Últimos itens adicionados do Acervo: Centro Hospitalar do Porto

O CHP é um hospital central e universitário pela sua associação ao Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto.

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‣ Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2

Wen, J.; Lopes, F.; Soares, G.; Farrell, S.; Nelson, C.; Qiao, Y.; Martell, S.; Badukke, C.; Bessa, C.; Ylstra, B.; Lewis, S.; Isoherranen, N.; Maciel, P.; Rajcan-Separovic, E.
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
Background Rare, recurrent genomic imbalances facilitate the association of genotype with abnormalities at the “whole body” level. However, at the cellular level, the functional consequences of recurrent genomic abnormalities and how they can be linked to the phenotype are much less investigated. Method and results We report an example of a functional analysis of two genes from a new, overlapping microdeletion of 2p13.2 region (from 72,140,702-72,924,626). The subjects shared intellectual disability (ID), language delay, hyperactivity, facial asymmetry, ear malformations, and vertebral and/or craniofacial abnormalities. The overlapping region included two genes, EXOC6B and CYP26B1, which are involved in exocytosis/Notch signaling and retinoic acid (RA) metabolism, respectively, and are of critical importance for early morphogenesis, symmetry as well as craniofacial, skeleton and brain development. The abnormal function of EXOC6B was documented in patient lymphoblasts by its reduced expression and with perturbed expression of Notch signaling pathway genes HES1 and RBPJ, previously noted to be the consequence of EXOC6B dysfunction in animal and cell line models. Similarly, the function of CYP26B1 was affected by the deletion since the retinoic acid induced expression of this gene in patient lymphoblasts was significantly lower compared to controls (8% of controls). Conclusion Haploinsufficiency of CYP26B1 and EXOC6B genes involved in retinoic acid and exocyst/Notch signaling pathways...

‣ Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate Species

Arezes, J.; Costa, M.; Vieira, I.; Dias, V.; Kong, X.; Fernandes, R.; Vos, M.; Carlsson, A.; Rikers, Y.; Porto, G.; Rangel, M.; Hider, R.; Pinto, J.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

‣ Predisposition, Insult/Infection, Response and Organ Dysfunction (PIRO): A Pilot Clinical Staging System for Hospital Mortality in Patients with Infection

Cardoso, T.; Teixeira-Pinto, A.; Rodrigues, P.; Aragão, I.; Costa-Pereira, A.; Sarmento, A.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
Purpose To develop a clinical staging system based on the PIRO concept (Predisposition, Infection, Response and Organ dysfunction) for hospitalized patients with infection. Methods One year prospective cohort study of all hospitalized patients with infection (n = 1035), admitted into a large tertiary care, university hospital. Variables associated with hospital mortality were selected using logistic regressions. Based on the regression coefficients, a score for each PIRO component was developed and a classification tree was used to stratify patients into four stages of increased risk of hospital mortality. The final clinical staging system was then validated using an independent cohort (n = 186). Results Factors significantly associated with hospital mortality were • for Predisposition: age, sex, previous antibiotic therapy, chronic hepatic disease, chronic hematologic disease, cancer, atherosclerosis and a Karnofsky index<70; • for Insult/Infection: type of infection • for Response: abnormal temperature, tachypnea, hyperglycemia and severity of infection and • for Organ dysfunction: hypotension and SOFA score≥1. The area under the ROC curve (CI95%) for the combined PIRO model as a predictor for mortality was 0.85 (0.82–0.88). Based on the scores for each of the PIRO components and on the cut-offs estimated from the classification tree...

‣ Renal amyloidosis: classification of 102 consecutive cases

Tavares, I.; Vaz, R.; Moreira, L.; Pereira, P.; Sampaio, S.; Vizcaíno, J.; Costa, P.P.; Lobato, L.
Fonte: Portuguese Journal of Nephrology and Hypertension Publicador: Portuguese Journal of Nephrology and Hypertension
Tipo: Artigo de Revista Científica
Publicado em /09/2014 Português
Amyloidoses are a group of heterogeneous diseases classified according to the nature of their causative amyloid proteins. Commonly, paraffin-embedded tissue is used for the typing of amyloid by immunohistochemistry. DNA analysis should always be considered if hereditary amyloidosis is suspected. Since the kidneys are one of the organs that are most commonly involved in amyloid deposition in systemic amyloidoses, we screened 102 consecutive cases with biopsy-proven amyloid disease by immunohistochemistry. DNA analysis was performed to confirm a diagnosis of hereditary amyloidosis. Demographic characteristics, underlying disease and clinical data at the time of renal biopsy were obtained by retrospective review of medical records. The amyloidosis type according to immunohistochemical amyloid protein identification was AA in 60 (58.8%) patients, AL in 21 (20.6%), AFib in four (3.9%), ATTR in two (2.0%), AApoAI in one (1.0%), ALys in one (1.0%) and combined AL and AA in one (1.0%). The type of protein could not be classified in 12 (11.7%) patients: eight (7.8%) because of negative immunohistochemistry and four (3.9%) due to the lack of adequate tissue. DNA analysis confirmed AFib and ATTR cases by the identification of the point mutations FGA p.Glu545Val and TTR p.Met51Val...

‣ Terapêutica após progressão do carcinoma do pulmão de não pequenas células precoce ou localmente avançado tratado com quimioterapia

Araujo, A.; Magalhães, M.; Febra, J.; Coutinho, F.; Rosendo, E.; Castro, A.; Araujo, A.; Ferreira, G.; Marinho, C.; Rocha, E.
Fonte: Grupo de Estudos do Cancro do pulmão Publicador: Grupo de Estudos do Cancro do pulmão
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
O carcinoma do pulmão de não pequenas células continua tendo um prognóstico sombrio. Nos estádios IB a alguns IIIB, o tratamento recomendado passará por cirurgia e quimioterapia (QT), radioterapia e QT ou pelas três modalidades em conjunto. Infelizmente, a maioria destes doentes apresenta progressão da sua doença ao fim de alguns meses. Se a progressão envolver múltiplos locais, terá que ser considerada uma nova terapia oncológica sistémica e esta deverá ter em consideração o doente, o tumor, a QT prévia realizada e o tempo que decorreu entre o fim da QT e a progressão. Para a escolha dos fármacos que se poderão utilizar, deverá ter -se em consideração, ainda, as características e a toxicidade próprias de cada um deles. Sublinha -se que não havendo uma dose limitadora da sua administração, é o desenvolvimento dos efeitos laterais que limita a sua utilização

‣ O cancro no concelho de Santa Maria da Feira

Araujo, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 15/03/2014 Português
Palestra proferida no âmbito da iniciativa Um dia para a vida, promovida pela Liga Portuguesa Contra o Cancro, em Santa Maria da Feira

‣ New modalities and new drugs in the NSCLC treatment

Araujo, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 28/03/2014 Português

‣ Diagnóstico e Tratamento do Cancro do Pulmão: Estado da Arte

Araujo, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 30/04/2014 Português

‣ Terapêutica após progressão do CPNPC precoce ou localmente avançado tratado com QT

Araujo, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 17/05/2014 Português
Palestra proferida no âmbito da Reunião da Primavera - 2014 do Grupo de Estudos do Cancro do Pulmão que se realizou em Tomar nos dias 16 e 17 de maio de 2014

‣ Immuno-oncology in lung cancer

Araujo, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 07/06/2014 Português
Palestra proferida no âmbito do Fórum Imuno-Oncologia que decorreu na Alfandega do Porto no dia 7 de junho de 2014

‣ Clinical practice: approaching the reality of individual patients

Araujo, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 04/07/2014 Português
Palestra realizada do encontro Meet the Expert organizada pela Lilly e que se realizou em Barcelona e Madrid nos dias 5 e 5 de julho de 2014 respetivamente

‣ Estado da arte no tratamento do cancro de cabeça e pescoço - Update

Castro, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Artigo de Revista Científica
Publicado em 20/09/2014 Português

‣ Classic DMARD’s, biologic drugs and cancer risk

Araujo, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 25/09/2014 Português

‣ Objetivos e avaliação das terapêuticas dos NET G1 e G2: Combinações e sequências terapêuticas

Castro, A.
Fonte: Centro Hospitalar do Porto Publicador: Centro Hospitalar do Porto
Tipo: Aula
Publicado em 17/10/2014 Português

‣ HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysis

Carreira, H.; Coutinho, F.; Carrilho, C.; Lunet, N.
Fonte: Lewis Publicador: Lewis
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. METHODS: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%)...

‣ Effects of highly conserved major histocompatibility complex (MHC) extended haplotypes on iron and low CD8+ T lymphocyte phenotypes in HFE C282Y homozygous hemochromatosis patients from three geographically distant areas

Costa, M.; Cruz, E.; Barton, J.; Thorstensen, K.; Morais, S.; da Silva, B.; Pinto, J.; Vieira, C.; Vieira, J.; Acton, R.; Porto, G.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em /11/2013 Português
Hereditary Hemochromatosis (HH) is a recessively inherited disorder of iron overload occurring commonly in subjects homozygous for the C282Y mutation in HFE gene localized on chromosome 6p21.3 in linkage disequilibrium with the human leukocyte antigen (HLA)-A locus. Although its genetic homogeneity, the phenotypic expression is variable suggesting the presence of modifying factors. One such genetic factor, a SNP microhaplotype named A-A-T, was recently found to be associated with a more severe phenotype and also with low CD8(+)T-lymphocyte numbers. The present study aimed to test whether the predictive value of the A-A-T microhaplotype remained in other population settings. In this study of 304 HH patients from 3 geographically distant populations (Porto, Portugal 65; Alabama, USA 57; Nord-Trøndelag, Norway 182), the extended haplotypes involving A-A-T were studied in 608 chromosomes and the CD8(+) T-lymphocyte numbers were determined in all subjects. Patients from Porto had a more severe phenotype than those from other settings. Patients with A-A-T seemed on average to have greater iron stores (p = 0.021), but significant differences were not confirmed in the 3 separate populations. Low CD8(+) T-lymphocytes were associated with HLA-A*03-A-A-T in Porto and Alabama patients but not in the greater series from Nord-Trøndelag. Although A-A-T may signal a more severe iron phenotype...

‣ Group B Streptococcus Hijacks the Host Plasminogen System to Promote Brain Endothelial Cell Invasion

Magalhães, V.; Andrade, E.; Alves, J.; Ribeiro, A:; Kim, K.; Lima, M.; Trieu-Cuot, P.; Ferreira, P.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em /05/2013 Português
Group B Streptococcus (GBS) is the leading cause of meningitis in neonates. We have previously shown that plasminogen, once recruited to the GBS cell surface and converted into plasmin by host-derived activators, leads to an enhancement of bacterial virulence. Here, we investigated whether plasmin(ogen) bound at the GBS surface contributes to blood-brain barrier penetration and invasion of the central nervous system. For that purpose, GBS strain NEM316 preincubated with or without plasminogen plus tissue type plasminogen activator was analyzed for the capacity to adhere to, invade and transmigrate the human brain microvascular endothelial cell (hBMEC) monolayer, and to penetrate the central nervous system using a neonatal mouse model. At earlier times of infection, plasmin(ogen)-treated GBS exhibited a significant increase in adherence to and invasion of hBMECs. Later, injury of hBMECs were observed with plasmin(ogen)-treated GBS that displayed a plasmin-like activity. The same results were obtained when hBMECs were incubated with whole human plasma and infected with untreated GBS. To confirm that the observed effects were due to the recruitment and activation of plasminogen on GBS surface, the bacteria were first incubated with epsilon-aminocaproic acid (εACA)...

‣ Urinary ATP may be a dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome

Silva-Ramos, M.; Silva, I.; Oliveira, O.; Ferreira, S.; Reis, M.; Oliveira, J.; Correia-de-Sá, P.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em /05/2013 Português
Background Nowadays, there is a considerable bulk of evidence showing that ATP has a prominent role in the regulation of human urinary bladder function and in the pathophysiology of detrusor overactivity. ATP mediates nonadrenergic-noncholinergic detrusor contractions in overactive bladders. In vitro studies have demonstrated that uroepithelial cells and cholinergic nerves from overactive human bladder samples (OAB) release more ATP than controls. Here, we compared the urinary ATP concentration in samples collected non-invasively from OAB women with detrusor overactivity and age-matched controls. Methods Patients with neurologic diseases, history of malignancy, urinary tract infections or renal impairment (creatinine clearance <70 ml/min) were excluded. All patients completed a 3-day voiding diary, a 24 h urine collection and blood sampling to evaluate creatinine clearance. Urine samples collected during voluntary voids were immediately freeze-preserved for ATP determination by the luciferin-luciferase bioluminescence assay; for comparison purposes, samples were also tested for urinary nerve growth factor (NGF) by ELISA. Results The urinary content of ATP, but not of NGF, normalized to patients’ urine creatinine levels (ATP/Cr) or urinary volume (ATP.Vol) were significantly (P<0.05) higher in OAB women with detrusor overactivity (n = 34) than in healthy controls (n = 30). Significant differences between the two groups were still observed by boosting urinary ATP/Cr content after water intake...

‣ Circulating endothelial cells in patients with venous thromboembolism and myeloproliferative neoplasms

Torres, C.; Fonseca, A.; Leander, M.; Matos, R.; Morais, S.; Campos, M.; Lima, M.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em /12/2013 Português
Background Circulating endothelial cells (CEC) may be a biomarker of vascular injury and pro-thrombotic tendency, while circulating endothelial progenitor cells (CEP) may be an indicator for angiogenesis and vascular remodelling. However, there is not a universally accepted standardized protocol to identify and quantify these cells and its clinical relevancy remains to be established. Objectives To quantify CEC and CEP in patients with venous thromboembolism (VTE) and with myeloproliferative neoplasms (MPN), to characterize the CEC for the expression of activation (CD54, CD62E) and procoagulant (CD142) markers and to investigate whether they correlate with other clinical and laboratory data. Patients and Methods Sixteen patients with VTE, 17 patients with MPN and 20 healthy individuals were studied. The CEC and CEP were quantified and characterized in the blood using flow cytometry, and the demographic, clinical and laboratory data were obtained from hospital records. Results We found the CEC counts were higher in both patient groups as compared to controls, whereas increased numbers of CEP were found only in patients with MPN. In addition, all disease groups had higher numbers of CD62E+ CEC as compared to controls...

‣ The impact of healthcare-associated infection on mortality: failure in clinical recognition is related with inadequate antibiotic therapy

Cardoso, T.; Ribeiro, O.; Aragão, I.; Costa-Pereira, A.; Sarmento, A.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em /03/2013 Português
Purpose To understand if clinicians can tell apart patients with healthcare-associated infections (HCAI) from those with community-acquired infections (CAI) and to determine the impact of HCAI in the adequacy of initial antibiotic therapy and hospital mortality. Methods One-year prospective cohort study including all consecutive infected patients admitted to a large university tertiary care hospital. Results A total of 1035 patients were included in this study. There were 718 patients admitted from the community: 225 (31%) with HCAI and 493 (69%) with CAI. Total microbiologic documentation rate of infection was 68% (n = 703): 56% in CAI, 73% in HCAI and 83% in hospital-acquired infections (HAI). Antibiotic therapy was inadequate in 27% of patients with HCAI vs. 14% of patients with CAI (p<0.001). Among patients with HCAI, 47% received antibiotic therapy in accordance with international recommendations for treatment of CAI. Antibiotic therapy was inadequate in 36% of patients with HCAI whose treatment followed international recommendations for CAI vs. 19% in the group of HCAI patients whose treatment did not follow these guidelines (p = 0.014). Variables independently associated with inadequate antibiotic therapy were: decreased functional capacity (adjusted OR = 2.24)...