5-Fluorouracil: mechanisms of action and clinical strategies

5-fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such as DNA microarray profiling, have the potential to identify novel genes that are involved in mediating resistance to 5-FU. Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy.

The “re-socialization” of Gypsy women in the literacy courses aimed to the recipients of the Social Integration Revenue Policy of the Region of Madrid

This article studies the gender values that are promoted both in the literacy courses for gypsy women beneficiaries of the Social Integration Revenue Policy of the Region of Madrid and in the events that are organized for this group by public institutions and NGOs. The process of “socialization” that occurs in the educative groups for Gypsy women is focused on constructing an image of what it is to be a “Gypsy modern woman”. Through multiple mechanisms and discursive techniques a specific conception of gender equality is transmitted in these educative spaces. In addition to this, Gypsy women are continually urged to assume certain values and social practices (of gender identity, of "citizenship", of parenting, etc..), while an archetype of "Gypsy Woman" which condenses powerful stereotypes and prejudices about the "Gypsy culture" and the gender relations characteristics of this group is constructed.

The University Programmes for Senior Citizens and their contribution of lifelong learning

The study addresses the essential features of University Programmes for senior citizens (PUM). It committed to the lifelong education through the integration of the elderly in the University. Part of the base that is learned during the entire life cycle, there is no age, no specific space for education. Learning is constructed from knowledge, abilities, skills and aptitudes that are enriched continuously. It is necessary to ensure the elderly to age in a healthy way. It calls for active ageing, effective tool against isolation and social exclusion. The aim is to discover aspects of the UNED Senior training programme that contribute to lifelong learning and satisfaction produced. The PUM are ways for the promotion of aging along with other activities aimed to enhance a creative leisure, access to culture, facilitate training on topics of interest and create a means of participation in all spheres of society. In this research has resorted to a mixed methodology. Their wealth combines the methods of quantitative and qualitative allowing us to obtain information and contrast from different perspectives. The purpose is to verify the results of the investigation. The sample consists of 639 students, 57 teachers and 15 coordinators. The results indicate that the PUM of the UNED Senior is highly satisfactory for those involved, by the adequacy between interests and expectations. Fruit of this research are the conclusions and suggestions for improvement.

A new teaching category at the Spanish University of Franco’s regime: the appearance on the scene of the senior lecturer

The Law of 17 July 1965 on the structure of university faculties and their teaching staff placed the figure of the university senior lecturer on stage. During the sixties, the gestation process, adoption and subsequent integration of the new figure in the academic pyramid did not escape controversy, leading to a complex phenomenon to which, however, non comprehensive studies have been devoted to reveal: how, when, why and under which conditions this teacher appeared in the Spanish University of Franco’s regime. This paper aims to provide an overview of the process of materialization of the senior lecturer, the legislative framework that definitely established this new educational category and the provisions that were in charge of regulating the processes to get tenure. Also, the first approved aggregate endowments and their distribution among universities, colleges and studies will be discussed. Finally, it was a first approach to the possible motivations that led to the creation of this new educational category in a university afflicted by serious problems waiting for a solution that had been delayed sine die. Asimismo, se analizarán las primeras dotaciones de agregados aprobadas y la distribución de las mismas por universidades, facultades y estudios. Para terminar, se realiza un primer acercamiento a las posibles motivaciones que condujeron a la creación de esta nueva figura docente en una universidad aquejada de graves problemas que esperaban a una solución que venía demorándose sine die.

Probabilistic classification of acute myocardial infarction from multiple cardiac markers

Logistic regression and Gaussian mixture model (GMM) classifiers have been trained to estimate the probability of acute myocardial infarction (AMI) in patients based upon the concentrations of a panel of cardiac markers. The panel consists of two new markers, fatty acid binding protein (FABP) and glycogen phosphorylase BB (GPBB), in addition to the traditional cardiac troponin I (cTnI), creatine kinase MB (CKMB) and myoglobin. The effect of using principal component analysis (PCA) and Fisher discriminant analysis (FDA) to preprocess the marker concentrations was also investigated. The need for classifiers to give an accurate estimate of the probability of AMI is argued and three categories of performance measure are described, namely discriminatory ability, sharpness, and reliability. Numerical performance measures for each category are given and applied. The optimum classifier, based solely upon the samples take on admission, was the logistic regression classifier using FDA preprocessing. This gave an accuracy of 0.85 (95% confidence interval: 0.78-0.91) and a normalised Brier score of 0.89. When samples at both admission and a further time, 1-6 h later, were included, the performance increased significantly, showing that logistic regression classifiers can indeed use the information from the five cardiac markers to accurately and reliably estimate the probability AMI. © Springer-Verlag London Limited 2008.

Novel biomarkers in early diagnosis of acute myocardial infarction compared with cardiac troponin T

Aims: To evaluate the role of novel biomarkers in early detection of acute myocardial infarction (MI) in patients admitted with acute chest pain.
Methods and results: A prospective study of 664 patients presenting to two coronary care units with chest pain was conducted over 3 years from 2003. Patients were assessed on admission: clinical characteristics, ECG (electrocardiogram), renal function, cardiac troponin T (cTnT), heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, NT-pro-brain natriuretic peptide, D-dimer, hsCRP (high sensitivity C-reactive protein), myeloperoxidase, matrix metalloproteinase-9, pregnancy associated plasma protein-A, soluble CD40 ligand. A =12 h cTnT sample was also obtained. MI was defined as cTnT = 0.03 µg/L. In patients presenting <4 h of symptom onset, sensitivity of H-FABP for MI was significantly higher than admission cTnT (73 vs. 55%; P = 0.043). Specificity of H-FABP was 71%. None of the other biomarkers challenged cTnT. Combined use of H-FABP and cTnT (either one elevated initially) significantly improved the sensitivities of H-FABP or cTnT (85%; P = 0.004). This combined approach also improved the negative predictive value, negative likelihood ratio, and the risk ratio.
Conclusion: Assessment of H-FABP within the first 4 h of symptoms is superior to cTnT for detection of MI, and is a useful additional biomarker for patients with acute chest pain.

Chronic cough in children: bronchoalveolar lavage findings

Isolated chronic cough in childhood is a common complaint. Although the symptom cough is included in the definition of clildhood asthma, there is debate as to whether the majoritv of these children have asthma. The authors studied children with isolated chronic cough looking for evidence of airway inflammation typical of asthma, with increased numbers of airway eosinophils as assessed from bronchoalveolar lavage (BAL).

The investigations were carried out on 23 children (median age: 6.7 yrs; range: 1.7-12.75 yrs), attending the Royal Belfast Hospital for Sick Children for elective surgery, who also had a chronic unexplained cough. Written informed consent was obtained from the parent(s) and a nonbronchoscopic BAL was performed. BAL samples were analysed for total and differential white cell counts and also for the inflammatory mediators, eosinophil cationic protein (ECP) and histamine. Results were compared with a group of normal nonatopic children and also a group of atopic asthmatic children, who had been recruited for other studies on airway inflammation.

There was a small but statistically significant increase in BAL percentage eosinophils in the children with chronic cough compared with nonasthmatic controls (0.28% versus 0.10%, p=0.03). However, the children with cough had lower percentage eosinophils than the atopic asthmatic controls (0.28% versus 0.66%, p=0.01). Three out of 23 children with chronic cough had BAL eosinophils greater than the normal upper 95% reference interval in BAL. There was a small but statistically significant increase in percentage neutrophils in the children with cough compared with the nonasthmatic controls (5.85% versus 3.21%, p=0.03). Four out of the 23 children had BAL neutrophils greater than the normal upper 95% reference interval in BAL.

The authors conclude that only a minority of children with chronic unexplained cough have asthmatic-type airway inflammation. It is speculated that the increased percentage neutrophils in bronchoalveolar lavage from children with cough could relate to underlying persistent airways infection.

Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein

Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(N epsilon-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(N epsilon-lysino)propane (LML)] and lysine-HNE [3-(N epsilon-lysino)-4-hydroxynonan-l-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70-80% of total lysine loss during the reaction with MDA. LM and LML (0.002-0.12 mmol/ mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of <1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo.

Abnormal Glycogen Storage by Retinal Neurons in Diabetes

PURPOSE: It is widely held that neurons of the central nervous system do not store glycogen and that accumulation of the polysaccharide may cause neurodegeneration. Since primary neural injury occurs in diabetic retinopathy, we examined neuronal glycogen status in the retina of streptozotocin-induced diabetic and control rats.

METHODS: Glycogen was localized in eyes of streptozotocin-induced diabetic and control rats using light microscopic histochemistry and electron microscopy, and correlated with immunohistochemical staining for glycogen phosphorylase and phosphorylated glycogen synthase (pGS).

RESULTS: Electron microscopy of 2-month-old diabetic rats (n = 6) showed massive accumulations of glycogen in the perinuclear cytoplasm of many amacrine neurons. In 4-month-old diabetic rats (n = 11), quantification of glycogen-engorged amacrine cells showed a mean of 26 cells/mm of central retina (SD ± 5), compared to 0.5 (SD ± 0.2) in controls (n = 8). Immunohistochemical staining for glycogen phosphorylase revealed strong expression in amacrine and ganglion cells of control retina, and increased staining in cell processes of the inner plexiform layer in diabetic retina. In control retina, the inactive pGS was consistently sequestered within the cell nuclei of all retinal neurons and the retinal pigment epithelium (RPE), but in diabetics nuclear pGS was reduced or lost in all classes of retinal cell except the ganglion cells and cone photoreceptors.

CONCLUSIONS: The present study identifies a large population of retinal neurons that normally utilize glycogen metabolism but show pathologic storage of the polysaccharide during uncontrolled diabetes.

Prognostic and predictive markers in colorectal cancer - The role of new genomic technologies

Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide, and the second leading cause of cancer related death in the Western World. Although early stage disease is curable by surgical resection alone, one half of patients with CRC will present with metastatic disease at some stage in the course of their disease. The most active drug in the treatment of CRC is 5-fluorouracil (5-FU) which is used in both the adjuvant and advanced settings. The use of adjuvant therapy is of proven benefit in Stage III CRC, however, its role in Stage II disease is less clear. There is therefore a need to identify those patients with early stage disease who will develop recurrent disease, and who would therefore benefit most from adjuvant treatment. In the advanced setting, the use of irinotecan and oxaliplatin in combination with 5-FU has proven beneficial, with yet further improvements in survival reported with the addition of new targeted agents such as bevacizamab. Despite this, a significant number of patients with advanced disease do not derive any benefit from the chemotherapy they receive, highlighting a need for the development of molecular or genomic markers predictive of response to these chemotherapeutic agents. This review will evaluate the recent advances in pharmacogenomics in CRC, in particular the development of predictive markers of response to chemotherapy. The successful identification of these markers of response will herald an era of personalised treatment, reducing treatment-related toxicity and improving outcome of patients with CRC. -cr 2007 Bentham Science Publishers Ltd.

Estudo de extractos de Genista tenera actividade antioxidante e inibição de enzimas do metabolismo da glucose

Objectivo: Estudar a actividade antidiabética e antioxidante de extractos de Genista tenera. Materiais e métodos: Investigou-se a actividade antioxidante pelo método das espécies reactivas ao ácido tiobarbitúrico e o método do MTT (3-(4,5- dimetiltiazol-2-il)-2,5-difenil brometo de tetrazolio). Procurou-se clarificar o mecanismo de acção antidiabética pelo estudo da actividade inibitória nas enzimas α-glucosidase, glucose-6-fosfatase e glicogénio fosforilase. Resultados: No ensaio de MTT os extractos em éter, butanol e acetato de etilo possuem boa actividade antioxidante (87,80 %, 67,82 % e 67,70 % de viabilidade celular respectivamente). Na α-glucosidase os extractos em butanol e acetato de etilo apresentaram inibição (0,97% e 2,36% de actividade enzimática). Os extractos em acetato de etilo, butanol e éter são inibidores da glucose-6- fosfatase (48,33%, 80,25% e 64,42% de actividade enzimática). Conclusões: Os extractos de Genista tenera em acetato de etilo, butanol e éter poderão ser no futuro incluídos em nutracêuticos para prevenir ou tratar a diabetes tipo 2.

Critérios de decisão na realização de ecografias obstétricas

Dissertação, Mestrado, Marketing, Instituto Politécnico de Santarém, Escola Superior de Gestão e Tecnologia, 2016

O processo de transição do familiar a cuidador da pessoa com depressão

Atualmente o internamento em unidades de saúde é considerado um recurso de última linha, sendo no contexto familiar e social que a pessoa vive a sua depressão. Os familiares, através de uma atitude pro ativa, devem adotar um papel diferençado e ser vistos como aliados importantes na prestação de cuidados, tendo que se adaptar às novas formas de gerir o quotidiano. Este papel não é passivo e tem consequências importantes, sobretudo nos estilos de vida e relações interpessoais. É esperado que os familiares se assumam como cuidadores informais de uma pessoa, cuja situação clínica desconhecem e para a qual não estão preparados, por não saber que fazer. Vivem um processo de mudança; mas como ocorre essa mudança? Como é que o elemento da família se torna cuidador do seu familiar com depressão? Objetivos:- caraterizar o processo de adoecer com depressão, na perspetiva do familiar e doente; - Identificar reações que o familiar desenvolve na relação com o doente - Descrever estratégias utilizadas pelo familiar para cuidar do elemento com depressão; - Conceituar padrões de resposta presentes no processo de transição do familiar a cuidador. Metodologia: desenho de natureza qualitativa e indutiva com recurso à Grounded Theory. Dois polos das consultas externas do departamento psiquiatria e saúde mental, Hospital de Évora, em duas cidades diferentes, de fevereiro a julho 2009. Seleção de participantes não probabilística intencional: adultos ou idosos com diagnóstico de depressão, habitar com familiares e ter capacidade cognitiva que permita recolher informação. Realizadas entrevistas a 20 participantes (8 doentes e 12 familiares), num total de 8 famílias. Resultados: - a narrativa do processo de adoecer é multifacetada e assume contornos distintos para o doente e para o familiar, englobando o início, causas, características da doença e manifestações; - mudança no comportamento dos familiares caracterizada pela alteração de papeis, isolamento, diminuição da comunicação, revolta, vergonha, absentismo laboral ou insucesso escolar; - estratégias de cuidados do familiar polarizadas na compreensão e conflito, no afastamento e proximidade, recorrendo também ao controlo da terapêutica, à procura de ajuda médica e à autoaprendizagem.. Conclusão: quando há uma pessoa com depressão na família tudo se altera; para dar resposta ao novo contexto, os familiares mudam, construindo o seu papel de cuidador na interação quotidiana. As estratégias de cuidados desenvolvem-se de modo reativo em função do comportamento do doente, adquirindo contornos particulares de conteúdo desadequado à situação de saúde vivida. Palavras-chave: cuidador familiar, transição, depressão Ali, L. [et al] (2012) - Daily life for Young adults who care for a person with mental illness: a qualitative study. Journal of Psychiatric and Mental Health Nursing, 19, pp.610-617 Meleis, A. I. (2010) - Transitions Theory. Middle-range and situation-specific theories in nursing research and practice. New York: Springer Publishing Company. Pereira, Helder Rocha (2013) – Subitamente cuidadores informais! Dando voz(es) às experiências vividas. Loures: Lusociência Sant’Ana, Marília Mazzuco [et al] (2011) – O significado de ser familiar cuidador do portador de transtorno mental. Texto Contexto de Enfermagem, 20(1), pp.50-58.

Estágio em clínica de animais de companhia: síndrome de disfunção cognitiva canina

Este estágio foi realizado em clínica de animais de companhia. Observou e acompanhou-se tanto consultas com carácter preventivo como de clínica médica e cirúrgica. As consultas de medicina preventiva consistiram essencialmente em vacinações e desparasitações, enquanto outras foram meramente informativas. As consultas de clínica médica incidiram em diversas áreas, incluíndo dermatologia, gastroenterologia e cardiologia. As cirurgias efetuadas foram sobretudo eletivas, mas também se assistiu a cirurgias corretivas. Um dos casos observados foi um cão com disfunção cognitiva. Este foi o caso escolhido para ser alvo do estudo mais aprofundado que é apresentado na segunda secção deste relatório. A disfunção cognitiva canina é o equivalente à doença humana de Alzheimer. Esta condição é relativamente desconhecida e os seus sinais clínicos são frequentemente considerados normais da idade. No entanto, quando detetada e tratada atempadamente é possível abrandar a sua evolução, devendo os proprietários de cães afetados ser sensibilizados a procurar assistência profissional; Internship in small animal practice: canine cognitive dysfunction syndrome Abstract: This internship was conducted in small animal clinic. The attended appointments consisted mostly of cases of preventive and internal medicine and also surgical assistance. The appointments of preventive medicine included vaccinations, deworming and some merely informative sessions. The cases of internal medicine concerned areas such as dermatology, gastroenterology and cardiology. The surgical interventions were mainly optional but also corrective procedures. One of the observed cases was a dog with cognitive dysfunction. This case was elected to be the target of further study which is presented in the second section of this report. The canine cognitive dysfunction is the equivalent to the human Alzheimer’s disease. This condition is still largely unknown and its clinical presentation is often considered normal of aging. However, if detected and treated early it is possible to slow down its progress, thus the owners of affected dogs should be encouraged to seek professional assistance.

Clínica de ruminantes

O presente relatório surge na sequência da realização do estágio curricular na coo-perativa Fomento Extremeño Ovino Sociedad Agraria de Transformación no âmbito do Mestrado Integrado em Medicina Veterinária na Universidade de Évora. Este relatório apresenta-se dividido em duas partes. Na primeira são descritas as atividades desenvolvi-das no controlo reprodutivo, profilaxia médica e clínica médica. A segunda parte é cons-tituída por uma revisão bibliográfica sobre o tétano em ovinos, patologia que tem especial importância nesta espécie devido aos procedimentos realizados no maneio ainda muito tradicionais, e no final são apresentados dois casos clínicos e a sua respetiva discussão à luz do estado de arte; Ruminants clinics Abstract: This report follows up on the completion of the internship at the Fomento Extre-meño Ovino Sociedad Agraria de Transformación as part of the Master Degree in Vete-rinary Medicine at the University of Évora. Thereby the present repor is divided into two parts. The first part describes the activities performed in reproductive control, medical prophylaxis and medical clinic. The second part is composed by a bibliographical review about tetanus in sheeps, a pathology that has special importance in this species due to animal management procedures performed wich are still very tradicional. Lastly, this re-port presents two clínical cases and its respective discussion according to presente knowledge.