A acromegalia é uma doença multissistêmica decorrente da hipersecreção do hormônio do crescimento (GH) e do fator de crescimento semelhante à insulina tipo I (IGF-I), o que resulta no crescimento somático exagerado e alterações nas proporções corporais, estando associada à considerável aumento da morbidade e mortalidade. Estima-se ainda que os problemas respiratórios contribuam com 25% de todas as mortes encontradas neste grupo de pacientes. Diferenças metodológicas entre os diversos estudos levaram ao surgimento de dados inconsistentes sobre o papel do crescimento alveolar no desenvolvimento do aumento do volume pulmonar em acromegálicos, o que reforça a importância de novos trabalhos e outras abordagens sobre o tema. Ao mesmo tempo, com o desenvolvimento tecnológico, os métodos de imagem propostos em alguns estudos foram substituídos por outros mais sensíveis como a tomografia computadorizada (TC) multislice (Q-MDCT) que garante adequada mensuração do volume pulmonar, o que proporciona diferentes tipos de comparação e análise e, ainda, permite o estudo anatômico do tórax e vias pulmonares. Nossos objetivos foram identificar os principais achados da tomografia computadorizada (TC) em pacientes acromegálicos, determinar por meio da TC de tórax o volume pulmonar e comparar os achados da densitometria pulmonar com os da função pulmonar entre pacientes acromegálicos com doença ativa e doença controlada e, secundariamente, correlacionar estes achados. Foi realizado um estudo transversal com 29 portadores de acromegalia que tiveram diagnóstico da acromegalia suspeitado por características clínicas e confirmado por níveis elevados de GH não suprimido ou com níveis de IGF-I acima do limite normal. Posteriormente, os pacientes foram subdivididos nos grupos doença ativa(11 indivíduos) e doença controlada(18 indivíduos), segundo os níveis séricos de IGF-I. Houve ainda um grupo controle (17 indivíduos) em que os pacientes, após já terem realizado TC de tórax por alguma razão, foram convidados à realizar os testes de função pulmonar. A Q-MDCT e os testes de função pulmonar apresentaram excelente correlação: o volume total do pulmão (VTP) medido na TC inspiratória apresentou correlação significante com a capacidade pulmonar total (rs=0,742, p=0,0001), enquanto VTP medido na TC expiratória apresentou correlação significante com a capacidade residual funcional (rs=0,606, p=0,0005). Os pacientes acromegálicos com doença ativa apresentaram pulmões mais pesados em relação aos controles [885 (723994) vs. 696 (599769) g, p=0.017]. Os pacientes com acromegalia ativa também apresentaram maiores quantidades de compartimentos pobremente aerados em relação aos outros dois grupos, sendo esta diferença observada em %VTP [3,25 (2,553,46) vs. 2,24 (1,702,56) vs. 1,70 (1,452,15), p = 0,001] e g [82,6 (75,4 100,2) vs. 63,9 (49,180,3) vs. 54,2 (42,259,2), p = 0,0001]. O compartimento pobremente aerado medido na TC inspiratória apresentou correlação significante com os níveis de GH e IGF (rs=0,407, p=0,029; rs=0,467, p=0,011, respectivamente). Em conclusão, a Q-MDCT mostra que os pacientes acromegálicos com doença ativa apresentam pulmões mais pesados e maiores quantidades de compartimentos não aerados e pobremente aerados. Há relações entre os achados da densitovolumetria pulmonar e os parâmetros dos testes de função pulmonar na acromegalia.

Background: Measurements of lung function are routinely used in patients with cystic fibrosis (CF) to provide information that may be clinically relevant. Spirometry is the conventional lung function measurement used, however young children find spirometry difficult to perform and often cannot achieve the strict acceptability criteria for the test. The forced oscillation technique (FOT) is a lung function measurement that only requires tidal breathing and is easy for young children to perform. However, there is limited information about the utility of this technique in the clinical assessment of young children with CF who are unable to perform spirometry. Aims: The aim of this project was to evaluate the FOT for clinical assessment in 2 to 7 year old children with CF. Specifically this involved: 1. Technical assessment of the FOT in children with CF; 2. Comparisons of lung function using the FOT in children with CF and healthy children; 3. Evaluation of associations with factors known to be associated with lung disease including: i) inflammation ii) infection and iii) structural damage. Methods Lung function was measured in a cohort of 59 children between the ages of 2 and 7 years with CF at the time of quarterly clinic visits. Resistance and reactance at 6, 8 and 10Hz (Rrs6, Rrs8, Rrs10, Xrs6, Xrs8, Xrs10, respectively) were reported and expressed as Z scores. Children were classified as asymptomatic or symptomatic based on a respiratory questionnaire and physical examination at the time of testing. Bronchoalveolar lavage and high resolution computed tomography (HRCT) were performed annually under general anaesthesia annually. BAL fluid was assessed for the presence of micro-organisms and quantification of a range of inflammatory markers and HRCT used to determine the extent of structural abnormalities. Results: The between test repeatability (n=25) for lung function was within limits previously described in healthy children. No systematic bias was observed and repeatability was not affected by the presence of respiratory symptoms. Children with CF (n=57) had significantly increased Rrs6-10 (p<0.0001) and decreased Xrs6-10 (p<0.004) compared to healthy children. Rrs6 and Xrs6-10 were significantly worse in the presence of respiratory symptoms, and Rrs6-10 progressively worsened from an asymptomatic to a symptomatic clinic visit. Children with CF (n=48) had no greater bronchodilator response (BDR) compared to healthy children. BDR was not influenced by the presence of an infection or respiratory symptoms. No relationships between inflammatory markers and lung function (n=39) were identified when the presence of an infection was adjusted for. Children with a current infection (n=20) had increased Rrs6-10 (p<0.01) and decreased Xrs6-10 (p<0.04) compared to children who were uninfected (n=23). These relationships were most marked for children infected with Pseudomonas aeruginosa, with children having a reduced lung function between 0.95 and 1.47 of a Z score. No relationships with the presence or absence of mild structural abnormalities (bronchiectasis, bronchial wall thickening and air trapping) and lung function at the time of HRCT were identified (n=34). Conclusion: The FOT is a repeatable measurement of lung function in children with CF and reliable results can be obtained in children as young as 2 years old. Young children with CF exhibit altered respiratory function which was affected by the presence of factors known to be associated with lung disease. The FOT has the potential to provide useful information about changes in clinical status in young children with CF and may be used to direct management of patient lung disease.

Thesis (M.S.)--California Polytechnic State University, 2009. / Mode of access: Internet. Title from PDF title page; viewed on Jan. 20, 2010. Major professor: Dr. Lynne Slivovsky. "Presented to the faculty of the College of Engineering, California Polytechnic State University." "In partial fulfillment of the requirements for the degree [of] Master of Science in Electrical Engineering." "July 2009." Includes bibliographical references (p. 102-104).

Thesis (M. Aud.)--University of Canterbury, 2009. / Typescript (photocopy). Includes bibliographical references (p. 87-98). Also available via the World Wide Web.

published_or_final_version / Medicine / Master / Doctor of Medicine

[Truncated abstract] The hepatitis C virus (HCV) is a significant human pathogen for which there are limited post-infection therapies and no effective vaccine. Research into HCV is notoriously difficult due to the absence of suitable in vitro and in vivo model systems with which to study the virus. Furthermore, our understanding of HCV host interaction is limited and the mechanisms by which it subverts the host immune system remains largely unknown. Due to the difficult nature associated with studying HCV, the work presented in this thesis was designed to addresses a broad range of issues relating to both clinical and molecular aspects of HCV. Chronic HCV infection is often associated with the development of cirrhosis, end stage liver disease and hepatocellular carcinoma. To date, histological examination of liver biopsies provides the only approved method with which to assess the level of liver damage. While clinically informative, liver biopsies are highly invasive and may be contraindicative for patients such as haemophiliacs. Cytokine specific ELISPOT assays were used to determine whether cytokine secretion from PBMCs isolated from chronically infected HCV patients could be used as a non-invasive method to assess liver damage. Chronically infected patients with sever liver fibrosis demonstrated a significantly reduced ability to produce IFN-γ in response to HCV Core, but not other unrelated antigens, indicating that decreased IFN-γ secretion by PBMCs in response to HCV antigen could be used as a non-invasive marker for the development of liver fibrosis ... A series of HCV expression vectors covering the full length of the HCV ORF were constructed and their expression extensively tested before being used to assess the ability of HCV proteins to interact with Jak/STAT mediated Type I IFN signalling. Additionally, an alternative set of HCV IRES-EGFP reporter vectors were developed and used to access HCV IRES functionality between different eukaryotic cell lines. HCV Core protein expressed alone or in concert with E1-P7 and non-structural protein NS5B were shown to significantly reduce Jak/STAT mediated IFN expression. While the influence of HCV Core on Type I IFN signalling is consistent with previous reports in the literature, these results identify a new role for NS5B as a possible candidate protein involved in inhibition of Type I IFN signalling.

Thesis (M.S.)--University of Texas at El Paso, 2007. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, 2005. / Bibliyografya var.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 7 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.