Implementa����o de um sistema para simula����o por Monte Carlo da passagem de fot��es atrav��s do olho humano mediante a utiliza����o da plataforma GEANT4 - I

Disserta����o para obten����o do Grau de Mestre em Engenharia Biom��dica

Peritubular Capillaries C4d Deposits in Renal Allograft Biopsies and Anti HLA I/II Alloantibodies Screening. Incidence and Clinical Importance

Aim: To characterise clinically the patients with C4d in peritubular capillaries deposits (C4dPTCD) and/or circulating anti-HLA class I/II alloantibodies. To determine the correlation between positive C4dPTCD and circulating anti-HLA class I/II alloantibodies during episodes of graft dysfunction. Subjects and Methods: C4d staining was performed in biopsies with available frozen tissue obtained between January 2004 and December 2006. The study was prospective from March 2005, when a serum sample was obtained at the time of biopsy to detect circulating anti-HLA class I/II alloantibodies. Results: We studied 109 biopsies in 86 cadaver renal transplant patients. Sixteen of these (14.7%) presented diffuse positive C4dPTCD. There was a 13.5% rate of +C4dPTCD incidence within the first six months of transplantation and 16% after six months (p>0.05). Half of the +C4dPTCD in the first six months was associated with acute humoral rejection. After six months, the majority of +C4dPTCD (n=7/8) was present in biopsies with evidence of interstitial fibrosis/tubular atrophy and/or transplant glomerulopathy. The C4dPTCD was more frequent in patients with positive anti-HCV antibodies(p<0.0001), a previous renal transplant (p=0.007), and with a panel reactivity antibody (PRA) ��� 50%(p=0.0098). The anti-HCV+ patients had longer time on dialysis (p=0.0019) and higher PRA(p=0.005). Circulating anti-HLA I/II alloantibodies were screened in 46 serum samples. They were positive in 10.9% of samples, all obtained after six months post transplant. Circulating alloantibodies were absent in 92.5% of the C4d negative biopsies. Conclusion: We found an association between the presence of C4dPTCD and 2nd transplant recipients,higher PRA and the presence of anti-HCV antibodies. The presence of HCV antibodies is not a risk factor for C4dPTCD per se, but appears to reflect longer time on dialysis and presensitisation. In renal dysfunction a negative alloantibody screening is associated with a reduced risk of C4dPTCD (<10%).

Biological predictors of survival in limphoma and mechanisms underlying follicular lymphoma transformaion into diffuse large B cell lymphoma (vol I e II)

RESUMO: Os biomarcadores tumorais permitem identificar os doentes com maior risco de recorr��ncia da doen��a, predizer a resposta tumoral �� terap��utica e, finalmente, definir candidatos a novos alvos terap��uticos. Novos biomarcadores s��o especialmente necess��rios na abordagem cl��nica dos linfomas. Actualmente, esses tumores s��o diagnosticados atrav��s de uma combina����o de caracter��sticas morfol��gicas, fenot��picas e moleculares, mas o progn��stico e o planeamento terap��utico est��o quase exclusivamente dependentes de caracter��sticas cl��nicas. Estes factores cl��nicos s��o, na maioria dos linfomas, insuficientes numa propor����o significativa dos doentes, em particular, aqueles com pior progn��stico. O linfoma folicular (LF) ��, globalmente, o segundo subtipo mais comum de linfoma. �� tipicamente uma doen��a indolente com uma sobrevida m��dia entre os 8 e 12 anos, mas �� geralmente fatal quando se transforma num linfoma agressivo de alto grau, habitualmente o linfoma difuso de grandes c��lulas B (LDGCB). Morfologicamente e funcionalmente, as c��lulas do LF recapitulam as c��lulas normais do centro germinativo na sua depend��ncia de sobreviv��ncia do microambiente n��o-tumoral, especialmente das c��lulas do sistema imunol��gico. Biomarcadores preditivos de transforma����o n��o existem pelo que um melhor conhecimento da biologia intr��nseca de progress��o do LF poder�� revelar novos candidatos. Nesta tese descrevo duas abordagens distintas para a descoberta de novos biomarcadores. A primeira, o estudo da express��o global de genes ('genomics') obtidos por t��cnicas de alto rendimento que analisam todo o genoma humano sequenciado, permitindo identificar novas anomalias gen��ticas que possam representar mecanismos biol��gicos importantes de transforma����o. S��o descritos novos genes e altera����es gen��micas associados �� transforma����o do LF, sendo especialmente relevantes as relacionadas com os eventos iniciais de transforma����o em LDGCB. A segunda, baseou-se em v��rias hip��teses centradas no microambiente do LF, rico em v��rios tipos de c��lulas n��omalignas. Os estudos imunoarquitectural de macr��fagos, c��lulas T regulat��rias e densidade de microvasos efectuado em biopsias de diagn��stico de doentes com LF tratados uniformemente correlacionaram-se significativamente, e independentemente dos crit��rios cl��nicos, com a evolu����o cl��nica e, mais importante, com o risco de transforma����o em LDGCB. Nesta tese, foram preferencialmente utilizadas (e optimizadas) t��cnicas que permitam o uso de amostras fixadas em parafina e formalina (FFPET). Estas s��o facilmente acess��veis a partir das biopsias de diagn��stico de rotina presentes nos arquivos de todos os departamentos de patologia, facilitando uma transi����o r��pida dos novos marcadores para a pr��tica cl��nica. Embora o FL fosse o tema principal da tese, os novos achados permitiram estender facilmente hip��teses semelhantes a outros subtipos de linfoma. Assim, s��o propostos e validados v��rios biomarcadores promissores e relacionados com o microambiente n��o tumoral, sobretudo dependentes das c��lulas do sistema imunol��gico, como contribuintes importantes para a biologia dos linfomas. Estes sugerem novas op����es para a abordagem cl��nica destas doen��as e, eventualmente, novos alvos terap��uticos.------------- ABSTRACT: Cancer biomarkers provide an opportunity to identify those patients most at risk for disease recurrence, predict which tumours will respond to different therapeutic approaches and ultimately define candidate biomarkers that may serve as targets for personalized therapy. New biomarkers are especially needed in the management of lymphoid cancers. At present, these tumours are diagnosed using a combination of morphologic, phenotypic and molecular features but prognosis and overall survival are mostly dependent on clinical characteristics. In most lymphoma types, these imprecisely assess a significant proportion of patients, in particular, those with very poor outcomes. Follicular lymphoma (FL) is the second most common lymphoma subtype worldwide. It is typically an indolent disease with current median survivals in the range of 8-12 years, but is usually fatal when it transforms into an aggressive high-grade lymphoma, characteristically Diffuse Large B Cell Lymphoma (DLBCL). Morphologically and functionally it recapitulates the normal cells of the germinal center with its survival dependency on non-malignant immune and immunerelated cells. Informative markers of transformation related to the intrinsic biology of FL progression are needed. Within this thesis two separate approaches to biomarker discovery were employed. The first was to study the global expression of genes (���genomics���) obtained using high-throughput, wholegenome-wide approaches that offered the possibility for discovery of new genetic abnormalities that might represent the important biological mechanisms of transformation. Gene signatures associated with early events of transformation were found. Another approach relied on hypothesis-driven concepts focusing upon the microenvironment, rich in several non-malignant cell types. The immunoarchitectural studies of macrophages, regulatory T cells and microvessel density on diagnostic biopsies of uniformly treated FL patients significantly predicted clinical outcome and, importantly, also informed on the risk of transformation. Techniques that enabled the use of routine formalin fixed paraffin embedded diagnostic specimens from the pathology department archives were preferentially used in this thesis with the goal of fulfilling a rapid bench-to-beside��� translation for these new findings. Although FL was the main subject of the thesis the new findings and hypotheses allowed easy transition into other lymphoma types. Several promising biomarkers were proposed and validated including the implication of several non-neoplastic immune cells as important contributors to lymphoma biology, opening new options for better treatment planning and eventually new therapeutic targets and candidate therapeutics.

Induction of phagocytic activity and nitric-oxide production in natural populations of Trypanosoma Cruzi I and II from the state of Paran��, Brazil

Twelve strains of Trypanosoma cruzi isolated from wild reservoirs, triatomines, and chronic chagasic patients in the state of Paran��, southern Brazil, and classified as T. cruzi I and II, were used to test the correlation between genetic and biological diversity. The Phagocytic Index (PI) and nitric-oxide (NO) production in vitro were used as biological parameters. The PI of the T. cruzi I and II strains did not differ significantly, nor did the PI of the T. cruzi strains isolated from humans, triatomines, or wild reservoirs. There was a statistical difference in the inhibition of NO production between T. cruzi I and II and between parasites isolated from humans and the strains isolated from triatomines and wild reservoirs, but there was no correlation between genetics and biology when the strains were analyzed independently of the lineages or hosts from which the strains were isolated. There were significant correlations for Randomly Amplified Polymorphic Deoxyribonucleic acid (RAPD) and biological parameters for T. cruzi I and II, and for humans or wild reservoirs when the lineages or hosts were considered individually.

A Communication Intervention for Training Southern European Oncologists to Recognize Psychosocial Morbidity in Cancer. I - Development of the Model and Preliminary Results on Physicians' Satisfaction

BACKGROUND: The detection of psychosocial distress is a significant communication problem in Southern Europe and other countries. Work in this area is hampered by a lack of data. Because not much is known about training aimed at improving the recognition of psychosocial disorders in cancer patients, we developed a basic course model for medical oncology professionals. METHODS: A specific educational and experiential model (12 hours divided into 2 modules) involving formal teaching (ie, journal articles, large-group presentations), practice in small groups (ie, small-group exercises and role playing), and discussion in large groups was developed with the aim of improving the ability of oncologists to detect emotional disturbances in cancer patients (ie, depression, anxiety, and adjustment disorders). RESULTS: A total of 30 oncologists from 3 Southern European countries (Italy, Portugal, and Spain) participated in the workshop. The training course was well accepted by most participants who expressed general satisfaction and a positive subjective perception of the utility of the course for clinical practice. Of the total participants, 28 physicians (93.3%) thought that had they been exposed to this material sooner, they would have incorporated the techniques received in the workshop into their practices; 2 participants stated they would likely have done so. Half of the doctors (n = 15) believed that their clinical communication techniques were improved by participating in the workshop, and the remaining half thought that their abilities to communicate with cancer patients had improved. CONCLUSIONS: This model is a feasible approach for oncologists and is easily applicable to various oncology settings. Further studies will demonstrate the effectiveness of this method for improving oncologists skills in recognizing emotional disorders in their patients with cancer.

Tension-Free Vaginal Tape (T.V.T) - Nova e Revolucion��ria T��cnica para o Tratamento Cir��rgico da Incontin��ncia Urin��ria de Esfor��o (I.U.E.) Feminina Introduzida na MAC pelo N��cleo de Ginecologia Urol��gica

Este artigo pretende fazer uma revis��o de uma das ��ltimas e inovadoras alternativas cir��rgicas vi��veis para a cura da incontin��ncia urin��ria de esfor��o feminina, com um sucesso superior a 86%. �� uma cirurgia mini invasiva e que induz um suporte da uretra m��dia livre de tens��o, muito eficaz. Tem vantagens, poucas complica����es, curto tempo operat��rio e benef��cios para a doente no p��s-operat��rio imediato e tardio.

Brazilian mosquito (Diptera: Culicidae) fauna: I. Anopheles species from Porto Velho, Rond��nia state, western Amazon, Brazil

This study contributes to knowledge of Anopheles species, including vectors of Plasmodium from the western Brazilian Amazon in Porto Velho, Rond��nia State. The sampling area has undergone substantial environmental changes as a consequence of agricultural and hydroelectric projects, which have caused intensive deforestation and favored habitats for some mosquito species. The purpose of this study was to diagnose the occurrence of anopheline species from collections in three locations along an electric-power transmission line. Each locality was sampled three times from 2010 to 2011. The principal adult mosquitoes captured in Shannon trap were Anopheles darlingi, An. triannulatus, An. nuneztovari l.s., An.gilesi and An. costai. In addition, larvae were collected in ground breeding sites for Anopheles braziliensis, An. triannulatus, An. darlingi, An. deaneorum, An. marajoara, An. peryassui, An. nuneztovari l.s. and An. oswaldoi-konderi. Anopheles darlingi was the most common mosquito in the region. We discuss Culicidae systematics, fauna distribution, and aspects of malaria in altered habitats of the western Amazon.

"I was a maoist intelectual". Uma leitura cr��tica em torno dos conceitos "industria cultural" e "popular music" segundo adorno

Reflectir sobre no����es como liberdade individual, democracia, o papel dos meios de comunica����o e dos produtos culturais, �� uma das principais tarefas das ci��ncias sociais e humanas, reflex��o particularmente pertinente nestes primeiros anos do s��c. XXI marcados pela populariza����o de dispositivos tecnol��gicos destinados �� circula����o de informa����o em rede e pela virtualiza����o de mecanismos de distribui����o de bens de consumo cultural. Adomo constitui hoje uma das fontes mais importantes surgidas nos ��ltimos 50 anos para esta reflex��o. Marcado pelo advento do Nacional Socialismo e a persegui����o de todos os "degenerados da condi����o ariana" (judeus, comunistas e homossexuais), Adomo produziu ao longo de quatro d��cadas, uma reflex��o que marcou indelevelmente muitos autores que, escrevendo sobre a contemporaneidade, a adoptaram ou a ela se opuseram. A pergunta que coloco, e que serve de ponto de partida para este artigo, �� proposta por Jameson: �� hoje poss��vel ler Adomo e Horkheimer junto �� piscina? (1990: 248), ou posto de outra forma, que lugar ocupa a obra de Adomo como ferramenta para perspectivar o mundo actual.

Anemia Cong��nita Diseritropoi��tica Tipo I. Um Caso Cl��nico Raro de Anemia

Os autores descrevem um caso cl��nico raro de anemia cong��nita diseritropoi��tica tipo I numa adolescente de 15 anos, em que s�� as altera����es morfol��gicas da medula ��ssea e os testes serol��gicos (hem��lise ��cida, aglutina����o anti-I e anti-i) permitiram o diagn��stico. O estudo familiar efectuado foi negativo. Atendendo a raridade destas anemias heredit��rias s��o discutidos alguns dos seus aspectos.