Abstract not available

Previous research on quality of life (QOL) and its relation to BNP levels in heart failure (HF) has been widely studied. However, the impact of physicians' knowledge of BNP levels at time of clinic visit on QOL and hospital length of stay (LOS) has yet to be fully investigated. The purpose of this study were to determine if physicians' knowledge of BNP levels affected a change in QOL scores at 90 days and reduce hospital length of stay among heart failure patients. QOL data from HF clinic patients (N = 108, 67.5 ± 12.3, 56% male, ejection fraction 26.5 ± 8.2) were analyzed. QOL was measured at time of clinic visit (T1) and at 90 days (T2) using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). An independent t-test was utilized to compare the two groups. Findings: Both groups were comparable regarding demographic and baseline characteristics. There was no significant association observed between the experimental and control group at 90 days, although the data indicated a decrease in the mean QOL scores at 90 days (37.46 ± 28.67) as compared to the mean QOL scores at baseline (46.87 ± 29.63) for both groups. Because the QOL scale is reversed, this indicated that there was a positive change in QOL scores during the 90 day time interval. Hospital LOS was similar for both groups (mean=3 days). BNP levels were significantly correlated with both baseline QOL scores (r=.25, p=.01) and physical subscale scores (r=.24, p=.01). Mortality was higher in the control when compared to the experimental group (t=1.99, df=90, p=.04). Conclusion: While physicians' awareness of BNP levels had not shown a significant change in QOL at 90 days, patients' QOL might already have been quite positive. Chronic HF patients may have adapted to their disease and have adjusted their perception of their QOL. Therefore, QOL may be a stable construct at this time. Findings may have been different on newly diagnosed HF patients since they may not have adapted to their health condition.

Current drugs used to treat Congestive Heart Failure target the renin-angiotensin and adrenergic systems. Studies showed increased mortality rates in patients treated with a combination of these medications. Angiotensin-AT1 and ?2-Adrenergic receptors were shown to form receptor heteromers. Blockade of one receptor in the complex can affect the signal transmitted by the other; suggesting that ligand-based therapy is not as selective as we might think. Modulating receptor trafficking after synthesis might prove to be a valid therapeutic strategy. Unfortunately, little is known about receptor assembly and transport from Endoplasmic Reticulum to Plasma Membrane. The objectives of this study are to identify the proteins that participate in the assembly of AT1R-?2AR heteromer and the regulators of the anterograde trafficking of G-Protein Coupled Receptors. This thesis introduces the role of important targets in those poorly understood processes. The identification of such targets could lead to developing better drugs with fewer adverse effects.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 6 uppsatser.

Thesis (M.S.)--University of Michigan, 1998. / Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1998. / Includes bibliographical references.

Introdução: O benefício da restrição hidrossalina em pacientes internados por insuficiência cardíaca (IC) descompensada não está bem estabelecido. Objetivo: Comparar o efeito de uma dieta com restrição hídrica de 800 ml e 800 mg de sódio adicional/dia (grupo intervenção: GI) com uma dieta sem restrição hidrossalina (grupo controle: GC) na redução do peso e na estabilidade clínica em três dias em pacientes internados por IC aguda descompensada. Delineamento: Ensaio clínico randomizado que incluiu pacientes adultos com IC aguda descompensada, disfunção sistólica e admissão hospitalar k 36 horas. Avaliou-se diariamente o estado congestivo por meio do Escore Clínico de Congestão (ECC); a sensação de sede por meio da escala visual analógica (escala 0-10), até k sete dias de internação. As readmissões foram avaliadas em 30 dias. Resultados: Incluídos 75 pctes (GI: 38; GC: 37), predominantemente homens com fração de ejeção média de 26±8,7%, 22% com etiologia isquêmica. Os grupos não foram diferentes nas características basais. O delta do peso (GI: -4,42±2,85 e GC: -4,67±5,6/ P=0,82) e o delta do ECC (GI: - 4,03±3,3 e GC: - 3,44±3,35/ P=0,47) no terceiro dia não foram diferentes entre os grupos. A sede foi significativamente maior no GI durante o período do estudo (P=0,002). Readmissão em 30 dias foi semelhante entre o GI 11(28,9%) e GC 7 (18,9%), (P=0,41). Conclusão: A intervenção agressiva de restrição hidrossalina não teve impacto na redução do peso e na estabilidade clínica em três dias. Além disso, foi responsável por significativo aumento da sensação de sede. / Introduction: The benefits of fluid and sodium restriction in patients hospitalized with acute decompensated heart failure (HF) are unclear. Objective: To compare the effects of a fluid-restricted (800 mL/day) and sodium additional-restricted (800 mg/day) diet (intervention group, IG) versus a diet with no such restrictions (control group, CG) on weight loss and clinical stability over a 3-day period in patients hospitalized with acute decompensated HF. Methods: Randomized clinical trial of adult patients with acute decompensated HF, systolic dysfunction, and a length of stay k36 hours. Congestion was assessed daily by means of a clinical congestion score (CCS). Perceived thirst was assessed with a 10-point visual analog scale. Patients were followed until the 7th hospital day. Readmissions were assessed at 30 days. Results: Seventy-five patients were enrolled (38 allocated to intervention, 37 to the control group). Most were male; ischemic heart disease was the predominant cause of HF (22%), and the mean ejection fraction was 26±8.7%. Both groups were homogeneous in terms of baseline characteristics. There were no between-group differences in weight loss (IG, -4.42±2.85 kg; CG, -4.67±5.6 kg; P=0.82) or change in CCS (IG, -4.03±3.3; CG, -3.44±3.35; P=0.47) at 3 days. Thirst was significantly worse in the IG during the study period (P=0.002). There were no between-group differences in the readmission rate at 30 days (IG, 11 patients [28.9%]; CG, 7 patients [18.9%]; P=0.41). Conclusion: Aggressive fluid and additional sodium restriction had no impact on weight loss or clinical stability at 3 days, and was associated with a significant increase in perceived thirst.

Cardiomiopatia dilatada (CMD) é uma doença miocárdica caracterizada por dilatação cardíaca e redução da contratilidade da parede do ventrículo esquerdo ou de ambos os ventrículos, sendo a etiologia de origem genética ou desconhecida. Em suínos existem raros relatos de CMD, sendo frequentemente relacionados com intoxicações por ionóforos ou gossipol. Surtos de CMD de etiologia desconhecida em suínos de rebanhos comerciais no Brasil sugeriram a existência de nova etiologia, possivelmente nutricional. Este estudo teve como objetivo investigar as possíveis causas dos surtos de CMD em suínos, a partir de análises macroscópicas, microscópicas, bioquímicas, cromatográficas, moleculares, imuno-histoquímica (IHQ) e reprodução experimental. E teve como resultado 2 artigos científicos. O primeiro artigo descreve os achados clínicos, patológicos, químicos e toxicológicos de três surtos de CMD em suínos de crescimento, além da reprodução experimental desta condição utilizando a ração de uma das propriedades afetadas. Para o estudo experimental utilizou-se 9 animais divididos em 3 grupo; Grupo 1 recebendo ração suspeita, Grupo 2 metade ração suspeita mais metade de ração controle e o grupo 3 recebeu ração controle. Dois suínos do grupo 1 apresentaram condições clínicas e patológicas semelhantes aos casos naturais após 8 dias de consumo da ração suspeita. Os principais sinais clínicos observados eram tosse e dispneia grave. Na necropsia foram constatados dilatação cardíaca bilateral acentuada, hidrotórax, hidropericárdio, edema pulmonar, ascite e fígado com aspecto de noz moscada. O segundo artigo teve como objetivo fazer a caracterização histológica, histoquímica e imuno-histoquímica das lesões cardíacas em 8 suínos com CMD e compara-las com dois suínos controles. As principais lesões evidenciadas foram atrofia de cardiomiócitos, vacuolização sarcoplasmática, ruptura de miofibras e fibras com padrão ondulado evidenciadas nas colorações de hematoxilina e eosina (HE), Tricrômico de Masson e Picrosírius. Na análise imuno-histoquímica utilizando o anticorpo anti-desmina houve uma imunomarcação reduzida ou inexistente em áreas com lesões histopatológicas. A imuno-histoquímica anti-desmina demonstrou ser uma importante ferramenta diagnóstica para caracterização de lesões de CMD em suínos. / Dilated cardiomyopathy (DCM) is a myocardial disease characterized by cardiac dilatation and reduced contractility of the left ventricular wall or both ventricles, the etiology of which is genetic or unknown. In pigs there are rare reports of DCM and are often related to ionosphere or gossypol poisoning. DCM outbreaks of unknown etiology in swine from herds in Brazil suggested the existence of a new, possibly nutritional, etiology. This study aimed to investigate the possible causes of DCM in pigs through macroscopic, microscopic, biochemical, chromatographical, molecular and immunohistochemical (IHC) evaluations, as well as the experimental reproduction of the disease. The project resulted in 2 scientific papers. The first article describes the clinical, pathological, chemical and toxicological findings of three DCM outbreaks in grower pigs, in addition to the experimental reproduction of this condition using the ration of one of the affected farms. For the experimental trial, 9 animals were divided into 3 groups; Group 1 received suspected ration only, Group 2 was fed a diet composed of half suspected ration plus half control ration, and group 3 received control ration only. Two pigs from group 1 presented clinical and pathological conditions similar to the natural cases after 8 days of consumption of the suspected ration. The main clinical signs observed were cough and severe dyspnea. At necropsy, bilateral cardiac dilatation, hydrothorax, hydropericardium, pulmonary edema, ascites and liver with the appearance of nutmeg were observed. The second article aimed to perform the histological, histochemical and immunohistochemical characterization of the cardiac lesions in 8 pigs with DCM and compare it with two control pigs. The main lesions evidenced were cardiomyocyte atrophy, sarcoplasmic vacuolization, rupture of myofibers and fibers with corrugated pattern evidenced in the staining of hematoxylin and eosin (HE), Masson's trichrome (MT) and Picrosírius (PS). Immunohistochemistry analysis using the anti-desmin antibody showed reduced or non-existent immunostaining in areas with histopathological lesions. The anti-desmin IHC proved to be an important tool for the diagnosis and characterization of DCM lesions in pigs.

Cardiomiopatia dilatada (CMD) é uma doença miocárdica caracterizada por dilatação cardíaca e redução da contratilidade da parede do ventrículo esquerdo ou de ambos os ventrículos, sendo a etiologia de origem genética ou desconhecida. Em suínos existem raros relatos de CMD, sendo frequentemente relacionados com intoxicações por ionóforos ou gossipol. Surtos de CMD de etiologia desconhecida em suínos de rebanhos comerciais no Brasil sugeriram a existência de nova etiologia, possivelmente nutricional. Este estudo teve como objetivo investigar as possíveis causas dos surtos de CMD em suínos, a partir de análises macroscópicas, microscópicas, bioquímicas, cromatográficas, moleculares, imuno-histoquímica (IHQ) e reprodução experimental. E teve como resultado 2 artigos científicos. O primeiro artigo descreve os achados clínicos, patológicos, químicos e toxicológicos de três surtos de CMD em suínos de crescimento, além da reprodução experimental desta condição utilizando a ração de uma das propriedades afetadas. Para o estudo experimental utilizou-se 9 animais divididos em 3 grupo; Grupo 1 recebendo ração suspeita, Grupo 2 metade ração suspeita mais metade de ração controle e o grupo 3 recebeu ração controle. Dois suínos do grupo 1 apresentaram condições clínicas e patológicas semelhantes aos casos naturais após 8 dias de consumo da ração suspeita. Os principais sinais clínicos observados eram tosse e dispneia grave. Na necropsia foram constatados dilatação cardíaca bilateral acentuada, hidrotórax, hidropericárdio, edema pulmonar, ascite e fígado com aspecto de noz moscada. O segundo artigo teve como objetivo fazer a caracterização histológica, histoquímica e imuno-histoquímica das lesões cardíacas em 8 suínos com CMD e compara-las com dois suínos controles. As principais lesões evidenciadas foram atrofia de cardiomiócitos, vacuolização sarcoplasmática, ruptura de miofibras e fibras com padrão ondulado evidenciadas nas colorações de hematoxilina e eosina (HE), Tricrômico de Masson e Picrosírius. Na análise imuno-histoquímica utilizando o anticorpo anti-desmina houve uma imunomarcação reduzida ou inexistente em áreas com lesões histopatológicas. A imuno-histoquímica anti-desmina demonstrou ser uma importante ferramenta diagnóstica para caracterização de lesões de CMD em suínos. / Dilated cardiomyopathy (DCM) is a myocardial disease characterized by cardiac dilatation and reduced contractility of the left ventricular wall or both ventricles, the etiology of which is genetic or unknown. In pigs there are rare reports of DCM and are often related to ionosphere or gossypol poisoning. DCM outbreaks of unknown etiology in swine from herds in Brazil suggested the existence of a new, possibly nutritional, etiology. This study aimed to investigate the possible causes of DCM in pigs through macroscopic, microscopic, biochemical, chromatographical, molecular and immunohistochemical (IHC) evaluations, as well as the experimental reproduction of the disease. The project resulted in 2 scientific papers. The first article describes the clinical, pathological, chemical and toxicological findings of three DCM outbreaks in grower pigs, in addition to the experimental reproduction of this condition using the ration of one of the affected farms. For the experimental trial, 9 animals were divided into 3 groups; Group 1 received suspected ration only, Group 2 was fed a diet composed of half suspected ration plus half control ration, and group 3 received control ration only. Two pigs from group 1 presented clinical and pathological conditions similar to the natural cases after 8 days of consumption of the suspected ration. The main clinical signs observed were cough and severe dyspnea. At necropsy, bilateral cardiac dilatation, hydrothorax, hydropericardium, pulmonary edema, ascites and liver with the appearance of nutmeg were observed. The second article aimed to perform the histological, histochemical and immunohistochemical characterization of the cardiac lesions in 8 pigs with DCM and compare it with two control pigs. The main lesions evidenced were cardiomyocyte atrophy, sarcoplasmic vacuolization, rupture of myofibers and fibers with corrugated pattern evidenced in the staining of hematoxylin and eosin (HE), Masson's trichrome (MT) and Picrosírius (PS). Immunohistochemistry analysis using the anti-desmin antibody showed reduced or non-existent immunostaining in areas with histopathological lesions. The anti-desmin IHC proved to be an important tool for the diagnosis and characterization of DCM lesions in pigs.

Introdução: O benefício da restrição hidrossalina em pacientes internados por insuficiência cardíaca (IC) descompensada não está bem estabelecido. Objetivo: Comparar o efeito de uma dieta com restrição hídrica de 800 ml e 800 mg de sódio adicional/dia (grupo intervenção: GI) com uma dieta sem restrição hidrossalina (grupo controle: GC) na redução do peso e na estabilidade clínica em três dias em pacientes internados por IC aguda descompensada. Delineamento: Ensaio clínico randomizado que incluiu pacientes adultos com IC aguda descompensada, disfunção sistólica e admissão hospitalar k 36 horas. Avaliou-se diariamente o estado congestivo por meio do Escore Clínico de Congestão (ECC); a sensação de sede por meio da escala visual analógica (escala 0-10), até k sete dias de internação. As readmissões foram avaliadas em 30 dias. Resultados: Incluídos 75 pctes (GI: 38; GC: 37), predominantemente homens com fração de ejeção média de 26±8,7%, 22% com etiologia isquêmica. Os grupos não foram diferentes nas características basais. O delta do peso (GI: -4,42±2,85 e GC: -4,67±5,6/ P=0,82) e o delta do ECC (GI: - 4,03±3,3 e GC: - 3,44±3,35/ P=0,47) no terceiro dia não foram diferentes entre os grupos. A sede foi significativamente maior no GI durante o período do estudo (P=0,002). Readmissão em 30 dias foi semelhante entre o GI 11(28,9%) e GC 7 (18,9%), (P=0,41). Conclusão: A intervenção agressiva de restrição hidrossalina não teve impacto na redução do peso e na estabilidade clínica em três dias. Além disso, foi responsável por significativo aumento da sensação de sede. / Introduction: The benefits of fluid and sodium restriction in patients hospitalized with acute decompensated heart failure (HF) are unclear. Objective: To compare the effects of a fluid-restricted (800 mL/day) and sodium additional-restricted (800 mg/day) diet (intervention group, IG) versus a diet with no such restrictions (control group, CG) on weight loss and clinical stability over a 3-day period in patients hospitalized with acute decompensated HF. Methods: Randomized clinical trial of adult patients with acute decompensated HF, systolic dysfunction, and a length of stay k36 hours. Congestion was assessed daily by means of a clinical congestion score (CCS). Perceived thirst was assessed with a 10-point visual analog scale. Patients were followed until the 7th hospital day. Readmissions were assessed at 30 days. Results: Seventy-five patients were enrolled (38 allocated to intervention, 37 to the control group). Most were male; ischemic heart disease was the predominant cause of HF (22%), and the mean ejection fraction was 26±8.7%. Both groups were homogeneous in terms of baseline characteristics. There were no between-group differences in weight loss (IG, -4.42±2.85 kg; CG, -4.67±5.6 kg; P=0.82) or change in CCS (IG, -4.03±3.3; CG, -3.44±3.35; P=0.47) at 3 days. Thirst was significantly worse in the IG during the study period (P=0.002). There were no between-group differences in the readmission rate at 30 days (IG, 11 patients [28.9%]; CG, 7 patients [18.9%]; P=0.41). Conclusion: Aggressive fluid and additional sodium restriction had no impact on weight loss or clinical stability at 3 days, and was associated with a significant increase in perceived thirst.