Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 3 uppsatser.

Thesis (M.S.)--University of Florida, 2003. / Title from title page of source document. Includes vita. Includes bibliographical references.

Introdução: Neurocisticercose (NCC) é a doença parasitária do sistema nervoso central (SNC) mais freqüente no mundo, afetando mais de 50 milhões de pessoas. No entanto, alguns de seus achados clínicos, tais como comprometimento cognitivo, é um aspecto pouco estudado na literatura e ainda permanece mal caracterizado. Objetivos: Avaliar o desempenho cognitivo de pacientes portadores de NCC e comparar o desempenho deste grupo em testes de avaliação cognitiva com o desempenho de indivíduos saudáveis (GC) e de indivíduos com epilepsia criptogênica (GE). O estudo objetivou também relacionar os achados com o tipo morfológico, número, localização dos cisticercos e fase de desenvolvimento do parasita. Métodos: 32 pacientes (média de idade = 45,2 ± 10,2 anos) com diagnóstico de NCC, com ou sem tratamento específico e em ambas as fases de desenvolvimento do parasita (formas ativa e inativa) foram submetidos a uma avaliação cognitiva, constituída de dez testes (memória, habilidades visuoespaciais, cálculo, abstração, praxias e gnosias e o Mini Exame do Estado Mental - MEEM), sendo comparados a 32 GC e 24 GE emparelhados por idade, gênero e nível educacional. Resultados: Pacientes com NCC apresentam prejuízo cognitivo, em comparação aos controles saudáveis em tarefas de memória visual, memória lógica imediata e recente. Pacientes com NCC e aqueles do GC apresentaram um desempenho cognitivo superior, em comparação ao GE; nos testes que envolveram a atenção e a memória operacional e na praxia reflexiva. Não houve diferença estatisticamente significativa no desempenho cognitivo nos três grupos estudados nos testes cognitivos que avaliaram a praxia construcional e ideomotora, cálculo e capacidade de abstração e julgamento. Não foi encontrada correlação entre alterações nos testes cognitivos dos pacientes com NCC e número de lesões e a fase de desenvolvimento do parasita. Em relação ao tipo morfológico, foi observado que os indivíduos que apresentavam a forma racemosa obtiveram um desempenho inferior no teste do Mini Exame do estado mental (MEEM), quando comparados aos que apresentavam a forma cística simples. Em relação à localização dos cisticercos, pode-se notar que os indivíduos com lesões de localização parenquimatosa demonstraram escores inferiores no teste de Faces Famosas e no teste de memória lógica recente, quando comparados àqueles com lesões ventriculares e no espaço subaracnóide. Conclusões: O declínio cognitivo foi uma manifestação clínica muito freqüente em nossa amostra de pacientes com NCC. Estes dados podem fornecer um conhecimento mais abrangente das manifestações clínicas presentes na NCC / Introduction: Neurocysticercosis (NCC) is the most frequent parasitic disease of the central nervous system (CNS), affecting more than 50 million people. However, some its clinical findings, such as cognitive impairment, are is an aspect little studied in the literature and remain poorly characterized. Aim: Assess the cognitive performance of patients with NCC and compare the performance of this group healthy controls (HC) and cryptogenic epilepsy (CE) patients. The study also aimed to relate the findings with the morphological type, number, location of cysticerci and development phase of the parasite. Methods: thirty-two patients (mean age = 45.2 ± 10.2 years) with diagnosis of NCC, with or without specific treatment and in both stages of parasite development (active and inactive forms) underwent a cognitive evaluation, constituted of ten tests. They were then compared to HC 32 and 24 CE, matched for age, gender and educational level. Results: NCC patients presented cognitive impairment compared to healthy controls in tasks of visual memory, immediate and recent logical memory. NCC patients and the HC presented a higher cognitive performance, compared to CE, in tests involving attention, working memory and reflective praxis. There was no statistically significant difference in cognitive performance among the three groups on cognitive tests that assessed ideomotor and constructional praxis, calculation and capacity for abstraction and trial. No correlation was found between changes in cognitive tests of patients NCC and number of lesions and stage of parasite development. Regarding to the morphological type, it was observed that individuals with the racemose form a lower performance in tests of the Mini Mental State Examination (MMSE), when compared to those who had the simple cystic form. Regarding location of cysticerci, it was noted that individuals with parenchymal lesions showed lower scores in the Famous Faces Test and recent test of logical memory when compared to those with lesions in the ventricular and subarachnoid space. Conclusions: The cognitive decline was a very frequent clinical manifestation in our sample of patients NCC. This data provide a better understanding of the broader clinical manifestations in patients with NCC

Introdução: Neurocisticercose (NCC) é a doença parasitária do sistema nervoso central (SNC) mais freqüente no mundo, afetando mais de 50 milhões de pessoas. No entanto, alguns de seus achados clínicos, tais como comprometimento cognitivo, é um aspecto pouco estudado na literatura e ainda permanece mal caracterizado. Objetivos: Avaliar o desempenho cognitivo de pacientes portadores de NCC e comparar o desempenho deste grupo em testes de avaliação cognitiva com o desempenho de indivíduos saudáveis (GC) e de indivíduos com epilepsia criptogênica (GE). O estudo objetivou também relacionar os achados com o tipo morfológico, número, localização dos cisticercos e fase de desenvolvimento do parasita. Métodos: 32 pacientes (média de idade = 45,2 ± 10,2 anos) com diagnóstico de NCC, com ou sem tratamento específico e em ambas as fases de desenvolvimento do parasita (formas ativa e inativa) foram submetidos a uma avaliação cognitiva, constituída de dez testes (memória, habilidades visuoespaciais, cálculo, abstração, praxias e gnosias e o Mini Exame do Estado Mental - MEEM), sendo comparados a 32 GC e 24 GE emparelhados por idade, gênero e nível educacional. Resultados: Pacientes com NCC apresentam prejuízo cognitivo, em comparação aos controles saudáveis em tarefas de memória visual, memória lógica imediata e recente. Pacientes com NCC e aqueles do GC apresentaram um desempenho cognitivo superior, em comparação ao GE; nos testes que envolveram a atenção e a memória operacional e na praxia reflexiva. Não houve diferença estatisticamente significativa no desempenho cognitivo nos três grupos estudados nos testes cognitivos que avaliaram a praxia construcional e ideomotora, cálculo e capacidade de abstração e julgamento. Não foi encontrada correlação entre alterações nos testes cognitivos dos pacientes com NCC e número de lesões e a fase de desenvolvimento do parasita. Em relação ao tipo morfológico, foi observado que os indivíduos que apresentavam a forma racemosa obtiveram um desempenho inferior no teste do Mini Exame do estado mental (MEEM), quando comparados aos que apresentavam a forma cística simples. Em relação à localização dos cisticercos, pode-se notar que os indivíduos com lesões de localização parenquimatosa demonstraram escores inferiores no teste de Faces Famosas e no teste de memória lógica recente, quando comparados àqueles com lesões ventriculares e no espaço subaracnóide. Conclusões: O declínio cognitivo foi uma manifestação clínica muito freqüente em nossa amostra de pacientes com NCC. Estes dados podem fornecer um conhecimento mais abrangente das manifestações clínicas presentes na NCC / Introduction: Neurocysticercosis (NCC) is the most frequent parasitic disease of the central nervous system (CNS), affecting more than 50 million people. However, some its clinical findings, such as cognitive impairment, are is an aspect little studied in the literature and remain poorly characterized. Aim: Assess the cognitive performance of patients with NCC and compare the performance of this group healthy controls (HC) and cryptogenic epilepsy (CE) patients. The study also aimed to relate the findings with the morphological type, number, location of cysticerci and development phase of the parasite. Methods: thirty-two patients (mean age = 45.2 ± 10.2 years) with diagnosis of NCC, with or without specific treatment and in both stages of parasite development (active and inactive forms) underwent a cognitive evaluation, constituted of ten tests. They were then compared to HC 32 and 24 CE, matched for age, gender and educational level. Results: NCC patients presented cognitive impairment compared to healthy controls in tasks of visual memory, immediate and recent logical memory. NCC patients and the HC presented a higher cognitive performance, compared to CE, in tests involving attention, working memory and reflective praxis. There was no statistically significant difference in cognitive performance among the three groups on cognitive tests that assessed ideomotor and constructional praxis, calculation and capacity for abstraction and trial. No correlation was found between changes in cognitive tests of patients NCC and number of lesions and stage of parasite development. Regarding to the morphological type, it was observed that individuals with the racemose form a lower performance in tests of the Mini Mental State Examination (MMSE), when compared to those who had the simple cystic form. Regarding location of cysticerci, it was noted that individuals with parenchymal lesions showed lower scores in the Famous Faces Test and recent test of logical memory when compared to those with lesions in the ventricular and subarachnoid space. Conclusions: The cognitive decline was a very frequent clinical manifestation in our sample of patients NCC. This data provide a better understanding of the broader clinical manifestations in patients with NCC

Introdução: Neurocistcercose (NC) é a doença parasitária do SNC mais frequente no mundo. Afeta mais de 50 milhões de pessoas. No entanto, algumas de suas manifestações clínicas, como comprometmento cognitivo e demência, ainda permanecem caracterizadas de modo incompleto, sem que haja estudos controlados disponíveis na literatura até o momento. Objetvos: Investigar a frequência e o perfil clínico do comprometimento cognitivo associado à NC ativa, comparando o desempenho em testes de avaliação cognitiva de pacientes com a doença ao de controles saudáveis (CS) e de pacientes com epilepsia criptogênica (EC). Métodos: Quarenta pacientes (idade média = 39,25 ± 10,50 anos), com diagnóstco de NC ativa segundo critérios absolutos à ressonância magnética (RM) de crânio e sem tratamento antiparasitário prévio foram submetdos à avaliação cognitiva e funcional extensas, sendo comparados a 49 CS e 28 pacientes com EC emparelhados por idade, nível educacional e frequência de crises epilépticas (grupo EC). Resultados: Pacientes com NC apresentaram comprometimento significativo em relação ao grupo CS nos testes que avaliam funções executivas, memória verbal e não verbal, praxia construtiva e fluência verbal (p<0,05). Demência foi diagnosticada em 12,5% dos pacientes com NC de acordo com os critérios do DSM-IV. Os doentes do grupo NC apresentaram desempenho significativamente inferior em testes de memória operacional, memória episódica verbal, funções executivas, nomeação, praxia construtiva e orientação visual-espacial, quando comparados àqueles do grupo EC. Não se encontrou correlação entre as alterações nos testes cognitivos nos pacientes com NC e os achados à RM (carga de doença, tipo e localização das lesões). Conclusões: Comprometimento cognitivo foi muito frequente na amostra de pacientes com NC avaliada, sendo que demência foi identificada em uma proporção significativa dos doentes. Estes dados aumentam o nosso conhecimento sobre a apresentação clínica da NC e sobre seu potencial impacto na saúde pública. / Introducton: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, afecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of NCYST patents in comparison to cognitvely healthy controls (HC) and to cryptogenic epilepsy (CE) patents. Methods: Forty treatment-naïve NCYST patients aged 39.25 ± 10.50 years and fulfilling absolute criteria for definitive active NCYST on magnetic resonance imaging (MRI), underwent a comprehensive cognitive and functional evaluation and were compared to 49 HC and 28 CE patients of similar age, educational level, and seizure frequency. Results: NCYST patients displayed significant impairment in executive functions, verbal and non-verbal memory, constructive praxis, and verbal fluency when compared to HC (p<0.05). Dementia was diagnosed in 12.5% of NCYST patients according to the DSM-IV criteria. When compared to CE patients, NCYST patients presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatal orientation. No correlation emerged between cognitive scores and number, localization or type of NCYST lesions on MRI. Conclusions: Cognitive impairment was ubiquitous in this sample of active NCYST patients. Antepileptic drug use and seizure frequency could not account for these features. Dementia was present in a signifcant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in public health

Orientador: Vanda Maria Gimenes Gonçalves / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T15:33:08Z (GMT). No. of bitstreams: 1 Carvalho_MariaImaculadaMerlinde_M.pdf: 5079620 bytes, checksum: 57af6f7ff10156c4b75c019bc0f1d9e2 (MD5) Previous issue date: 2009 / Resumo: Essa pesquisa foi proposta tendo como objetivo o estudo dos sinais neurológicos, utilizando semiologia neurológica detalhada, em um grupo de escolares portadores de dislexia do desenvolvimento, comparados a um grupo sem queixa escolar. O grupo disléxico foi constituído por 12 escolares com diagnóstico de dislexia do desenvolvimento comprovada pelas avaliações neuropsicológica, fonoaudiológica e neurológica; projeto de pesquisa aprovado pelo Comitê de Ética em Pesquisa da instituição e os pais assinaram o Termo de Consentimento Livre e Esclarecido; idade cronológica mínima de 8 anos. O grupo controle foi composto por escolares bons leitores, sem dificuldades ou distúrbios de aprendizagem, indicados por professores e avaliados pela fonoaudióloga, pareados com os disléxicos por gênero e idade. Foram excluídos os escolares com diagnóstico de distúrbio de aprendizagem, com deficiência auditiva e visual, deficiência mental, síndromes genéticas ou grandes malformações, não comparecimento à primeira avaliação após três convocações sucessivas. Foram avaliados pelo Exame Neurológico Tradicional (ENT), Exame Neurológico Evolutivo (ENE) e Quick Neurological Screening Test II (QNST-II). O ENT foi normal em todos os escolares do grupo controle e em três do grupo disléxico; a alteração mais freqüente foi leve hipotonia muscular global ou localizada em membros superiores, observada em oito escolares como um achado isolado ou associado a outras alterações. O ENE foi normal em todos os escolares do grupo controle e alterado em todos do grupo disléxico. Nenhum participante apresentou dificuldade em equilíbrio dinâmico. Dentre os setores alterados os mais freqüentes foram persistência motora e tono muscular. As alterações detectadas foram heterogêneas, não constituindo um padrão ao exame do grupo disléxico. O QNST-II foi normal em todos os escolares do grupo controle e alterado em todos os participantes do grupo disléxico. O QNST-II identificou o grupo disléxico, com mediana de pontuação total 33 ± 11,95, classificado como desvio moderado e o grupo controle com pontuação total de 13,5 ± 4,57, classificado como normal, com diferença significativa entre os grupos (p-valor = 0,0005, teste de Wilcoxon). Alguns subtestes mostraram mediana de pontuação significativamente maior no grupo disléxico: habilidade manual, reconhecimento e reprodução de figuras, reprodução de formas na palma da mão, padrões sonoros, movimentos manuais reversos rápidos e repetitivos, extensão de braços e pernas, ficar em uma só perna, irregularidades comportamentais. Concluiuse que o uso desta técnica de avaliação neurológica acrescentou novos elementos semióticos no estudo do grupo disléxico. / Abstract: The objective was to propose a study of neurological signs, using detailed neurological semiology in a group of school aged children that had developmental dyslexia, compared to a group without learning disabilities. A group of 12 students were identified as dyslexic group, (1 girl and 11 boys), after neuropsychological, speech therapist and neurological evaluations. Ethical approval was obtained from the Research Ethics Committee of the institution and the families provided full informed consent; minimal chronological age of 8 years. They were matched on age and sex with the control group recruited in regular classroom placement, who were reading at grade level according to their school-teacher and the evaluation of the speech therapist. Those with learning disabilities, mental retardation, visual deficiency and hearing loss, genetic syndromes or malformations, or absence after three invitations were excluded. The Traditional Neurological Examination (TNE), Neurological Evolutional Examination (NEE) and Quick Neurological Screening Test II (QNST II) were used. The TNE was normal in the control group and in three of the dyslexic group. Muscular hypotonia was the most frequent alteration, observed in 8 schoolchildren. The NEE was normal in the control group and showed alterations in the entire dyslexic group. Nobody showed alteration in dynamic balance. The most altered items were the motor persistence and muscle tone. There was heterogeneous alterations, without a standard examination for the dislexic group. QNST II was normal in the control group and showed alterations in the entire dyslexic group. QNST II total scores correctly identified the dyslexic group, with median punctuation of total score 33 ± 11,95, classified as moderate discrepancy (MD) and the control group with 13,5 ± 4,57, classified as normal range (NR). The dyslexic group showed significantly higher scores than the control group (p-value = 0,0005, Wilcoxon test). Some subtests acted as a discriminator between the groups, with significantly higher scores in the dyslexic group in the subtests: hand skill, figure recognition and production, palm form recognition, sound patterns, rapidly reversing repetitive hand movements, arm and leg extension, stand on one leg, behavioral irregularities. We concluded that this technique of neurological evaluation added new semiotic elements in the study of the dyslexic group. / Mestrado / Neurologia / Mestre em Ciências Médicas

Introdução: Neurocistcercose (NC) é a doença parasitária do SNC mais frequente no mundo. Afeta mais de 50 milhões de pessoas. No entanto, algumas de suas manifestações clínicas, como comprometmento cognitivo e demência, ainda permanecem caracterizadas de modo incompleto, sem que haja estudos controlados disponíveis na literatura até o momento. Objetvos: Investigar a frequência e o perfil clínico do comprometimento cognitivo associado à NC ativa, comparando o desempenho em testes de avaliação cognitiva de pacientes com a doença ao de controles saudáveis (CS) e de pacientes com epilepsia criptogênica (EC). Métodos: Quarenta pacientes (idade média = 39,25 ± 10,50 anos), com diagnóstco de NC ativa segundo critérios absolutos à ressonância magnética (RM) de crânio e sem tratamento antiparasitário prévio foram submetdos à avaliação cognitiva e funcional extensas, sendo comparados a 49 CS e 28 pacientes com EC emparelhados por idade, nível educacional e frequência de crises epilépticas (grupo EC). Resultados: Pacientes com NC apresentaram comprometimento significativo em relação ao grupo CS nos testes que avaliam funções executivas, memória verbal e não verbal, praxia construtiva e fluência verbal (p<0,05). Demência foi diagnosticada em 12,5% dos pacientes com NC de acordo com os critérios do DSM-IV. Os doentes do grupo NC apresentaram desempenho significativamente inferior em testes de memória operacional, memória episódica verbal, funções executivas, nomeação, praxia construtiva e orientação visual-espacial, quando comparados àqueles do grupo EC. Não se encontrou correlação entre as alterações nos testes cognitivos nos pacientes com NC e os achados à RM (carga de doença, tipo e localização das lesões). Conclusões: Comprometimento cognitivo foi muito frequente na amostra de pacientes com NC avaliada, sendo que demência foi identificada em uma proporção significativa dos doentes. Estes dados aumentam o nosso conhecimento sobre a apresentação clínica da NC e sobre seu potencial impacto na saúde pública. / Introducton: Neurocysticercosis (NCYST) is the most frequent CNS parasitic disease worldwide, afecting more than 50 million people. However, some of its clinical findings, such as cognitive impairment and dementia, remain poorly characterized, with no controlled studies conducted so far. We investigated the frequency and the clinical profile of cognitive impairment and dementia in a sample of NCYST patents in comparison to cognitvely healthy controls (HC) and to cryptogenic epilepsy (CE) patents. Methods: Forty treatment-naïve NCYST patients aged 39.25 ± 10.50 years and fulfilling absolute criteria for definitive active NCYST on magnetic resonance imaging (MRI), underwent a comprehensive cognitive and functional evaluation and were compared to 49 HC and 28 CE patients of similar age, educational level, and seizure frequency. Results: NCYST patients displayed significant impairment in executive functions, verbal and non-verbal memory, constructive praxis, and verbal fluency when compared to HC (p<0.05). Dementia was diagnosed in 12.5% of NCYST patients according to the DSM-IV criteria. When compared to CE patients, NCYST patients presented altered working and episodic verbal memory, executive functions, naming, verbal fluency, constructive praxis, and visual-spatal orientation. No correlation emerged between cognitive scores and number, localization or type of NCYST lesions on MRI. Conclusions: Cognitive impairment was ubiquitous in this sample of active NCYST patients. Antepileptic drug use and seizure frequency could not account for these features. Dementia was present in a signifcant proportion of patients. These data broaden our knowledge on the clinical presentations of NCYST and its impact in public health

Lee Nga Lan. / Thesis submitted in: June 1997. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references. / Abstract also in Chinese. / Abstract --- p.i / Acknowledgment --- p.iii / Table of contents --- p.iv / List of tables --- p.viii / List of figures --- p.x / Glossary of abbreviations --- p.xi / Chapter CHAPTER 1. --- INTRODUCTION --- p.1 / Chapter CHAPTER 2. --- BACKGROUND --- p.3 / Chapter 2.1 --- OUTBREAKS OF SOLVENT INDUCED NEUROPATHY IN MAN --- p.3 / Chapter 2.2 --- WORLD-WIDE INVESTIGATIONS ON ORGANIC SOLVENTS HAZARDS --- p.5 / Chapter 2.3 --- HEALTH EEFECTS OF ORGANIC SOLVENTS --- p.8 / Chapter 2.3.1 --- Effects on the Nervous System --- p.9 / Chapter (a) --- Peripheral Nervous System / Chapter (b) --- Central Nervous System / Chapter 2.3.2 --- Other Effects --- p.13 / Chapter 2.4 --- METHODOLOGICAL ISSUES IN THE INVESTIGATION OF SOLVENT NEUROTOXICITY --- p.14 / Chapter 2.4.1 --- Study Design --- p.15 / Chapter 2.4.2 --- Exposure Measurements --- p.17 / Chapter 2.4.3 --- Outcome Effects Measurements --- p.18 / Chapter 2.5 --- UNSOLVED PROBLEMS IN THE STUDY OF SOLVENT NEUROTOXICITY --- p.20 / Chapter 2.6 --- ORGANIC SOLVENTS IN THE PRINTING INDUSTRY --- p.21 / Chapter 2.7 --- PRINTING METHODS --- p.25 / Chapter 2.8 --- OFFSET LITHOGRAPHY --- p.27 / Chapter 2.8.1 --- Principles of Offset Lithography --- p.28 / Chapter 2.8.2 --- Image Carriers for Offset Lithography --- p.29 / Chapter 2.8.3 --- Lithographic Presses --- p.32 / Chapter 2.8.4 --- Printing Process --- p.34 / Chapter CHAPTER 3. --- STUDY OBJECTIVES AND METHODS --- p.37 / Chapter 3.1 --- OBJECTIVES --- p.37 / Chapter 3.2 --- METHODS --- p.38 / Chapter 3.2.1 --- Study Population --- p.38 / Chapter 3.2.2 --- Visits --- p.41 / Chapter 3.2.3 --- Workers' Health Assessment --- p.42 / Chapter 3.2.4 --- Air Sampling --- p.44 / Chapter 3.2.5 --- Definition of Exposures --- p.48 / Chapter 3.3 --- DATA ANALYSIS --- p.49 / Chapter CHAPTER 4. --- RESULTS --- p.51 / Chapter 4.1 --- RESPONSE RATE --- p.51 / Chapter 4.2 --- CHARACTERISTICS OF THE STUDY POPULATION --- p.53 / Chapter 4.2.1 --- Printing Companies --- p.53 / Chapter 4.2.2 --- Study Subjects --- p.56 / Chapter 4.3 --- HEALTH PROBLEMS OF STUDY SUBJECTS --- p.60 / Chapter 4.3.1 --- Sick Leave --- p.60 / Chapter 4.3.2 --- Prevalence of Subjective Symptoms --- p.61 / Chapter 4.3.3 --- Mean Number of Symptoms --- p.64 / Chapter 4.4 --- AIR SAMPLING RESULTS --- p.66 / Chapter 4.4.1 --- Mean Concentration Levels of Solvents --- p.71 / Chapter 4.4.2 --- Mean Concentration Levels of Solvents by Printing Plants --- p.73 / Chapter 4.4.3 --- Mean Concentration Levels of Solvents by Locations --- p.75 / Chapter 4.5 --- EXPOSURE-RESPONSE RELATIONSHIPS BETWEEN ORGANIC SOLVENTS AND SYMPTOMS --- p.77 / Chapter 4.6 --- RISK FACTORS FOR SUBJECTIVE SYMPTOMS --- p.85 / Chapter CHAPTER 5. --- DISCUSSIONS --- p.90 / Chapter 5.1 --- RESPONSE RATE --- p.90 / Chapter 5.2 --- SOURCES OF BIAS --- p.91 / Chapter 5.3 --- STUDY SUBJECTS --- p.92 / Chapter 5.4 --- SOLVENT EXPOSURES --- p.93 / Chapter 5.4.1 --- Occupational Hygiene --- p.93 / Chapter 5.4.2 --- Exposure Classification --- p.95 / Chapter 5.4.3 --- Chemical Interaction --- p.98 / Chapter 5.5 --- HEALTH PROBLEMS --- p.99 / Chapter CHAPTER 6. --- CONCLUSION --- p.103 / REFERENCES --- p.105 / APPENDICES --- p.120 / Appendices A1 to A9: Newspaper reports on polyneuropathy induced by organic solvents in a Hong Kong printing factory --- p.120 / Appendix B: Telephone follow up form --- p.129 / Appendix C: Letter to the printing factory employer --- p.130 / Appendix D: Subjective symptom questionnaire for solvent workers --- p.131 / Appendix E: Questionnaire for exposed group workers --- p.132 / Appendix F: Questionnaire for non-exposed group workers --- p.140 / Appendix G: NIOSH Sampling and Analytical Method 1400 --- p.145 / Appendix H: NIOSH Sampling and Analytical Method 1500 --- p.150 / "Appendix I: Chemical Analytical Method from Department of Hygiene, School of Public Health, Sun Yat Sen University of Medical Sciences" --- p.157 / Appendix J: Air Sampling Worksheet --- p.159 / BIBLIOGRAPHY --- p.162

Song Hong. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves ). / Abstracts in English and Chinese; questionnaire in Chinese. / Abstract (English) --- p.i / Abstract (Chinese) --- p.iv / Acknowledgments --- p.vi / Table of Contents --- p.vii / List of tables --- p.x / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Printing industry and organic solvents exposure --- p.1 / Chapter 1.2 --- Risk of low level exposures to organic solvents --- p.2 / Chapter 1.3 --- Using neurobehavioral methods to study the subclinical effects --- p.3 / Chapter Chapter 2 --- Literature review --- p.4 / Chapter 2.1 --- Organic solvents and neurobehavioral impairment --- p.4 / Chapter 2.2 --- Methodology of Neurobehavioral Test --- p.6 / Chapter 2.2.1 --- Criteria for selecting test battery --- p.7 / Chapter 2.2.2 --- Standardization of neurobehavioral test battery --- p.8 / Chapter 2.2.3 --- Reliability and validity --- p.9 / Chapter 2.2.4 --- Confounding factors of neurobehavioral test --- p.10 / Chapter 2.3 --- Neurobehavioral effects of different levels of solvent exposures --- p.12 / Chapter 2.3.1 --- Positive results in field studies --- p.12 / Chapter 2.3.2 --- Negative results in field studies --- p.17 / Chapter 2.3.3 --- Dose-response relationship in the field studies --- p.18 / Chapter 2.3.4 --- To separate acute and chronic effects --- p.20 / Chapter 2.3.5 --- The long-term effects of solvent exposure --- p.21 / Chapter 2.4 --- Limitations of these studies --- p.23 / Chapter 2.5 --- Summary --- p.26 / Chapter Chapter 3 --- Aims and Objectives --- p.31 / Chapter 3.1 --- Aims of the present research --- p.31 / Chapter 3.2 --- Position of this study cm this research domain --- p.32 / Chapter Chapter 4 --- Subjects and Method --- p.33 / Chapter 4.1 --- Study design --- p.33 / Chapter 4.2 --- Study population and sampling --- p.33 / Chapter 4.2.1 --- Participation --- p.33 / Chapter 4.2.2 --- Exposed group --- p.34 / Chapter 4.2.3 --- Reference group --- p.34 / Chapter 4.2.4 --- Sample size estimation --- p.34 / Chapter 4.3 --- Data collection --- p.36 / Chapter 4.3.1 --- Exposure assessment --- p.36 / Chapter 4.3.1.1 --- Air sample measurements --- p.36 / Chapter 4.3.1.2 --- Biological monitoring --- p.38 / Chapter 4.3.2. --- Medical assessment --- p.38 / Chapter 4.3.2.1 --- Pre-test questionnaire --- p.39 / Chapter 4.3.2.2 --- Neurobehavioral assessment --- p.39 / Chapter 4.4 --- Data Analysis --- p.43 / Chapter 4.4.1 --- Data Processing --- p.43 / Chapter 4.4.2 --- Statistical analysis --- p.44 / Chapter 4.4.2.1 --- Descriptive analysis --- p.44 / Chapter 4.4.2.2 --- Identifying the main confounding factories --- p.44 / Chapter 4.4.2.3 --- Comparing the tests score adjusted for confounding --- p.45 / Chapter 4.4.2.4 --- Dose-response analysis --- p.45 / Chapter Chapter 5 --- Results --- p.47 / Chapter 5.1 --- Demographic characteristics of the subjects --- p.47 / Chapter 5.2 --- Comparison of the basic characteristics between the exposed group and the reference group --- p.48 / Chapter 5.3 --- Comparison of the symptoms between the exposed group and the reference group --- p.49 / Chapter 5.4 --- Comparison of the scores of neurobehavioral tests between the exposed group and the reference group --- p.51 / Chapter 5.5 --- Identifying potential confounding of neurobehavioral test --- p.51 / Chapter 5.5.1 --- Main confounding factors of NCTB test on performance tests --- p.51 / Chapter 5.5.2 --- Main confounding factors of Profile of Mood States --- p.54 / Chapter 5.6 --- Groups comparison of the neurobehavioral effects --- p.57 / Chapter 5.6.1 --- Comparison of the adjusted mean scores between the exposed group and the reference group --- p.57 / Chapter 5.6.2 --- Groups comparison of the adjusted tests score in Factories C and G respectively --- p.58 / Chapter 5.7 --- Exposure assessment --- p.61 / Chapter 5.7.1 --- Air sampling results of the printing factories --- p.62 / Chapter 5.7.2 --- Relationship between results of active and passive sampling systems --- p.63 / Chapter 5.7.3 --- Biological monitoring --- p.63 / Chapter 5.8 --- Dose-response relationship --- p.65 / Chapter Chapter 6 --- Discussion --- p.69 / Chapter 6.1 --- Findings of this study --- p.69 / Chapter 6.1.1 --- Subjective symptoms --- p.69 / Chapter 6.1.2 --- Neurobehavioral effects --- p.70 / Chapter 6.1.3 --- Exposure intensity --- p.72 / Chapter 6.1.4. --- Dose-response relationship --- p.75 / Chapter 6.2 --- Applications of the study results --- p.76 / Chapter 6.2.1 --- The need for prevention measures --- p.77 / Chapter 6.2.2 --- Contributing to re-setting of OELs --- p.77 / Chapter 6.2.3. --- The evidence on neurotoxicology --- p.78 / Chapter 6.3 --- Limitations of the study --- p.79 / Chapter 6.3.1. --- Possibility of bias --- p.79 / Chapter 6.3.2. --- Lack of historical hygiene measurement data --- p.80 / Chapter 6.3.3. --- Influence of workshift --- p.81 / Chapter 6.3.4. --- Combined exposures to noise and organic solvents --- p.82 / Chapter 6.4 --- Conclusion --- p.83 / Appendices --- p.84 / Appendix 1 --- p.84 / Appendix 2 --- p.97 / Appendix 3 --- p.102 / Appendix 4 --- p.103 / Appendix 5 The Administration of The WHO-NCTB Tests --- p.114 / Test 1 Profile of Mood States Test --- p.115 / Test 2. Simple Reaction Time Test --- p.116 / Test 3. Digit Span Test Test --- p.119 / Test 4. Santa Ana Test --- p.120 / Test 5. Digit Symbol Test --- p.122 / Test 6. Benton Visual Retention Test --- p.123 / Test 7. Pursuit Aiming Test --- p.125 / Appendix 6 --- p.126 / Reference List --- p.127

Introdução: As síndromes de Apert (SA) e Crouzon (SC) estão relacionadas a mutações do gene FGFR2. O desenvolvimento cognitivo é variável e está associado à presença de alterações do sistema nervoso central (SNC), idade da descompressão cirúrgica do crânio, estimulação e convivência social, escolarização, institucionalização dos individuos assim como aos aspectos sociais, econômicos, educacionais e a qualidade de vida da família. A influência do tipo de mutação do FGFR2 no desempenho cognitivo é mais um elemento a ser esclarecido para o melhor entendimento do desenvolvimento global dos indivíduos. Objetivo: Identificar, por estudo molecular, as mutações conhecidas do gene FGFR2 e apresentar esses dados de forma comparativa com o quociente de inteligência (QI) e alterações do SNC. Casuística e Método: A casuística foi composta por oito casos de SA e seis casos de SC, com diagnóstico genético clínico confirmado, que apresentavam avaliação cognitiva baseada no teste do QI e estudo anatômico do SNC por ressonância magnética (RM), ambos realizados previamente. Todos os casos foram submetidos à sequenciamento direto dos exons IIIa e IIIc do FGFR2. Os resultados foram comparados aos do QI e às alterações do SNC. Resultados: Seis casos apresentaram a mutação típica p.Ser252Trp e quociente de inteligência total (QIT) de 47 a 78 (média de 67.2). Um caso apresentou a mutação típica p.Pro253Arg, alterações do SNC (ventriculomegalia, hipoplasia do corpo caloso e do septo pelúcido) e QIT de 108. Um caso apresentou a mutação atípica c.940-2A>G splicing, QIT de 104 e ausência de alteraçoes encefálicas. Nos seis casos de SC foram identificadas diversas mutações do FGFR2, exceto em dois irmãos, que apresentaram a mesma mutação (p.Tyr328Cys). Esses indivíduos apresentaram QIT de 82 a 102 (média de 93.5). Conclusão: A análise da presente casuística evidenciou uma relação de mutação típica p.Ser252Trp a resultados de QI inferiores aos dos indivíduos com síndrome de Apert causada por outras mutações. A mutação p.Pro253Arg e a mutação atípica c.940-2A>G splicing apresentaram um resultado de QI acima da média para a SA, independentemente das alterações encefálicas identificadas por RM. Não houve correlação, na síndrome de Crouzon, do tipo de mutação identificada com o resultado do QI e as alterações encefálicas. / Introduction: Apert syndrome (AS) and Crouzon syndrome (CS) are related to mutations of the FGFR2 gene. Cognitive development is variable and usually related abnormalities of the central nervous system (CNS), age of surgical decompression of the skull, stimulation and social interaction, education, institutionalization of individuals as well as the social, economic, educational and quality of life family. The influence of mutation of FGFR2 in cognitive performance on the SA and SC would be a further element to be clarified for better understanding of the overall development of these individuals. Objective: Identified by molecular analysis of gene mutations known FGFR2 and present these data in comparison with the alterations found in the CNS and the intelligence quotient (IQ). Method: The sample included eight cases of AS and six cases of CS with clinical genetic diagnosis confirmed, who exhibited cognitive assessment based on IQ tests, and study of the CNS by magnetic resonance imaging (MRI), both previously. All cases were subjected by direct sequencing analysis of FGFR2 exons IIIa / IIIc and the results were compared to IQ and changes in the CNS. Results: Six patient showed the typical mutation of the FGFR2 p.Ser252Trp and TIQ (total intelligence quotient) from 47 to 78 (67.2). One case showed the typical mutation p.Pro253Arg, CNS changes (ventriculomegaly, hypoplasia of the corpus callosum and septum pellucidum) and TIQ 108. One patient had atypical mutation c.940-2A>G splicing, no changes in the brain and TIQ 104. In the six cases with CS identified several mutations in FGFR2, except for two brothers who had the same mutation (p.Tyr328Cys). These patients had TIQ 82 to 102 (93.5). Conclusion: The analysis of this series showed a relationship between the typical mutation p.Ser252Trp to IQ scores of less than individuals with other mutations and AS. The mutation p.Pro253Arg and atypical mutation c.940-2A>G splicing had an IQ score above average for AS, regardless of changes in the brain MRI identified. There was no correlation in the CS of these mutations with the results of IQ and brain changes.