O objetivo desse estudo foi comparar a habilidade da avaliação subjetiva do disco óptico e da camada de fibras nervosas (CFN) por oftalmologistas generalistas e por um glaucomatólogo com medidas objetivas pela tomografia de coerência óptica (Stratus OCT), oftalmoscopia confocal de varredura a laser (HRTIII), e a polarimetria de varredura a laser (GDxECC) para discriminar olhos glaucomatosos de olhos normais. 61 olhos glaucomatosos e 57 olhos normais de 118 indivíduos foram incluídos nesse estudo. Três oftalmologistas generalistas independentes e um glaucomatólogo avaliaram fotografias estereoscópicas do disco óptico. Curvas ROC (Receiver Operator Characteristic) foram construídas para cada técnica de imagem e a sensibilidade a uma especificidade fixa foi determinada. Comparações das áreas sob essas curvas (AROC) e a concordância (k) foram determinadas entre a graduação das fotografias estereoscópicas e o melhor parâmetro de cada exame de imagem computadorizado. O melhor parâmetro de cada técnica de imagem computadorizada (CFN temporal inferior do Stratus OCT = 0,92; área integrada vertical da topografia do disco óptico pelo Stratus OCT = 0,86; espessura macular do setor inferior externo fornecido pelo Stratus OCT = 0,82; NFI do GDxECC = 0,91; razão área E/D do HRT3 = 0,83) mostrou AROC maior do que a graduação das fotografias estereoscópicas por oftalmologistas generalistas (0,80) para separar olhos glaucomatosos de olhos normais. A graduação por glaucomatólogo forneceu AROC igual ou maior (0,92) do que o melhor parâmetro de exame computadorizado de imagem. A avaliação das fotografias estereoscópicas por glaucomatólogo mostrou melhor concordância com o melhor parâmetro de cada técnica de imagem quantitativa na classificação de olhos como glaucomatosos ou normais comparadas à avaliação de fotografias estereoscópicas por oftalmologistas generalistas. A combinação da avaliação subjetiva do disco óptico por oftalmologistas generalistas com parâmetros objetivos da CFN melhorou a identificação de olhos com glaucoma em uma proporção maior do que a combinação desses parâmetros objetivos com a avaliação do disco óptico por um glaucomatólogo (29,5% versus 19,7%, respectivamente). Os resultados sugerem que a habilidade diagnóstica de todos os exames de imagem computadorizados estudados mostrou melhor desempenho que a avaliação subjetiva do disco óptico por oftalmologistas generalistas, mas não por um glaucomatólogo. Medidas objetivas da CFN podem permitir um aperfeiçoamento na detecção de glaucoma quando combinados com a avaliação subjetiva do disco óptico por oftalmologistas generalistas ou por um glaucomatólogo. / The purpose of this study was to compare the ability of subjective assessment of optic nerve head and retinal nerve fiber layer by general ophthalmologists and by a glaucoma expert with objective measurements by optical coherence tomography (Stratus OCT, Carl Zeiss Meditec, Inc.), confocal scanning laser ophthalmoscope (HRT III; Heidelberg Engineering, Heidelberg, Germany), and scanning laser polarimetry (GDx ECC; Carl Zeiss Meditec, Inc., Dublin, CA) in discriminating glaucomatous and normal eyes. 61 glaucomatous and 57 normal eyes of 118 subjects were included in the study. Three independent general ophthalmologists and one glaucoma expert evaluated ONH stereophotographs. Receiver operating characteristic curves were constructed for each imaging technique and sensitivity at fixed specificity was estimated. Comparisons of areas under these curves (aROC) and agreement (k) were determined between stereophoto grading and best parameter from each technique. Best parameter from each technique showed larger aROC (StratusOCT RNFL = 0.92; StratusOCT ONH vertical integrated area = 0.86; StratusOCT macular thickness = 0.82; GDxECC = 0.91; HRT3 global cup-to-disc area ratio = 0.83) compared to stereophotograph grading by general ophthalmologists (0.80) in separating glaucomatous and normal eyes. Glaucoma expert stereophoto grading provided equal or larger aROC (0.92) than best parameter of each computerized imaging device. Stereophoto evaluated by a glaucoma expert showed better agreement with best parameter of each quantitative imaging technique in classifying eyes either as glaucomatous or normal compared to stereophoto grading by general ophthalmologists. The combination of subjective assessment of the optic disc by general ophthalmologists with RNFL objective parameters improved identification of glaucoma patients in a larger proportion than the combination of these objective parameters with subjective assessment of the optic disc by a glaucoma expert (29.5% versus 19.7%, respectively). The results suggests that the diagnostic ability of all imaging techniques showed better performance than subjective assessment of the ONH by general ophthalmologists, but not by a glaucoma expert. Objective RNFL measurements may provide improvement in glaucoma detection when combined with subjective assessment of the optic disc by general ophthalmologists or by a glaucoma expert.

O diagnóstico precoce dos Segundos Tumores Primários (STP) em pacientes já tratados por um carcinoma de cabeça e pescoço deve ser realizado, pois possibilita um tratamento resolutivo com baixa morbidade. O objetivo deste trabalho é avaliar se a cromoscopia com Lugol permite uma melhora na identificação de lesões malignas ou pré malignas em fases iniciais na boca e orofaringe, bem como se a imunoexpressão do p53 e da Metalotioneína no tumor índice predizem o aparecimento de um STP. Foi realizado um estudo prospectivo onde dois grupos comparáveis de portadores de carcinoma epidermóide de cabeça e pescoço foram formados (um com 106 pacientes e outro com 105 pacientes). Foram acompanhados durante um período médio de 25 meses aproximadamente. No primeiro grupo (grupo A) não foram utilizados corantes, já no segundo (grupo B) utilizou-se o Lugol. Foi observado um número de diagnósticos 200% maior no grupo em que foi utilizada a coloração de Lugol (grupo B) em relação ao grupo A. A imunoexpressão aumentada do p53 no tumor índice foi estatisticamente significante quando o paciente desenvolveu um segundo tumor primário diagnosticado pelo Lugol, não visível sem o corante, o que não ocorreu com a metalotioneína. / The early diagnosis of seconds primary tumors (STP) in patients already treated for carcinoma of the head and neck should be done, because enables a resolutive treatment with low morbidity. The objective of this paper is to evaluate whether chromoscopia using Lugols solution allows an improvement in the identification of malignant or pre malignant lesions in early stages in the mouth and oropharynx, and whether the expression of P53 and metallothionein in tumor index predict the emergence of a STP. A prospective study was conducted, where two groups statistically similar of patients with head and neck squamous cell carcinoma (one with 106 patients and another with 105 patients) were followed-up for a median period of 25 months, approximately. In the first group dyes were not used, and in the second Lugols solution was employed. It was observed a number of diagnoses 100%i higher in the group that Lugols solution was used. The increasing of P53 expression in tumor index was statistically significant when the patient developed a second primary tumor diagnosed by Lugol, not visible without dye, which has not occurred with metallothionein.

Wong, Wai Ki Vicky. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 105-131). / Abstracts in English and Chinese. / Abstract --- p.ii / 摘要 --- p.iv / Acknowledgements --- p.vi / Table of contents --- p.vii / List of tables --- p.xii / List of figures --- p.xiii / List of abbreviations --- p.xiv / Chapter Chapter 1: --- Introduction --- p.1 / Chapter Chapter 2: --- Colorectal cancer / Chapter 2.1 --- Literature Review / Chapter 2.1.1 --- Colorectal cancer --- p.8 / Chapter 2.1.2 --- Incident rate of colorectal cancer --- p.8 / Chapter 2.1.3 --- Hereditary colorectal cancer --- p.9 / Chapter 2.1.4 --- Sporadic colorectal cancer and Wnt signaling pathway --- p.10 / Chapter 2.1.5 --- Chemotherapy treatment of colorectal cancer --- p.11 / Chapter 2.1.5.1 --- 5-Fluorouracil --- p.12 / Chapter 2.1.5.2 --- Oxaliplatin --- p.14 / Chapter 2.1.5.3 --- Irinotecan --- p.14 / Chapter 2.1.6 --- Biomarkers for colorectal cancer --- p.15 / Chapter 2.1.6.1 --- Thymidylate synthase --- p.15 / Chapter 2.1.6.2 --- Dihydropyrimidine dehydrogenase --- p.16 / Chapter 2.1.6.3 --- Thymidine phosphorylase --- p.16 / Chapter 2.1.6.4 --- Microsatellite-instability status --- p.16 / Chapter 2.1.6.5 --- Clinical uses of biomarkers for colorectal cancer --- p.17 / Chapter 2.1.7 --- Choice of cell line as colorectal cancer model --- p.17 / Chapter 2.1.8 --- Aims of study --- p.17 / Chapter 2.2 --- Materials and Methods / Chapter 2.2.1 --- Verification of SW480 as a nuclear β-catenin positive cell line / Chapter 2.2.1.1 --- Maintenance of cell lines --- p.21 / Chapter 2.2.1.2 --- Antibody --- p.21 / Chapter 2.2.1.3 --- Agar block preparation for SW480 and CCD-18C0 cells --- p.22 / Chapter 2.2.1.4 --- Immunocytochemical staining --- p.22 / Chapter 2.2.2 --- Effect of anti-cancer drugs on cell viability / Chapter 2.2.2.1 --- Maintenance of cell lines --- p.22 / Chapter 2.2.2.2 --- MTT cell viability assay --- p.23 / Chapter 2.3 --- Results / Chapter 2.3.1 --- SW480 is a β-catenin positive cell line --- p.24 / Chapter 2.3.2 --- Antiproliferative effects of cytotoxic drugs in SW480 cells / Chapter 2.3.2.1 --- 5-Fluorouracil --- p.26 / Chapter 2.3.2.2 --- Oxaliplatin --- p.29 / Chapter 2.3.2.3 --- Irinotecan --- p.31 / Chapter 2.4 --- Discussion / Chapter 2.4.1 --- SW480 as a nuclear β-catenin positive cell line --- p.33 / Chapter 2.4.2 --- Antiproliferative effects of 5-fluorouracil in SW480 cells --- p.33 / Chapter 2.4.3 --- Summary --- p.34 / Chapter Chapter 3: --- Effect of 5-fluorouracil on mRNA expression in SW480 cells / Chapter 3.1 --- Literature Review / Chapter 3.1.1 --- Application of quantitative real-time polymerase chain reaction in cancer research / Chapter 3.1.1.1 --- Principles of quantitative real-time polymerase chain reaction --- p.36 / Chapter 3.1.1.2 --- Advantages of quantitative real-time polymerase chain reaction over conventional polymerase chain reaction --- p.39 / Chapter 3.1.1.3 --- Determination of colorectal cancer biomarkers by quantitative real-time polymerase chain reaction --- p.39 / Chapter 3.2 --- Materials and Methods / Chapter 3.2.1 --- Determination of the effect of 5-fluorouracil on mRNA expression in SW480 cells / Chapter 3.2.1.1 --- Treatment of cells --- p.40 / Chapter 3.2.1.2 --- Extraction of total RNA from SW480 cells --- p.40 / Chapter 3.2.1.3 --- Removal of genomic DNA --- p.41 / Chapter 3.2.1.4 --- Determination of the efficiency of genomic DNA removal --- p.42 / Chapter 3.2.1.5 --- Determination of the purity and concentration of RNA --- p.42 / Chapter 3.2.1.6 --- Determination of the integrity of RNA --- p.43 / Chapter 3.2.1.7 --- First strand cDNA synthesis --- p.44 / Chapter 3.2.1.8 --- Real-time polymerase chain reaction using human Wnt signaling pathway RT2 ProfileŕёØ PCR array --- p.44 / Chapter 3.2.1.9 --- Calculation of the fold-change in genes expression between the 5-FU treated and control SW480 cells --- p.45 / Chapter 3.3 --- Results / Chapter 3.3.1 --- The quality and quantity of RNA --- p.46 / Chapter 3.3.2 --- Effects of 5-fluorouracil on genes expression in SW480 cells --- p.48 / Chapter 3.4 --- Discussion / Chapter 3.4.1 --- Alterations in mRNA expression in 5-fluorouracil treated SW480 cells --- p.55 / Chapter 3.4.1.1 --- Extracellular signaling molecules --- p.55 / Chapter 3.4.1.2 --- Canonical Wnt signaling pathway --- p.56 / Chapter 3.4.1.3 --- Regulators of cell cycle --- p.57 / Chapter 3.4.1.4 --- Regulators of growth and proliferation --- p.58 / Chapter 3.4.1.5 --- Regulators of transcription --- p.58 / Chapter 3.4.1.6 --- Regulators of Wnt receptor signaling pathway --- p.60 / Chapter 3.4.1.7 --- Other genes involved in Wnt signaling --- p.61 / Chapter 3.4.2 --- Limitations of Q-RT-PCR --- p.61 / Chapter 3.4.3 --- Summary --- p.62 / Chapter Chapter 4: --- Effect of 5-fluorouracil on proteins expression in SW480 cells / Chapter 4.1 --- Literature Review / Chapter 4.1.1 --- From mRNA to proteins --- p.63 / Chapter 4.1.2 --- Application of proteomics in cancer research --- p.63 / Chapter 4.1.3 --- Two-dimensional gel electrophoresis --- p.64 / Chapter 4.1.4 --- Principles of MALDI TOF mass spectrometry --- p.64 / Chapter 4.1.5 --- Peptide mass fingerprinting --- p.65 / Chapter 4.1.6 --- Drug response proteins detected by proteomics in colorectal cancer cell lines --- p.65 / Chapter 4.1.7 --- Detection of biomarker in colorectal cancer formation using proteomics --- p.66 / Chapter 4.2 --- Materials and Methods / Chapter 4.2.1 --- Determination of the effect of 5-fluorouracil on proteins expression in SW480 cells / Chapter 4.2.1.1 --- Treatment of cells --- p.67 / Chapter 4.2.1.2 --- Cell lysis --- p.67 / Chapter 4.2.1.3 --- Protein quantitation of cell lysate --- p.67 / Chapter 4.2.1.4 --- Sample preparation for two-dimensional electrophoresis --- p.68 / Chapter 4.2.1.5 --- Two-dimensional electrophoresis --- p.69 / Chapter 4.2.1.6 --- Silver staining --- p.69 / Chapter 4.2.1.7 --- Image analysis --- p.70 / Chapter 4.2.1.8 --- In-gel protein digestion --- p.70 / Chapter 4.2.1.9 --- Peptide mass fingerprinting using mass spectrometry --- p.71 / Chapter 4.3 --- Results / Chapter 4.3.1 --- Protein expression patterns of 5-fluorouracil treated and untreated SW480 cells by 2-dimensional electrophoresis --- p.72 / Chapter 4.3.2 --- Identification of the differentially expressed proteins after 5-fluorouracil treatment in SW480 cells --- p.75 / Chapter 4.4 --- Discussion / Chapter 4.4.1 --- Effects of 5-fluorouracil on protein expression in SW480 cells --- p.82 / Chapter 4.4.1.1 --- Identified upregulated proteins after 5-fluorouracil treatment in SW480 cells / Chapter 4.4.1.1.1 --- Cyclophilin A --- p.83 / Chapter 4.4.1.1.2 --- Cytokeratin 19 --- p.83 / Chapter 4.4.1.1.3 --- Cytokeratin 8 --- p.84 / Chapter 4.4.1.1.4 --- RAN --- p.84 / Chapter 4.4.1.1.5 --- Heat shock protein 27 --- p.84 / Chapter 4.4.1.1.6 --- Peroxiredoxin 6 --- p.85 / Chapter 4.4.1.2 --- Identified dowiiregulated proteins after 5-fluorouracil treatment in SW480 cells / Chapter 4.4.1.2.1 --- Heat shock protein 60 --- p.86 / Chapter 4.4.1.2.2 --- Cytokeratin 18 --- p.86 / Chapter 4.4.1.2.3 --- Cytokeratin 9 --- p.86 / Chapter 4.4.1.2.4 --- Carbamoylphosphate synthetase I --- p.87 / Chapter 4.4.1.2.5 --- a-Enolase --- p.87 / Chapter 4.4.1.2.6 --- Heat shock protein 70 --- p.87 / Chapter 4.4.1.2.7 --- nm23 --- p.88 / Chapter 4.4.1.2.8 --- β-actin --- p.88 / Chapter 4.4.2 --- Limitations of proteomics profiling --- p.89 / Chapter 4.4.3 --- Summary --- p.90 / Chapter Chapter 5: --- Verification of proteinśة identities by immunocytochemical staining / Chapter 5.1 --- Materials and Methods / Chapter 5.1.1 --- Antibodies --- p.91 / Chapter 5.1.2 --- Treatment of cells --- p.91 / Chapter 5.1.3 --- Agar block preparation of SW480 cells --- p.92 / Chapter 5.1.4 --- Immunocytochemical staining and evaluation --- p.92 / Chapter 5.1.5 --- Polymer-based immunohistochemical detection system --- p.93 / Chapter 5.1.6 --- Statistical analyses --- p.93 / Chapter 5.2 --- Results / Chapter 5.2.1 --- Confirmation of proteomic findings using immunocytochemical stainings in paraffin-embedded sections of 5-fluorouracil treated and untreated SW480 cells --- p.94 / Chapter 5.3 --- Discussion / Chapter 5.3.1 --- Immunocytochemical staining to verify proteomics findings of 5-fluorouracil treated and untreated SW480 cells --- p.99 / Chapter 5.3.2 --- Limitations of ICC staining --- p.100 / Chapter 5.3.3 --- Summary --- p.100 / Chapter Chapter 6: --- Conclusions and future perspectives / Chapter 6.1 --- Significance of study --- p.101 / Chapter 6.2 --- Future perspectives --- p.102 / References --- p.105

A pressão positiva contínua nas vias aéreas (CPAP) é o tratamento de escolha para pacientes com Apnéia Obstrutiva do Sono, mas muitos sintomas nasais conseqüentes da terapia são relatados. Vazamentos aéreos pela boca e alterações do epitélio respiratório são importantes no desenvolvimento de sintomas nasais e a umidificação aquecida é utilizada no alívio destes sintomas. O objetivo deste trabalho foi o de investigar os efeito agudos do nCPAP e o impacto da umidificação aquecida e vazamento aéreo no transporte mucociliar e inflamação nasal de indivíduos sadios. Para este fim avaliamos o transporte mucociliar nasal in vivo (através do Teste da Sacarina), a transportabilidade in vitro do muco nasal (através do Método Palato de Rã), lavado nasal e sintomas respiratórios (através de uma Escala Visual Analógica) de dezesseis indivíduos sadios antes e após aplicação aguda do CPAP sobre diferentes condições: CPAP com e sem umidificação aquecida e CPAP com e sem vazamento aéreo. O transporte mucociiar nasal in vivo aumentou significativamente após todas as intervenções com CPAP. Não houve diferença significativa da transportabilidade do muco, contagem total e diferencial de células inflamatórias provenientes do lavado nasal após nenhuma das intervenções com o CPAP. Houve um aumento significante da percepção subjetiva dos sintomas respiratórios estudados após o uso do CPAP sem umidificação e com vazamento aéreo. Concluimos que o uso agudo do CPAP independente da umidificação ou vazamento aéreo, aumenta significativamente o transporte mucociliar nasal in vivo, não altera significativamente a transportabilidade do muco nasal nem a composição celular de amostras de lavado nasal. Já o uso do CPAP sem umidificação e com vazamento aéreo causa aumento significativo dos sintomas de ressecamento nasal e de garganta, coriza e obstrução nasal. / Continuous positive airway pressure (CPAP) is the treatment of choice for patients with Obstructive Sleep Apnea but yet nasal symptoms are often reported. Air leaks and changes of the respiratory epithelium are important in the development of nasal symptoms and heated humidification is used to alleviate these symptoms. The aim of this study was to investigate the acute effects of CPAP and the impact of heated humidification and air leak on the nasal mucociliary clearance and nasal inflammation of healthy volunteers. To this end we evaluated nasal mucociliary clearance in vivo (through the Saccharin Test), in vitro nasal mucus transportability (through the Frog Palate Model), nasal lavage and respiratory symptoms (through a Visual Analogue Scale) of sixteen healthy volunteers before and after acute CPAP application under different conditions: CPAP with and without heated humidification and with and without air leak. In vivo nasal mucociliary clearance increased significantly after all CPAP interventions. There was no significant difference in mucus transportability, total or differential inflammatory cell count from the nasal lavage after any CPAP intervention. There was a significant increase in the subjective perception of the respiratory symptoms studied after the use of CPAP without humidification and with air leak. We conclude that the acute use of CPAP independently of humidification or air leak significantly increases in vivo nasal mucociliary clearance, doesn\'t change mucus transportability and total or differential cell count. However, the use o CPAP without humidification and with air leak significantly increased nasal and throat dryness, coryza and nasal obstruction subjective perception.

[Truncated abstract] Background: A review of the literature indicated there was a need for more long-term randomised controlled studies on the effects of BRCA counselling/testing on high risk women, including improved strategies for risk communication. Reviews have also shown women are confused about the significance of inconclusive or non informative results with a need for more research in this area. Aims: The general aim of this study was to evaluate the impact of breast cancer genetic counselling on psychological distress levels, perception of risk, genetic knowledge and understanding of BRCA testing/test results in a cohort of 207 women from high risk breast cancer families who were referred for genetic counselling in Perth during the period 1997 to 2001. Short- and long-term impact of BRCA genetic counselling/testing was determined in women with and without cancer in a randomised controlled trial as part of which women were randomised to either receive immediate versus delayed genetic counselling. This included family communication patterns before BRCA testing, anticipated outcomes of testing on oneself and family including intentions for result disclosure. Comprehension of index and predictive BRCA testing with possible results was assessed both in the short- and the long-term and understanding of individual or family BRCA test results was evaluated at long-term. The effect of genetic counselling on breast cancer risk perception in unaffected women was evaluated. This study considered a theoretical framework of educational learning theories to provide a basis for risk communication with possible relevance for future research. ... Only 25% of the original study population (52/207) reported BRCA results and women's understanding of results is concerning. Key findings were: 1. The majority of affected women received an inconclusive result. 2. Out of twelve unaffected women who reported results, seven were inconclusive which are not congruent with predictive testing. This implies that these women did not understand their test result. 3. A minority of untested relatives did not know whether a family mutation had or had not been found in their tested family member or what their actual test result was. This implies either a lack of disclosure or that woman did not understand the rationale for and significance of testing for a family mutation. 4. Three relatives did not understand a positive result was a mutation. Conclusion: The implication of this research for breast cancer counselling and testing services is that women who wait for counselling are no worse off in terms of short- or long-term general psychological distress than women who receive the intervention early. There is a suggestion that unaffected women without the disease found counselling more advantageous than affected women. The meaning of BRCA results as reported by women is concerning particularly women's understanding of negative and inconclusive results and further research is needed in this area. Too much information presented at counselling may affect women's comprehension of risk, BRCA testing and future test results and further research is required to evaluate the effects of information overload.

A pressão positiva contínua nas vias aéreas (CPAP) é o tratamento de escolha para pacientes com Apnéia Obstrutiva do Sono, mas muitos sintomas nasais conseqüentes da terapia são relatados. Vazamentos aéreos pela boca e alterações do epitélio respiratório são importantes no desenvolvimento de sintomas nasais e a umidificação aquecida é utilizada no alívio destes sintomas. O objetivo deste trabalho foi o de investigar os efeito agudos do nCPAP e o impacto da umidificação aquecida e vazamento aéreo no transporte mucociliar e inflamação nasal de indivíduos sadios. Para este fim avaliamos o transporte mucociliar nasal in vivo (através do Teste da Sacarina), a transportabilidade in vitro do muco nasal (através do Método Palato de Rã), lavado nasal e sintomas respiratórios (através de uma Escala Visual Analógica) de dezesseis indivíduos sadios antes e após aplicação aguda do CPAP sobre diferentes condições: CPAP com e sem umidificação aquecida e CPAP com e sem vazamento aéreo. O transporte mucociiar nasal in vivo aumentou significativamente após todas as intervenções com CPAP. Não houve diferença significativa da transportabilidade do muco, contagem total e diferencial de células inflamatórias provenientes do lavado nasal após nenhuma das intervenções com o CPAP. Houve um aumento significante da percepção subjetiva dos sintomas respiratórios estudados após o uso do CPAP sem umidificação e com vazamento aéreo. Concluimos que o uso agudo do CPAP independente da umidificação ou vazamento aéreo, aumenta significativamente o transporte mucociliar nasal in vivo, não altera significativamente a transportabilidade do muco nasal nem a composição celular de amostras de lavado nasal. Já o uso do CPAP sem umidificação e com vazamento aéreo causa aumento significativo dos sintomas de ressecamento nasal e de garganta, coriza e obstrução nasal. / Continuous positive airway pressure (CPAP) is the treatment of choice for patients with Obstructive Sleep Apnea but yet nasal symptoms are often reported. Air leaks and changes of the respiratory epithelium are important in the development of nasal symptoms and heated humidification is used to alleviate these symptoms. The aim of this study was to investigate the acute effects of CPAP and the impact of heated humidification and air leak on the nasal mucociliary clearance and nasal inflammation of healthy volunteers. To this end we evaluated nasal mucociliary clearance in vivo (through the Saccharin Test), in vitro nasal mucus transportability (through the Frog Palate Model), nasal lavage and respiratory symptoms (through a Visual Analogue Scale) of sixteen healthy volunteers before and after acute CPAP application under different conditions: CPAP with and without heated humidification and with and without air leak. In vivo nasal mucociliary clearance increased significantly after all CPAP interventions. There was no significant difference in mucus transportability, total or differential inflammatory cell count from the nasal lavage after any CPAP intervention. There was a significant increase in the subjective perception of the respiratory symptoms studied after the use of CPAP without humidification and with air leak. We conclude that the acute use of CPAP independently of humidification or air leak significantly increases in vivo nasal mucociliary clearance, doesn\'t change mucus transportability and total or differential cell count. However, the use o CPAP without humidification and with air leak significantly increased nasal and throat dryness, coryza and nasal obstruction subjective perception.

Alterações no aspecto do disco óptico e da camada de fibras nervosas da retina (CFN) freqüentemente precedem o aparecimento de defeitos de campo visual no glaucoma, o que faz com que a avaliação destas estruturas seja essencial para o diagnóstico precoce e prevenção da perda visual nesta doença. A polarimetria de varredura a laser (GDx VCC), a oftalmoscopia confocal de varredura a laser (HRT II [Heidelberg Retina Tomograph]) e a tomografia de coerência óptica (Stratus OCT) são tecnologias que permitem a avaliação objetiva e quantitativa do disco óptico e da CFN. No presente estudo, estas tecnologias foram comparadas em sua habilidade para diferenciar pacientes glaucomatosos de indivíduos normais. Pacientes com glaucoma foram selecionados com base na presença de defeitos reprodutíveis de campo visual na perimetria acromática automatizada (glaucoma perimétrico), ou com base na evidência documentada de progressão do dano glaucomatoso ao disco óptico, sem presença de defeitos de campo visual (glaucoma pré-perimétrico). Indivíduos normais apresentaram campos visuais e exame clínico dentro da normalidade. Todos os indivíduos foram submetidos a exames com o GDx VCC, HRT II, Stratus OCT e campo visual dentro de um período de três meses. Diversas medidas foram utilizadas para avaliação da acurácia diagnóstica, incluindo áreas sob as curvas receiver operating characteristic (AROC), sensibilidades para especificidades fixas, e razões de probabilidade. Modelos estatísticos foram utilizados para avaliação da influência da severidade do glaucoma e tamanho do disco óptico na performance diagnóstica dos diferentes instrumentos. Um olho de cada indivíduo foi utilizado para análise. Dos 258 sujeitos inicialmente avaliados, 33 (13%) foram posteriormente excluídos por apresentarem imagens de baixa qualidade em pelo menos um dos aparelhos, restando 225 indivíduos (133 glaucomatosos e 92 normais) para análise. Na comparação entre os parâmetros de cada instrumento com maiores valores de AROC, o parâmetro do GDx VCC, Nerve Fiber Indicator (NFI; AROC = 0,91), e o parâmetro do Stratus OCT, Espessura Média (AROC = 0,90), apresentaram áreas sob as curvas ROC significativamente superiores à do parâmetro do HRT II, função discriminante de Bathija (AROC = 0,84). A severidade do defeito de campo visual exerceu influência significativa sob a acurácia diagnóstica dos três instrumentos, com melhora no poder diagnóstico em casos mais avançados da doença. Para o GDx VCC e Stratus OCT, o aumento no tamanho do disco óptico foi associado à diminuição na sensibilidade para detecção do glaucoma; enquanto que, para o HRT II, diminuição no tamanho do disco óptico foi associada à diminuição na sensibilidade. Razões de probabilidade para resultados anormais nas xxv classificações finais de cada instrumento foram associadas a grandes efeitos de mudança na probabilidade pós-teste em relação à probabilidade préteste, sugerindo que o encontro de um resultado anormal em qualquer um destes testes, durante a avaliação de um paciente com suspeita de glaucoma, tem impacto significativo em aumentar a probabilidade de que a doença esteja presente. Além disso, os resultados obtidos na avaliação de pacientes com glaucoma pré-perimétrico sugerem que todos os três instrumentos sejam capazes de detectar alterações estruturais precoces no glaucoma, antes do aparecimento de defeitos de campo visual na perimetria acromática / Changes in the structural appearance of the optic nerve head (ONH) and retinal nerve fiber layer (RNFL) have been reported to precede the development of visual field loss in glaucoma. Detection of ONH and RNFL damage is therefore crucial for early diagnosis of glaucoma and prevention of functional loss from the disease. Scanning laser polarimetry (GDx VCC), confocal scanning laser ophthalmoscopy (HRT II [Heidelberg Retina Tomograph]) and optical coherence tomography (Stratus OCT) are different technologies capable of providing objective and quantitative information related to these structures. The purpose of the present study was to compare, in a single population, the diagnostic abilities of these technologies in the discrimination of glaucomatous patients from healthy subjects. Glaucoma patients were selected based on the presence of repeatable visual field defects, as identified by standard automated perimetry (perimetric glaucoma), or documented evidence of progressive damage to the optic disc, in the absence of detectable visual field loss (preperimetric glaucoma). Normal subjects had normal visual fields and normal clinical examination. All subjects underwent imaging with the GDx VCC, HRT II and Stratus OCT within a 3-month period. Several measures were used for evaluation of diagnostic accuracy, including the area under the receiver operating characteristic curve (AROC), sensitivities at fixed specifities, and likelihood ratios. Statistical models were used to evaluate the influence of glaucoma severity and optic disc size on the diagnostic performance of the different instruments. One eye of each individual was randomly selected for statistical analysis. From an initial group of 258 eligible subjects, 33 (13%) had images of unacceptable quality, leaving 133 glaucoma patients and 92 healthy subjects for further analysis. In the comparison of the parameters with highest values of AROC from each instrument, the GDx VCC Nerve Fiber Indicator (AROC = 0.91) and the Stratus OCT Average Thickness (AROC = 0.90) perfomed significanlty better than the HRT II Bathija discriminant function (AROC = 0.84). For all instruments, the diagnostic accuracy increased with increasing severity of visual field defects. For the GDx VCC and Stratus OCT parameters, an increase in the size of the optic disc was related to a decrease in the sensitivity for glaucoma detection. An opposite effect was observed with the HRT II: a decrease in the size of the optic disc was related to a decrease in the sensitivity for glaucoma diagnosis. Abnormal results for each of the instruments were associated with strong positive likelihood ratios, indicating a large change from prestest to posttest probability of glaucoma. These results suggest that the finding of an abnormal result in any of these tests, when assessing a patient suspect of having glaucoma, would substantially raise the probability of disease. Results of the evaluation of patients with preperimetric glaucoma also suggest that all three instruments are able to detect early glaucomatous structural damage in the absence of visual field loss

As afecções que acometem a via óptica anterior podem acarretar perda de fibras das células ganglionares retinianas, gerando alterações na camada de fibras nervosas da retina (CFNR). O objetivo deste trabalho foi o de comparar a capacidade da tomografia de coerência óptica (OCT-1), do OCT 3 (Stratus OCT) e do polarímetro de varredura a laser (GDx) em diferenciar olhos normais de olhos com atrofia em banda do nervo óptico e hemianopsia temporal, assim como, comparar o desempenho de tais tecnologias entre si. Foram estudados 37 indivíduos num total de 46 olhos divididos igualmente em dois grupos. O Stratus OCT, o OCT 1 e o GDx se mostraram capazes de identificar corretamente a redução global (average) da espessura da CFNR dos indivíduos com AB comparados com uma população normal. Observamos uma melhora progressiva das sensibilidades/especificidades e das AROC, com o desempenho melhor do OCT1 sobre o GDx e do Stratus OCT sobre o OCT 1 / Most diseases that affect the optic pathways present clinically with loss of one or more visual functions.When optic pathway injuries involve the anterior visual pathways they may cause loss of the retinal nerve fiber layer (RNFL) and "band atrophy" (BA). The purpose of this study was therefore to compare the ability of the optical coherence tomography (OCT) 1, the OCT 3 (Stratus OCT) and the scanning laser polarimetry (GDx) to differentiate normal eyes from eyes with BA of the optic nerve and temporal hemianopsia. Thirty-seven individuals in a total of 46 eyes divided equally in two groups were studied. Each one of the parameters, except the values from the nasal quadrant measured by the GDx, showed statistically significant difference when we compare normal patients with the BA group. The study also showed a gradual improvement of the sensibilities/specificities and of the AROC, with a better performance of the OCT1 compared to GDx and of the Stratus OCT compared to the OCT 1

Objetivos: Analisar o potencial da oftalmoscopia confocal de varredura a laser, através do Heidelberg Retina Tomograph (HRT), para predizer o risco de progressão em pacientes com suspeita de glaucoma. Comparar os resultados obtidos com o índice de probabilidade de glaucoma (GPS) do HRT aos resultados da análise de regressão de Moorfields (ARM), dos parâmetros morfométricos e da avaliação das fotografias estereoscópicas. Métodos: Uma coorte foi selecionada com 223 pacientes com suspeita de glaucoma, que foram seguidos por um período médio de 64,9 ± 37,3 meses. A suspeita de glaucoma baseou-se na aparência do disco óptico e/ou na pressão intraocular elevada (> 21 mmHg). Todos os participantes apresentavam dois exames de campo visual normais ao entrar no estudo. Conceituou-se progressão como o desenvolvimento de um defeito confirmado de campo visual ou deterioração do disco óptico na avaliação seriada das estereofotografias. A associação entre os resultados do HRT na época do início do acompanhamento e a progressão para glaucoma foi investigada através de modelos de regressão do tipo Cox. Usou-se o C-index para a comparação entre os modelos com os diversos parâmetros do HRT, isolados ou ajustados para os outros já conhecidos fatores de risco para progressão (idade, espessura corneana, pressão intraocular e pattern standard deviation PSD). Resultados: No período do estudo, 46 pacientes (21%) apresentaram progressão. Na análise multivariada, o GPS, a ARM e diversos parâmetros morfométricos foram preditivos para progressão, assim como a avaliação subjetiva das estereofotografias. Cada GPS 0,1 maior foi associado com um aumento de 23% no risco de progressão (C-index de 0,69). Os resultados anormais nas classificações finais do GPS e da ARM foram associados a aumentos de 3 e 2 vezes no risco de progressão, respectivamente (C-indexes de 0,70 e 0,68, respectivamente). O parâmetro com o melhor C-index foi a área seccional tranversa da camada de fibras nervosas (0,72). Uma área 0,3 mm2 menor foi associada a um risco 62% maior de progressão. A comparação do valor preditivo entre os modelos com o GPS e com a avaliação subjetiva das estereofotografias foi similar (C-indexes de 0,69 e 0,68, respectivamente). Conclusão: Nesse estudo observamos que as análises objetivas do disco óptico e da região peripapilar obtidas com o HRT contribuíram na avaliação do risco de progressão em pacientes com suspeita de glaucoma. O GPS mostrou-se tão eficaz quanto os parâmetros morfométricos e a análise de regressão de Moorfields, e a comparação do desempenho dos modelos contendo a avaliação subjetiva das estereofotografias e aqueles contendo a avaliação objetiva pelo GPS não mostrou diferenças significativas / Purpose: To evaluate the ability of baseline confocal scanning laser ophthalmoscopy, using the Heidelberg Retina Tomograph (HRT), in predicting the development of progression in patients suspected of having glaucoma. In addition, the study also aimed to compare the predictive abilities of the glaucoma probability score (GPS) with those of the Moorfields regression analysis (MRA) and stereometric parameters, and to compare the performance of the HRT with that of subjective evaluation of optic disc stereophotographs. Methods: This longitudinal study included a cohort of 223 eyes suspected of having glaucoma, which were followed for an average of 64.9 ± 37.3 months. Included suspects had a suspicious appearance of the optic disc and/or elevated intraocular pressure, but normal visual fields. Progression was defined as the development of either repeatable abnormal visual fields or glaucomatous structural deterioration in the appearance of the optic disc during the study period. The association between baseline HRT parameters and progression was investigated by Cox regression models. The comparison between models with HRT parameters, individually or combined with other known risk factors (age, central corneal thickness, pattern standard deviation and intraocular pressure), performed by comparing their C-indexes. Results: Forty-six (21%) eyes converted during the study period. In multivariable models, the GPS, the MRA, and the stereometric parameters were all predictive of progression. A GPS 0.1 larger was associated with an increase of 23% in the risk of progression (C-index of 0.69). Abnormal final classifications for the GPS or the MRA were associated with a three-fold and two-fold increase in the risk of progression, respectively (with C-indexes of 0.70 and 0.68, respectively). The parameter with the best C-index was the nerve fiber layer cross-sectional area (0.72). An area 0.3 mm2 smaller was associated with a 62% higher risk of an individual progress. The comparison between models with the HRT parameters and those with the subjective stereophotograph evaluation had similar results (C-indexes of 0.69 and 0.68, respectively). Conclusion: In this study, we were able to show that the objective structural assessment of the optic disc and peripapillary area obtained with the HRT was significantly predictive for progression in suspected individuals. The GPS was as predictive as the other HRT parameters, and no significant differences were observed between models with the GPS and those with the subjective assessment of the stereophotographs.

INTRODUÇÃO: A realização de procedimentos invasivos e o comprometimento da função hepática têm sido apontados como importantes fatores predisponentes à peritonite bacteriana primária (PBE) em pacientes cirróticos. Apesar das bactérias gram-negativas ainda serem os agentes mais freqüentemente isolados, a incidência de infecção por bactérias gram positivas tem aumentado. OBJETIVOS: Analisar os fatores de risco para PBE em pacientes cirróticos e relacionar o perfil da flora infectante do líquido ascítico com o uso de antibióticos. MÉTODOS: Estudo retrospectivo de resultados de 1.114 paracenteses realizadas em 348 pacientes no período de 2005 a 2007 no Departamento de Gastroenterologia do Hospital das Clínicas da Universidade de São Paulo. Foram definidos dois grupos: com e sem PBE, segundo resultado da leucometria do líquido ascítico. Os seguintes fatores foram analisados: aspartato aminotransferase (AST); alanina aminotransferase (ALT); bilirrubinas totais; INR; creatinina; uso do propranolol e sua resposta hemodinâmica; antecedente de hemorragia digestiva alta; choque hipovolêmico; tratamento endoscópico de varizes de esôfago; sondagem vesical; cateteres intravenosos; gravidade da doença hepática (escores de Child-Pugh, MELD e MELD-Na); infecções associadas e o perfil da flora infectante, segundo o uso de antibióticos. RESULTADOS: 852 paracenteses em 303 pacientes foram incluídas. A etiologia mais freqüente da cirrose hepática foi hepatite crônica C (25,4%), seguida por álcool (24,1%). O diagnóstico de PBE foi estabelecido em 82 (9,6%) paracenteses, 27 (33%) da forma clássica e 55 (67%) com cultura negativa. No grupo com PBE, observamos níveis mais elevados de bilirrubinas totais e INR (p<0,0001 e p= 0,0016, respectivamente). Não houve diferença entre os grupos, quanto ao uso de betabloqueadores e risco de PBE (32,9% versus 37,3%, p=0,533) e a resposta hemodinâmica ao propranolol (68,2% versus 70%, p=1,00), assim como em relação às seguintes variáveis: hemorragia digestiva alta (6,1% versus 2,5%, p=0,074), escleroterapia endoscópica (2,4% versus 0,8%, p=0,178), sondagem vesical (4,9% versus 2,3%, p=0,138), cateterismo venoso (2,4% versus 1,7%, p= 0,649). O grupo com PBE apresentou maior percentual de pacientes Child C, 51% versus 37%, (p=0,022) e maior frequência de choque hipovolêmico 2,5% versus 0,3% (p=0,0484). Não houve diferença quanto às infecções associadas (p=1,00). No grupo com PBE, as bactérias gram-positivas foram isoladas em 55,6% e as gram-negativas em 44,4% (p=0,3848). Não houve relação entre a presença de infecção por gram positivos e o uso de quinolonas (p=1,00). O aumento de um ponto no escore MELD aumentou o risco de infecção em 1,059 vezes [IC 95% : 1,0266; 1,0930] ou 6%. Não houve diferença no risco de PBE quando analisamos faixas de valores do MELD. O aumento de um ponto no MELD-Na aumentou o risco de infecção em 1,0283 vezes [IC 95%: 1,0073; 1,0497] ou 2,8%. Entretanto, o aumento de um ponto de MELD-Na na faixa entre 6 e 15 aumentou a probabilidade de infecção em 1,3371vezes [IC 95%: 1,0230; 1,7476], entre 16 e 24 aumentou em 3,2371 vezes [IC 95%: 0,1958; 53,5291] e acima de 24 pontos em 14,2663 vezes [IC 95%: 1,2441; 163,5990]. CONCLUSÕES: Pacientes com PBE apresentaram níveis mais elevados das bilirrubinas e de INR, maior frequência de choque hipovolêmico e maior gravidade da cirrose hepática, avaliada pelos escores Child-Pugh, MELD e MELD-Na, sendo o declínio da função hepática, o principal fator de risco para desenvolvimento de PBE. O uso de betabloqueadores e a resposta hemodinâmica ao propranolol não foram associados à proteção contra PBE. O MELD-Na discriminou o risco de infecção em faixas de pontuação e de gravidade. Não houve diferença significante na frequência de infecção por bactérias gram positivas e gram negativas nos pacientes com PBE. Não observamos relação entre a frequência de infecção por gram positivos e uso de quinolonas / INTRODUCTION: Invasive procedures and the decline of the liver function have been considered predisposing factors for spontaneous bacterial peritonitis (SBP) in cirrhotic patients. In spite of the predominance of gram negative, the incidence of gram positive agents is increasing in literature. OBJETIVES: To analyze the risk factors for SBP in cirrhotic patients and to assess if there is increase in the frequency of infection by gram positive agents, according to the use of antibiotics. METHODS: In this retrospective study, the results of 1.114 paracentesis carried out in 348 patients from 2005 to 2007 in the Department of Gastroenterology of the University of São Paulo were enrolled. According to the result of ascitic fluid leucometry, two groups were formed: with and without SBP. The following factors were assessed: aspartate aminotransferase; alanine aminotransferase; bilirubin; INR; creatinine; use of propranolol and hemodynamic response; previous gastrointestinal hemorrhage; hypovolemic shock; endoscopic therapy of esophageal varices; vesical catheter, indwelling vascular catheter, severity of the underlying liver disease (scores Child-Pugh, MELD and MELD-Na); concurrent bacterial infections and the frequency of gram positive bacteria according to the use of antibiotics. RESULTS: 852 paracentesis performed in 303 patients were included. The most prevalent etiology of cirrhosis was hepatitis C virus infection (25.4%), followed by alcoholic (24.1%). The diagnosis of SBP was established in 82 (9.6%) paracentesis, 27 (33%) of them were classical SBP and 55 (67%) were negative-culture SBP. In the SBP group, we found higher levels of bilirubin and more enlarged INR (p<0.0001 e p= 0.0016, respectively). There was no difference between the groups regarding the risk of SBP and the use of betablockers (32.9% versus 37.3%, p=0.533) or hemodynamic response to propranolol therapy (68.2% versus 70%, p=1.00). The following parameters did not reach statistical significance: gastrointestinal bleeding (6.1% versus 2.5%, p=0.074), endoscopic sclerotherapy of varices (2.4% versus 0.8%, p=0.78), vesical catheters (4.9% versus 2.3%, p=0.138), vascular catheters (2.4% versus 1.7%, p= 0.649). The SBP group had a higher frequency of Child C status patients, 51% versus 37%, (p=0.022) and higher frequency of hypovolemic shock 2.5% versus 0.3% (p=0.0484). There was no difference in the frequency of SBP in patients with or without concurrent bacterial infections (p=1,00). In the SBP group, gram positive staining bacteria were found in 55.6% and gram negative in 44.4% (p=0.3848). We found no relationship between gram positive bacteria infection and the use of quinolones (p=1.00). Every single point increased in the MELD score increased the risk of SBP in 1.059 times [95% IC: 1.0266; 1.0930] or by 6%. There was no significant difference in the odds ratio for SBP according to the stratification of MELD values. Every single point increased in the MELD-Na increased the risk of infection in 1.0283 times [95% IC: 1.0073; 1.0497] or 2.8%. Nevertheless, every point increased in the MELDNa between 6 and 15 increased the probability of infection in 1.3371 times [95%] IC: 1.0230; 1.7476], between 16 and 24 in 3.2371 times [95% IC: 0.1958; 53.5291] and higher than 24 points in 14.2663 times [95% IC: 1.2441; 163.5990]. CONCLUSIONS: Patients with SBP had higher levels of bilirubin and INR, higher frequency of hypovolemic shock and more severe underlying liver cirrhosis, as assessed by the Child-Pugh score, MELD and MELD-Na, indicating that the decline of the liver function is the main risk factor for developing SBP in cirrhosis. The use of betablockers and the hemodynamic response to propranolol were not associated to protection against developing SBP. The odds ratios for developing SBP increased according to the stratification of MELD-Na values, but not according to MELD stratification. There was no significant difference in the frequency of gram positive and gram negative infections in patients with SBP. The use of quinolones was not associated with increased frequency of gram positive infections in this series .