Browsing by Author "Costa, Paulo Pinho"
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- Cardiac Amyloidosis Associated with Apolipoprotein A-IV Deposition Diagnosed by Mass Spectrometry-Based Proteomic AnalysisPublication . Martins, Elisabete; Urbano, Joana; Leite, Sérgio; Pinto, Adriana; Garcia, Raquel; Bergantim, Rui; Rodrigues-Pereira, Pedro; Costa, Paulo Pinho; Osório, Hugo; Tavares, IsabelAmyloidosis is a group of disorders characterised by the accumulation of extracellular deposits of insoluble protein aggregates. Clinical management depends on the accurate identification of the amyloid precursor and underlying cause. We describe a rare case of apolipoprotein A-IV cardiac amyloidosis, the diagnosis of which required mass spectrometry-based proteomic analysis.
- Fibrinogen A alpha-chain amyloidosis: a non-negligible cause of chronic kidney disease in dialysis patientsPublication . Tavares, Isabel; Moreira, Luciana; Costa, Paulo Pinho; Lobato, LuísaBackground: Fibrinogen A alpha-chain (AFib) amyloidosis is a rare and late-onset disease, that result from amyloidogenic autosomal dominant mutations in the gene-encoding AFib (FGA). Patients invariably develop chronic kidney disease (CKD), typically progressing to end-stage renal failure within 5 years of recognition of renal involvement [1]. In Portugal, four apparently unrelated patients with AFib amyloidosis were identified in the district of Braga, Northern Portugal. They all carried the FGA p.Glu545Val mutation, three were heterozygous and one homozygous [2,3]. This observation led us to assess the prevalence of AFibE526V (p.Glu545Val) amyloidosis among Portuguese patients undergoing hemodialysis in the same district, through genetic screening for the FGA p.Glu545Val mutation.
- A paramiloidose em Portugal: reflexão sobre o paradigma da transplantação hepática motivada por um caso clínicoPublication . Lacerda, Pedro Castro; Moreira, Luciana; Vitorino, Rui; Costa, Paulo PinhoA Polineuropatia Amiloidótica Familiar de tipo português (PAF) ou ATTR V30M é uma doença hereditária cuja prevalência em Portugal é elevada, sendo diagnosticados cerca de 60 novos casos todos os anos. Uma doente com PAF submeteu-se a um segundo transplante hepático de um dador cadavérico depois de se ter constatado que o primeiro dador era portador de TTR V30M. Com este artigo breve pretende-se realizar uma reflexão sobre o interesse, a prática e o enquadramento legal que condicionam a realização de testes genéticos preditivos em dadores de fígado na transplantação de doentes com paramiloidose. A determinação da presença (ou não) de proteína mutada no soro do segundo dador foi realizada por espectrometria de massa precedida de imunoprecipitação da proteína transtirretina. A realização de testes genéticos que permitam determinar a condição de portador de TTR V30M em dadores de fígado, deveria ser considerada no quadro das políticas de transplante em Portugal.
- Refractory myasthenia gravis: Characteristics of a portuguese cohortPublication . Santos, Ernestina; Bettencourt, Andreia; Duarte, Sara; Gabriel, Denis; Oliveira, Vanessa; da Silva, Ana Martins; Costa, Paulo Pinho; Lopes, Carlos; Gonçalves, Guilherme; da Silva, Berta Martins; Leite, Maria IsabelIntroduction: Some myasthenia gravis (MG) patients are refractory to conventional treatments. Methods: To describe the clinical features of refractory MG (RMG) and explore the association with human leukocyte antigen HLA-DRB1 alleles, a cohort study of 114 consecutive MG patients was performed. Patients were classified as RMG based on predefined criteria. Results: Twenty-two patients were found to have RMG (19.3%). There were no differences between non-RMG and RMG patients with respect to sex, age of onset, abnormal 3-Hz repetitive nerve stimulation, anti-acetylcholine receptor antibody positivity, thymectomy, thymoma or thymic hyperplasia, and polyautoimmunity. HLA-DRB1*03 was more frequent in the non-RMG vs. control population (P = 3 × 10-6 ). The HLA-DRB1*13 allele was less frequent in non-RMG patients compared with controls (P = 0.002), and less frequent in the non-RMG group compared with the RMG group (P = 0.003). Discussion: HLA-DRB1*03 was more common in non-RMG, and the HLA-DRB1*13 allele appeared to have a protective role, as reported previously in other autoimmune disorders. Muscle Nerve 60: 188-191, 2019.
- Serum 25-hydroxyvitamin D levels in a healthy population from the North of PortugalPublication . Bettencourt, Andreia; Boleixa, Daniela; Reis, Júlia; Oliveira, José Carlos; Mendonça, Denisa; Costa, Paulo Pinho; Silva, Berta Martins da; Marinho, António; Silva, Ana Martins daVitamin D status in human populations has become a matter of great concern, in the wake of a multitude of published works that document widespread vitamin D deficiency across Europe, even in countries with abundant sunlight. In Portugal there are no measures of 25-hydroxyvitamin D - 25(OH)D - levels in the general adult population. The purpose of this study was to measure 25(OH)D levels in a healthy population cohort and investigate the possible association with season and selected demographic and laboratory measurements. A cohort of 198 participants (18-67 years) living in the north of Portugal, Porto, conducted in July and August 2015 (summer time) and April 2016 (winter time) was studied to evaluate serum 25(OH)D levels. Sociodemographic characteristics (age, sex and body mass index) and season of the year were taken into account as possible 25(OH)D levels codeterminants. In the whole group, the mean level of serum 25(OH)D was 55.4±23.4 nmol/L, with 48% of the population presenting levels compatible with vitamin D deficiency (below 50 nmol/L). In the winter period, this value reaches 74%. No statistically significant differences were observed between genders (57.4±23.9 vs. 53.3±22.8 nmol/L, p=0.219) as well as no statistically significant correlation was found between age and 25(OH)D levels (p=0.349). As expected higher levels of 25(OH)D were observed in summer than in winter (68.2±21.5 vs. 42.2±16.9 nmol/L; p<0.0001). Serum 25(OH)D levels were significantly lower in obese compared to non-obese subjects (46.6±17.6 vs. 57.7±24.2 nmol/L, p=0.012). Vitamin D deficiency is prevalent in this area, affecting almost half of the population. Body mass index and season are predictors for lower 25-hydroxyvitamin D levels and vitamin D status. An effective strategy to prevent vitamin D deficiency and insufficiency should be envisaged and implemented in our population.
- Serum 25-hydroxyvitamin D levels in multiple sclerosis patients from the north of PortugalPublication . Bettencourt, Andreia; Boleixa, Daniela; Reguengo, Henrique; Samões, Raquel; Santos, Ernestina; Oliveira, José Carlos; Silva, Berta; Costa, Paulo Pinho; da Silva, Ana MartinsIncreasing evidence has shown that individuals with Multiple Sclerosis (MS) have lower 25-hydroxyvitamin D [25(OH)D] levels compared to healthy controls. There is no information regarding 25(OH)D levels and MS in Portugal. Therefore the aim of the current study was to examine the levels of 25(OH)D in a group of patients with MS and in healthy matched controls, as well as the association of 25(OH)D levels with disease course, disability and severity. A group of 244 unrelated Portuguese patients, with a definitive diagnosis of MS, and 198 ethnically matched healthy controls were included in the study. A sub-group of patients with recent disease onset was included. Serum 25(OH)D was measured using an electrochemiluminescence binding assay. The mean serum level of 25(OH)D in patients with MS was 39.9±22.0 nmol/L, which was significantly lower (p<0.0001) than those in healthy controls, 55.4±23.4 nmol/L. There was a negative correlation between 25(OH)D levels and EDSS (r=-0.293, p<0.0001) and MSSS scores (r=-0.293, p<0.0001). In multiple logistic regression analysis adjusted for age, gender, disease form, EDSS, disease duration and MSSS, 25(OH)D levels were independently associated with EDSS (p=0.004) and disease duration (p=0.016), and with MSSS (p=0.001). In accordance with the majority of the literature, low serum 25(OH)D levels were associated with susceptibility and disability in MS patients from Portugal. Lower serum 25(OH)D levels were also found in patients with a recent disease onset, supporting vitamin D levels as a risk factor for MS.
- Short-term complications after renal transplantation in AFibE526V (p.Glu545Val) amyloidosisPublication . Tavares, Isabel; Silvano, José; Moreira, Luciana; Oliveira, Márcia E.; Silva, Roberto; Sampaio, Susana; Costa, Paulo Pinho; Lobato, LuísaIntroduction: Fibrinogen Aa chain (AFib) amyloidosis is an autosomal dominant disease that typically presents with predominant renal involvement and has a predictable progressive clinical course [1]. The p.Glu545Val AFib gene (FGA) mutation is at the origin of all AFib amyloidosis cases (AFibE526V [p.Glu545Val]) that have been identified in Portugal so far, and accounts for the disease in 17 families. Current treatment of AFib amyloidosis comprises both supportive measures and disease-modifying approaches, such as liver transplantation [2,3]. Renal transplantation (RTx) is a supportive therapy with risk of premature graft loss due to amyloid recurrence or other unexpected complications related to progression of extrarenal amyloid deposition. The aim of this study was to evaluate the outcome of Portuguese patients with AFibE526V (p.Glu545Val) amyloidosis after RTx.
- The Potential of Circulating Cell-Free DNA Methylation as an Epilepsy BiomarkerPublication . Martins-Ferreira, Ricardo; Leal, Bárbara Guerra; Costa, Paulo PinhoCirculating cell-free DNA (cfDNA) are highly degraded DNA fragments shed into the bloodstream. Apoptosis is likely to be the main source of cfDNA due to the matching sizes of cfDNA and apoptotic DNA cleavage fragments. The study of cfDNA in liquid biopsies has served clinical research greatly. Genetic analysis of these circulating fragments has been used in non-invasive prenatal testing, detection of graft rejection in organ transplants, and cancer detection and monitoring. cfDNA sequencing is, however, of limited value in settings in which genetic association is not well-established, such as most neurodegenerative diseases.Recent studies have taken advantage of the cell-type specificity of DNA methylation to determine the tissue of origin, thus detecting ongoing cell death taking place in specific body compartments. Such an approach is yet to be developed in the context of epilepsy research. In this article, we review the different approaches that have been used to monitor cell-type specific death through DNA methylation analysis, and recent data detecting neuronal death in neuropathological settings. We focus on the potential relevance of these tools in focal epilepsies, like Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (MTLE-HS), characterized by severe neuronal loss. We speculate on the potential relevance of cfDNA methylation screening for the detection of neuronal cell death in individuals with high risk of epileptogenesis that would benefit from early diagnosis and consequent early treatment.
- The vitamin D receptor gene FokI polymorphism and Multiple Sclerosis in a Northern Portuguese populationPublication . Bettencourt, Andreia; Boleixa, Daniela; Guimarães, Ana Luísa; Leal, Bárbara; Carvalho, Cláudia; Brás, Sandra; Samões, Raquel; Santos, Ernestina; Costa, Paulo Pinho; Silva, Berta; da Silva, Ana MartinsThe cause of Multiple Sclerosis (MS) remains poorly understood, but it is widely believed to be an autoimmune disease occurring in genetically susceptible individuals after exposure to as-yet undefined environmental factors. One of these environmental factors is vitamin D, a well-known immune modulator. The biologically active form of vitamin D, 1,25-dihydroxyvitamin D3, has been shown to exert its immune modulatory properties through its nuclear receptor (VDR) namely by inhibiting the proliferation of Th cells. The purpose of this study was to evaluate the influence of FokI VDR polymorphism in MS development and progression.
- Unrecognized Fibrinogen A α-Chain Amyloidosis: Results From Targeted Genetic TestingPublication . Tavares, Isabel; Oliveira, João Paulo; Pinho, Ana; Moreira, Luciana; Rocha, Liliana; Santos, Josefina; Pinheiro, Joaquim; Costa, Paulo Pinho; Lobato, LuísaFibrinogen A α-chain (AFib) amyloidosis results from autosomal-dominant mutations in the gene encoding AFib (FGA). Patients with this disorder typically present with proteinuria. Isolated cases of AFib amyloidosis, carrying the FGA p.Glu545Val variant, were identified in the district of Braga, in northwest Portugal. This observation led us to hypothesize that this disorder might be an unrecognized cause of kidney disease in that region and prompted us to carry out targeted genetic testing for the p.Glu545Val variant in the local hemodialysis population and family members of identified cases.