OBJETIVOS: Comparar as respostas do Teste de Esforço Cardiopulmonar (TECP) em imersão, numa esteira subaquáticas, com as de solo; investigar e entender o desempenho cardiorrespiratório de coronariopatas (DAC) durante esforço em imersão comparando-os aos do grupo de indivíduos saudáveis. Entender os procedimentos, materiais e equipamentos necessários na realização do teste em imersão e na coleta de dados reprodutíveis e confiáveis. MÉTODOS: O estudo contou com 40 indivíduos, sendo: 20 pacientes com diagnóstico médico de DAC, 63,7 ± 8,89 anos de idade e classificação I e II segundo New York Heart Association (NYHA) e 20 sujeitos saudáveis, 64,7 ± 7,09 anos; realizaram dois testes ergoespirométricos em uma instalação equipada com esteira no solo, piscina aquecida, esteira subaquática, analisador de gases e Eletrocardiograma (ECG). Foi calculado o Poder Estatístico do teste para ANOVA com erro beta de 0.861. Por ser um exame normatizado tecnicamente e reconhecidamente seguro, o primeiro teste foi realizado em esteira no solo de 3 a 7 dias deste, o segundo teste foi realizado em esteira subaquática com imersão ao nível do manúbrio, em uma piscina com temperatura controlada entre 33 e 34°C. Os dados foram coletados em 5 momentos expressivos: 1- Repouso; 2- Limiar Anaeróbio; 3- Ponto de Compensação Respiratória; 4- Esforço Máximo e 5- Recuperação. RESULTADOS: A análise de variância deste estudo revelou haver efeito principal para DAC nas variáveis: FC, VO2 e VCO2; (p > 0.01) em relação ao ambiente. O teste em imersão apresentou significância nas variáveis FC, VO2, VCO2 e VO2/FC (p > 0.01). As interações com estágio caracterizam o comportamento dos sujeitos ao longo do experimento e neste contexto, as variáveis PEB, FC, VO2, VCO2 e VO2/FC (p > 0.01) mostraram interações significantes entre estágio e ambiente. Em adição, há interação significante entre etiologia e estágio para as variáveis FC, VO2 e VCO2 (p > 0.01). DAC e saudáveis possuem comportamentos diferentes no decorrer dos estágios do experimento em relação a estas variáveis. Alterações eletrocardiográficas compatíveis com isquemia miocárdica ou arritmia não foram observadas e a Pressão Arterial Sistólica e Diastólica (PAS/D) não se alterou significativamente. Os indivíduos deste estudo tiveram percepção de esforço na Escala de Borg menor na água em todos os estágios do que em terra (p > 0.01). CONCLUSÃO: Os achados deste estudo mostram que os procedimentos operacionais, materiais e equipamentos utilizados no TECP em piscina produziram dados reprodutíveis, confiáveis e que atenderam as determinações estabelecidas no \"Clinician´s Guide to Cardioplulmonary Exercice Testing in Adults\". O esforço foi bem tolerado por todos os participantes, sem ocorrência de evento adverso. As diferenças estatísticas observadas nos testes na água contra os de solo nos levam a entender que o exercício em imersão pode ser realizado por pacientes com DAC e que os efeitos fisiológicos da imersão não causam qualquer risco para este grupo. Conclui-se também que por ser reprodutível e confiável, o teste em imersão pode ser adotado para prognosticar capacidades individuais de pacientes coronariopatas ao exercício dinâmico em piscina / OBJECTIVES: To compare responses to a Cardiopulmonary Exercise Test (CPX) conducted in water, (on a underwater treadmill), with the responses to the same tests conducted on land, (on a land treadmill); to investigate and assess the cardiorespiratory performance of coronary artery disease (CAD) patients while immersed in warm water when compared to the performance of healthy individuals; to assess the procedures, feasibility, resources and equipment required for conducting a CPX in individuals in water so as to collect reliable and replicable data. METHODS: The sample was comprised by 40 subjects, 20 of whom diagnosed with coronary artery disease (CAD) and aged 63.7 ± 8.89, functional class I and II (in compliance with the New York Heart Association [NYHA]), and 20 healthy subjects aged 64.7 ± 7.09. Two CPX tests were conducted in a facility equipped with a land treadmill, a warm pool, an underwater treadmill, a gas analyzer and an electrocardiogram (ECG) device. The statistical significances were calculated through a ANOVA test with (1 - beta) power of 0.861. As CPX is technically regulated and acknowledged as safe the first test was conducted on a land treadmill and the second test was conducted 3-7 days later on an underwater treadmill. Subjects were submerged in a temperature-controlled pool (33-34oC) with water at manubrium level. Data were collected at 5 relevant test stages or cardiorespiratory levels: 1- Rest; 2- Anaerobic Threshold (AT); 3- Respiratory Compensation Point (RCP); 4- Maximum Effort (ME); and 5- Recovery (R). FINDINGS: ANOVA analysis showed a major significance for CAD subjects regarding variables HB, VO2 and VCO2 (p < 0.01) in relation to the environment. The test performed with submerged patients showed some significance for variables HB, VO2, VCO2 and VO2/HB (p < 0.01). The stages for data collected featured the subjects performance throughout this experiment, and within the given context, variables RPE, HB, VO2, VCO2 and VO2/HB (p < 0.01) showed significant interactions between test stage and environment. Additionally, there was a significant interaction between the etiology and the test stage for variables HB, VO2 and VCO2 (p < 0.01). CAD patients and healthy subjects showed different performances throughout the test stages in relation to the referred variables. Electrocardiographic (ECG) changes that are compatible with myocardial ischemia or arrhythmia were not observed. Systolic and diastolic blood pressure (SDBP) did not show significant changes. The subjects of this study showed lower rates of Borg\'s perceived exertion scale in the water than at every one of the test stages on land (p < 0.01). CONCLUSION: This study show that the procedures, resources and equipment used during CPX conducted in a warm pool demonstrated to be feasible and yielded replicable and reliable data, which complied with the provisions of the \"Clinician´s Guide to Cardiopulmonary Exercise Testing in Adults\". The effort exerted was well tolerated by all the participants without any adverse events. Statistical differences observed in water versus on land allow us to conclude that patients with CAD are able to carry out physical activities in water and that the physiological effects of immersion do not present any risk for such patients. We may also conclude that given its replicability and reliability, CPX conducted in water may be used to diagnose and to estimate the exertion capability of CAD patients to perform dynamic exercise in a warm pool

INTRODUÇÃO: A sobrecarga hemodinâmica pulmonar (SHP) está associada a entidades clínicas de elevada morbimortalidade como: o edema pulmonar pós-pneumonectomia, o tromboembolismo pulmonar, o transplante pulmonar e a situações fisiológicas como o exercício físico. Vários pontos da sua fisiopatologia não estão elucidados. OBJETIVOS: Estudar as alterações fisiopatológicas pulmonares e cardíacas induzidas pela SHP. MÉTODOS: Vinte porcos Large White foram anestesiados, intubados e submetidos à ventilação mecânica a volume seguida por toracotomia bilateral trans-esternal. Os elementos dos lobos pulmonares foram isolados através de dissecção cirúrgica, com reparo das artérias pulmonares do lobo inferior direito, lobo mediastinal e pulmão esquerdo. Os animais foram randômicamente alocados em 4 grupos de estudo (n=5), sendo um controle (C) e três de SHP (LI, LII e LIII) induzida através da oclusão das artérias pulmonares específicas. No grupo C (controle), todos os lobos tiveram sua perfusão mantida. No grupo LI, somente o pulmão direito foi perfundido. No grupo LII, o pulmão direito menos o lobo inferior e no grupo LIII, o pulmão direito menos os lobos mediastinal e inferior, obstruindo a vasculatura pulmonar em 42, 76 e 82% respectivamente. Variáveis de hemodinâmica e de trocas gasosas foram monitoradas durante 60 minutos de SHP. Ao final do regime de SHP o lobo médio foi ressecado para análise de variáveis estruturais: morfometria (alveolar e vascular) e cálculo da relação peso úmido / peso seco. Na análise estatística foram utilizados ajustes de modelos lineares mistos com estrutura de variâncias e covariâncias, ANOVA a um fator, regressão linear simples e regressão linear de efeitos mistos com intercepto e tendência aleatório. RESULTADOS: Nas comparações intergrupos houve diferenças significativas ao longo dos 60 minutos de SHP nas variáveis hemodinâmicas: Frequencia cardíaca (p=0,004), Pressão arterial média (p=0,01), Índice sistólico (p=0,002), Pressão arterial pulmonar (p=0,001) e Pressão capilar pulmonar (p<0,0001). Trocas gasosas: Relação PaO2/FiO2 (p=0,002), PaCO2 (p<0,0001), pH (p<0,0001), Índice de consumo tecidual de O2 (p=0,02), Fração de shunt (p=0,03). Estruturais: Edemas alveolar e perivascular (p<0,0001) em ambos e Relação peso úmido / peso seco (p=0, 005). Nas comparações intergrupos, não houve diferenças significativas das variáveis: Índice cardíaco (p=0,94), HCO3 (p=0,63), Índice de oferta tecidual de O2 (p=0,89) e Taxa de extração tecidual de O2 (p=0,08). CONCLUSÕES: A SHP promoveu disfunção pulmonar significativa em pulmões previamente hígidos com alterações estruturais (edema alveolar e perivascular) e elevação das pressões arterial e capilar pulmonar. A função cardíaca foi preservada apesar de grande redução no leito vascular pulmonar (82% no grupo LIII). No grupo LII houve melhora da disfunção pulmonar ao longo do tempo de SHP / INTRODUCTION: The pulmonary hemodynamic overload (PHO) is associates to high mortality and morbidity clinical entities as: postpneumonectomy pulmonary edema, pulmonary thromboembolism, lung transplantation and physiological situations as physical exercise. Some pathophysiological aspects related to PHO are not elucidated. OBJECTIVES: To study pulmonary and cardiac pathopysiological alterations induced by PHO. METHODS: Twenty Large White pigs were anesthetized, intubated and subjected to volume controlled mechanical ventilation followed to median sternotomy. Pulmonary lobes structures were isolated by surgical dissection and pulmonary arteries of left lung, right lower lobe and mediastinal lobe were completely isolated. The animals were randomized into 4 groups (n=5 each) with one control (C) and three of PHO (LI, LII and LIII) induced by pulmonary arterial occlusions specifics for each group. In the control group (C), all lobes were perfused, ie none of arteries were occluded. In the LI group, only the right lung was perfused; in the LII group, the right lung but the lower lobe; in LIII group, the right lung but the lower and mediastinal lobes, obstructing the pulmonary vasculature in 42, 76 and 82% respectively. Hemodynamics and gas exchange variables were monitored during 60 minutes of PHO. At the end of the study, the middle lobe was resected for analysis of structural variables: morphometry (alveolar and vascular) and calculation of the wet weight / dry weight ratio. Statistical analysis settings were used with mixed linear models of variance and covariance structure, a one-way ANOVA, simple linear regression and mixed effects linear regression with random intercept and trend. RESULTS: In intergroup comparisons there were significant differences during the 60 minutes of PHO in hemodynamic variables: Heart rate (p=0, 004), Systemic arterial pressure (p=0,01), Systolic index (p=0,002), Pulmonary arterial pressure (p=0,001) and Pulmonary capillary pressure (p <0,0001). Gas exchange: for PaO2/FiO2 ratio (p=0,002), PaCO2 (p<0,0001), arterial pH (p<0,0001), O2 consumption index (p=0,02), Shunt (p=0,03). Structural: perivascular and alveolar edema (p<0,0001) in both and the wet weight / dry weight ratio (p=0,005). There were no significant differences in intergroup comparisons of variables: Cardiac index (p=0,94), arterial HCO3 (p=0,63), O2 offer index (p=0,89) and O2 extraction (p=0,08). CONCLUSIONS: The PHO promoted significant pulmonary dysfunction in previously healthy lungs with structural changes (alveolar and perivascular edema) and increased arterial and pulmonary capillary pressures. Cardiac function was preserved despite the large reduction in pulmonary vascular bed (82% in group LIII). In LII group occurred reverse of pulmonary dysfunction with past of PHO time

<p>Raloksifen je predstavnik selektivnih modulatora estrogenih receptora koji se koristi u terapiji osteoporoze i invazivnog oblika raka dojke u postmenopauzi. Raloksifen se relativno dobro resorbuje iz gastrointestinalnog trakta, ali pri prvom prolasku kroz jetru podleže biotransformaciji u značajnom procentu, &scaron;to je uzrok njegove niske biolo&scaron;ke raspoloživosti. Bioraspoloživost kod ljudi iznosi 2%, a kod Wistar pacova 39%. Različite supstance se koriste da bi se pobolj&scaron;ala bioraspoloživost lekova. Žučne kiseline, kao &scaron;to je deoksiholna kiselina, omogućavaju bolji prolazak kroz biolo&scaron;ke membrane drugim supstancama, te mogu povećati bioraspoloživost lekova. Apigenin je &scaron;iroko rasprostranjeni flavonoid koji inhibi&scaron;e različite metaboličke puteve i na taj način može usporiti metabolizam i eliminaciju i povećati koncentraciju lekova u krvi. Ciljevi ovog istraživanja su bili da se ispita da li apigenin i natrijum-deoksiholat mogu povećati bioraspoloživost raloksifena, njihov uticaj na biohemijske parametre i parametre hemostaze, kao i da se ispita antioksidativni potencijal apigenina. Ispitan je i uticaj apigenina na akutno o&scaron;tećenje jetre usled primene toksične doze paracetamola. U istraživanju su kori&scaron;ćeni zdravi, beli pacovi mu&scaron;kog roda, soja Wistar. U ogledu su ukupno kori&scaron;ćene 84 eksperimentalne životinje. Sva ispitivanja na životinjama je odobrila Etička komisija Univerziteta u Novom Sadu. Raloksifen je primenjen intravenski i per os, dok su natrijum-deoksiholat i apigenin aplikovani peroralno. Uzorci krvi, urina i fecesa su kori&scaron;ćeni za određivanje farmakokinetskih parametara, dok su za određivanje biohemijskih, hemostatskih i parametara oksidativnog stresa kori&scaron;ćeni serum i uzorci jetre laboratorijskih životinja. Pretretman natrijum-deoksiholatom je doveo do smanjenja koncentracije raloksifena u krvi zbog olak&scaron;anog i brzog prodora raloksifena u periferne kompartmane. Time je značajno produženo poluvreme eliminacije i srednje vreme zadržavanja raloksifena i značajno je povećan volumen distribucije raloksifena. Apigenin je doveo do manjeg pada koncentracije raloksifena u prvim satima nakon intravenske primene raloksifena, dok su koncentracije raloksifena bile značajno vi&scaron;e nakon osmog časa od primene leka. Uticaj raloksifena na biohemijske parametre je bio značajno veći nakon intravenske nego nakon peroralne primene. Nakon intravenske primene raloksifena je značajno povećana aktivnost enzima jetre, ALP, ALT, AST i GGT, dok su pokazatelji funkcije bubrega, urea, mokraćna kiselina i kreatinin bili sniženi. U grupama koje su pretretirane natrijum-deoksiholatom i apigeninom vrednosti ovih parametara bile su niže u odnosu na grupu tretiranu samo raloksifenom. Statistički najznačajniji uticaj je imala primena trojne kombinacije, raloksifena, natrijum-deosiholata i apigenina, koja je dovela do značajnog pada aktivnosti enzima jetre, i u odnosu na grupu tretiranu raloksifenom i u odnosu na kontrolnu grupu. Kod životinja tretiranih kombinacijom apigenina i paracetamola pokazatelji toksičnosti su bili značajno niži, naročito vrednosti ALT i ALP, u odnosu na grupu koja je dobijala samo paracetamol. Hepatotoksičnost izazvana toksičnom dozom paracetamola je potvrđena i histopatolo&scaron;kim promenama na jetri, koje nisu primećene u grupi životinja tretiranih kombinacijom apigenina i paracetamola. Ispitivanjem je utvrđeno da apigenin može da spreči paracetamolom indukovano povećanje nivoa MDA, &scaron;to ukazuje da apigenin pozitivno utiče na očuvanje integriteta ćelije. Aktivnost enzima CAT i GR u homogenatima jetre je bila značajno povećana nakon primene toksične doze paracetamola u odnosu na kontrolnu grupu. Aktivnost enzima CAT i GR u grupi tretiranoj kombinacijom apigenina i paracetamola je bila približna vrednostima u kontrolnoj grupi. Na osnovu rezultata istraživanja može se zaključiti da natrijum-deoksiholat i apigenin značajno utiču na farmakokinetiku raloksifena. Primena natrijum-deoksiholata dovela je do pada koncentracije raloksifena u krvi, značajnog prelaska raloksifena iz krvi u periferne kompartmane i povećanja njegovog volumena distribucije, dok je apigenin značajno usporio metabolizam i eliminaciju raloksifena i doveo do njegovog produženog zadržavanja u krvi. Natrijum-deoksiholat i apigenin su pokazali pozitivan uticaj na biohemijske parametre, parametre hemostaze i smanjenje nivoa oksidativnog stresa. Kombinacija natrijum-deoksiholata i apigenina je pokazala sinergistički uticaj na navedene parametre, odnosno dovela je do značajnih promena u odnosu na pojedinačnu primenu ovih supstanci. Rezultati ispitivanja ukazuju na to da apigenin smanjuje stepen lipidne peroksidacije i da dovodi do značajnog povećanja enzimskih antioksidantnih mehanizama odbrane kod pacova kod kojih je hepatotoksičnost indukovana paracetamolom.</p> / <p>Raloxifene is selective estrogen receptor modulator used in treatment of osteoporosis and invasive breast cancer in postmenopausal women. Raloxifene is well absorbed from the gastrointestinal tract, but undergoes extensive first-pass metabolism, which results in very low bioavailability of raloxifene, 2% in humans, and 39% in Wistar rats. Various supstances are used for increasing bioavailability of other drugs. Bile acids, such as deoxycholic acid, promote transport of other supstances through biological membranes, and consequently, may increase their bioavailability. Apigenin is a widespread flavonoid, which inhibits different metabolic pathways. Thus, apigenin can slow down metabolism and elimination of drugs, and raise drug concentration in blood. Aims of this study were to investigate if apigenin and sodium deoxycholate could increase bioavailability of raloxifene, their influence on biochemical and hemostasis parameters, and to investigate antioxidative potential of apigenin. Furthermore, influence of apigenin on acute liver damage after toxic dose of paracetamol was examined. In vivo experiments were performed on 84 laboratory healthy male Wistar rats. All experiments were approved by Ethics Committee of University of Novi Sad. Raloxifene was applied intravenously and per os, while sodium deoxycholate and apigenin were given perorally. Blood, urine and feces samples were used for pharmacokinetic parameters measurement, whereas serum and liver samples were used for evaluation of biochemical, hemostasis and oxidative stress parameters. Pretreatment of sodium deoxycholate led to raloxifene blood concentration decrease due to easier penetration of raloxifene in peripher compartments. As a result, raloxifene half-life and mean residence time were significantly longer and volume of distribution was increased. Apigenin caused lower decrease in raloxifene concentration in first few hours after raloxifene intravenous application, while raloxifene concentrations after apigenin pretreatment were significantlny higher 8 hours after raloxifene application. Influence of raloxifene on biochemical parameters was more significant after intravenous than after per os application. Intravenous application of raloxifene led to increased activity of liver enzymes, ALP, ALT, AST and GGT, while parameters of kidney function, urea, uric acid and creatinine were decreased in comparison to the control group. In experimental groups pretreated with sodium deoxycholate and apigenin these parameters were lower than in the group treated only with raloxifene. Statistically the most significant effects were in the group treated with combination of raloxifene, sodium deoxycholate and apigenin, which caused significant decrease in activity of liver enzymes compared both with raloxifene and control group of animals. In experimental animals treated with combination of apigenin and paracetamol bioindicators of paracetamol toxicity were significantly lower, especially activity of ALT and ALP, in comparison to the group treated only with paracetamol. Hepatotoxicity induced by toxic dose of paracetamol was also confirmed by histopathological alterations in liver, which were not observed in the experimental group treated with combination of apigenin and paracetamol. In this study it was confirmed that apigenin could prevent paracetamol-induced MDA level increase, which suggests that apigenin have positive effects on cell integrity. Activity of CAT and GR in liver homogenates was significantly increased after toxic dose of paracetamol in comparison to the control group, while activity of these enzymes in the group treated with apigenin and paracetamol was similar to values in the control group. Results of this study showed that sodium deoxycholate and apigenin can significantly change pharmacokinetic parameters of raloxifene. Sodium deoxycholate caused signicant decrease in raloxifene blood concentration, extensive distribution from blood to peripheral compartments and increase of raloxifene volume of distribution. Apigenin inhibited metabolism and elimination of raloxifene and thus prolonged half-life and mean residence time of raloxifene. Sodium deoxycholate and apigenin showed positive effects on biochemical and hemostasis parameters and decreased the level oxidative stress. Combination of sodium deoxycholate and apigenin showed synergistic effects on these parameters in comparison to effects of separate application of sodium deoxycholate and apigenin. The result of our study indicates that apigenin inhibits the level of lipid peroxidation and significantly increase the enzyme antioxidant defence mehanisms in paracetamol induced hepatotoxicity in rats.</p>

In title 12, 22, 11 are in subscript. / Thesis (PhD)--Stellenbosch University, 2002. / ENGLISH ABSTRACT: The aim of this study was to test a synthetic protein-free surfactant preparation, LPM-l, with the same chemical composition as commercially available Exosurf (Glaxo Wellcome), but containing in addition, a sugar, trehalose (TRE). Towards this end, a study was designed to firstly test the hypothesis that the true difference in acute physiological effects between a mixture of oppe, tyloxapol, hexadecanol and trehalose (LPM-l), and Exosurf, (Oppe, tyloxapol and hexadecanol) is zero, in a surfactantdeficient animal model. A second study addressed the physiological effects of oppe, hexadecanol, tyloxapol and trehalose (LPM-l) compared to treatment with trehalose (TRE) or saline, in order to determine (1) the contribution of TRE to the mixture of oppe, hexadecanol and tyloxapol, and (2) to assess the effect of the LPM-l surfactant replacement on the epithelial lining fluid composition by means of analysing bronchoalveolar lavage fluid. Thirdly, the effects of TRE and / or calcium were studied on the surface properties of oppe suspensions, by in vitro analysis using the ring detachment method of Du Nouy The in vivo research comprised of two studies, performed in randomised controlled fashion. In the first study, 24 New Zealand White adult rabbits were randomised into 4 groups, while in the second study, 15 animals were randomised into 3 groups. In the first in vivo study, three synthetic surfactants, LPM-l, Exosurf and LPM-2, and a saline group were tested. LPM-l is a new formulation that consists ofa mixture of Df'PC, TRE, hexadecanol and tyloxapol. LPM-2 is a formulation with a composition equivalent to that of commercially available Exosurf, prepared on site. In both studies animals were subjected to repeated lavage with large volumes of warm saline (25 ml/kg) in order to establish surfactant deficiency and acute lung injury. Five minutes after the last lavage, vehicle, i.e. surfactants LPM-l, Exosurf, or LPM-2, or saline, in the first in vivo study, and LPM-l, TRE or saline in the second in vivo study, was instilled, and the course of the animals followed over the next 3 hours. Ventilator settings were standardized before and after lavage. The effects of surfactant treatment on gas exchange (arterial Pa02, oxygenation index (Ol), arterial-alveolar oxygen (a/A) ratio), percentage calculated shunt, and total dynamic respiratory compliance (CRSdyn), and histopathological changes were compared with changes in saline treated controls. Arterial blood gases in 100% oxygen and CRSdynwere measured before and after lavage, at 15 minute intervals for the first 30 min, then at 60, 90, 120, and 180 min after vehicle instillation. Oxygenation improved to a similar extent after LPM-l and Exosurf instillation, surpassing that of LPM-2 or saline. Overall, intratracheal instillation of both Exosurf and LPM-l, rapidly improved the gas exchange and reduced the intrapulmonary shunt, but did not restore the lung to its pre-lavage condition. From the 2nd in vivo study it was evident that trehalose-only, was inefficient as a lung surfactant, failing to improve oxygenation indices or the calculated percentage shunt, or influencing respiratory compliance. The addition of the sugar, trehalose (TRE), to the on-site 'Exosurf mixture (LPM-2) brought the activity of the resultant LPM-l to the same level as that of commercial Exosurf, but failed to raise the activity above that of Exosurf. These physiological improvements were sustained for up to 3 hours. Saline-treated animals had no improvement in gas exchange despite management with variable PIP (to maintain a tidal volume of -1 0 ml / kg) and constant PEEP of 5 cm H20. In-vitro results, obtained by the Ou Nouy tensiometer, showed higher mean ordinate surface tension values for the OPPC-only and DPPC + TRE mixtures, and the slopes of their respective graphs smaller in magnitude than those of the other formulations, suggesting that these formulations had less surface tension-lowering capability than the other surfactants. At 20°C (20 mg / ml DPPC-surfactants) the mean ordinate values of OPPC and OPPC + TRE, 70.13 and 69.47 dyne / cm, respectively, were not significantly different from each other. The mean ordinate values of LPM-l and the formulation containing OPPC + TRE + tyloxapol + CaCh were lower, but similar, as were the values of LPM-2 (on-site Exosurf) and LPM-2 + CaCho Thus, three internally homogeneous subgroups could be identified which differed significantly, namely: DPPC and DPPC + TRE, LPM-2 and LPM-2 + CaCh, and DPPC + TRE + tyloxapol + CaCh and LPM-l. Similar conclusions apply to the ordinate values of the surfactants at 37°C, and to the mean slope values at 20°C, with the exception that the subgroups, LPM-2 and LPM-2 + CaCh, and LPM-l and OPPC + TRE + tyloxapol + CaCh are not so clearly separated. A similar analysis of mean slope values was performed. Here too a significant difference between substances was found, OPPC alone or in combination with TRE, again being significantly different from the other surfactants. The most prominent light microscopy findings of the lungs of animals included general lymphatic dilatation, congestion and lung polymorphonuclear infiltration, with no difference between study groups. Hyaline membranes were present in all surfactant groups, but significantly more so in the saline treated group. In the first in vivo study, the presence of neutrophils in the lung interstitiwn as well as alveoli, was a common finding in all of the study groups towards the end of the study protocol. A significant increase in the BAL-fluid neutrophil count occurred in all animals, concurrent with a significant decrease in the BAL macrophage count. No significant change occurred in the peripheral neutrophil count during the 3-hour study, suggesting recruitment of neutrophils from storage pools. Treatment with synthetic surfactant (LPM -1) did not have a significant effect on modifying the inflammatory response, since there was no significant difference in the BAL-derived cell counts between the LPM-1 and -saline groups. Epithelial damage was a consistent finding in all groups. The damage was more evident by electron microscopy examination and included hydropic changes, most readily observed in the mitochondria. The airspaces of study subjects showed the presence of oedema fluid. This luminal oedema appeared to be more prominent in the control group and LPM-2 (on site 'Exosurf') group. Organellar debris, probably originating from lysis of epithelial cells, was present, despite treatment with synthetic surfactant. The electron microscopical appearance of the epithelial-lined substance ("hyaline membranes") in the present study showed a marked variability within groups as well as within the same case. The majority of cases showed a mix of membrane types with both granular and fibrillar materials present within the same membrane. In some cases there were layering of the membranes into distinct bands. The instillation of LPM-l resulted in the formation of a slightly different type of epithelial lining fluid after lavage, when compared to the prelavage composition. The most pronounced changes occurred within the fatty acids, whilst the phosphatidylcholine values remained unchanged. Palmitic acid concentrations (C16:0) increased significantly, suggesting enrichment of the epithelial lining fluid after instillation of LPM-l. This increase in C16:0 was concurrent with significant decreases in the percentage C16:1, C18:0, and C18:2. In contrast to previous studies, we describe higher levels for phosphatidyldimethylethanolarnine (PEA). An explanation may be that the lipid identified as PEA, was in fact partly phosphatidylglycerol (PG)-a lipid whose accurate identification was precluded for technical reasons. After surfactant instillation, the PC/SM ratio, a reflection of the lecithin / sphingomyelin (LIS), decreased significantly in the TRE-group between the first and final lavage, but remained statistically unchanged in the animals treated with LPM-l or saline. The change in ratio was mainly accounted for by a decrease in BAL-fluid PC content together with a rise in SM content. A poor correlation existed between the BAL-derived PC/SM ratio and indices reflecting oxygenation status (a/A ratio, Ol), as well as the CRSdynat the time of the final lavage. In conclusion, the primary hypothesis was accepted, LPM-l performed similarly to Exosurf in vivo, improving oxygenation, but not CRSdyn.None was clearly superior to the other. Some questions remain. The reason why LPM-l (LPM-2 + TRE) did not behave in a superior manner, in vivo, to Exosurf, is partly unclear. This finding was somewhat surprising since the chemical composition of Exosurf and LPM-2 did not differ, and the addition of TRE to LPM-2 (on-site Exosurf), did improve the in vivo activity of the resultant LPM-l, above that of LPM-2. A possible explanation for observed differences in performance include methodological issues, i.e. the preparation of the on-site formulations, especially that of LPM-2 (on-site Exosurf), may differ from the way in which true commercial Exosurf is prepared. / AFRIKAANSE OPSOMMING: Die doel van die studie was om 'n sintetiese proteïn vrye surfaktant te ontwikkel en die produk te vergelyk met 'n kunsmatige surfaktant reeds in kliniese gebruik. Die bekende uit die literatuur en die onbekende van die produk wat evalueer sou word, lei op tot die samestelling van die nul hipotese van die PhD naamlik dat geen verskil in longfunksie sou gewys word tussen die toetsproduk en reeds gebruikte kommersiële surfaktant nie. Die hipotese was dat 'n suiker (trehalose), in kombinasie met Dipalmitoiel fosfatidielcholine (DPPC), gaswisseling en longfunksies sal verbeter vir 'n long met 'n lae surfaktant konsentrasie. Vir die studie is jong volwasse wit New Zealand konyne gebruik en is hulle met 'n gestandaardiseerde en menslike manier gebruik in eksperimentele werk. Die diere is onder intraveneuse narkose geplaas en verskillende kardiovaskulêre en pulmonologiese aspekte is gemeet. Die long surfaktant is uitgewas deur middel van fisiologiese soutoplossing wat tot liggaam temperatuur verhit is en daarna is die diere prospektief gerandomiseer tot eksperimentele groepe. Met vooraf bepaalde tydsintervalle is die fisiologiese metings herhaal en was die metings toegespits daarop om longmeganiese funksie en gasoordrag vermoë te evalueer. Lig mikroskopiese en elektron mikroskopiese studies is ook op die longe gedoen en verder is brongoalveolêre vloeistof ook ontleed. Die groepe met ondersoek was: I. oppe, heksadekanol, tyloxapol en trehalose (LPM-I). 2. oppe, heksadekanol, tyloxapol (LPM-2 :. LPM-I sonder trehalose). Hierdie is 'n proteïnvrye surfaktant plaaslik berei ( dieselfde samestelling as Exosurf). 3. Exosurf®. (Kommersiële preperaat reeds in gebruik). Hierdie is 'n proteïnvrye sintetiese surfaktant. 4. Trehalose, 'n non-reduserende disakklaried van glukose. Addisioneel is daar ook in vitro studies gedoen waann die oppervlakte spanmngs aktiwiteite van die verskillende surfaktant oplossings vergelyk is. Die statistiese analise is gedoen in samewerking met Prof. J. Maritz wat 'n unieke metode ontwikkel en gepubliseer het om herhalende veranderlikes op 'n statisties verantwoordbare manier te ontleed. In die eerste van die studies, is LPM-I, Exosurf®, fisiologiese soutoplossing en 'n plaaslik bereide "Exosurf" (LPM-2), met 'n chemiese samestelling identies aan dié van kommersiële Exosurf®, evalueer. In 'n tweede studie is die fisologiese effekte van LPM-I vergelyk met trehalose of fisiologiese soutoplossing om die volgende te ondersoek: 1) Die bydrae van trehalose tot 'n mengsel van oppe, heksadekanol en tyloxapol (LPM-2). 2) Die gevolg van LPM-l surfaktant toediening op die konyn se brongo-alveolêre vloeistof samestelling. 'n Derde, in vitro studie, het die oppervlaktespannings-effekte van trehalose en of kalsiumbyvoegings tot DPPC-oplossings gemeet deur middel van die ring metode van Du Nouy, In die eerste in vivo studie verbeter oksigenasie en persentasie longaftakking tot dieselfde mate na LPM-l en Exosurf® toediening en word die hipotese van die proefskrif bevestig. In die breë gesien, is die tydsprofiele van LPM-l en Exosurf® ten opsigte van oksigenasie en persentasie longaftakking statisties betekenisvol beter en van 'n sneller aard, as die tydsprofiele van dieselfde indekse na die toediening van fisiologiese soutoplossing of LPM-2. Die tydsprofiel van dinamiese longvervormbaarheid, na die toediening van LPM-I of Exosurf®, is dieselfde, maar betekenisvol beter as die vervormbaarheid na toediening van LPM-2 of fisiologiese soutoplossing. Alhoewel die oksigenasie indekse in die geval van LPM-l en Exosurf® betekenisvol verbeter oor die studietydperk, vind volkome herstel tot die basislynwaardes (voor spoeling) nie plaas nie. Bykomend, geen van die surfaktante het na toediening enige noemenswaardige verbetering in longvervormbaarheid tot gevolg gehad nie. Die rede vir die swakker vertoning van LPM-2 en Exosurf is onbekend en sal in opvolg studie ondersoek word. In die tweede in vivo studie is dit duidelik dat trehalose op sy eie, 'n oneffektiewe surfaktant is aangesien die preperaat na toediening geen verbetering teweegbring ten opsigte van oksigenasie indekse, persentasie longaftakking, of long-dinamiese vervormbaarheid nie. Die toevoeging van trehalose tot LPM-2, om LPM-l te lewer, neem wel die aktiwiteit van LPM-l tot dieselfde in vivo vlak as dié van kommersiële Exosurf®, maar slaag nie daarim om 'n hoër fisiologiese in vivo aktiwiteit as dié produk te bereik nie. Die diere wat met fisiologiese soutoplossing behandel is toon geen verbetering in enige fisiologiese parameter nie. Die in vitro resultate wat verkry is deur die Du Nouy tensiometer toon hoër gemiddelde ordinaat oppervlaktespannings waardes vir 'n formule wat slegs uit DPPC bestaan, asook vir 'n mengsel van DPPC + trehalose. Die helling van die grafieke van hierdie oplossings is ook kleiner as die van die ander formulas wat daarop dui dat DPPC op sigself, en DPPC + trehalose, weinig vermoë het om oppervlaktespanning te verminder. Daarteenoor verlaag die volgende oplossings die oppervlaktespanning ten opsigte van gedistilleerde water betekenisvol en wel in In konsentrasie afhanklike manier by beide 21°C en 3rc: LMP-I-, LPM-2-, DPPC + trehalose + tyloxapol + CaCf2-, en LPM-2 + CaCf2. Die prominentste ligmikroskopiese bevindinge van die longe van die diere sluit in: Algemene limfvat dilatasie, stuwing, en long neutrofiel infiltrasie. Betreffende hierdie histologiese bevindinge is daar geen verskille aangetoon tussen die groepe nie. Hialienmembrane was teenwoordig in al die groepe, maar betekenisvol meer in die groep wat fisiologiese soutoplossing ontvang as vervangingsterapie. In die tweede in vivo studie is daar 'n betekenisvolle styging in die neutrofiel- en daling in makrofaagtelling, van die brongoalveolêre vloeistof spoeling in al drie die groep aangetoon. Terselfdertyd vind geen noemenswaardige daling in die perifêre (sistematiese) neutrofieltelling plaas nie. Hierdie bevindinge dui daarop dat die brongoalveolêre selveranderinge toegeskryf kan word aan verwerwing van neutrofiele vanuit 'n longstoringspoel eerder as rekrutering vanuit die sistemiese sirkulatoriese poel. Surfaktant (LPM-l), behandeling het geen betekenisvolle vermindering in long inflammasie teweeggebring nie. Epiteelskade was 'n algemene ligmikroskopiese bevinding in al die groepe. Die samestelling van die brongoalveolêre vloeistof verander na installering van LPM-I. Die prominentste verandering word waargeneem in die vetsuur samestelling terwyl die DPPC waardes onveranderd bly. Die vetsuur, palmitiensuur (palmitic acid), (CI6:0), verhoog betekenisvol na toediening van LPM-l. Daarteenoor verminder die konsentrasie van C16:1, C18:0 en C18:2. In kontras met vorige studies, beskryf die huidige studie hoër konsentrasies van fosfatidieletanolamien, moontlik as gevolg van tegniese verskille in die metingsmetodes. 'n Betekenisvolle verlaging in die fosfatidielcholine:sfingomiëlien (PC/SM) verhouding word waargeneem tussen die eerste en die finale longspoeling van die trehalose-groep, terwyl dit onveranderd bly in die diere wat LPM-1 of fisiologiese soutoplossing ontvang.

Thesis (PhD)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: Although the effect of inhaled corticosteroids (ICS) on the hypothalamic- pituitary-adrenal axis (HPA) has been regarded as a “benign physiological response”, a survey published in 2002 suggested that adrenal crisis is more common in asthmatic children on ICS than previously thought. Relying on clinical features to detect chronic adrenal insufficiency secondary to corticosteroids may not be wise, as these are non-specific and can therefore easily be missed. Accurate biochemical assessment of the whole axis to detect subclinical HPA suppression (HPAS) is thus desirable. A review of the literature indicates that basal adrenal function tests, including plasma cortisol profiles, do not identify which children can appropriately respond to stress. There is no evidence to suggest that the degree of the physiological adjustment of the HPA to ICS and/or nasal steroids (by reducing basal cortisol production), predicts HPAS. Cortisol profiles should therefore only be used to demonstrate differences in systemic activity of various ICS and delivery devices. Only two tests, considered as gold standard adrenal function tests [the insulin tolerance test (ITT) and the metyrapone test] can assess the integrity of the whole axis. / AFRIKAANSE OPSOMMING: Die outeurs van ´n opname wat in 2002 gepubliseer is stel voor dat ´n bynierkrisis meer algemeen by asmatiese kinders, wat inhalasie kortikosteroïede ontvang, voorkom as wat voorheen gedink is. Dit is strydig met die gevestigde opvatting dat die effek van IKS op die hipotalamiese-hipofise-bynier-as (HHB) ’n “goedaardige fisiologiese reaksie” is. Die kliniese kenmerke van kroniese bynierontoereikendheid sekondêr tot die gebruik van kortikosteroïede (KS) is nie-spesifiek en gevolglik onbetroubaar. ´n Akkurate biochemiese toets van subkliniese HBB onderdrukking (HHBO) sou gevolglik waardevol wees. ´n Literatuur oorsig toon dat toetse van basale bynierfunksie, insluitend plasma kortisol (K) profiele, nie kinders uitken wat toepaslik op stres sal reageer nie. Daar is geen bewyse dat die graad van fisiologiese aanpassing van die HHB, soos aangedui deur laer K-vlakke, na die gebruik van IKS en/of nasale steroïede (NS), HHBO voorspel nie. Serum K profiele is dus slegs van waarde om die sistemiese aktiwiteit van verskillende IKS en toedieningsstelsels te ondersoek. Slegs twee toetse, naamlik die insulien toleransie toets (ITT) en die metyrapone -(MTP)-toets (wat beide as die goue standaard van bynier funksie beskou word), kan die integriteit van die hele as meet. / Stellenbosch University / Medical Research Council / SA Thoracic Society / Harry Crossley Foundation / Red Cross Children’s Hospital.

A linfangioleiomiomatose pulmonar é uma enfermidade cística progressiva que afeta mulheres jovens e cuja sobrevida média estimada em algumas casuísticas é de cerca de dez anos após o diagnóstico. A deterioração da função pulmonar é uma de suas principais características e resulta em dispnéia progressiva e hipoxemia grave nos casos avançados. O esforço físico é um desencadeador de dessaturação e correlaciona-se com a progressão funcional da doença. Assim como o esforço, o sono é um importante momento fisiológico durante o qual o sistema cardiorrespiratório dessas pacientes pode ser estressado. A partir da ocorrência de hipoxemia durante o sono ao longo dos anos pode surgir elevação progressiva da pressão na circulação pulmonar, resultando em cor pulmonale. Com o intuito de estudar o comportamento da saturação de oxigênio durante o sono e sua correlação com variáveis funcionais respiratórias estáticas e dinâmicas e de qualidade de vida, foram avaliadas consecutivamente 21 pacientes com diagnóstico de linfangioleiomiomatose pulmonar (LAM) atendidas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no período de março de 2005 a dezembro de 2007. Todas as pacientes realizaram polissonografia completa (PSG), prova de função pulmonar (PFP), teste de caminhada de 6 minutos (TC6M) e responderam aos questionários de Berlim, Epworth e SF-36, após assinatura de termo de consentimento livre e esclarecido. Verificou-se que a idade média das pacientes foi de 38 8 anos ao início dos sintomas, 41 10 ao diagnóstico e 45 11 anos à realização dos testes. O sintoma clínico mais freqüente foi dispnéia aos esforços, presente em 20 das 21 pacientes. Funcionalmente as pacientes apresentavam um padrão obstrutivo leve (%VEF1 72% e VEF1/CVF 0,68) com redução moderada da DLCO (48% predito). Das 21 pacientes, 14 apresentaram queda da saturação de hemoglobina abaixo de 90% durante a PSG. O tempo médio de queda da saturação foi de 2 horas e 25 minutos, com os principais períodos de dessaturação ocorrendo durante o sono REM e de ondas lentas. Estes caracterizaram-se por períodos de hipoventilação, sem aumento do índice de apnéia-hipopnéia (mediana IAH = 1,7). As principais variáveis que se correlacionaram através do teste de Pearson com a dessaturação abaixo de 90% durante o sono foram o delta de dessaturação durante o TC6M (r = 0,57), o %VEF1 (r = -0,80), %CVF (r = -0,80) e %DLCO (r = - 0,64) em relação ao predito, todas com p < 0,01. A partir da estratificação pela ocorrência de SpO2 < 90% durante a PSG e análise pelo teste de Wilcoxon, evidenciou-se que além das variáveis acima a relação VR/CPT mostrou-se significativamente diferente do ponto de vista estatístico (p = 0,04) nos grupos com e sem hipoxemia noturna. Em relação à qualidade de vida observou-se redução em todos os domínios particularmente quanto aos aspectos emocionais nas pacientes com hipoxemia noturna. O ecocardiograma evidenciou ocorrência de hipertensão pulmonar em cinco pacientes. Verificou-se com esse estudo pela primeira vez a ocorrência de hipoxemia durante o sono em pacientes com LAM. A hipoxemia noturna, apesar de não rotineiramente avaliada nessa população de pacientes, correlacionou-se com aspectos corriqueiramente avaliados no seguimento ambulatorial dessas pacientes como parâmetros da PFP e do TC6M, além de indicar uma tendência a prejuízo da qualidade de vida avaliada pelo SF-36. / Pulmonary lymphangioleiomyomatosis (LAM) is a progressive cistic lung disease of unknown etiology and no established medical treatment. It basically occurs in child bearing age women and its mean survival is about 10 years in some case series. LAM is caractherized by pulmonary function deterioration: obstructive pattern on espirometry and progressive impairment on DLCO capacity which results in rest dyspnea and hypoxemia in advanced cases. Exercise is an important factor that causes hypoxemia in this set of patients and correlates with progressive functional impaiment. Sleep is also another important physiologic moment when cardiorespiratory system may be stressed in these patients, leading to chronic hypoxemia though the years. This phenomenum may be responsible by cor pulmonale observed in advanced stages of LAM. In order to study hemoglobin saturation by oxygen during sleep and its correlation with lung function test (LFT), six minute walk test (6MWT), ecocardiography and SF-36 quality of life variables, 21 consecutive patients with LAM from Hospital das Clínicas University of São Paulo Medical School were evaluated from march 2005 to december 2007. All patients performed full polysomnography (PSG), lung function test, 6MWT and answered Berlim, Epworth and SF-36 quality of life questionnaire. Mean age at beginning of symptoms was 38 8 years, 41 10 years at diagnosis and 45 11 years by the time of the protocol. Dyspnea during routine daily activities was the most frequent symptom (20 / 21). LFT yielded mild obstruction (% FEV1 = 72%; FEV1/FVC = 0,68) and moderate impairment in DLCO (48%). Fourteen patients presented desaturation with SpO2 lower than 90% on PSG. Mean time with SpO2 lower than 90% was 2 hours and 25 minutes (mainly during REM and S3 and S4). Median apnea-hipopnea index (AHI) was 1,7 (normal). Pearson and Spearman correlations yielded that the main variables related to desaturation below 90% on PSG with p < 0.01 were: Desaturation on TC6M rs = 0,57 Spearman %FEV1 r = -0,80 Pearson %FVC r = -0,80 Pearson %DLCO rs = -0,64 Spearman After that, functional variables were stratified by SpO2 < 90% during PSG. Wilcoxon test showed that besides all 4 previous variables RV/TLC (p=0.04) was also statistically different between patients who did and did not desaturate. SF-36 yielded impairments in all domains, particularly in emotional aspects among patients who desaturated on PSG. Heart ecocardiography detected pulmonary hypertension in 5 patients. Our study found out for the first time that patients with LAM desaturate during sleep. Although pulmonary function variables are related to sleep desaturation, desaturation occured even in patients with mild or no impairments in lung function. 6MWT desaturation ,but not distance walked, correlated to sleep desaturation. SF-36 analysis yielded impairments in all domains of quality of life, particularly in emotional aspects in patients who desaturated.

Além do comprometimento motor, os pacientes com Distrofia Muscular de Duchenne cursam com queda da função respiratória que está associada à fraqueza muscular. O objetivo do estudo foi avaliar a evolução da função pulmonar e a força dos músculos respiratórios em diferentes estágios da doença, comparando-os com o tempo e idade de início da corticoterapia e com o quadro motor. A função pulmonar e as pressões respiratórias de 87 pacientes com idade entre sete e 23 anos foram avaliadas durante dois anos, totalizando cinco visitas para função pulmonar e três para as pressões respiratórias. Além disto, parte da amostra (n: 21) completou três avaliações de função pulmonar com aproximadamente um ano de intervalo. Para a comparação, considerouse: idade cronológica; idade de início e tempo de duração da corticoterapia, e se o paciente deambulava ou não. Na avaliação transversal, observou-se que em valores absolutos a CVF, o VEF1 e a PImáx, mantiveram-se até a faixa etária de 13 a 14 anos e a PEmáx até nove a 10 anos; em valores relativos (aos valores de pacientes saudáveis) notou-se queda constante da função pulmonar e das pressões respiratórias. No acompanhamento longitudinal, a função pulmonar e a força muscular respiratória mostraram aumento em valores absolutos, principalmente nos pacientes deambuladores, sendo este aumento influenciado pelo crescimento; em valores relativos houve manutenção pelo período de dois anos. Em conclusão, durante o tempo de estudo, a corticoterapia pode ter contribuído para o retardo da progressão da doença, através da intervenção na musculatura respiratória da mesma forma que atua na musculatura proximal dos membros. O tempo e a idade de início do medicamento não mostraram relação clara com a manutenção da função respiratória, porém o início da corticoterapia abaixo de sete anos de idade parece ser mais efetivo para a preservação da força dos músculos respiratórios e da função pulmonar / Besides motor impairment, patients with DMD show loss of respiratory function which one is associated to muscle weakness. The aim of the study was to evaluate the pulmonary function evolution and the respiratory muscle strength in different stages and then to compare them to duration and initial age of corticostheroids treatment age as well as the function motor. The pulmonary function and the maximal respiratory pressure of the 87 patients aged 7-23 years were evaluated over the course of two years. The patients\' pulmonary function was assessed over five visits and their maximum respiratory pressure was assessed during three visits. Moreover, the sample (n = 21) completed three assessments of lung function with approximately one year apart. For comparison, we considered: chronological age, age of onset and duration of corticosteroid therapy, and if patient were ambulant or not. In the transversal evaluation we noticed that CVF, VEF1and PImax in absoluts values showed no changes until age of 13-14 years and no changes for the PEmax until age of 9-10 years. In predicted for their actual height values we noticed a constant decline for loss of pulmonary function and maximal respiratory pressure. In the longitudinal follow, the pulmonary function and the respiratory muscle strength raised in absolutes values, mainly in ambulatory patients due to the growth. In relatives values the pulmonary function and maximal respiratory pressure showed stability for 2 years. In conclusion, during the study, corticosteroid treatment may have contributed to the delay of disease progression, through intervention in the respiratory muscles in the same way that acts in the proximal muscles of limbs. Both time and the initial age of corticosteroids treatment didn´t show relationship with respiratory function. But the beginning of corticosteroids bellow seven years old seems to be more effective for preserving respiratory muscle strength and pulmonary function

Introdução: Indivíduos obesos e pacientes asmáticos eutróficos apresentam, frequentemente, hiperinsuflação dinâmica (HD) e redução da capacidade de exercício. No entanto, não há estudos que tenham investigado a causa da redução da tolerância ao exercício em asmáticos obesos. Objetivo: Verificar os fatores limitantes do exercício físico em asmáticos obesos. Métodos: Esse estudo transversal incluiu mulheres asmáticas com obesidade grau II (G-Ob; IMC 35,0 - 39,9 kg/m2) e não obesas (G-NOb; IMC 18,5 - 29,9 kg/m2). Os pacientes realizaram um teste cardiopulmonar máximo para verificar a potência aeróbia (VO2 pico) e um teste submáximo para avaliar a HD. Medidas antropométricas, força e endurance muscular do quadríceps e função pulmonar também foram avaliadas. O teste qui-quadrado foi utilizado para comparar os dados categóricos e os teste-t e Mann-Whitney para comparar os dados numéricos. Uma regressão forward stepwise foi utilizada para avaliar a associação entre a tolerância ao exercício físico e os fatores limitantes do exercício. Resultados: Cinquenta e quatro pacientes completaram o estudo (G-Ob, n=36; G-NOb, n=18). A tolerância ao exercício apresentou correlação linear com endurance de quadríceps (r=0,65; p < 0, 001), pulso de oxigênio (r=0,52; p < 0,05) e HD (r=-0,46; p < 0,05). Embora o G-Ob (72,2%) tenha apresentado maior frequência de HD quando comparado ao G-NOb (38,9%; p < 0,05) e maior redução na capacidade inspiratória (respectivamente, -18,0% vs. -4,6%; p < 0,05), a regressão forward stepwise mostrou que o endurance muscular de quadríceps foi o único preditor da tolerância ao exercício nos pacientes do G-Ob (r=0,82; r2=0,67; p < 0,001). Conclusão: Apesar da hiperinsuflação dinâmica ser frequente nos asmáticos obesos, a limitação periférica foi o principal fator associado com a redução da tolerância ao exercício físico em asmáticos obesos. Uma possível implicação clínica destes achados é a necessidade de treinamento muscular de membros inferiores nos programas de reabilitação pulmonar em asmáticos obesos / Background: Obese individuals and patients with asthma can present dynamic hyperinflation (DH) and reduction of capacity exercise. However, no previous study has investigated the cause of intolerance exercise in obese asthmatics. Aim: To verify the limiting factors during exercise in obese asthmatics. Methods: This cross sectional study included asthmatic women with either obesity grade II (Ob-G; BMI 35.0 -39.9kg/m2; n=36) and non-obese (NOb-G; BMI 18.5 - 29.9kg/m2). Patients performed a cardiopulmonary test to quantify peak VO2 and a submaximal exercise test to assess DH. Anthropometric measurement, quadriceps muscle endurance and lung function were also evaluated. Chi-square test was used to compare categorical and t-test and Mann-Whitney test for numerical outcomes. A forward stepwise regression was used to evaluate the association between exercise tolerance and limiting exercise factors. Results: Fifty four patients completed the protocol (Ob-G; n=36; NOb-G; n=18). The exercise tolerance was associated with quadriceps endurance (r=0.65; p < 0.001), oxygen pulse (r=0.52; p < 0.05) and DH (r=-0.46; p < 0.05). Although Ob-G (72.2%) had showed a higher frequency of DH than NOb-G (38.9%; p < 0.05) and a greater reduction in the inspiratory capacity (-18.0% vs. -4.6%, respectively; p < 0.05), the forward stepwise regression showed that the exercise tolerance could be predicted from a linear association only for muscular endurance (r=0.82; r2=0.67; p < 0.001). Conclusion: In spite of DH to be a common condition in obese asthmatics, the peripheral limitation was the main factor associated with exercise intolerance in these patients. A possible clinical implication of these findings is the need for lower limb training in obese asthmatics

A Distrofia Muscular de Duchenne (DMD) é a distrofia muscular mais comum e severa da infância, resultando em fraqueza e perda de massa muscular progressiva, que leva a múltiplas incapacidades e diminuição da sobrevivência. Os tratamentos disponíveis incluem corticoterapia e gerenciamento das funções ventilatória e motora com o objetivo de postergar os acometimentos provocados pela doença. Objetivo: Avaliar a função respiratória de crianças com DMD. Método: Foi realizado um estudo do tipo transversal, sendo coletados dados referentes a avaliações de função respiratória realizadas em 101 pacientes com DMD. Foram considerados elegíveis, todos os pacientes, do sexo masculino, que estavam em seguimento clínico pelo Ambulatório de DMD e com diagnóstico confirmado por método molecular ou por análise imunohistoquímica da distrofina na biópsia muscular e que tivessem passado por avaliação da função respiratória durante as visitas de seguimento clínico entre janeiro de 2012 e junho de 2013. Resultados: Os pacientes avaliados tinham em média 14,4 anos (dp=4,4 anos), 147cm de altura (dp=17,1), com mediana de peso de 45kg e capacidade vital forçada de 65,1 por cento (dp=24,6) em média em relação ao predito e aproximadamente 45 por cento dos avaliados possuiam entre 60 a 89 por cento de capacidade vital forçada em relação ao seu predito. Sobre as demais variáveis espirométricas, os valores mais altos foram obtidos na faixa etária de 13 e 15 anos, seguida de um declínio da função respiratória. Após os 18 anos de idade, todos os parâmetros foram menores do que 50 por cento em relação ao predito. Conclusão: a casuística estudada apresentou resultados de avaliação da função respiratória semelhantes aos de grandes centros de pesquisa e seguimento de pacientes com DMD em países desenvolvidos, demonstrando a boa qualidade do serviço oferecido aos pacientes. / Duchenne Muscular Dystrophy (DMD) is the most common and severe muscular dystrophy of childhood, resulting in weakness and progressive loss of muscle mass, which leads to multiple disabilities and decrease of the survival. The available treatments include corticosteroids and management of respiratory and motor functions in order to postpone the damages caused by the disease. Objective: To evaluate the respiratory function of children with DMD. Method: A cross-sectional study was made in order to collect data based on the evaluation of the respiratory function applied in 101 patients with DMD. It was considered eligible all the patients, males, who were being followed up by the clinical ambulatory DMD, with the diagnosis confirmed by molecular method or by the immunohistochemical analysis of dystrophin in muscle biopsy and for the once who had passed by an evaluation of the respiratory function during the visits between January 2012 and June 2013. Results : All patients had an average of 14.4 years ( SD = 4.4 years ) , height 147cm ( SD = 17.1 ) with a median weight of 45kg and forced vital capacity of 65.1 per cent (SD = 24.6) related to the predicted and approximately 45 per cent of the evaluated had 60 per cent to 89 per cent FVC related to its predicted. About the other spirometric variables, the highest values were obtained from the age of 13 to 15 years, followed by a decline in respiratory function. After the age of 18, all parameters were lower than 50 per cent compared to predicted. Conclusion: the population studied showed similar results of respiratory function assessment with major centers of research and follow-up of patients with DMD in developed countries, showing the good quality of the service offered to the patients

A Distrofia Muscular de Duchenne (DMD) é a distrofia muscular mais comum e severa da infância, resultando em fraqueza e perda de massa muscular progressiva, que leva a múltiplas incapacidades e diminuição da sobrevivência. Os tratamentos disponíveis incluem corticoterapia e gerenciamento das funções ventilatória e motora com o objetivo de postergar os acometimentos provocados pela doença. Objetivo: Avaliar a função respiratória de crianças com DMD. Método: Foi realizado um estudo do tipo transversal, sendo coletados dados referentes a avaliações de função respiratória realizadas em 101 pacientes com DMD. Foram considerados elegíveis, todos os pacientes, do sexo masculino, que estavam em seguimento clínico pelo Ambulatório de DMD e com diagnóstico confirmado por método molecular ou por análise imunohistoquímica da distrofina na biópsia muscular e que tivessem passado por avaliação da função respiratória durante as visitas de seguimento clínico entre janeiro de 2012 e junho de 2013. Resultados: Os pacientes avaliados tinham em média 14,4 anos (dp=4,4 anos), 147cm de altura (dp=17,1), com mediana de peso de 45kg e capacidade vital forçada de 65,1 por cento (dp=24,6) em média em relação ao predito e aproximadamente 45 por cento dos avaliados possuiam entre 60 a 89 por cento de capacidade vital forçada em relação ao seu predito. Sobre as demais variáveis espirométricas, os valores mais altos foram obtidos na faixa etária de 13 e 15 anos, seguida de um declínio da função respiratória. Após os 18 anos de idade, todos os parâmetros foram menores do que 50 por cento em relação ao predito. Conclusão: a casuística estudada apresentou resultados de avaliação da função respiratória semelhantes aos de grandes centros de pesquisa e seguimento de pacientes com DMD em países desenvolvidos, demonstrando a boa qualidade do serviço oferecido aos pacientes. / Duchenne Muscular Dystrophy (DMD) is the most common and severe muscular dystrophy of childhood, resulting in weakness and progressive loss of muscle mass, which leads to multiple disabilities and decrease of the survival. The available treatments include corticosteroids and management of respiratory and motor functions in order to postpone the damages caused by the disease. Objective: To evaluate the respiratory function of children with DMD. Method: A cross-sectional study was made in order to collect data based on the evaluation of the respiratory function applied in 101 patients with DMD. It was considered eligible all the patients, males, who were being followed up by the clinical ambulatory DMD, with the diagnosis confirmed by molecular method or by the immunohistochemical analysis of dystrophin in muscle biopsy and for the once who had passed by an evaluation of the respiratory function during the visits between January 2012 and June 2013. Results : All patients had an average of 14.4 years ( SD = 4.4 years ) , height 147cm ( SD = 17.1 ) with a median weight of 45kg and forced vital capacity of 65.1 per cent (SD = 24.6) related to the predicted and approximately 45 per cent of the evaluated had 60 per cent to 89 per cent FVC related to its predicted. About the other spirometric variables, the highest values were obtained from the age of 13 to 15 years, followed by a decline in respiratory function. After the age of 18, all parameters were lower than 50 per cent compared to predicted. Conclusion: the population studied showed similar results of respiratory function assessment with major centers of research and follow-up of patients with DMD in developed countries, showing the good quality of the service offered to the patients