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Entamoeba histolytica is an invasive intestinal amoeba morphologically indistinguishable from Entamoeba dispar, a closely related organism that is not able to invade tissues. Differential diagnosis under conventional microscopy is therefore impossible. Reliable tools are needed for clinical diagnosis and for the reevaluation of the prevalence of infection with the invasive species worldwide. Monoclonal Antibody (MAb) 20/7D exhibited promising results when ascites was used to identify cultured isolates of E. histolytica by indirect immunofluorescence assays (IFA), and when used in a Faecal Antigen Capture Enzyme-Linked Immunosorbent Assay (FAC-ELISA) for laboratory diagnosis of amoebic dysentery and colitis. Here, further development of the assay was attempted to increase its sensitivity and use it for detection of asymptomatic carriers of E. histolytica. After purification and subsequent titration in ELISA, MAb 20/7D did not adequately distinguish between crude lysates of cultured E. histolytica and E. dispar trophozoites. MAb 20/7D reacted with a similar soluble antigen of E. histolytica and E. dispar, which confirmed previous observations in western blot analysis under non-reducing conditions. Therefore, the use of the FAC-ELISA for diagnosis in areas where E. dispar is endemic is probably not viable. A nucleic acid detection method was therefore developed. Polymerase Chain Reaction was used to amplify specific tandem sequences in the 24.5 Kb episome of E. histolytica and E. dispar. After PCR, internal sequences of digoxigenin-labelled PCR products were hybridized to specific biotin-labelled probes for E. histolytica or E. dispar and detected in Enzyme- Linked Immunosorbent Assay (ELISA). The Polymerase Chain Reaction Solution- Hybridisation Immunosorbent Assay (PCR-SHELA) was evaluated on samples from travellers returning from the tropics to Barcelona. The sensitivity and specificity were 98% and 100% respectively, when results were compared with microscopy. PCR-SHELA was also useful for differential diagnosis in cases of amoebic abscesses, amoebic dysentery, salmonellosis, ulcerative colitis and in asymptomatic carriage of E. histolytica. The new test gives sensitive and specific differentiation between E. histolytica and E. dispar in clinical specimens and it has proved successful in screening faecal samples in endemic areas for epidemiological purposes.

Alzheimer's Disease (AD) is a major concern for the elderly population, currently affecting over 670,000 people in the UK. With the continual increase in the age of the population the problem is expected to rise. There is no known cure to the condition and a definite diagnosis cannot be made in life. Clinical diagnosis is considered to be approximately 80% - 90% accurate, sometimes taking up to a year to assess. Early detection could aid in the care and possible development of better treatments or even a cure. AD has been shown to alter the structure and global texture of the brain. Studies using Magnetic Resonance imaging (MRI) and Computerised Tomography (CT) have been used to detect these changes with some success by some researchers. Positron Emission Tomography (PET) imaging is a functional imaging modality and in theory before structural changes are evident functional changes should be apparent. Therefore we utilise PET images for this study. This thesis will exploit the fact that AD alters the global texture of the brain. Texture features extracted from fluoro-deoxy-glucose (FDG) PET images and sinograms of the brain will be used. Most texture feature extraction methods fail, due to poor signal to noise ratio so we will use a novel texture feature extraction method known as the Trace transform - triple features, which can extract features directly from raw data acquired by PET scanners. Classifiers will be used to aid in the separation of the two groups, namely AD patients and normal controls. The Trace transform - triple feature method has proven its potential as a good feature extraction technique. It enabled us to achieve classification accuracy of up to 93% on raw sinogram data using a combination of five features. This result is very good compared with the clinical accuracy of 80% reported by most researcher. It is comparable to results obtained by Kippenhan et al [52, 53, 51, 50], who used regional metabolic activity using PET and a neural network classifier. Monomial features extracted from images achieved accuracies as high as 87%. These features are good discriminators, however, they suffer from lack of scaling invariance. This is problematic as brain sizes do vary considerably. The use of registration and extraction of regional information failed to produce fruitful results. This is principally due to poor registration. The registration failed primarily because a very small cross section of the brain was available. Also the effect of AD alters the structure of the brain. Since the registration relies on matching structure, it becomes questionable whether one can actually register automatically a very degraded AD brain. Gender and age are crucial to the progress of Alzheimer's disease. Age and gender matching is not sufficient to get the best results. This thesis has shown that performance gains of up to 11% can be attained by simply incorporating age and/or gender into the classification model. However, the maximum classification accuracy was not improved any further.

Introdução: Atualmente o uso de fluoroquinolonas na prática clínica tem sido associado a um aumento da incidência da infecção com bactérias resistentes as quinolonas, especialmente Escherichia coli. O Brasil tem uma das mais altas taxas de resistência as quinolonas entre os países da America Latina. Diferentes mecanismos de resistência estão envolvidos no desenvolvimento de resistência as quinolonas. Os principais mecanismos dividem se em três categorias: i) alteração na DNA girase e topoisomerase IV; ii) diminuição do acúmulo de antibióticos no interior da bactéria e iii) produção de proteínas protetoras da DNA girase e topoisomerase IV. No ano de 2010 foram observadas elevadas taxas de resistência às fluorquinolonas em Escherichia coli isoladas de hemoculturas de pacientes atendidos em hospitais privados da cidade de São Paulo, pelo Fleury Medicina e Saúde. As taxas de resistência à ciprofloxacina variaram de 26,1% a 43,9% em três hospitais diferentes. Considerando que há determinantes cromossômicos não transferíveis e determinantes plasmidiais transferíveis da resistência às fluorquinolonas, a avaliação da clonalidade dos isolados e dos determinantes genéticos da resistência às fluorquinolonas poderá contribuir para o entendimento de alguns dos fatores que possam contribuir para essa progressiva elevação nas taxas de resistência a essa classe de antimicrobianos. Objetivo: Avaliar o fenótipo, a diversidade genética, determinantes cromossômicos e plasmidiais da resistência a fluorquinolonas em Escherichia coli isoladas de corrente sanguínea. Materiais e métodos: Foram estudados 47 E. coli resistentes a ciprofloxacino isoladas de hemoculturas de pacientes atendidos em cinco centros hospitalares da cidade de São Paulo. A caracterização fenotípica foi realizada por determinação da concentração mínima inibitória para fluoroquinolonas. A confirmação genotípica da resistência foi confirmada por PCR para os genes qnrA, qnrB, qnrS. As regiões determinantes da resistência a fluorquinolonas dos genes gyrA, parC foram sequenciadas. A tipagem molecular foi realizada pela técnica de ERIC-PCR. Resultados e conclusões: Os genes qnrA e qnrS não foram detectados nos isolados avaliados neste estudo. Os genes qnrB foram detectados em 42,5% dos isolados. Em todos os isolados, exceto o F4991, foram detectadas as substituições S83L e D87N na GyrA Em todos os isolados, exceto o F4991, foram detectadas as substituições S80I em ParC. Foi detectada a substituição E84V em ParC 23,4% dos isolados. Foi observada a disseminação dos grupos clonais ERIC1 e ERIC2 entre hospitais e disseminação intrahospitalar dos grupos clonais ERICS, ERIC6 e ERIC7. / Introduction: The use of fluoroquinolones in clinicai practice has been associated with an increased incidence of infection with bacteria resistant to quinolones, especially Escherichia coli. Brazil has one of the highest rates of resistance to quinolones among the countries in Latin America. Different resistance mechanisms are involved in the development of resistance to quinolone. The main mechanisms fall into three categories: i) alteration in DNA gyrase and topoisomerase IV, ii) reduction in the accumulation of antibiotics within the bacterium and iii) production of proteins that protect DNA gyrase and topoisomerase IV. In the year of 2010 high rates of resistance to fluoroquinolones in E. coli were observed blood cultures isolates from of patients from private hospitais in São Paulo. Ciprofloxacin resistance rates ranged from 26.1 to 43% 9% at three different hospitais. There are chromosomal and transferable plasmid-determined resistance to fluoroquinolones. The evaluation of the clonality of the isolates and the genetic determinants of resistance to fluoroquinolones may contribute to the understanding of some of the factors that may contribute to the progressive increase in resistance rates to this class of antimicrobials. Objective: To evaluate the phenotype, genetic diversity, chromosomal and plasmid determinants of resistance to fluoroquinolones in E. coli isolated from bloodstream. Materiais and methods: We studied 47 ciprofloxacin resistant E. coli isolated from blood cultures of patients treated at five hospitais in the city of Sao Paulo. Phenotypic characterization was performed by determining the minimum inhibitory concentration for fluoroquinolones. Genotypic resistance was confirmed by PCR to genes qnrA, qnrB and qnrS. The quinolone resistance determining regions of genes gyrA and parC were sequenced. Molecular typing was performed using ERIC-PCR. Results and conclusions: The qnrA and qnrS genes were not detected in the isolates evaluated in this study. The qnrB genes were detected in 42.5% of isolates. In all isolates, except for F4991, substitutions were detected in gyrA S83L and D87N. In all isolates, except for F4991, substitution S80I were detected in ParC. E84V substitution in ParC was detecxted in 23.4% of isolates. We observed the spread of clonal groups ERIC1 and ERIC2 and between hospitais and alsdo intra-hospital spread of clonal groups ERIC5, and ERIC6 ERIC7.

INTRODUÇÃO: A síndrome de Kabuki (SK) é uma desordem genética de etiologia desconhecida caracterizada por atraso mental moderado à severo, deficiência do crescimento pós-natal, e à face típica com fissuras palpebrais longas, eversão do terço lateral das pálpebras, orelhas proeminentes e ponte nasal larga e deprimida. Manifestações orais são comumente observadas em pacientes com SK e podem compreender: fissura lábiopalatina, úlvula bífida, maloclusão, atraso na erupção dentária, anomalias dentárias e cárie. CASUÍSTICA E MÉTODOS: Foram avaliados 9 pacientes com diagnóstico clínico de síndrome de Kabuki do Departamento de Genética do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Foram feitos exames clínicos odontológicos e avaliadas radiografias panorâmicas de face de todos os pacientes para coleta de dados. Como a maioria dos pacientes apresentou dentição mista ou permanente, a presença ou ausência de dentes na dentição decídua foi avaliada segundo a informação dada pelos pais ou responsáveis. RESULTADOS: Um paciente apresentou fissura palatina; três apresentaram cáries; sete tiveram ausências dentárias. Os dentes incisivos laterais superiores e os incisivos centrais inferiores foram os mais freqüentemente ausentes. Todos os dentes ausentes são permanentes, e não foi relatada nenhuma alteração na cronologia de erupção dental ou na morfologia dos dentes. Devido aos dentes ausentes, os pacientes apresentaram alteração, que poderia ser corrigida através de tratamento ortodôntico. Curiosamente, um paciente apresentou ausência de um canino superior, fato ainda não relatado na literatura sobre a SK até o momento. CONCLUSÕES: Os achados odontológicos contribuem para o diagnóstico clinico da síndrome de Kabuki, podendo contribuir como características adicionais nos casos de crianças com fenótipo com características leves / INTODUCTION: Kabuki syndrome (KS) is a genetic disorder of unknown etiology characterized by moderate to severe mental retardation, postnatal growth deficiency, and peculiar face with long palpebral fissures and eversion of the lateral third of the lower eyelids, prominent ears and broad and depressed nasal tip. Oral manifestations are commonly observed in KS and may comprise: cleft lip/palate, bifid tongue and uvula, malocclusion, delayed tooth eruption pattern, dental abnormalities and caries. METHODS: Were evaluated nine patients of the Department of Genetics (Instituto da Criança Hospital das Clínicas da Universidade de São Paulo) with clinical diagnosis of Kabuki syndrome. For data collection, were made clinical examinations and panoramic x-rays of all patients. Since most patients had mixed dentition, the presence or absence of primary teeth were assessed through the parents´ reports. RESULTS: One presented cleft palate; three presented caries; seven had missing teeth. Upper lateral incisors and inferior central incisors were the commonest absent teeth. All missing teeth are permanent, and there was no alteration of dental chronology or in morphology. Due to the absent teeth, patients present occlusal alteration, and they need orthodontic treatment. Curiously, one patient presented an absent upper canine, which was not reported in the literature up to now. CONCLUSIONS: Dental findings may be helpful for clinical diagnosis, or they may be an additional finding to substantiate the diagnosis of KS in children with mild phenotype

Submitted by Suzana Dias (suzana.dias@famerp.br) on 2018-11-08T15:27:32Z No. of bitstreams: 1 LaraGuedes_dissert.pdf: 1235458 bytes, checksum: 36745426251f7a7ada61993715db4f7b (MD5) / Made available in DSpace on 2018-11-08T15:27:32Z (GMT). No. of bitstreams: 1 LaraGuedes_dissert.pdf: 1235458 bytes, checksum: 36745426251f7a7ada61993715db4f7b (MD5) Previous issue date: 2017-08-18 / The doctor-patient communication does not end with the disclosure of the diagnosis, it extends to the discussion of therapeutic planning and prognosis. However, due to the association of cancer diagnosis to death and suffering, and despite the patient’s right to know it, there are barriers to the disclosure of such information. Objective: investigate the patients’ awareness of their diagnosis, treatment and prognosis in the Clinical Oncology sector of the Hospital de Base in São José do Rio Preto (HB). Method: 87 patients were interviewed between the second and third appointment of the clinical Oncology service. The second appointment was with the third-year residents of the medical residence program in Clinical Oncology. Two standardized instruments, the Hospital Anxiety and Depression Scale and the Questionnaire applied to cancer patients were used; as well as sociodemographic data and information about the service of the multi-professional team. Results: The participants were mostly men (71%), average age of 60; low level of education (illiterates 11,5% and 55,2% hasn’t completed middle school); diagnosed with colorectal cancer (26,4%), oral cavity (C00- C10, 12,6%) and lung (9,2%); clinical staging IV (49,4%); exclusive or combined chemotherapy treatment (94,2%); didn’t report any difficulty in understanding the disclosure of the diagnosis (91,9%) nor treatment (87,4%); felt capable (86,2%) and free (85%) to decide on the treatment; aware of the evolution of the disease (67,8%); wanted to obtain all the information about their disease (74,7%) and presented unlikely scores to anxiety and/or depression (74,7%). Conclusions: According to the results, the participants knew about their disease, treatment and prognosis, and presented low rates to anxiety and depression symptoms. / A comunicação médico-paciente não se encerra na revelação do diagnóstico, estende-se à discussão do planejamento terapêutico e prognóstico. No entanto, devido o diagnóstico de câncer ser associado à morte e ao sofrimento; e, apesar do direito do paciente de conhecê-lo, existem barreiras à comunicação dessas informações. Objetivo: investigar o conhecimento dos pacientes do setor de Oncologia Clínica do Hospital de Base de São José do Rio Preto (HB) sobre seu diagnóstico, tratamento e prognóstico. Método: foram entrevistados 87 pacientes, entre a segunda e a terceira consulta do serviço de Oncologia Clínica, sendo que a segunda consulta foi realizada pelos médicos-residentes do 3º ano do programa de residência médica em cancerologia clínica. Foram utilizados dois instrumentos padronizados, a Escala Hospitalar de Ansiedade e Depressão e o Questionário aplicado aos pacientes com câncer; além de dados sociodemográficos e informações sobre atendimentos pela equipe multiprofissional. Resultados: Os participantes, eram em sua maioria homens (71%), média de idade de 60 anos; baixa escolaridade (analfabetos 11,5% e ensino fundamental incompleto 55,2%); diagnosticados com câncer de colón e reto (26,4%), cavidade oral (C00-C10, 12,6%) e pulmão (9,2%); estadiamento clínico IV (49,4%); indicação de tratamento quimioterápico exclusivo ou combinado (94,2%); não relataram nenhuma dificuldade de entendimento quanto a comunicação do diagnóstico (91,9%) e tratamento (87,4%); se sentiam capazes (86,2%) e livres (85%) para decidir sobre o tratamento; sabiam sobre a evolução da doença (67,8%); desejavam obter todas as informações sobre a sua doença (74,7%) e apresentaram escores improváveis para ansiedade e/ou depressão (74,7%). Conclusões: De acordo com os resultados os participantes sabiam sobre sua doença, tratamento e prognóstico, e apresentaram baixos índices para sintomas de ansiedade e depressão.

INTRODUÇÃO: A síndrome de Kabuki (SK) é uma desordem genética de etiologia desconhecida caracterizada por atraso mental moderado à severo, deficiência do crescimento pós-natal, e à face típica com fissuras palpebrais longas, eversão do terço lateral das pálpebras, orelhas proeminentes e ponte nasal larga e deprimida. Manifestações orais são comumente observadas em pacientes com SK e podem compreender: fissura lábiopalatina, úlvula bífida, maloclusão, atraso na erupção dentária, anomalias dentárias e cárie. CASUÍSTICA E MÉTODOS: Foram avaliados 9 pacientes com diagnóstico clínico de síndrome de Kabuki do Departamento de Genética do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Foram feitos exames clínicos odontológicos e avaliadas radiografias panorâmicas de face de todos os pacientes para coleta de dados. Como a maioria dos pacientes apresentou dentição mista ou permanente, a presença ou ausência de dentes na dentição decídua foi avaliada segundo a informação dada pelos pais ou responsáveis. RESULTADOS: Um paciente apresentou fissura palatina; três apresentaram cáries; sete tiveram ausências dentárias. Os dentes incisivos laterais superiores e os incisivos centrais inferiores foram os mais freqüentemente ausentes. Todos os dentes ausentes são permanentes, e não foi relatada nenhuma alteração na cronologia de erupção dental ou na morfologia dos dentes. Devido aos dentes ausentes, os pacientes apresentaram alteração, que poderia ser corrigida através de tratamento ortodôntico. Curiosamente, um paciente apresentou ausência de um canino superior, fato ainda não relatado na literatura sobre a SK até o momento. CONCLUSÕES: Os achados odontológicos contribuem para o diagnóstico clinico da síndrome de Kabuki, podendo contribuir como características adicionais nos casos de crianças com fenótipo com características leves / INTODUCTION: Kabuki syndrome (KS) is a genetic disorder of unknown etiology characterized by moderate to severe mental retardation, postnatal growth deficiency, and peculiar face with long palpebral fissures and eversion of the lateral third of the lower eyelids, prominent ears and broad and depressed nasal tip. Oral manifestations are commonly observed in KS and may comprise: cleft lip/palate, bifid tongue and uvula, malocclusion, delayed tooth eruption pattern, dental abnormalities and caries. METHODS: Were evaluated nine patients of the Department of Genetics (Instituto da Criança Hospital das Clínicas da Universidade de São Paulo) with clinical diagnosis of Kabuki syndrome. For data collection, were made clinical examinations and panoramic x-rays of all patients. Since most patients had mixed dentition, the presence or absence of primary teeth were assessed through the parents´ reports. RESULTS: One presented cleft palate; three presented caries; seven had missing teeth. Upper lateral incisors and inferior central incisors were the commonest absent teeth. All missing teeth are permanent, and there was no alteration of dental chronology or in morphology. Due to the absent teeth, patients present occlusal alteration, and they need orthodontic treatment. Curiously, one patient presented an absent upper canine, which was not reported in the literature up to now. CONCLUSIONS: Dental findings may be helpful for clinical diagnosis, or they may be an additional finding to substantiate the diagnosis of KS in children with mild phenotype

This thesis examined the factors correlated with rapid and benign progression of disease in a group of 1452 Parkinsons disease (PD) patients. The data were collected in a movement disorders clinic at the Royal University Hospital, University of Saskatchewan run by Dr. Alex Rajput and Dr. Ali Rajput. This data is a clinical dataset of PD patients collected from 1970 through to February, 2005. This was a retrospective cases-only study, with anticipated analytical follow-up if any correlations were detected between progression type of PD and the many independent variables available in the dataset. <p>Rapid progression was defined as those subjects who reached Hoehn and Yahr stage 3 within three years or H&Y stage 4 or 5 within five years. Subjects who remained in Hoehn and Yahr stage 1 or 2, ten years after onset of disease, were defined as having benign progression. The study analyzed demographic and clinical findings at first visit to this clinic associated with rapid and benign progression of PD. <p> Analysis revealed that, at first clinic visit, benign progression was positively associated with disease duration (OR=1.41; 95% CI 1.27, 1.57), male sex (OR=3.23; 95% CI 1.70, 6.16), and current smoking habit (OR=2.33; 95% CI 0.67, 8.11). Benign progression was negatively associated with older age of onset (OR=0.36; 95% CI 0.25, 0.50), past history of smoking (OR=0.46; 95% CI 0.24, 0.89), current or past use of levodopa (OR=0.45; 95% CI 0.21, 0.98), and mild to severe rigidity (OR=0.43; 95% CI 0.23, 0.80). <p>Analysis also revealed that, at first clinic visit, rapid progression was positively associated with older age of onset (OR=2.45; 95% CI 1.80, 3.33) and mild to severe rigidity (OR=1.73; 95% CI 1.02, 2.94). Rapid progression was negatively associated with disease duration (OR=0.52; 95% CI 0.44, 0.62), male sex (OR=0.58; CI 0.35, 0.95), and mild to severe resting tremor (OR=0.47; CI 0.28, 0.77). <p>The results of this study indicate that age of onset, disease duration, male sex, and rigidity are good potential predictors of disease progression in PD because they have opposite associations with rapid and benign progression. History of levodopa use was negatively associated with benign progression and as such may be good indicator of non-benign progression. Although previous studies found no predictive value for smoking history, the current study reported a unique association between smoking history and benign progression. Past smoking history was negatively associated with benign progression. While there was a positive association with current smoking history, the result was not statistically significant. Resting tremor was negatively associated with rapid progression and as such may be a good indicator of non-rapid progression. <p> Disease characteristics collected at first clinic visit are useful in predicting the course of progression of PD. With more rapid progression of PD closer and more frequent follow-up of patients may be necessary.

This thesis examined the factors correlated with rapid and benign progression of disease in a group of 1452 Parkinsons disease (PD) patients. The data were collected in a movement disorders clinic at the Royal University Hospital, University of Saskatchewan run by Dr. Alex Rajput and Dr. Ali Rajput. This data is a clinical dataset of PD patients collected from 1970 through to February, 2005. This was a retrospective cases-only study, with anticipated analytical follow-up if any correlations were detected between progression type of PD and the many independent variables available in the dataset. <p>Rapid progression was defined as those subjects who reached Hoehn and Yahr stage 3 within three years or H&Y stage 4 or 5 within five years. Subjects who remained in Hoehn and Yahr stage 1 or 2, ten years after onset of disease, were defined as having benign progression. The study analyzed demographic and clinical findings at first visit to this clinic associated with rapid and benign progression of PD. <p> Analysis revealed that, at first clinic visit, benign progression was positively associated with disease duration (OR=1.41; 95% CI 1.27, 1.57), male sex (OR=3.23; 95% CI 1.70, 6.16), and current smoking habit (OR=2.33; 95% CI 0.67, 8.11). Benign progression was negatively associated with older age of onset (OR=0.36; 95% CI 0.25, 0.50), past history of smoking (OR=0.46; 95% CI 0.24, 0.89), current or past use of levodopa (OR=0.45; 95% CI 0.21, 0.98), and mild to severe rigidity (OR=0.43; 95% CI 0.23, 0.80). <p>Analysis also revealed that, at first clinic visit, rapid progression was positively associated with older age of onset (OR=2.45; 95% CI 1.80, 3.33) and mild to severe rigidity (OR=1.73; 95% CI 1.02, 2.94). Rapid progression was negatively associated with disease duration (OR=0.52; 95% CI 0.44, 0.62), male sex (OR=0.58; CI 0.35, 0.95), and mild to severe resting tremor (OR=0.47; CI 0.28, 0.77). <p>The results of this study indicate that age of onset, disease duration, male sex, and rigidity are good potential predictors of disease progression in PD because they have opposite associations with rapid and benign progression. History of levodopa use was negatively associated with benign progression and as such may be good indicator of non-benign progression. Although previous studies found no predictive value for smoking history, the current study reported a unique association between smoking history and benign progression. Past smoking history was negatively associated with benign progression. While there was a positive association with current smoking history, the result was not statistically significant. Resting tremor was negatively associated with rapid progression and as such may be a good indicator of non-rapid progression. <p> Disease characteristics collected at first clinic visit are useful in predicting the course of progression of PD. With more rapid progression of PD closer and more frequent follow-up of patients may be necessary.