Avaliação da distribuição de dose em doentes com cancro da mama: cobertura e homogeneidade no volume alvo e dose nos órgãos de risco

Mestrado em Radioterapia

OPTIMAX 2014 - Radiation dose and image quality optimisation in medical imaging

Medical imaging is a powerful diagnostic tool. Consequently, the number of medical images taken has increased vastly over the past few decades. The most common medical imaging techniques use X-radiation as the primary investigative tool. The main limitation of using X-radiation is associated with the risk of developing cancers. Alongside this, technology has advanced and more centres now use CT scanners; these can incur significant radiation burdens compared with traditional X-ray imaging systems. The net effect is that the population radiation burden is rising steadily. Risk arising from X-radiation for diagnostic medical purposes needs minimising and one way to achieve this is through reducing radiation dose whilst optimising image quality. All ages are affected by risk from X-radiation however the increasing population age highlights the elderly as a new group that may require consideration. Of greatest concern are paediatric patients: firstly they are more sensitive to radiation; secondly their younger age means that the potential detriment to this group is greater. Containment of radiation exposure falls to a number of professionals within medical fields, from those who request imaging to those who produce the image. These staff are supported in their radiation protection role by engineers, physicists and technicians. It is important to realise that radiation protection is currently a major European focus of interest and minimum competence levels in radiation protection for radiographers have been defined through the integrated activities of the EU consortium called MEDRAPET. The outcomes of this project have been used by the European Federation of Radiographer Societies to describe the European Qualifications Framework levels for radiographers in radiation protection. Though variations exist between European countries radiographers and nuclear medicine technologists are normally the professional groups who are responsible for exposing screening populations and patients to X-radiation. As part of their training they learn fundamental principles of radiation protection and theoretical and practical approaches to dose minimisation. However dose minimisation is complex – it is not simply about reducing X-radiation without taking into account major contextual factors. These factors relate to the real world of clinical imaging and include the need to measure clinical image quality and lesion visibility when applying X-radiation dose reduction strategies. This requires the use of validated psychological and physics techniques to measure clinical image quality and lesion perceptibility.

Ibuprofen-loaded poly(trimethylene carbonate-co-ϵ- caprolactone) electrospun fibres for nerve regeneration

The development of scaffolds that combine the delivery of drugs with the physical support provided by electrospun fibres holds great potential in the field of nerve regeneration. Here it is proposed the incorporation of ibuprofen, a well-known non-steroidal anti-inflammatory drug, in electrospun fibres of the statistical copolymer poly(trimethylene carbonate-co-ε-caprolactone) [P(TMC-CL)] to serve as a drug delivery system to enhance axonal regeneration in the context of a spinal cord lesion, by limiting the inflammatory response. P(TMC-CL) fibres were electrospun from mixtures of dichloromethane (DCM) and dimethylformamide (DMF). The solvent mixture applied influenced fibre morphology, as well as mean fibre diameter, which decreased as the DMF content in solution increased. Ibuprofen-loaded fibres were prepared from P(TMC-CL) solutions containing 5% ibuprofen (w/w of polymer). Increasing drug content to 10% led to jet instability, resulting in the formation of a less homogeneous fibrous mesh. Under the optimized conditions, drug-loading efficiency was above 80%. Confocal Raman mapping showed no preferential distribution of ibuprofen in P(TMC-CL) fibres. Under physiological conditions ibuprofen was released in 24h. The release process being diffusion-dependent for fibres prepared from DCM solutions, in contrast to fibres prepared from DCM-DMF mixtures where burst release occurred. The biological activity of the drug released was demonstrated using human-derived macrophages. The release of prostaglandin E2 to the cell culture medium was reduced when cells were incubated with ibuprofen-loaded P(TMC-CL) fibres, confirming the biological significance of the drug delivery strategy presented. Overall, this study constitutes an important contribution to the design of a P(TMC-CL)-based nerve conduit with anti-inflammatory properties.

Relatório de estágio em reabilitação neurológica: intervenção da fisioterapia em crianças com necessidades especiais

Mestrado em Fisioterapia

Complex order biped rhythms

Animal locomotion is a complex process, involving the central pattern generators (neural networks, located in the spinal cord, that produce rhythmic patterns), the brainstem command systems, the steering and posture control systems and the top layer structures that decide which motor primitive is activated at a given time. Pinto and Golubitsky studied an integer CPG model for legs rhythms in bipeds. It is a four-coupled identical oscillators' network with dihedral symmetry. This paper considers a new complex order central pattern generator (CPG) model for locomotion in bipeds. A complex derivative Dα±jβ, with α, β ∈ ℜ+, j = √-1, is a generalization of the concept of an integer derivative, where α = 1, β = 0. Parameter regions where periodic solutions, identified with legs' rhythms in bipeds, occur, are analyzed. Also observed is the variation of the amplitude and period of periodic solutions with the complex order derivative.

Optimisation of paediatrics computed radiography for full spine curvature measurements using a phantom: a pilot study

Aim: Optimise a set of exposure factors, with the lowest effective dose, to delineate spinal curvature with the modified Cobb method in a full spine using computed radiography (CR) for a 5-year-old paediatric anthropomorphic phantom. Methods: Images were acquired by varying a set of parameters: positions (antero-posterior (AP), posteroanterior (PA) and lateral), kilo-voltage peak (kVp) (66-90), source-to-image distance (SID) (150 to 200cm), broad focus and the use of a grid (grid in/out) to analyse the impact on E and image quality (IQ). IQ was analysed applying two approaches: objective [contrast-to-noise-ratio/(CNR] and perceptual, using 5 observers. Monte-Carlo modelling was used for dose estimation. Cohen’s Kappa coefficient was used to calculate inter-observer-variability. The angle was measured using Cobb’s method on lateral projections under different imaging conditions. Results: PA promoted the lowest effective dose (0.013 mSv) compared to AP (0.048 mSv) and lateral (0.025 mSv). The exposure parameters that allowed lower dose were 200cm SID, 90 kVp, broad focus and grid out for paediatrics using an Agfa CR system. Thirty-seven images were assessed for IQ and thirty-two were classified adequate. Cobb angle measurements varied between 16°±2.9 and 19.9°±0.9. Conclusion: Cobb angle measurements can be performed using the lowest dose with a low contrast-tonoise ratio. The variation on measurements for this was ±2.9° and this is within the range of acceptable clinical error without impact on clinical diagnosis. Further work is recommended on improvement to the sample size and a more robust perceptual IQ assessment protocol for observers.

Neuroartropatia de Charcot do pé diabético: identificação, tratamento conservador e prevenção das suas complicações

Mestrado em Gestão e Avaliação de Tecnologias em Saúde

Estabilização dinâmica em patologia degenerativa da coluna lombar: estado da arte e contributo pessoal

Resumo Este trabalho encontra-se dividido em três capítulos distintos. No primeiro, é caracterizada a doença degenerativa lombar, demorando-se o autor na descrição pormenorizada das alterações anatómicas, biomecânicas, e bioquímicas inerentes à sua ocorrência. Segue-se a descrição da evolução das diferentes formas de terapêutica, enumerando as que de forma clássica mais frequentemente são utilizadas (cirúrgicas e não cirúrgicas). No segundo capítulo, são referidos os mais recentes avanços tecnológicos nesta área, mencionando, nas suas vertentes biomecânicas, clínicas e terapêuticas, as particularidades das estabilizações dinâmicas interespinhosas e pediculares, bem como da artroplastia de disco. Após esta longa introdução, inicia-se o terceiro capítulo no qual se apresenta um estudo prospectivo da avaliação clínica, funcional, imagiológica e da variação da densidade mineral óssea vertebral em 20 doentes com patologia degenerativa, tratados com sistemas de estabilização dinâmica semi-rígida interespinhosa, e seguidos durante dois anos. Do estudo realizado conclui-se que os sistemas referidos são eficazes clínica e funcionalmente no tratamento de doentes com doença degenerativa lombar. Mais ainda, estes instrumentais proporcionam um aumento da altura do disco confirmado na incidência radiográfica de perfil no nível instrumentado. Constatámos ainda que a densidade mineral óssea vertebral dos doentes intervencionados, avaliada com sistema DXA, não demonstra diferenças com significância estatística ao longo do tempo, omparativamente à determinada em idêntica população mas sem qualquer patologia lombar. Acresce que se obteve uma correlação entre a funcionalidade física e a BMD radial, com significância estatística crescente nas duas medições realizadas. Abstract This study is divided in three different chapters. In the first one the author describes the anatomical, biomechanical and biochemical changes that go along with degenerative lumbar spine disease. The therapeutically possibilities are mentioned, mainly with the classic fusion and decompression as well as the non surgical options. Then, in the second chapter, the author describes, from the biomechanical, clinical and therapeutically point of view, the new techniques of dynamic stabilization, interspinous and pedicular systems, as well as disc replacement. After this introduction, in the third chapter a prospective clinical, functional, imagiologic and vertebral bone mineral density variation study is presented. Twenty patients with degenerative lumbar spine disease are selected, and operated with a semi rigid interspinous system device, and followed for a two year period. The author concludes that the interspinous semi rigid systems were clinically and functionally effective in lumbar degenerative patients. It was also founded that the disc height at the implant segment level increased after surgery. Bone density was assessed with a DXA system device. As far as vertebral bone density is concerned, the author found no differences what so ever inside the group during the study, or to an identical control group without any lumbar pathology. The correlation study between the BMD and physical function showed that there was only significant statistically data in radial BMD measurement, and this happened with growing correlation from year 2006 to 2007.

O impacto de um programa de exercícios com o Inspirómetro de Incentivo na função pulmonar em doentes com Escoliose Idiopática

Introdução: A escoliose é uma deformidade vertebral muito comum e de grande importância social. A etiologia da escoliose idiopática da adolescência é desconhecida e descrita como multifatorial. Segundo a literatura existe uma forte correlação entre a função pulmonar anormal e a gravidade da deformidade da coluna vertebral. Tem sido proposto como abordagem terapêutica o uso de Inspirómetro de Incentivo, contudo, ainda se encontra incerto a sua eficácia nesta patologia. Objetivo: Analisar o impacto de um programa de exercícios domiciliários com o Inspirómetro de Incentivo em doentes com Escoliose Idiopática nos volumes pulmonares e na força muscular dos músculos respiratórios. Metodologia: Foram avaliados, por meio de um estudo experimental, 12 indivíduos do sexo feminino (com média e desvio padrão correspondentes a 15,1 e 1,6 respetivamente) com diagnóstico de Escoliose Idiopática antes e 3meses após a cirurgia corretiva e 12 indivíduos saudáveis também do sexo feminino (com média e desvio padrão correspondentes a 15,2 e 1,4 respetivamente). A função pulmonar foi avaliada através do espirómetro computorizado Spinolab®, a força dos músculos respiratórios avaliou-se através da mensuração da PImáx e PEmáx com o Microrpm®. Para finalizar a avaliação o participante foi sujeito a aplicação do THRESHOLD® com 30% da PImáx obtida. O protocolo domiciliário, referente à parte experimental, baseou-se no uso bi-diário do Inspirómetro de Incentivo Respiflo FS®, que foi fornecido aos participantes no dia da alta hospitalar. Resultados: Foram encontrados valores menores da função respiratória e força muscular (p<0,05) no grupo de doentes com Escoliose em relação ao grupo dos Saudáveis, excepto em relação ao Índice de Tiffeneau (p=0,17). No entanto, quando se comparou o grupo Controlo e o Grupo Experimental não severificaram diferenças estatisticamente significativas em relação às variáveis estudadas. Por fim, na análise dos parâmetros nos dois momentos de avaliação (inicial e final) entre o grupo dos Saudáveis e grupo Experimental verificou-se que existiam diferenças estatisticamente significativas ao nível da CFV (pi=0,02; pf=0,00), FEV1 (pi=0,01; pf=0,00) e PImáx inicial (p=0,02) e PImáx th inicial (p=0,03). Conclusão: A função pulmonar e a força dos músculos respiratórios em indivíduos com diagnóstico de Escoliose Idiopática encontra-se diminuída quando comparada com uma população saudável. Dentro das condições propostas no presente estudo, verificou-se que a aplicação de um programa de exercícios com o Inspirómetro de Incentivo com duração de 3 meses não revela resultados significativos ao nível da função pulmonar e da força dos músculos respiratórios.

O efeito da aplicação da Estimulação Elétrica Funcional na reabilitação em adultos com lesão medular completa. Revisão Sistemática

Introdução: A Lesão Medular (LM) é um dos mais devastadores e traumáticos eventos que um Ser Humano pode vivenciar do ponto de vista clínico e emocional, demonstrando-se fundamental a disponibilização de recursos específicos para que o indivíduo possa enfrentar e gerir a sua nova realidade da melhor maneira possível. Alguns estudos têm vindo a demonstrar os benefícios de programas de reabilitação com estimulação elétrica funcional (EEF). Portanto, é de importante relevância perceber os reais efeitos da intervenção na recuperação de indivíduos com este diagnóstico. Objetivo: Analisar as evidências de abordagens de aplicação de correntes de estimulação elétrica funcional (EEF) para coadjuvar na reabilitação em adultos com lesão medular completa. Métodos: Foi conduzida uma pesquisa dos artigos preferencialmente estudos randomized controlled trials RCT´s e estudos quasi-experimentais com os mesmos participantes foram admitidos complementarmente aos experimentais compreendidos entre 2004 e 2013, bem como as citações e as referências bibliográficas de cada estudo nas principais bases de dados de ciências da saúde (Elsevier – Science Direct, Highwire Press, PEDro, PubMed, Scielo Portugal, Clinical Key, B-on, Biomed Central, LILACS- Literatura Latino-Americana e do Caribe em Ciências da Saúde) com as palavras-chave: “spinal cord injuries”, “rehabilitation, electric stimulation funtional”, “FES”, “therapy” em todas as combinações possíveis. Os estudos RCT’s foram analisados independentemente por dois revisores quanto aos critérios de inclusão e qualidade dos estudos. Resultados: Dos 857 estudos identificados apenas sete foram incluídos. Destes, dois apresentaram um score 3/10, um apresentou 4/10, um apresentou um score 5/10. O score total bem como o preenchimento ou não de cada critério encontram-se detalhados na tabela 1 e organizados por ordem alfabética de autores. Todos os estudos incluíram indivíduos com Lesão Medular Completa, idades entre 16 e 68 anos com diagnóstico de acordo com a American Spinal Injury Association (ASIA).Os programas de intervenção dividiram-se em programas de programas de força, densidade mineral óssea, cardiorrespiratório e de atividade física. Dos estudos incluídos, cinco apresentaram melhorias na reabilitação funcional para o grupo experimental, demonstrando assim uma influência positiva da estimulação elétrica funcional em lesões medulares completas. Apenas dois estudos não apresentaram diferenças estatisticamente significativas com relevância clínica. Conclusão: Há uma tendência notória do benefício dos programas com EEF em pacientes com lesões medulares completas parece melhorar a capacidade cardiorrespiratória, a densidade mineral óssea, a força e atividade física, dos indivíduos. Contudo, mais estudos com elevada qualidade metodológica serão essenciais para conceber o real efeito da sua aplicação. Palavras-chave: lesão medular completa; estimulação elétrica funcional, randomized controlled trials, revisão sistemática.

A CASE REPORT OF INTRASPINAL PARACOCCIDIOIDOMYCOSIS

The authors report a case of paraplegia caused by a lumbar intraspinal paracoccidioidomycosis (PCM) granuloma. Clinical neurological diagnosis of a compressive spinal cord lesion was confirmed by spinal magnetic resonance imaging (MRI). Patient was submitted to surgery with total excision of the lesion. Histopathological analysis confirmed the diagnosis of PCM. Patient is on sulfamethoxazole/trimethoprim combined with fluconazole and is experiencing positive neurological recovery.

The use of cyclosporine modifies the clinical and histopathological presentation of tuberculosis after renal transplantation

Tuberculosis is one of the most frequent opportunistic infections after renal transplantation and occurred in 30 of 1264 patients transplanted between 1976 and 1996 at Hospital São Paulo - UNIFESP and Hospital Dom Silvério, Brazil. The incidence of 2.4% is five times higher than the Brazilian general population. The disease occurred between 50 days to 18 years after the transplant, and had an earlier and worse development in patients receiving azathioprine, prednisone and cyclosporine, with 35% presenting as a disseminated disease, while all patients receiving azathioprine and prednisone had exclusively pulmonary disease. Ninety percent of those patients had fever as the major initial clinical manifestation. Diagnosis was made by biopsy of the lesion (50%), positivity to M. tuberculosis in the sputum (30%) and spinal cerebral fluid analysis (7%). Duration of treatment ranged from 6 to 13 months and hepatotoxicity occurred in 3 patients. The patients who died had a significant greater number of rejection episodes and received higher doses of corticosteroid. In conclusion, the administration of cyclosporine changed the clinical and histopathological pattern of tuberculosis occurring after renal transplantation.

Descending pain modulation in a Kaolin-induced hydrocephalus rat model

Pain transmission at the spinal cord is modulated by descending actions that arise from supraspinal areas which collectively form the endogenous pain control system. Two key areas involved of the endogenous pain control system have a circunventricular location, namely the periaqueductal grey (PAG) and the locus coeruleus (LC). The PAG plays a crucial role in descending pain modulation as it conveys the input from higher brain centers to the spinal cord. As to the LC, it is involved in descending pain inhibition by direct noradrenergic projections to the spinal cord. In the context of neurological defects, several diseases may affect the structure and function of the brain. Hydrocephalus is a congenital or acquired disease characterized by an enlargement of the ventricles which leads to a distortion of the adjacent tissues, including the PAG and LC. Usually, patients suffering from hydrocephalus present dysfunctions in learning and memory and also motor deficits. It remains to be evaluated if lesions of the periventricular brain areas involved in pain control during hydrocephalus may affect descending pain control and, herein, affect pain responses. The studies included in the present thesis used an experimental model of hydrocephalus (the rat injected in the cisterna magna with kaolin) to study descending modulation of pain, focusing on the two circumventricular regions referred above (the PAG and the LC). In order to evaluate the effects of kaolin injection into the cisterna magna, we measured the degree of ventricular dilatation in sections encompassing the PAG by standard cytoarquitectonic stanings (thionin staining). For the LC, immunodetection of the noradrenaline-synthetizing enzyme tyrosine hydroxylase (TH) was performed, due to the noradrenergic nature of the LC neurons. In general, rats with kaolin-induced hydrocephalus presented a higher dilatation of the 4th ventricle, along with a tendency to a higher area of the PAG. Due to the validated role of detection the c-fos protooncogene as a marker of neuronal activation, we also studied neuronal activation in the several subnuclei which compose the PAG, namely the dorsomedial, dorsolateral, lateral and ventrolateral (VLPAG) parts. A decrease in the numbers of neurons immunoreactive for Fos protein (the product of activation of the c-fos protooncogene) was detected in rats injected with kaolin, whereas the remaining PAG subnuclei did not present changes in Fos-immunoreactive nuclei. Increases in the levels of TH in the LC, namely at the rostral parts of the nucleus, were detected in hydrocephalic animals. The following pain-related parameters were measured, namely 1) pain behavioural responses in a validated pain inflammatory test (the formalin test) and 2) the nociceptive activation of spinal cord neurons. A decrease in behavioral responses was detected in rats with kaolin-induced hydrocephalus was detected, namely in the second phase of the test (inflammatory phase). This is the phase of the formalin test in which the motor behaviour is less important, which is important since a semi-quantitative analysis of the motor performance of rats injected with kaolin indicates that these animals may present some motor impairments. Collectively, the results of the behavioral studies indicate that rats with kaolin-induced hydrocephalus exhibit hypoalgesia. A decrease in Fos expression was detected at the superficial dorsal layers of the spinal cord in rats with kaolin-induced hydrocephalus, further indicating that hydrocephalus decreases nociceptive responses. It remains to be ascertained if this is due to alterations in the PAG and LC in the rats with kaolin-induced hydrocephalus, which may affect descending pain modulation. It remains to be evaluated what are the mechanisms underlying the increased pain inhibition at the spinal dorsal horn in the hydrocephalus rats. Regarding the VLPAG, the decrease in neuronal activity may impair descending modulation. Since the LC has higher levels of TH in rats with kaolininduced hydrocephalus, which also appears to increase the noradrenergic innervation in the spinal dorsal horn, it is possible that an increase in the release of noradrenaline at the spinal cord accounts for pain inhibition. Our studies also determine the need to study in detail patients with hydrocephalus namely in what concerns their thresholds to pain and to perform imaging studies focused on the structure and function of pain control areas in the brain.

Confluent peripheral multiple mononeuropathy associated to acute hepatitis B: a case report

A thirty three year-old, male patient was admitted at the Hospital of the São Paulo University School of Medicine, at the city of São Paulo, Brazil, with complaint of pains, tingling and decreased sensibility in the right hand for the last four months. This had progressed to the left hand, left foot and right foot, in addition to a difficulty of flexing and stretching in the left foot. Tests were positive for HBeAg, IgM anti-HBc and HBsAg, thus characterizing the condition of acute hepatitis B. The ALT serum level was 15 times above the upper normal limit. Blood glucose, cerebral spinal fluid, antinuclear antibodies (ANA) and anti-HIV and anti-HCV serum tests were either normal or negative. Electroneuromyography disclosed severe peripheral neuropathy with an axon prevalence and signs of denervation; nerve biopsy disclosed intense vasculitis. The diagnosis of multiple confluent mononeuropathy associated to acute hepatitis B was done. This association is not often reported in international literature and its probable cause is the direct action of the hepatitis B virus on the nerves or a vasculitis of the vasa nervorum brought about by deposits of immune complexes.

Hand Involvement in Ollier Disease and Maffucci Syndrome: a Case Series

Ollier Disease and Maffucci Syndrome are two rare diseases that can cause tumors in several organs, having a special predilection for the hand. However, there have been very few reports in the literature focusing on hand manifestations of these diseases. We report the cases of three female patients: one with Ollier Disease, and two other with Maffucci Syndrome. All patients had hand involvement as their initial primary complaint. The Ollier Disease patient developed chondrosarcomas of two digits and had to have these fingers amputated. One of the Maffucci patients died one year after presentation from a brain glioblastoma. These cases emphasize the importance of early diagnosis of Ollier Disease and Maffucci Syndrome, as these two conditions are associated not only to crippling hand deformity, but also to a significant risk of chondrosarcoma, and other malignant tumors.