Thesis (M.S.)--University of Michigan, 2002. / Date from spine. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 41-44).

Thesis (M.S.)--University of Michigan, 2002. / Date from spine. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 41-44).

No description available.

Made available in DSpace on 2014-06-11T19:25:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-26Bitstream added on 2014-06-13T20:14:18Z : No. of bitstreams: 1 lima_df_me_botfm.pdf: 419278 bytes, checksum: 677dde7aa062755eb6e9f71846ebfbc7 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Introdução: A fase avançada de pneumopatias, cardiopatias e doenças sistêmicas está associada com o desenvolvimento de insuficiência respiratória crônica (IRespC). O tratamento desta complicação inclui o uso de oxigenoterapia domiciliar prolongada. Na literatura nacional poucos estudos avaliaram a sobrevida em pacientes com doença pulmonar obstrutiva crônica (DPOC) ou com IRespC recebendo oxigenoterapia domiciliar prolongada (ODP). Objetivo: O objetivo deste estudo foi avaliar os fatores de predição de mortalidade em pacientes com IRespC tratados com ODP no período de um, dois e três anos. Pacientes e Métodos: Foram avaliados e acompanhados pelo período mínimo de três anos ou até o óbito, 142 pacientes cadastrados no ambulatório de oxigenoterapia da Faculdade de Medicina de Botucatu (FMB) até julho de 2005. Na avaliação inicial, foram coletados dados de identificação pessoal, história de tabagismo, o uso de medicação, composição corporal, força de preensão manual, função pulmonar, gases sanguíneos e hemograma. Também foram aplicados a escala de dispnéia de Borg, o índice de dispnéia basal (BDI) e o questionário de qualidade de vida na doença respiratória do Hospital Saint George (SGRQ). Resultados: Durante os três anos de estudo; 83 pacientes (58%) morreram: 37 (26%) durante o primeiro ano de acompanhamento, 23 (16%) no segundo ano e 23 (16%) no período de três anos. O grupo óbito apresentou valores de hematócrito e hemoglobina significativamente menores, maior sensação de dispnéia, avaliada pelo BDI e Borg, e apresentou maior 18 comprometimento do estado de saúde, avaliado pelos domínios, impacto, atividade e total do SGRQ. Os principais preditores de mortalidade, na avaliação que incluía todos os pacientes, no período de três anos foram: gênero masculino (HR=2,67, CI=1,15-6,18, p=0,02), menores valores de hemoglobina... / Introduction: The advanced stage of lung, heart and systemic diseases is associated with the development of chronic respiratory failure (CRF). The treatment of this complication includes the use of long term oxygen therapy (LTOT). In the national literature few studies have assessed the survival of patients with chronic obstructive pulmonary disease (COPD) or with chronic respiratory failure treated with LTOT. Aim: The aim of this study was to evaluate the predictors of mortality in patients with CRF treated with oxygen in the period of one, two and three years. Patients and Methods: One hundred forty two patients were evaluated and followed for the minimum period of three years or until death. The study group consisted of patients with CRF, clinically stable, seen at the Oxygen Therapy Outpatient Clinic of Botucatu School of Medicine Hospital. Information about the demographic characteristics, smoking history, comorbidity conditions and treatment were collected during the first visit; evaluation of body composition, handgrip strength, lung function and blood gases and blood counts were also undertaken at this time. In addition, the dyspnea sensation (basal dyspnea index - BDI - and Borg scale) and health related quality of life (Saint George Respiratory Questionnaire) scores were calculated. Results: During the follow-up, 83 (58%) patients died; 37 (26%) during the first year of follow-up, 23 (16%) in the second year and 23 (16%) considering in three years. The group of death showed significantly lower 20 hematocrit and hemoglobin, increased sensation of breathlessness, measured by BDI and Borg, and showed greater impairment of health status as measured by impact, activity and total score of SGRQ. The main predictors of mortality, after three years of follow-up were male gender (HR=2.67, CI=1.15-6.18, p=0.02), lower values of hemoglobin (HR=0.85, CI=0.74-0.98, p=0.02), and PaCO2... (Complete abstract click electronic access below)

Abstract The aim of the study was to evaluate pulmonary endogenous and inhaled nitric oxide (NO) in neonates with severe respiratory failure. Infant autopsy documents were reviewed for fulminant early-onset bacterial pneumonia. 12 infants with the onset at < 72 h of age and three control groups were identified. Immunohistochemistry revealed that 11 of the infants with early-onset pneumonia (92%) had no or faint inducible nitric oxide synthase (NOS2) staining in their alveolar macrophages (AM). All control infants, regardless of their postnatal age, had NOS2-positive AM. The marker of NO-toxicity, nitrotyrosine, was low in all specimens. To confirm this finding, airway specimens of 21 newborns requiring mechanical ventilation were examined. Seven of them had fulminant early-onset pneumonia with maternal ascending intra-uterine infection (IUI). The controls had no infection at birth despite IUI or neither infection nor IUI. In early-onset pneumonia, NOS2 and nitrotyrosine immunoreactivity were low at birth and increased during the recovery phase (p < 0.05). Analyses of interleukin-1 and surfactant protein A showed the same pattern of age-dependent change. Of the autopsied infants, 12 had received inhaled NO (iNO) before death. Each case was paired with a matched control. Additional five infants without respiratory failure prior to death were also studied. The iNO-treated ones tended to have more intensive NOS2 staining in the bronchiolar epithelium and adjacent tissue than the controls. No differences in other NOS isoforms or nitrotyrosine were detected. A novel method for exhaled NO measurements of intubated infants was developed. Six preterm and six term newborns were prospectively recruited for expired and nasal NO measurements. During the first week of life, the preterm infants showed a different pattern of exhaled NO excretion compared to the term infants. For the pilot intervention study on very early iNO, the eligible patients had a birth weight < 1500 g and progressive, therapy-resistant respiratory failure before five hours of age. Five infants received iNO, showed immediately improved oxygenation and survived without deleterious side effects. Deficient production of NO in small premature infants is associated with severe infection and respiratory failure. Very early iNO therapy may be exceptionally effective in a select group of infants, and did not appear to cause oxidation lung injury.

No description available.

Orientador: Irma de Godoy / Banca: Suzana Erico Tanni / Banca: Maria Christina L. Machao / Resumo: Introdução: A fase avançada de pneumopatias, cardiopatias e doenças sistêmicas está associada com o desenvolvimento de insuficiência respiratória crônica (IRespC). O tratamento desta complicação inclui o uso de oxigenoterapia domiciliar prolongada. Na literatura nacional poucos estudos avaliaram a sobrevida em pacientes com doença pulmonar obstrutiva crônica (DPOC) ou com IRespC recebendo oxigenoterapia domiciliar prolongada (ODP). Objetivo: O objetivo deste estudo foi avaliar os fatores de predição de mortalidade em pacientes com IRespC tratados com ODP no período de um, dois e três anos. Pacientes e Métodos: Foram avaliados e acompanhados pelo período mínimo de três anos ou até o óbito, 142 pacientes cadastrados no ambulatório de oxigenoterapia da Faculdade de Medicina de Botucatu (FMB) até julho de 2005. Na avaliação inicial, foram coletados dados de identificação pessoal, história de tabagismo, o uso de medicação, composição corporal, força de preensão manual, função pulmonar, gases sanguíneos e hemograma. Também foram aplicados a escala de dispnéia de Borg, o índice de dispnéia basal (BDI) e o questionário de qualidade de vida na doença respiratória do Hospital Saint George (SGRQ). Resultados: Durante os três anos de estudo; 83 pacientes (58%) morreram: 37 (26%) durante o primeiro ano de acompanhamento, 23 (16%) no segundo ano e 23 (16%) no período de três anos. O grupo óbito apresentou valores de hematócrito e hemoglobina significativamente menores, maior sensação de dispnéia, avaliada pelo BDI e Borg, e apresentou maior 18 comprometimento do estado de saúde, avaliado pelos domínios, impacto, atividade e total do SGRQ. Os principais preditores de mortalidade, na avaliação que incluía todos os pacientes, no período de três anos foram: gênero masculino (HR=2,67, CI=1,15-6,18, p=0,02), menores valores de hemoglobina... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: The advanced stage of lung, heart and systemic diseases is associated with the development of chronic respiratory failure (CRF). The treatment of this complication includes the use of long term oxygen therapy (LTOT). In the national literature few studies have assessed the survival of patients with chronic obstructive pulmonary disease (COPD) or with chronic respiratory failure treated with LTOT. Aim: The aim of this study was to evaluate the predictors of mortality in patients with CRF treated with oxygen in the period of one, two and three years. Patients and Methods: One hundred forty two patients were evaluated and followed for the minimum period of three years or until death. The study group consisted of patients with CRF, clinically stable, seen at the Oxygen Therapy Outpatient Clinic of Botucatu School of Medicine Hospital. Information about the demographic characteristics, smoking history, comorbidity conditions and treatment were collected during the first visit; evaluation of body composition, handgrip strength, lung function and blood gases and blood counts were also undertaken at this time. In addition, the dyspnea sensation (basal dyspnea index - BDI - and Borg scale) and health related quality of life (Saint George Respiratory Questionnaire) scores were calculated. Results: During the follow-up, 83 (58%) patients died; 37 (26%) during the first year of follow-up, 23 (16%) in the second year and 23 (16%) considering in three years. The group of death showed significantly lower 20 hematocrit and hemoglobin, increased sensation of breathlessness, measured by BDI and Borg, and showed greater impairment of health status as measured by impact, activity and total score of SGRQ. The main predictors of mortality, after three years of follow-up were male gender (HR=2.67, CI=1.15-6.18, p=0.02), lower values of hemoglobin (HR=0.85, CI=0.74-0.98, p=0.02), and PaCO2... (Complete abstract click electronic access below) / Mestre

To investigate the possibility that malnutrition is an important factor that prolongs respiratory failure (PRF), I studied the effects of pharmacologic injections of recombinant human growth hormone (rhGH), an important anabolic stimulus, on nutritional and respiratory parameters in patients requiring mechanical ventilation for more than three days. Patients were excluded from consideration if dominating factors known to prolong ventilatory failure had not been stabilized. Over ten months, 106 patients in PRF were evaluated, but only six met the selection criteria. Three patients were randomized to receive standard nutritional support, and three into a group that received the equivalent nutrition plus 5 mg/day of rhGH for 14 days or until withdrawal of mechanical ventilation. Baseline characteristics of the selected patients were divergent as demonstrated by body mass indexes ranging from 14 to 42 (kg/m$ sp2),$ baseline maximal inspiratory pressures (PI$ sb{ max}$ from $-$15 to $-$70 cm H$ sb2$O, and Day 1 N balances from $-$13.5 to 1.2 g N/day. Despite increased plasma insulin-like growth factor-1 concentrations, the mean daily N balances of the rhGH-treated group were no better than the controls (1.3 $ pm$ 5.0 vs. 0.4 $ pm$ 2.6 g N/day; Mean $ pm$ SD), nor were there differences in PI$ sb{ max},$ level of ventilatory assistance required, and days to weaning. The persistence of respiratory failure in the overwhelming majority of patients in PRF appears to be due to factors already known to prevent weaning from mechanical ventilation. Even the carefully selected patients enrolled in the present study were insufficiently homogeneous or stable enough to allow proper testing of the experimental hypothesis.

El síndrome de distrés respiratorio del adulto (SDRA) se caracteriza por una disminución de la compilancia pulmonar, un aumento del shunt derecha-izquierda e hipertensión pulmonar aguda por vasoconstricción pulmonar, dando lugar a una alteración de la relación ventilación-perfusión (V./O) y profunda hipoxemia. El SDRA se puede inducir experimentalmente mediante lavados pulmonares repetidos. El descubrimiento del factor de relajación derivado del endotelio (EDRF), sU identificación como óxido nítrico (NO) o un compuesto donador de NO y el desarrollo de inhibidores de la enzima óxido nítrico sintetasa (NOS), ha puesto en evidencia un nuevo e importante mecanismo regulador de la circulación sistémica y pulmonar. Además, la reciente observación de que la inhalación del gas NO produce vasodilatación pulmonar sin vasodilatación sistémica, puede proporcionar una nueva estrategia terapéutica en la insuficiencia respiratoria aguda. El propósito de este estudio fue investigar los efectos del gas NO inhalado y la infusión de N°-nitro L-arginina metil ester (L-NAME), un inhibidor de la NOS, ambos independientemente y combinados en la hemodinámica sistémica y pulmonar e intercambie de gases en un modelo experimental de SORA. Las hipótesis fueron que la inhalación de NO gas produciría vasodilatación selectiva de las regiones pulmonares ventiladas, reduciendo la hipertensión pulmonar y disminuyendo el shunt al mejorar las relaciones V(A)/Q, independientemente del flujo pulmonar: la infusión de L-NAME aumentaría la vasoconstricción pulmonar hipóxica (VPH) mejorando también las relaciones V(A).Q y potenciaría los efectos del NO sobre el intercambio de gases, ya que al aumentar la VPH aumentaría el flujo hacia las zonas ventiladas y vasodilatadas por la inhalación de NO; y dado que el NO activa al enzima guanil ciclasa y produce un aumento de GMPc, responsable de la vasodilatación, los niveles plasmáticos de GMPc deberían aumentar con la inhalación de NO. Tras aprobación por el Subcomité de Protección de Animales para la Investigación del Hospital General de Massachusetts, se estudiaron 21 ovejas de la raza Suffolk de 30-35 kg., anestesiadas con pentobarbital, intubadas y ventiladas mecánicamente con FlO(2) entre 0,85-0,90. Fueron Instrumentadas para medir: presión arterial sistémica (PAS), presión de arteria pulmonar (PAP), presión venosa central (PVC) y presión de aurícula izquierda (PAI). El gasto cardíaco se medió por termodilución. Se realizaron análisis de gases en sangre arterial y venosa mixta. Las resistencias vasculares sistémicas (RVS), resistencias vasculares pulmonares (RVP) y shunt intrapulmonar o mezcla venosa (Q(VA)/Q(I)) se calcularon mediante fórmulas estándar. Los niveles plasmáticos de GMPc se midieron en sangre arterial y venosa mixta mediante radloinmunoensayo. Se efectuó lavado pulmonar bilateral con una solución de Tween 80 en suero fisiológico a 37°C. Los animales se estudiaron en dos fases: 1) Estudio preliminar: Se estudió la estabilidad del modelo de lavado, se hizo una curva de dosis-respuesta a diferentes concentraciones de NO y se estudiaron los efectos hemodinámicos y gasométricos de la infusión de L-NAME. 2) Estudio experimental: Se estudiaron en los siguientes tiempos: Basal (BASl), después del lavado pulmonar bilateral (LPB), tras 10 min. de la inhalación de 60 ppm de NO (NO), 10 min. después de interrumpir la inhalación de NO (BAS2), después de la infusión de 30 mg/kg de L-NAME (L-NAME), de nuevo durante 10 min. de la InhalacIón de 60 ppm de NO (L-NAME+NO), 10 min. tras cesar la inhalación de NO (BASJ) y tras la infusión de 1 g/kg de L-Arginina (L-ARG). Todas las mediciones se realizaron a tres niveles de GC excepto en los tiempos BL2, BLJ, L-ARG. La medición del GMPc se realizó también sin manipular el GC. Todos los valores se expresaron como media±error estándar. Se ha aplicado el test de la T de Student para datos apareados con corrección de Bonferroni, regresión lineal y análisis de la variancia según era conveniente. Los resultados del estudio preliminar demostraron que tras el lavado pulmonar bilateral se produce una lesión pulmonar caracterizada por hipoxemia severa, aumento del shunt o mezcla venosa, hipertensión pulmonar moderada y aumento de la presión inspiratoria máxima. Todos los cambios permanecieron estables a lo largo del período estudiado de 4 horas. La máxima reducción en la PAP se consiguió respirando entre 30 y 60 ppm de NO, mientras que la inhalación entre 60-120 ppm causó la máxima reducción en la Q(VA)/Q(I). La infusión de L-NAME provocó un aumento en la PAP, las RVS y RVP, y una marcada reducción del GC, así como de la (Q(VA)/Q(I)) En el estudio experimental, la inhalación de NO por un breve periodo de tiempo produjo una rápida disminución de la PAP y de las RVP: no produjo ningún efecto sobre la FAS ni sobre el GC y mejoró la eficacia del intercambio de gases, al aumentar la PAP y reducir el shunt intrapulmonar. La infusión de L-NAME, inhibidor de la síntesis endógena de óxido nítrico, provocó vasoconstricción pulmonar y sistémica y una marcada reducción del GC, sin modificar el intercambio de gases. La inhalación de NO después de la infusión de L-NAME produjo de nuevo una vasodilatación pulmonar selectiva sin vasodilatación sistémica y una mejoría del intercambio de gases al reducir el shunt intrapulmonar, pero su efecto sobre la oxigenación no se potenció por la infusión previa de L-NAME, por lo que la infusión de L-NAME no aumentó la vasoconstricción pulmonar de manera selectiva en las zonas hipóxicas del pulmón. Los efectos hemodinámicos y gasométricos durante la inhalación de NO, tanto antes como después de la infusión de L-NAME, fueron independientes del flujo pulmonar o GC. Mientras que los efectos de la infusión de L-NAME sobre la (Q(VA)/Q(I)) fueron dependientes del flujo pulmonar o GC. Finalmente, solo durante la inhalación de NO hubo liberación de GMPc por el pulmón a la circulación sistémica. En el presente modelo experimental podemos concluir que la inhalación de NO produce una vasodilatación pulmonar selectiva y una mejoría del intercambio de gases, independientemente del flujo pulmonar o GC y que sus efectos son mediados por el GMPC. / In the present study we examined the effects of inhaling nitric oxide (NO) on pulmonary hemodynamics and gas exchange in an ovine model of adult respiratory distress syndrome (AROS), induced by repeated lung lavages. In addition we investigated in this modal the effects of inhibition endogenous NO synthesis by NG-nitro-Larginine metyl ester (L-NAKE) and the combination with inhaled NO. Because NO activates guanylate cyclase, increasing guanosine 3’-5'- cyclic monophosphate (cGMP) we also we measured cGMP plasma levels. In anesthetized and mechanically ventilated sheep inhaling 60 ppm of NO after lung lavage decreased pulmonary artery pressure and resistance without any systemic hemodynamic effects, increased arterial PaO(2) and decreased venous admixture (Q(VA)/Q(I)). A L-NAME infusion produced pulmonary and systemic vasoconstriction without changes on PaO(2) or (Q(VA)/Q(I)) inhaling NO after L-NAME produced the same hemodynamics and gas exchange effects than inhaling NO alone. The effects on inhaled NO were independent of pulmonary blood flow or cardiac output. During NO inhalation plasma cGMP levels were increased significantly. We concluded that in this experimental model of AROS inhaled NO produced selective pulmonary vasodilatation and improved gas exchange by incressing cGMP concentration in ventilated lung regions and these effects were not potentiated with the inhibition of endogenous NO synthesis.

Thesis (Ph.D.)--University of Melbourne, Dept. of Medicine, Western Hospital, 2007. / Typescript. Includes bibliographical references (leaves 145-181).