Reduced surface expression of transforming growth factor beta receptor type II in mitogen-activated T cells from Sézary patients.

Sézary syndrome (SzS), the leukemic form of cutaneous T-cell lymphoma, is characterized by clonal proliferation of CD4+ T cells and immune dysfunctions, raising the possibility of cytokine-related abnormalities. We previously described a decreased response to the growth-inhibitory effects of transforming growth factor type beta (TGF-beta) in SzS T cells accompanied by apparent loss of surface type II TGF-beta receptor (TGF beta RII). To specifically determine if defects exist in TGF beta RII protein expression and/or transport in SzS patients, we developed a sensitive flow cytometric method to detect TGF beta RII on the surface and intracellularly in the CD4+ T cells. Our results indicate that unlike normal CD4+ T cells, CD4+ T cells from 9 of 12 SzS patients expressed little, if any, surface TGF beta RII in response to mitogen stimulation. At the intracellular level, however, pools of TGF beta RII were comparable to those in normal CD4+ T cells. This indicates that defective trafficking of this inhibitory cytokine receptor may contribute significantly to the development of this disease.

Validação do protocolo de avaliação do frênulo da língua em bebês

Este estudo teve por objetivo validar o Protocolo de avaliação do frênulo da língua em bebês. Para isso, a partir do cálculo amostral, foi aplicado o protocolo em 100 bebês saudáveis, nascidos a termo, com 30 dias de vida, em amamentação exclusiva. O processo de validação consistiu da análise da validade de conteúdo, de critério e de construto, bem como da confiabilidade, sensibilidade, especificidade, valor preditivo positivo e negativo. A validade de conteúdo foi realizada por três examinadores, por meio da classificação de cada item quanto à clareza e posterior aplicação do Índice de Validação do Conteúdo. As avaliadoras sugeriram modificações no protocolo, por consenso, possibilitando obter a versão final. Para a validade de critério, comparou-se o Protocolo de avaliação do frênulo da língua em bebês com o instrumento Bristol Tongue Assessment Tool (BTAT). A validade de construto foi analisada a partir da comparação dos escores do protocolo aplicado nos bebês com 30 e 75 dias. As avaliações foram realizadas por duas fonoaudiólogas especialistas em Motricidade Orofacial (denominadas A1 e A2), devidamente treinadas e calibradas, por meio da análise das filmagens realizadas durante a aplicação do protocolo, para verificação da concordância entre examinadores, bem como definição dos valores de sensibilidade, especificidade e valores preditivos. Para a análise da concordância intra-avaliador foi realizado o teste/reteste de 20% da amostra pela A2. Quanto ao tratamento estatístico, para a análise de concordância intra e entre avaliadores, foram utilizados o Coeficiente de Correlação Intraclasse e o cálculo do erro do método. Para análise da validade de construto foram aplicados os testes de Wilcoxon e Mann-Whitney. O nível de significância adotado em todos os testes foi de 5%. Houve 100% de concordância na validação do conteúdo. A validade de critério apresentou correlações fortes dos itens correspondentes do Protocolo de avaliação do frênulo da língua em bebês e do instrumento BTAT, sendo o valor do coeficiente de correlação de Spearman igual a -0,997. Os resultados obtidos evidenciaram uma concordância muito boa intra e entre avaliadores, com valores baixos de erro casual e valores de p>0,05 (evidenciando que não há diferença entre a análise dos avaliadores) e Coeficiente de Correlação Intraclasse maior que 0,75; mostrando ainda, uma capacidade significativa do protocolo em mensurar as mudanças resultantes da frenotomia lingual, pela história clínica, avaliação anatomofuncional e avaliação da sucção não nutritiva e nutritiva (p<0,05). Quando comparados os resultados dos bebês com alteração do frênulo lingual (grupo experimental) e sem alteração (grupo controle), com 30 e 75 dias, houve diferença nos escores parciais e no escore total do exame clínico e do protocolo completo. Os índices de sensibilidade, especificidade e valores preditivos positivo e negativo foram 100%. A ocorrência das alterações do frênulo lingual nesse estudo foi de 21%. Concluiu-se, com este estudo, que o Protocolo de avaliação do frênulo da língua em bebês mostrou ser um instrumento válido e confiável de avaliação, assegurando acurácia em diagnosticar as alterações do frênulo lingual dentro dos parâmetros investigados, podendo ser aplicado por diferentes avaliadores, desde que os mesmos sejam capacitados e treinados para sua aplicação.

Efeitos da remoção do disco e cartilagem articular no crescimento e microarquitetura óssea da mandíbula de ratos: análise por microtomografia

Alterações na articulação emporomandibular (ATM) comumente geram desequilíbrios musculares que estão associados à alterações no tecido ósseo. Esta articulação pode sofrer a influência de traumas, fatores congênitos ou desordens de crescimento. Estudos sobre alterações de crescimento do complexo maxilomandibular decorrentes de problemas da ATM são escassos. O objetivo deste trabalho foi avaliar por meio da microtomografia os efeitos da remoção do disco articular e a remoção conjugada do disco e cartilagem articular no crescimento e na microarquitetura óssea da mandíbula de ratos. Trinta ratos da raça Wistar com um mês de idade foram divididos em três grupos: CTR (controle operado); RD (remoção de disco articular) e RDC (remoção conjugada do disco e cartilagem articular). Apenas o lado direito foi operado; o lado esquerdo permaneceu intacto. Após dois meses de acompanhamento, os ratos foram sacrificados e as hemimandíbulas escaneadas em microtomógrafo A remoção do disco articular e a remoção conjugada do disco e cartilagem articular alteram o volume e microestrutura do osso trabecular da mandíbula de ratos jovens. Estas duas intervenções provocaram uma queda na qualidade de parâmetros da microestrutura do trabeculado do processo angular e diminuição do crescimento da hemimandíbula do lado operado.

Epidemiologia da oclusão dentária na infância e os sistemas de saúde

O propósito deste estudo foi contribuir para a análise da epidemiologia da oclusão dentária na infância e discutir a implicação para os sistemas de saúde, examinando dados de prevalência de uma amostra probabilística (n=985) da população de 5 e 12 anos de idade na cidade de São Paulo, Brasil (1996); e estudos epidemiológicos transversais publicados nos últimos 70 anos. A prevalência na cidade, cresceu de 49,0 ± 4,5 por cento na dentição decídua para 71,3 ± 3,9 por cento na dentição permanente (p<0,001), sendo que a chance de ocorrência de oclusopatia moderada/severa foi quase duas vezes maior na segunda dentição (OR=1,87; IC95 por cento =1,43-2,45; p

Mathematical modelling of the lower urinary tract

The lower urinary tract is one of the most complex biological systems of the human body as it involved hydrodynamic properties of urine and muscle. Moreover, its complexity is increased to be managed by voluntary and involuntary neural systems. In this paper, a mathematical model of the lower urinary tract it is proposed as a preliminary study to better understand its functioning. Furthermore, another goal of that mathematical model proposal is to provide a basis for developing artificial control systems. Lower urinary tract is comprised of two interacting systems: the mechanical system and the neural regulator. The latter has the function of controlling the mechanical system to perform the voiding process. The results of the tests reproduce experimental data with high degree of accuracy. Also, these results indicate that simulations not only with healthy patients but also of patients with dysfunctions with neurological etiology present urodynamic curves very similar to those obtained in clinical studies.

Défice do transportador de creatina : até onde investigar a causa de um atraso do desenvolvimento?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Síndrome de Melkersson-Rosenthal : um diagnóstico a ponderar numa doente com edema do lábio

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Rôle des cellules endothéliales dans l’immunité innée précoce induite lors d’infections par des coronavirus murins

Les cellules endothéliales (EC) constituent une première barrière physique à la dissémination de virus pléiotropiques circulant par voie hématogène mais leur contribution à la défense innée anti-virale est peu connue. Des dysfonctions des EC de la barrière hémato-encéphalique (BMEC) et des sinusoïdes hépatiques (LSEC) ont été rapportées dans des neuropathologies et des hépatites aiguës ou chroniques d’origine virale, suggérant que des atteintes à leur intégrité contribuent à la pathogenèse. Les sérotypes de coronavirus de l’hépatite murine (MHV), se différenciant par leur capacité à induire des hépatites et des maladies neurologiques de sévérité variable et/ou leur tropisme pour les EC, représentent des modèles viraux privilégiés pour déterminer les conséquences de l’infection des EC sur la pathogenèse virale. Lors d’infection par voie hématogène, le sérotype MHV3, le plus virulent des MHV, induit une hépatite fulminante, caractérisée par une réponse inflammatoire sévère, et des lésions neurologiques secondaires alors que le sérotype moins virulent, MHV-A59, induit une hépatite modérée sans atteintes secondaires du système nerveux central (SNC). Par ailleurs, le sérotype MHV3, à la différence du MHV-A59, démontre une capacité à stimuler la production de cytokines par la voie TLR2. Les variants atténués du MHV3, les virus 51.6-MHV3 et YAC-MHV3, sont caractérisés par un faible tropisme pour les LSEC et induisent respectivement une hépatite modérée et subclinique. Compte tenu de l’importance des LSEC dans le maintien de la tolérance hépatique et de l’élimination des pathogènes circulants, il a été postulé que la sévérité de l’hépatite et de la réponse inflammatoire lors d’infections par les MHV est associée à la réplication virale et à l’altération des propriétés tolérogéniques et vasculaires des LSEC. Les désordres inflammatoires hépatiques pourraient résulter d’une activation différentielle du TLR2, plutôt que des autres TLR et des hélicases, selon les sérotypes. D’autre part, compte tenu du rôle des BMEC dans la prévention des infections du SNC, il a été postulé que l’invasion cérébrale secondaire par les coronavirus est reliée à l’infection des BMEC et le bris subséquent de la barrière hémato-encéphalique (BHE). À l’aide d’infections in vivo et in vitro par les différents sérotypes MHV, chez des souris ou des cultures de BMEC et de LSEC, nous avons démontré, d’une part, que l’infection in vitro des LSEC par le sétotype MHV3, à la différence des variants 51.6- et YAC-MHV3, altérait la production du facteur vasodilatant NO et renversait leur phénotype tolérogénique en favorisant la production de cytokines et de chimiokines inflammatoires. Ces dysfonctions se traduisaient in vivo par une réponse inflammatoire incontrôlée et une dérégulation du recrutement intrahépatique de leucocytes, favorisant la réplication virale et les dommages hépatiques. Nous avons aussi démontré, à l’aide de souris TLR2 KO et de LSEC dont l’expression du TLR2 a été abrogée par des siRNA, que la sévérité de l’hépatite et de la réponse inflammatoire induite par le sérotype MHV3, dépendait en partie de l’induction et de l’activation préférentielle du TLR2 par le virus dans le foie. D’autre part, la sévérité de la réplication virale au foie et des désordres dans le recrutement leucocytaire intrahépatique induits par le MHV3, et non par le MHV-A59 et le 51.6-MHV3, corrélaient avec une invasion virale subséquente du SNC, au niveau de la BHE. Nous avons démontré que l’invasion cérébrale du MHV3 était associée à une infection productive des BMEC et l’altération subséquente des protéines de jonctions serrées occludine, VE-cadhérine et ZO-1 se traduisant par une augmentation de la perméabilité de la BHE et l’entrée consécutive du virus dans le cerveau. Dans l’ensemble, les résultats de cette étude mettent en lumière l’importance du maintien de l’intégrité structurale et fonctionnelle des LSEC et des BMEC lors d’infections virales aigües par des MHV afin de limiter les dommages hépatiques associés à l’induction d’une réponse inflammatoire exagérée et de prévenir le passage des virus au cerveau suite à une dissémination par voie hématogène. Ils révèlent en outre un nouveau rôle aggravant pour le TLR2 dans l’évolution de l’hépatite virale aigüe ouvrant la voie à de nouvelles avenues thérapeutiques visant à moduler l’activité inflammatoire du TLR2.

Terapia génica: conceitos e aplicações na medicina dentária

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Fármacos utilizados para controlo da dor em medicina dentária

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Description and Prediction of Freezing of Gait in Parkinson's Disease from Wearable Inertial Measurements Units

Parkinson's disease (PD) is a neuro-degenerative disorder, the second most common after Alzheimer's disease. After diagnosis, treatments can help to relieve the symptoms, but there is no known cure for PD. PD is characterized by a combination of motor and no-motor dysfunctions. Among the motor symptoms there is the so called Freezing of Gait (FoG). The FoG is a phenomenon in PD patients in which the feet stock to the floor and is difficult for the patient to initiate movement. FoG is a severe problem, since it is associated with falls, anxiety, loss of mobility, accidents, mortality and it has substantial clinical and social consequences decreasing the quality of life in PD patients. Medicine can be very successful in controlling movements disorders and dealing with some of the PD symptoms. However, the relationship between medication and the development of FoG remains unclear. Several studies have demonstrated that visual or auditory rhythmical cuing allows PD patients to improve their motor abilities. Rhythmic auditory stimulation (RAS) was shown to be particularly effective at improving gait, specially with patients that manifest FoG. While RAS allows to reduce the time and the effects of FoGs occurrence in PD patients after the FoG is detected, it can not avoid the episode due to the latency of detection. An improvement of the system would be the prediction of the FoG. This thesis was developed following two main objectives: (1) the finding of specifics properties during pre FoG periods different from normal walking context and other walking events like turns and stops using the information provided by the inertial measurements units (IMUs) and (2) the formulation of a model for automatically detect the pre FoG patterns in order to completely avoid the upcoming freezing event in PD patients. The first part focuses on the analysis of different methods for feature extraction which might lead in the FoG occurrence.

Incorporating nerve-gliding techniques in the conservative treatment of cubital Tunnel syndrome

Objective: To discuss the diagnosis and treatment of a patient with cubital tunnel syndrome and to illustrate novel treatment modalities for the ulnar nerve and its surrounding structures and target tissues. The rationale for the addition of nerve-gliding techniques will be highlighted. Clinical Features: Two months after onset, a 17-year-old female nursing student who had a traumatic onset of cubital tunnel syndrome still experienced pain around the elbow and paresthesia in the ulnar nerve distribution. Electrodiagnostic tests were negative. Segmental cervicothoracic motion dysfunctions were present which were regarded as contributing factors hindering natural recovery. Intervention and Outcomes: After 6 sessions consisting of nerve-gliding techniques and segmental joint manipulation and a home exercise program consisting of nerve gliding and light free-weight exercises, a substantial improvement was recorded on both the impairment and functional level (pain scales, clinical tests, and Northwick Park Questionnaire). Symptoms did not recur within a 10-month follow-up period, and pain and disability had completely resolved. Conclusions: Movement-based management may be beneficial in the conservative management of cubital tunnel syndrome. As this intervention is in contrast with the traditional recommendation of immobilization, comparing the effects of both interventions in a systematic way is an essential next step to determine the optimal treatment of patients with cubital tunnel syndrome.

Analysis of the acute postoperative pain experience following oral surgery: identification of 'unaffected', 'disabled' and 'depressed, anxious and disabled' patient clusters

Background: Pain is defined as both a sensory and an emotional experience. Acute postoperative tooth extraction pain is assessed and treated as a physiological (sensory) pain while chronic pain is a biopsychosocial problem. The purpose of this study was to assess whether psychological and social changes Occur in the acute pain state. Methods: A biopsychosocial pain questionnaire was completed by 438 subjects (165 males, 273 females) with acute postoperative pain at 24 hours following the surgical extraction of teeth and compared with 273 subjects (78 males, 195 females) with chronic orofacial pain. Statistical methods used a k-means cluster analysis. Results: Three clusters were identified in the acute pain group: 'unaffected', 'disabled' and 'depressed, anxious and disabled'. Psychosocial effects showed 24.8 per cent feeling 'distress/suffering' and 15.1 per cent 'sad and depressed'. Females reported higher pain intensity and more distress, depression and inadequate medication for pain relief (p

Retinal and systemic vascular function in health and disease: the effect of smoking and coronary artery disease

The purpose of the following studies was to explore the effect of systemic vascular and endothelial dysfunction upon the ocular circulation and functionality of the retina. There are 6 principal sections to the present work. Retinal vessel activity in smokers and non-smokers: the principal findings of this work were: chronic smoking affects retinal vessel motion at baseline and during stimulation with flickering light; chronic smoking leads to a vaso-constrictory shift in retinal arteriolar reactivity to flicker; retinal arteriolar elasticity is decreased in chronic smokers. The effect of acute smoking on retinal vessel dynamics in smokers and non-smokers: the principal finding of this work was that retinal reactivity in chronic smokers is blunted when exposed to clicker light provocation immediately after smoking one cigarette. Ocular blood flow in coronary artery disease: The principal findings of this work were: retrobulbar and retinal blood flow is preserved in CAD patients, despite a change pulse wave transmission; arterial retinal response to flickering light provocation is significantly delayed in CAD patients; retinal venular diameters are significantly dilated in CAD patients. Autonomic nervous system function and peripheral circulation in CAD: The principal findings in this work were: CAD patients demonstrate a sympathetic overdrive during a 24 period; a delay in peripheral vascular reactivity (nail-fold capillaries) as observed in patients suffering from CAD could be caused by either arteriosclerotic changes of the vascular walls or due to systemic haemodynamic changes. Visual function in CAD: The principal findings in this work were: overall visual function in CAD patients is preserved, despite a decrease in contrast sensitivity; applying a filtering technique selecting those with greater coefficient of variance which in turn represents a decrease in reliability, some patients appear to have an impaired visual function as assessed using FDT visual field evaluation. Multiple functional, structural and biochemical vascular endothelial dysfunctions in patients suffering from CAD: relationships and possible implications: The principal findings of this work were: BMI significantly correlated with vWF (a marker of endothelial function) in CAD patients. Retinal vascular reactivity showed a significant correlation with peripheral reactivity parameters in controls which lacked in the CAD group and could reflect a loss in vascular endothelial integrity; visual field parameters as assessed by frequency doubling technology were strongly related with systemic vascular elasticity (ambulatory arterial stiffness index) in controls but not CAD patients.

The effects of yoked prisms on body posture and egocentric perception in a normal population

The principal theme of this thesis is the effect of yoked prisms on body posture and egocentric perception. Yoked prisms have been clinically used in the management of a variety of visual and neuro-motor dysfunctions. Most studies have been conducted in pathological populations by studying the effects of prismatic adaptation, without distinguishing short and long term effects. In this study, postural and perceptual prismatic effects have been studied by preventing prism adaptation. A healthy population was selected in order to investigate the immediate prismatic effects, when there is no obvious benefit from their use for the individual. Posturography was used to assess changes in weight distribution and shifts in centre of pressure (barycentre). In addition, photographic analyses were used to assess effects on posture on the x and z axis. Experiments with space board and visual midline shift were used for the evaluation of spatial perception and egocentric localisation. One pair of 8 Δ yoked prisms base left (BL) and one pair of 8 Δ yoked prisms base up (BU) were applied randomly and compared to a pair of plano lenses. Results suggest that immediate prismatic effects take place on a perceptual level and are reflected on an altered body posture respectively without significant changes in weight distribution. Yoked prisms BL showed a rightward rotational effect on spatial perception by expanding space on the z axis when viewing through the base of the prism and constricting space through the apex of the prism. Body posture responded respectively to what was visually perceived by altering posture. A rightward shift and tilt of the head was recorded along with the hips shift and shoulders tilt in the dame direction. Additionally, right shoulder shifted backwards and an angular midline shift to the right was recorded. The egocentric localisation was affected by shifting the midline perception to the left. Yoked prisms BU resulted on a head shift forward and a reduction of the head-neck angle by bringing the chin closer to the chest. The egocentric localisation was altered on the vertical axis providing subjects the perception that their eye level was higher during the experiment. In conclusion, yoked prisms seemed to induce changes in body posture, mainly in the upper body and head, without any significant changes in weight distribution. These changes are partially reflected in spatial perception tests and egocentric localisation before any prismatic adaptation takes place.