Treatment of non-resectable hepatocellular carcinoma with autologous tumor-pulsed dendritic cells

Background: The response of hepatocellular carcinoma (HCC) to therapy is often disappointing and new modalities of treatment are clearly needed. Active immunotherapy based on the injection of autologous dendritic cells (DC) co-cultured ex vivo with tumor antigens has been used in pilot studies in various malignancies such as melanoma and lymphoma with encouraging results. Methods: In the present paper, the preparation and exposure of patient DC to autologous HCC antigens and re-injection in an attempt to elicit antitumor immune responses are described. Results: Therapy was given to two patients, one with hepatitis C and one with hepatitis B, who had large, multiple HCC and for whom no other therapy was available. No significant side-effects were observed. The clinical course was unchanged in one patient, who died a few months later. The other patient, whose initial prognosis was considered poor, is still alive and well more than 3 years later with evidence of slowing of tumor growth based on organ imaging. Conclusions: It is concluded that HCC may be a malignancy worthy of DC trials and sufficient details in the present paper are given for the protocol to be copied or modified. (C) 2002 Blackwell Publishing Asia Pty Ltd.

Osteonectin/SPARC induction by ectopic beta(3) integrin in human radial growth phase primary melanoma cells

Expression of the beta(3) integrin subunit in melanoma in situ has been found to correlate with tumor thickness, the ability to invade and metastasize, and poor prognosis. Transition from the radial growth phase (RGP) to the vertical growth phase (VGP) is a critical step in melanoma progression and survival and is distinguished by the expression of beta(3), integrin. The molecular pathways that operate in melanoma cells associated with invasion and metastasis were examined by ectopic induction of the beta(3), integrin subunit in RGP SBcl2 and WM1552C melanoma cells, which converts these cells to a VGP phenotype. We used cDNA representational difference analysis subtractive hybridization between beta(3)-Positive and -negative melanoma cells to assess gene expression profile changes accompanying RGP to VGP transition. Fourteen fragments from known genes including osteonectin (also known as SPARC and BM-40) were identified after three rounds of representational difference analysis. Induction of osteonectin was confirmed by Northern and Western blot analysis and immunohistochemistry and correlated in organotypic cultures with the beta(3)-induced progression from RGP to VGP melanoma. Expression of osteonectin was also associated with reduced adhesion to vitronectin, but not to fibronectin. Osteonectin expression was not blocked when melanoma cells were cultured with anti-alpha(v)beta(3) LM609 mAb, mitogen-activated protein kinase, or protein kinase C inhibitors, indicating that other signaling pathway(s) operate through a(v)beta(3) integrin during conversion from RGP to VGP.

Fas ligand and tumour counter-attack in colorectal cancer stratified according to microsatellite instability status

Expression of membrane-bound Fas ligand (FasL) by colorectal cancer cells may allow the development of an immune-privileged site by eliminating incoming tumour-infiltrating lymphocytes (TILs) in a Fas-mediated counter-attack. Sporadic colorectal cancer can be subdivided into three groups based on the level of DNA microsatellite instability (NISI). High-level NISI (NISI-High) is characterized by the presence of TILs and a favourable prognosis, while microsatellite-stable (MSS) cancers are TIL-deficient and low-level MSI (MSI-Low) is associated with an intermediate TIL density. The purpose of this study was to establish the relationship between MSI status and FasL expression in primary colorectal adenocarcinoma. Using immunohistochemistry and a selected series of 101 cancers previously classified as 31 MSI-High, 30 NISI-Low, and 40 MISS, the present study sought to confirm the hypothesis that increased TIL density in MSI-High cancers is associated with low or absent membrane-bound FasL expression, while increased FasL in MSS cancers allows the killing of host TILs. TUNEL/CD3 double staining was also used to determine whether MSS cancers contain higher numbers of apoptotic TILs in vivo than MSI-High or MSI-Low cancers. Contrary to the initial hypothesis, it was found that MSI-High cancers were associated with higher FasL expression (p = 0.04) and a stronger intensity of FasL staining (p = 0.007). In addition, mucinous carcinomas were independently characterized by increased FasL expression (p = 0.03) and staining intensity (p = 0.0005). Higher FasL expression and staining intensity did not correlate with reduced TIL density or increased numbers of apoptotic TILs. However, consistent with the hypothesis that curtailment of the host anti-tumour immune response contributes to the poor prognosis in MSS cancers, it was found that apoptotic TILs were most abundant in MSS carcinomas and metastatic Dukes' stage C or D tumours (p = 0.004; p = 0.046 respectively). This study therefore suggests that MSS colorectal cancers are killing incoming TILs in an effective tumour counter-attack, but apparently not via membrane-bound FasL. Copyright (C) 2003 John Wiley Sons, Ltd.

Quality of care of patients hospitalized with congestive heart failure

Background: Congestive heart failure (CHF) is an increasingly prevalent poor-prognosis condition for which effective interventions are available. It is -therefore important to determine the extent to which patients with CHF receive appropriate care in Australian hospitals and identify ways for improving suboptimal care, if it exists. Aim: To evaluate the quality of in-hospital acute care of patients with CHF using explicit quality indicators based on published guidelines. Methods: A retrospective case note review was -performed, involving 216 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between October 2000 and April 2001. Outcome measures were process-of-care quality -indicators calculated as proportions of all, or strongly -eligible (ideal), patients who received -specific interventions. Results: Assessment of underlying causes and acute precipitating factors was undertaken in 86% and 76% of patients, respectively, and objective evaluation of left ventricular function was performed in 62% of patients. Prophylaxis for deep venous thrombosis (DVT) was used in only 29% of ideal patients. Proportions of ideal patients receiving pharmacological treatments at discharge were: (i) angiotensin--converting enzyme inhibitors (ACEi) (82%), (ii) target doses of ACEi (61%), (iii) alternative vasodilators in patients ineligible for ACEi (20%), (iv) beta-blockers (40%) and (v) warfarin (46%). Conclusions: Opportunities exist for improving quality of in-hospital care of patients with CHF, -particularly for optimal prescribing of: (i) DVT prophylaxis, (ii) ACEi, (iii) second-line vasodilators, (iv) beta-blockers and (v) warfarin. More research is needed to identify methods for improving quality of in-hospital care.

Avaliação assistida informatizada : indicadores do potencial cognitivo de crianças com deficiência

A identificação e a avaliação de crianças com desenvolvimento atípico configuram um processo muito importante para subsidiar as estratégias de ensino voltadas para a promoção do potencial de aprendizagem. O interesse em relação ao prognóstico de crianças com deficiência tem impulsionado o desenvolvimento de novas tecnologias e pesquisas relacionadas à avaliação, prevenção e intervenção. Nesse contexto, torna-se relevante verificar com instrumentos adequados indicadores linguísticos, cognitivos e comportamentais, para assim traçar metas a partir daquilo que as crianças podem aprender. Dessa forma, esta pesquisa teve por objetivo verificar se a avaliação assistida informatizada se apresenta como uma modalidade de diagnóstico mais prescritivo do desenvolvimento cognitivo, quando comparada à avaliação psicométrica, na aplicação em crianças com deficiência. Na modalidade assistida há ajuda do examinador para conduzir a criança a um melhor nível de desempenho cognitivo. Participaram 11 crianças que frequentam uma instituição de atendimento clínico, em saúde, para crianças com deficiência, na Grande Vitória. Na avaliação psicométrica foram utilizados a Escala de Maturidade Mental Colúmbia computadorizada – Colúmbiacomp e o Teste de Vocabulário por Imagens Peabody - TVIPcomp. Na avaliação assistida informatizada foram aplicadas três provas voltadas para as habilidades de classificação e raciocínio analógico: Exclusão de Objetos, Exclusão de Figuras Geométricas e Jogo de Analogia de Figuras, no ambiente informatizado SINDAPSI. Protocolos de registro de fatores afetivo-motivacionais e de operações cognitivas foram utilizados durante as tarefas assistidas. Na avaliação do comportamento, o Child Behavior Checklist – CBCL foi respondido pelas mães. Dados documentais e dos instrumentos foram submetidos à análise estatística descritiva para verificar o desempenho das crianças nas duas formas de avaliação informatizada (psicométrica e assistida). Nos testes psicométricos, 64% das crianças alcançaram índice “abaixo da média” no TVIPcomp, e 55% “médio-inferior” no Colúmbiacomp. Em relação ao perfil de desempenho cognitivo, na Prova de Exclusão de Objetos computadorizada 55% das crianças foram avaliadas como “não-mantenedoras”. Na Prova de Exclusão de Figuras Geométricas computadorizada 55% da amostra foi classificada no perfil “alto-escore”, e no Jogo de Analogias de Figuras computadorizado 45% apresentou o perfil “ganhador”. A amostra demonstrou níveis de dificuldade na realização dos testes,tanto na modalidade psicométrica quanto assistida. Contudo, o desempenho nos testes assistidos foi relativamente melhor, evidenciando que o grupo se beneficiou da mediação,implementada na fase de assistência, para melhorar as habilidades cognitivas. Além disso, a apresentação informatizada dos testes apresentou-se como fator motivador para a realização e persistência nas tarefas.

Physical consequences of falls in the elderly: a literature review from 1995 to 2010

In the last decade, population ageing has been registered as a global phenomenon. A relation exists between falling and ageing, since falling frequency increases significantly with age. In fact, one in three older adult falls annually. Although ageing is generically associated with decrease and degeneration of psychological and physical functions, it is still not common for the correct identification of risk factors to lead to a clinical prognosis of the elder being in risk of falling. Therefore, the goal of this review article is to identify, categorise and analyse typical ageing and fall factors mentioned in the literature as well as to quantify the number of times they were referenced. The research considered hundreds of publications, but analysis was then restricted to the 87 most pertinent articles written in English and published in journals or scientific magazines between 1995 and 2010. We concluded that falls among older adults can be characterised by the following: anatomic characteristics and physiological consequences of ageing; the pathologies that induce falls, which can be neurological, musculoskeletal, cardiovascular and other diseases; causes and risk factors of falls that can be behavioural, biological, environmental or socio-economic; type of physical consequences of falls, including fractures, bruises, injuries or other physical consequences; and strategies to prevent, mitigate or rehabilitate, which can be of a physical, environmental or behavioural nature.

Physical consequences of falls in the elderly: a literature review from 1995 to 2010

In the last decade, population ageing has been registered as a global phenomenon. A relation exists between falling and ageing, since falling frequency increases significantly with age. In fact, one in three older adult falls annually. Although ageing is generically associated with decrease and degeneration of psychological and physical functions, it is still not common for the correct identification of risk factors to lead to a clinical prognosis of the elder being in risk of falling. Therefore, the goal of this review article is to identify, categorise and analyse typical ageing and fall factors mentioned in the literature as well as to quantify the number of times they were referenced. The research considered hundreds of publications, but analysis was then restricted to the 87 most pertinent articles written in English and published in journals or scientific magazines between 1995 and 2010. We concluded that falls among older adults can be characterised by the following: anatomic characteristics and physiological consequences of ageing; the pathologies that induce falls, which can be neurological, musculoskeletal, cardiovascular and other diseases; causes and risk factors of falls that can be behavioural, biological, environmental or socio-economic; type of physical consequences of falls, including fractures, bruises, injuries or other physical consequences; and strategies to prevent, mitigate or rehabilitate, which can be of a physical, environmental or behavioural nature.

An image processing application for quantification of protein aggregates in Caenorhabditis elegans

Protein aggregation became a widely accepted marker of many polyQ disorders, including Machado-Joseph disease (MJD), and is often used as readout for disease progression and development of therapeutic strategies. The lack of good platforms to rapidly quantify protein aggregates in a wide range of disease animal models prompted us to generate a novel image processing application that automatically identifies and quantifies the aggregates in a standardized and operator-independent manner. We propose here a novel image processing tool to quantify the protein aggregates in a Caenorhabditis elegans (C. elegans) model of MJD. Confocal mi-croscopy images were obtained from animals of different genetic conditions. The image processing application was developed using MeVisLab as a platform to pro-cess, analyse and visualize the images obtained from those animals. All segmenta-tion algorithms were based on intensity pixel levels.The quantification of area or numbers of aggregates per total body area, as well as the number of aggregates per animal were shown to be reliable and reproducible measures of protein aggrega-tion in C. elegans. The results obtained were consistent with the levels of aggrega-tion observed in the images. In conclusion, this novel imaging processing applica-tion allows the non-biased, reliable and high throughput quantification of protein aggregates in a C. elegans model of MJD, which may contribute to a significant improvement on the prognosis of treatment effectiveness for this group of disor-ders

Factors influencing amblyopia rehabilitation in occlusive therapy

Amblyopia develops in an early period and is a decrease of visual acuity (unilateral or bilateral) caused by a deprivation of vision or abnormal binocular interaction. Prognosis of Amblyopia is better when occlusive treatment is implemented in an early stage. Visual acuity of amblyopic eye does not improve without effective occlusive therapy. The aim of this study is to identify potential risk factors of noncompliance with treatment when it is implemented by parents in amblyopic children.

Quality of life in dilated cardiomyopathy with refractory chronic heart failure undergoing devices implantation

Heart failure is the final stage of most of cardiac diseases. It is a complex syndrome in which the patients should have the following features: symptoms of heart failure, typically shortness of breath at rest or during exertion, and/or fatigue; signs of fluid retention such as pulmonary congestion or ankle swelling; and objective evidence of an abnormality of the structure or function of the heart at rest. This progressive syndrome as a high incidence and prevalence and poor prognosis: four-year mortality is around 50% with 40% of the patients admitted to hospital dying or readmitted within a year. With ageing, many patients will develop chronic heart failure, which, because of its symptoms, patient’s awareness of their risk of dying, and the effects of therapy, together with frequent hospitalizations, has considerable impact on patient’s health-related quality of life.

A model to forecast financial failure, in non financial galician SMES

We are concerned with providing more empirical evidence on forecast failure, developing forecast models, and examining the impact of events such as audit reports. A joint consideration of classic financial ratios and relevant external indicators leads us to build a basic prediction model focused in non-financial Galician SMEs. Explanatory variables are relevant financial indicators from the viewpoint of the financial logic and financial failure theory. The paper explores three mathematical models: discriminant analysis, Logit, and linear multivariate regression. We conclude that, even though they both offer high explanatory and predictive abilities, Logit and MDA models should be used and interpreted jointly.

Monitorização da insuficiência cardíaca por parâmetros fisiológicos em portadores de cardioversor-desfibrilhador implantável e/ou sistema de ressincronização cardíaca: HF-PREDICT

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular. Área de especialização: Intervenção Cardiovascular.

Intervenção coronária percutânea no enfarte agudo do miocárdio: influência no prognóstico dos doentes

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular. Área de especialização: Intervenção Cardiovascular.

Imunorreatividade em material histológico arquivado durante um, quatro e sete anos

Quando aplicada no âmbito da Anatomia Patológica, a imuno-histoquímica tem constituído um poderoso meio de identificação/caracterização de várias estruturas histológicas, permitindo delinear prognóstico e terapêutica para várias patologias. Tendo em conta que as amostras histológicas analisadas podem ser conservadas ao longo de vários anos, interessa avaliar a manutenção da antigenicidade ao longo do tempo, de forma a garantir a qualidade final da técnica quando aplicada em material de arquivo. Assim, o principal objetivo deste trabalho foi comparar a imunorreatividade do material histológico arquivado durante um, quatro e sete anos. Foi utilizado material histológico de próstata, pulmão e mama, no qual se procedeu à imunomarcação de citoqueratinas (Clones AE1/AE3), CD34 e proteína p63, por método de multímero/HRP no sistema Ventana BenchMark Ultra®. Foi realizado um ensaio com recuperação antigênica por alta temperatura (RAAT) e outro sem esta etapa. As imunomarcações (n=162) foram classificadas por três avaliadores independentes num escore quantitativo final (escala 0-100). O par média/desvio-padrão do escore final para os casos com sete anos foi de 69,06/19,05, para os casos com quatro anos foi de 66,47/20,73 e para os casos com um ano foi de 69,08/19,35, não se tendo encontrado diferenças estatisticamente significativas. Os casos sem RAAT obtiveram um par média/desvio-padrão de 54,90/17,00, enquanto os casos com RAAT obtiveram 81,50/11,60, o que revelou diferenças estatisticamente significativas (p=0,000). Para os casos em estudo conclui-se que o fator “tempo de arquivo” não está associado a alterações da imunorreatividade. A importância da RAAT na obtenção de imunomarcação de qualidade sai fortemente realçada. ABSTRACT - When applied within the framework of Pathology, immunohistochemistry has been a powerful means of identification/characterization of various histological structures, allowing to outline prognosis and therapy for various diseases. Given that the analyzed histological samples can be preserved for several years, it is interesting to assess the retention of antigenicity over time in order to ensure the quality of the final technique, when applied to stored material. Thus, the main objective of this study was to compare the immunoreactivity of the histological material archived for one, four and seven years. It was used histological material from prostate, lung and breast, in which it was performed the immunostaining of cytokeratins (clones AE1/AE3), CD34 and p63 protein by the method of multimer/HRP system on a Ventana BenchMark Ultra®. It was conducted a test with heat induced epitope retrieval (HIER) and another one without this step. The stained slides (n=162) were classified by three independent assessors using a quantitative score (scale 0-100). The pair mean/standard deviation of the score for cases with seven years was 69,06/19,05, for cases with four years was 66,47/20,73 and for cases with one year was 69,08/19,35, which did not revealed any statistically significant differences. The cases without HIER had a couple mean/standard deviation of 54.90/17.00 while the cases with HIER obtained 81.50/11.60, which revealed statistically significant differences (p=0.000). For this case study it was concluded that the factor archive period is not associated with changes in immunoreactivity. The importance of HIER in obtaining high quality immunostaining comes out strongly highlighted.

Modern cancer epidemiological research: genetic polymorphisms and environment

Individual cancer susceptibility seems to be related to factors such as changes in oncogenes and tumor suppressor genes expression, and differences in the action of metabolic enzymes and DNA repair regulated by specific genes. Epidemiological studies on genetic polymorphisms of human xenobiotics metabolizing enzymes and cancer have revealed low relative risks. Research considering genetic polymorphisms prevalence jointly with environmental exposures could be relevant for a better understanding of cancer etiology and the mechanisms of carcinogenesis and also for new insights on cancer prognosis. This study reviews the approaches of molecular epidemiology in cancer research, stressing case-control and cohort designs involving genetic polymorphisms, and factors that could introduce bias and confounding in these studies. Similarly to classical epidemiological research, genetic polymorphisms requires considering aspects of precision and accuracy in the study design.