of respiratory muscles strength (maximal inspiratory pressure (MIP) and maximum expiratory pressure (MEP)), and Peak Cough Flow evaluation. Statistic Analysis: Were obtained characterizing data of the sample in study, and later correlated the value of the Peak Cough Flow with the results from the evaluation of the body mass index (BMI), the respiratory functional study the MIP and MEP, the arterial blood gas level and also with the ability to cough evaluation and the number of hospitalizations in the last year for COPD exacerbations. The values of correlation between the Peak Cough Flow and the other parameters were found. Results: After analyzing the results, were obtained the values of Peak Cough Flow for the population with COPD. There were decreased values compared with the population normal values, having been found higher values of PCF in males compared to female values. It was analyzed the relation between the PCF and the age, weight, height and BMI but no relation was found on account of the fact that the cough does not show a variation according to anthropometric parameters, such as the relation with spirometric values. As for the respiratory functional parameters were analyzed relations with the PCF. There were significant relations between the PCF and FEV1, the FVC, the PEF, presenting a positive relation, where higher values of these parameters are correlated with higher incidence of cough. Concerning the RAW and RV, the PCF has a negative relation, in which a higher airway resistance or in more hyperinflated patients, leads to lower values of PCF. On the other hand no correlation was found between the PCF and the FRC and TLC. Regarding the respiratory muscle strength, there was a significant relation with the MIP and MEP, in which the weakness at the level of respiratory muscles contribute to a lower value of PCF. For values of arterial blood gas level, there was no relation between the PCF and PaO2, in a positive way, in which patients with hypoxemia present lower values of cough, and PaCO2, in a negative way in which hypercapnic patients had lower values of PCF, having being founded a relation between the PCF and the pH and sO2. As for the relation between the number of hospitalizations for COPD exacerbation in the last year and the PCF was found a significant relation, in which a smaller value of PCF contributes to a higher rate of hospitalization for COPD exacerbation. Conclusion: This set of findings supports the hypothesis first formulated that Peak Cough Flow is decreased in individuals with Chronic Obstructive Pulmonary Disease, in which the variation of the PCF is directly related to the respiratory function parameters, the strength of respiratory muscles and the values of arterial blood gases.

Analysis of the Respiratory Dynamics During Normal Breathing by Means of Pseudophase Plots and Pressure–Volume Loops

This paper reports on the analysis of tidal breathing patterns measured during noninvasive forced oscillation lung function tests in six individual groups. The three adult groups were healthy, with prediagnosed chronic obstructive pulmonary disease, and with prediagnosed kyphoscoliosis, respectively. The three children groups were healthy, with prediagnosed asthma, and with prediagnosed cystic fibrosis, respectively. The analysis is applied to the pressure-volume curves and the pseudophase-plane loop by means of the box-counting method, which gives a measure of the area within each loop. The objective was to verify if there exists a link between the area of the loops, power-law patterns, and alterations in the respiratory structure with disease. We obtained statistically significant variations between the data sets corresponding to the six groups of patients, showing also the existence of power-law patterns. Our findings support the idea that the respiratory system changes with disease in terms of airway geometry and tissue parameters, leading, in turn, to variations in the fractal dimension of the respiratory tree and its dynamics.

Anemia de células falciformes na idade pediátrica : contribuição para o estudo das suas principais complicações e indicadores de prognóstico

RESMO: Introdução: A anemia de células falciformes doença hereditária, com repercussão multi-orgânica, tem grande variabilidade na sua expressão clínica. Daí o interesse do estudo de indicadores de prognóstico. A investigação realizada foi precedida de um resumo histórico incidindo sobre a compreensão de aspectos fundamentais da doença ao longo dos tempos. Na primeira parte do estudo e após revisão bibliográfica, foram referidos dados da fisiopatologia como base para os estudos que integram a presente dissertação. Abordou-se o estado da arte relativamente às complicações, aos indicadores de prognóstico e à terapêutica utilizada. Objectivos: Constituíram objectivos deste estudo realizado numa amostra populacional representativa: identificar as lesões a nível dos sistemas cardio-respiratório e nervoso central, avaliando-se as respectivas repercussões; avaliar a presença de indicadores de prognóstico entre as variáveis seleccionadas; estudar a eficácia e toxicidade da HU nos doentes com as formas graves da ACF. Para a prossecução destes objectivos foram delineados para além do estudo global três estudos específicos: Estudo 1- repercussão no sistema cardio-respiratório; Estudo 2- repercussão no sistema nervoso central; Estudo 3- terapêutica com hidroxiureia. Doentes e métodos: Procedeu-se a um estudo prospectivo e multi-institucional durante um período de três anos tendo-se seleccionado para a amostra, e de acordo com critérios pré-definidos, 30 doentes com ACF na fase estável da doença, com idades compreendidas entre os sete e os 18 anos, todos de origem africana à excepção de um caucasiano. O diagnóstico baseou-se em técnicas de electroforese e estudo molecular que definiu o genotipo da doença e a presença da delecção da -talassémia assim como os haplotipos da amostra populacional. Foram utilizadas diferentes metodologias para avaliar a existência de lesão pulmonar e cerebral. Através do estudo estatístico foram seleccionadas diversas variáveis como hipotéticos indicadores de prognóstico. Estudo 1. Para determinar a existência de lesão a nível pulmonar usaram-se duas metodologias diferentes, a avaliação da função pulmonar com estudo da saturação da Hb em O2 no sangue arterial e a tomografia computadorizada de alta resolução. Estudou-se também a possível disfunção cardíaca como repercussão da lesão pulmonar, através do ecocardiograma, e os indicadores de prognóstico com significado estatístico para a lesão encontrada. Estudo 2. O desenho deste estudo foi sobreponível ao anterior, mas com metodologia adequada para o SNC. Procedeu-se ao estudo das lesões cerebrais por meio de exames imagiológicos, (RMN-CE e DTC) e de testes psicológicos. Correlacionaram-se as três metodologias utilizadas e a importância de cada uma para a decisão de atitudes terapêuticas preventivas. Estudo 3. Consistiu num estudo aberto prospectivo não controlado com nove crianças e adolescentes com formas graves de ACF, com o objectivo de avaliar a eficácia da terapêutica com hidroxiureia, durante um período de 24 meses. Todos os doentes completaram no mínimo 15 meses de terapêutica, com uma dose final média de 194 mg/K/dia. Resultados globais: Durante o período anterior à investigação caracterizou-se a amostra populacional estudada quanto ao fenotipo genético, clínico e hematológico de acordo com os critérios utilizados por outros investigadores. Verificou-se: predomínio do haplotipo Bantu na forma homozigótica em 53% dos doentes; número total de EVO ≥3/ano em 87,5% dos doentes; crises de sequestração em 18,75%; dactilites no primeiro ano de vida em 31,2%; quadro de sépsis grave apenas num doente; crises de hiper-hemólise em 50%; e STA em 59,38% dos doentes. Quanto ao fenotipo hematológico evidenciaram-se como factores de risco reticulocitose (13,1x103/l) e hiperbilirrubinémia (2,5 mg/dl) e como factores de bom prognóstico a presença de delecção de um gene da -talassémia em 46,9% dos doentes e valor médio de Hb 8,1 g/dl. Resultados dos estudos parcelares: Estudo 1. Deste estudo infere-se que a DPR ligeira foi diagnosticada em 70% dos doentes, uma vez que as alterações da difusão não foram estatisticamente significativas, o estudo dos gases no sangue não evidenciaram resultados anormais e a TCAR evidenciou alterações em 43,3% dos doentes. Apenas num doente se verificou doença pulmonar obstrutiva relacionada com maior número da STA.O estudo da disfunção cardíaca encontrada em 86,7% dos doentes não reflecte a repercussão da DPR a nível cardíaco, podendo estar associada às alterações fisiopatológicas da própria anemia crónica. Encontraram-se indicadores de prognóstico hematológicos e clínicos. Entre os primeiros, valores de Hb ≥8,5 g/dl e de HbF ≥13% foram considerados indicadores de bom prognóstico para a lesão pulmonar. Em relação aos parâmetros clínicos, as STA não foram consideradas indicadoras de prognóstico para a DPR ao contrário do que se verificou com o número de EVO. Pela análise dos parâmetros genéticos e socio-económicos provou-se a ausência de relação estatisticamente significativa com lesão pulmonar. Estudo 2. Pela RMN-CE foram diagnosticados ES em 33,3% com uma localização preferencial na substância branca profunda em 26,6% dos doentes. Relativamente aos parâmetros hematológicos seleccionados, o valor médio da HbF 8,6% constituíu um indicador de bom prognóstico para o aparecimento de ES, enquanto o valor médio de leucócitos 12.39x103/μl foi considerado um indicador de mau prognóstico. No estudo do DTC apenas um doente apresentou aumento da velocidade do fluxo cerebral na ACM igual a 196 cm/segundos, associado a vasculopatia grave. Os testes psicológicos alterados em 80% dos doentes mostraram ser o método mais sensível para detectar alterações do neurodesenvolvimento, mas sem correlação com os ES em 10% dos doentes. Realça-se a baixa percentagem de DTC patológicos encontrados neste estudo em relação ao número elevado de ES e de testes psicológicos alterados, não se verificando concordância entre os três exames. Dos indicadores de prognóstico estudados a -talassémia foi considerada um factor de protecção para o coeficiente de inteligência da escala de Wechsler. Em relação a parâmetros clínicos estudados os doentes com maior número de EVO, tem em média valores inferiores nos testes psicológicos. Estudo 3. Neste estudo verificou-se que o valor médio da HbF aumentou significativamente de 7,0±4% para 13,7±5,3% (p=0,028) ao fim de 15 meses de terapêutica com hidroxiureia. Clinicamente todos os doentes responderam significativamente com uma redução de 80% no número de EVO, 69% no número de internamentos, 76% no número de dias de hospitalização e 67% no número de transfusões. Deste modo comprovou-se não só a eficácia desta terapêutica neste grupo pediátrico como também a falta de efeitos secundários significativos. Considera-se a necessidade de estudos mais prolongados e em grande séries, para com segurança se usar a HU antes que a lesão orgânica se estabeleça, portanto logo nos primeiros anos de vida. Conclusão: Na amostra populacional estudada foram evidenciadas lesões pulmonares e cerebrais na grande maioria dos doentes que condicionaram a sua qualidade de vida. Foram identificados indicadores de prognóstico que poderão eventualmente ditar medidas terapêuticas precoces com o objectivo de diminuir a morbilidade e a mortalidade neste grupo etário. Demonstrou-se que a terapêutica com a HU foi eficaz e bem tolerada----------ABSTRACT: Background: Sickle cell anemia (SCA), a hereditary disease characterized by pain and lifetime multi-organic lesion, is a challenge for all that work with carriers of this disease. The clinical expression variability of SCA is a constant reality and a problem to be solved in the current world of investigation, for which the knowledge of prognostic indicators responsible for the different aspects of clinical evolution diversity wiil be an added value. The study is preceded by a historical summary of the most important factors in the evolution of SCA, which are in themselves, an incentive for future research. In the first part of the study, after an extensive bibliographical revision, physiopathology data is referred to in general and specifically regarding the target organs, that constituted the base for the studies presented in the dissertation. The state of the art for the complications to be studied, the choice of prognostic indicators and the therapeutics application, were approached for the renewed interest in the theme. Aims: In regard to the investigation, the objective was to study the lesions in the most affected organs of a chosen pediatric group, to investigate prognostic indicators for lung and cerebral lesions and to evaluate the protective effect of hydroxyurea in children with severe outcomes. Patients and methods: A prospective and multi-institutional study was carried out during a three-year period, February 1998 to March 2001, with children and adolescents followed up at a Immunohematology Outpatient Clinic of Dona Estefânia's Hospital, Lisbon. Based in predefined criteria, 30 children with SCA were selected in a stable phase of the disease, aged from seven to 18 years old, all of whom were of African origin with exception of one who was Caucasian. The diagnosis was based on electrophoresis techniques and molecular study that allowed to define the genotype, the presence of deletional alpha-thalassemia as well as haplotypes in the population. Different methodologies were used to evaluate the existence of lung and cerebral lesion. Statistical study of the different variables selected the prognostic indicators. In Study 1, to determine the existence of lung lesion two different methodologies were used: pulmonar function study with arterial blood gases determination; and high resolution computerized tomography. Heart dysfunction as a repercussion of lung lesion was also studied through echocardiography, and prognostic indicators were statistically significant for lesions found. The design of Study 2 was similar to Study 1, but with the appropriate methodology for CNS. After neurological examination, which was normal in all patients (control group), cerebral lesions were studied with imagiologic exams (MRN-CE and TCD) and psychological tests. These three methodologies were correlated and the importance of each one in the decision of the therapeutic profilactic attitudes. Study 3 consisted of a controlled prospective open study in children with severe forms of SCA, with the aim of the evaluating therapeutic effectiveness of hydroxyurea, during a period of 24 months. Results: In the global overall study preceding the Studies 1,2 and 3, there were a prevalence of haplotype Bantu (53%) and other risk factors, namely the number of VOC (87,5%), sequestration crisis (18,75%), dactilytis in first year of life(31,2%), hyperhemolysis crisis (50%) and ATC in more than half of the patients (59,38%). This group of bad prognostic indicators, associated with the population of the lower class according to the Graffar scale, demonstrates the importance of primary health care services, information provided to the children and their relatives, as well as the interest in prophylactic therapeutics, specific screening and prenatal diagnosis. Study 1. It was evident from this study that slight RPD was diagnosed in 70% of the patients, because alterations of the diffusion had no statistical significance and arterial blood gases determinations were normal. Only one patient had restrictive lung disease related with numerous ACS. However ACS was not considered a prognostic indicator for RPD, contrary to the number of EVO. HRTC revealed discreet fibrotic lines that could be related with slight RPD, but the lack of correlation of these two exams (33%) supports the value of lung function tests for precocious diagnosis of RPD. Heart dysfunction was found in 86,7% of patients, does not reflect the repercussion of RPD, but with the physiopathology of chronic anemia. Hematologic and clinical prognostic indicators were found. Good prognostic indicators for the non-evolution of RPD with average Hb values of ≥ 8,5 g/dl and average HbF values of ≥13%, respectively. The genetic and social-economic factors had no statistical significance; nevertheless, they were more prevalent among Bantu haplotype (53,3%) in patients with RPD. Study 2. RMN-CE detected SI in 33,3% of the patients, with preferential location in deep white substance in 26,6% and in front lobe in 20%. This distribution can be related to structural aspects of the brain and with the high sensibility of this organ to hypoxia. From the hematological parameters selected, average HbF value 8,6% and average leucocyte count 12.39x103/μl were prognostic indicators with different meaning to SI. The increase in the total bilirubin related to hyperhemolysis clinically explains the genesis of SI In the TCD study, only one patient had increased cerebral flow speed >196 cm/sec in CMA, which corresponded to serious vasculopathy in AngioMR. This patient never present previously neurological symptoms and had several hyperhemolysis crisis and VOC as risk factors. Low percentage of pathological TCD in this study, in relation to the high number of SI and altered tests, although without correlation among the three exams, is probably attributed to factors related to the methodology, aspects of cerebral physiopathology or perhaps a sign of good prognostic if the duration of study had not been so short. TCD should be used as a screening method in the age groups with higher risk of AVC and should never be considered separately in prophylactic therapeutics indication. Psychological tests were the most sensitive method to detect neurodevelopment impairment; in 80% of patients the neuropsychologics tests were altered, but without correlation with SI (10%). Since SI can become evident during the first two years of life and develop with time, the first psychological tests should be carried out between 3 and 5 years of age to timely be referred to special education and stimulation programs. Prognostic indicators to psychological tests were also found: alpha-thalassemia was found to be a protection factor of the IQ, just as other hematologic factors (hematocrit, MGCV and erythrocytes count). In relation to clinical parameters, although without statistical significance, patients with larger number of VOC had average lower scores versus the average in tests, except in TP. Results from different studies were conclusive as to the type of lesion found and the importance of prognostic indicators. Study 3. All the patients completed a minimum of 15 months therapeutic treatment with the final average daily dose of 19±4 mg/kg/day. The average value of the fetal hemoglobin increased significantly from 7,0±3,9% to 13,7±5,3% (p=0.028). The HbF average values increased from 6% to 15% after 15 months of therapeutic treatment. Clinically there was a reduction of 80% in the number of VOE , 69% in the number of hospitalization, 76% in the number of days of hospitalization and 67% in the number of transfusions. Once again the effectiveness of this treatment in this pediatric group, as well as the lack of any significant secondary effects, was evident. The study confirms the need for further detailed research in order to safely effect the appropriate treatment prior to the development of organic lesions, which ideally should be in the first year of life. Conclusions: These results allow us to clarify the importance of either pulmonary lesions or either nervous central system impairment among patients, children and adolescents, with sickle cell anemia. These lesions were demonstrated in most of the patients studied compromising their quality of life and the mortality. The treatment with HU is proved to be effective and having low toxicity.

Pulmonary adiaspiromycosis: report of two cases

Two cases of human pulmonary adiaspiromycosis are reported. Patients were 29 and 54-year-old males, farm workers, with "grippe-like" symptoms and radiographic findings suggestive of granulomatous interstitial disease. Transthoracoscopic and transbronchial biopsies were performed. Pulmonary function was measured by spirometry. One patient used ketoconazole. Possibility of misdiagnosed pulmonary adiaspiromycosis is emphasized.

Thyroid function and prevalent and incident metabolic syndrome in older adults: the Health, Ageing and Body Composition Study.

OBJECTIVE: Both subclinical hypothyroidism and the metabolic syndrome have been associated with increased risk of coronary heart disease events. It is unknown whether the prevalence and incidence of metabolic syndrome is higher as TSH levels increase, or in individuals with subclinical hypothyroidism. We sought to determine the association between thyroid function and the prevalence and incidence of the metabolic syndrome in a cohort of older adults. DESIGN: Data were analysed from the Health, Ageing and Body Composition Study, a prospective cohort of 3075 community-dwelling US adults. PARTICIPANTS: Two thousand one hundred and nineteen participants with measured TSH and data on metabolic syndrome components were included in the analysis. MEASUREMENTS: TSH was measured by immunoassay. Metabolic syndrome was defined per revised ATP III criteria. RESULTS: At baseline, 684 participants met criteria for metabolic syndrome. At 6-year follow-up, incident metabolic syndrome developed in 239 individuals. In fully adjusted models, each unit increase in TSH was associated with a 3% increase in the odds of prevalent metabolic syndrome (OR, 1.03; 95% CI, 1.01-1.06; P = 0.02), and the association was stronger for TSH within the normal range (OR, 1.16; 95% CI, 1.03-1.30; P = 0.02). Subclinical hypothyroidism with a TSH > 10 mIU/l was significantly associated with increased odds of prevalent metabolic syndrome (OR, 2.3; 95% CI, 1.0-5.0; P = 0.04); the odds of incident MetS was similar (OR 2.2), but the confidence interval was wide (0.6-7.5). CONCLUSIONS: Higher TSH levels and subclinical hypothyroidism with a TSH > 10 mIU/l are associated with increased odds of prevalent but not incident metabolic syndrome.