Browsing by Author "Sousa, M."
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- AGREGADOS TUBULARES DE RETÍCULO ENDOPLASMÁTICO LISO EM OVÓCITOS HUMANOS E SUA INFLUÊNCIA NAS TAXAS DE FERTILIZAÇÃO E GRAVIDEZPublication . Luis, A.; Sá, R.; Oliveira, E.; Oliveira, C.; Silva, J.; Barros, A.; Sousa, M.O impacto da presença de anomalias morfológicas ovocitárias na fertilização e taxas de gravidez é um tema controverso na literatura. A presença de agregados tubulares de retículo endoplasmático liso (AT-REL) foi associada a taxas de gravidez mais baixas e a maior incidência de complicações obstétricas. A estrutura ultramiscroscópica destes AT-REL não está descrita. Este trabalho teve como objectivos: a) determinar a influência da presença de AT-REL nas taxas de fertilização e gravidez; b) descrever a ultrastrutura dos AT-REL de ovócitos humanos maduros
- Changes to TB care in an outpatient centre during the COVID‐19 pandemicPublication . Aguiar, A.; Furtado, I.; Sousa, M.; Pinto, M.; Duarte, R.
- Clinical and Genetic Analysis of Children with Kartagener SyndromePublication . Pereira, R.; Barbosa, T.; Gales, L.; Oliveira, E.; Santos, R.; Oliveira, J.; Sousa, M.Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterized by dysfunction of motile cilia causing ineffective mucus clearance and organ laterality defects. In this study, two unrelated Portuguese children with strong PCD suspicion underwent extensive clinical and genetic assessments by whole-exome sequencing (WES), as well as ultrastructural analysis of cilia by transmission electron microscopy (TEM) to identify their genetic etiology. These analyses confirmed the diagnostic of Kartagener syndrome (KS) (PCD with situs inversus). Patient-1 showed a predominance of the absence of the inner dynein arms with two disease-causing variants in the CCDC40 gene. Patient-2 showed the absence of both dynein arms and WES disclosed two novel high impact variants in the DNAH5 gene and two missense variants in the DNAH7 gene, all possibly deleterious. Moreover, in Patient-2, functional data revealed a reduction of gene expression and protein mislocalization in both genes' products. Our work calls the researcher's attention to the complexity of the PCD and to the possibility of gene interactions modelling the PCD phenotype. Further, it is demonstrated that even for well-known PCD genes, novel pathogenic variants could have importance for a PCD/KS diagnosis, reinforcing the difficulty of providing genetic counselling and prenatal diagnosis to families.
- Co-selection of the H63D mutation and the HLA-A29 allele: a new paradigm of linkage disequilibrium?Publication . Cardoso, C.; Alves, H.; Mascaranhas, M.; Gonçalves, R.; Oliveira, P.; Rodrigues, P.; Cruz, E.; Sousa, M.; Porto, G.The major histocompatibility complex (MHC) shows a remarkable conservation of particular HLA antigens and haplotypes in linkage disequilibrium in most human populations, suggesting the existence of a convergent evolution. A recent example of such conservation is the association of particular HLA haplotypes with the HFE mutations. With the objective of exploring the significance of that association, the present paper offers an analysis of the linkage disequilibrium between HLA alleles or haplotypes and the HFE mutations in a Portuguese population. Allele and haplotype associations between HLA and HFE mutations were first reviewed in a population of 43 hemochromatosis families. The results confirmed the linkage disequilibrium of the HLA haplotype HLA-A3-B7 and the HLA-A29 allele, respectively, with the HFE mutations C282Y and H63D. In order to extend the study of the linkage disequilibrium between H63D and the HLA-A29-containing haplotypes in a normal, random population, an additional sample of 398 haplotypes was analyzed. The results reveal significant linkage disequilibrium between the H63D mutation and all HLA-A29-containing haplotypes, favoring the hypothesis of a co-selection of H63D and the HLA-A29 allele itself. An insight into the biological significance of this association is given by the finding of significantly higher CD8+ T-lymphocyte counts in subjects simultaneously carrying the H63D mutation and the HLA-A29 allele.
- Corino de Andrade disease: mechanisms and impact on reproductionPublication . Lopes, R.; Coelho, T.; Barros, A.; Sousa, M.Familial amyloid polyneuropathy was first described by Corino de Andrade in 1952 in Northern Portugal. It is a fatal autosomal dominant neurodegenerative disorder characterized by a progression of neurologic symptoms, beginning early in the reproductive life. The Transthyretin gene mutation originates a mutated protein that precipitates in the connective tissue as amyloid deposits. This disease is presently named Transthyretin-related hereditary amyloidosis. We performed an extensive review on this disease based on searches in Medical databases and in paper references. In this review, we briefly summarize the epidemiology and the mechanisms involved on amyloid deposition; we detailed how to evaluate the mechanisms implicated on the development of the major signs and symptoms associated with reproductive dysfunction; and we discuss the mechanisms involved in secondary sexual dysfunction after psychological treatments. Treatment of the disease is directed towards relieving specific symptoms in association with liver transplant, and molecular and genetic therapeutics. Although the current clinical trials indicate symptoms relief, no data on the reproductive function was reported. Thus, preimplantation genetic diagnosis is presently the only available technique that eradicates the disease as it avoids the birth of new patients.
- Ecocardiografia por telemedicina em recém-nascidos num hospital de nível II - casuística de quatro anosPublication . Costa, A.M.; Carvalho, M.; Calviño, J.; Sousa, M.; Sousa, G.; Gaspar, E.; Castela, E.Introdução: A Ecocardiografia por Telemedicina (EcoTM) realiza-se desde Outubro de 2005 entre o serviço de pediatria do hospital nível dois e a cardiologia pediátrica do hospital de nível três. Objectivos: Caracterizar os recém-nascidos (RN) que realizaram EcoTM e avaliar a importância desta prática clínica na orientação dos doentes. Métodos: Estudo descritivo retrospectivo realizado através da revisão dos relatórios das EcoTM realizadas entre Outubro de 2005 e Setembro de 2009 e recolha das seguintes variáveis: idade, motivo da realização do exame, diagnóstico e orientação. Resultados: Foram realizadas 139 EcoTM a 122 RN (1,71% dos nados vivos). O sexo masculino predominou (57%); 30,9% realizaram EcoTM antes da alta da maternidade e 50% na primeira semana de vida. Em 11 casos foi realizada de urgência. Os principais motivos para a realização do exame foram: sopro cardíaco em RN assintomático (68,3%), alteração em EcoTM anterior (11,5%), presença malformações (5,8%) e hipoxia com cianose (3,6%). A comunicação inter-ventricular (CIV), a comunicação inter-auricular tipo ostium-secundum e a patência do canal arterial foram as cardiopatias mais frequentes. Foram transferidos para centro de referência em cardiologia pediátrica seis RN: transposição simples das grandes artérias (n=2), ventrículo único (n=1), ectasia da artéria subclávia esquerda (n=1), coarctação da aorta (n=1) e CIV sub-aórtica grande (n=1). Em 26,6% dos exames foi excluída cardiopatia congénita. Tiveram indicação para repetir exame 72% e 24% tiveram alta. Discussão: A programação da EcoTM antes da alta ou no primeiro mês, em RN com sopro assintomático, permite-nos fazer o diagnóstico precoce de cardiopatias. A EcoTM urgente possibilita o diagnóstico rápido e preciso, identificando RN com cardiopatia que necessita de intervenção imediata e transferência para centro de cardiologia pediátrica. A possibilidade de realização de Eco cardíaca utilizando a telemedicina trouxe benefícios nos cuidados de saúde prestados, evitando incómodos para os doentes e permitindo uma referenciação adequada a Cardiologia Pediátrica quando necessário. ABSTRACT Introduction: The Echocardiogram by Telemedicine (EcoTM) between the pediatric department of a level 2 hospital and the pediatric cardiology service of a level 3 hospital began in October 2005. Objective: To characterize the newborns (NB) who underwent EchoTM and emphasize the importance of this practice in the management of the patients. Methods: The authors reviewed the reports of EchoTM conducted between October 1, 2005 and September 30, 2009. The following variables were analyzed: age, sex, reason for the exam, diagnosis and orientation. Results: During this period, 139 EchoTM were done on 122 NB (1.71% of our live NB). Male patients predominated (57%). EchoTM was performed before discharge from the maternity in 30,9% and during the first week in 50%; it was urgent in 11 cases. The most frequent motives for EchoTM: asymptomatic heart murmur (68,3%), pervious abnormal EchoTM (11,5%), malformations (5,8%) and hypoxia (3,6%). The most frequent diagnosis were: ventricular septal defect (VSD) (31.3%), inter-auricular communication (25.8%) and patent ductus arteriosus (7%). Six infants were transferred (simple transposition of greater arteries (n=2), single ventricle (n=1), malformation of the aortic arch (n=1), aortic coarctation (n=1) and large sub-aortic VSD (n=1). In 26.6% it was excluded cardiopathy. EchoTM was repeated in 72 % of the infants and 24% were discharged. Discussion: The EchoTM scheduled before discharge or during the first month, in NB with asymptomatic murmur, allows us to make an early diagnosis of heart disease. The possibility of doing an emergency EchoTM allows a rapid and accurate diagnosis, identifying NB with critical heart disease requiring immediate intervention and transfer to a tertiary center. The EchoTM between these two hospitals of different level, brought benefits to the health care provided, avoiding discomfort to patients and allowing an adequate referral to pediatric cardiology when needed.
- Efficacy And Safety Of Implantable Loop Recorder: Experience Of A CenterPublication . Silveira, I.; Sousa, M.; Antunes, N.; Silva, V.; Roque, C.; Pinheiro-Vieira, A.; Lagarto, V.; Hipólito-Reis, A.; Luz, A.; Torres, S.Introduction: Symptoms like syncope or palpitations frequently present a diagnostic challenge. An implantable loop recorder (ILR) is an important aid in the management of these patients. Methods: A retrospective study of patients that underwent ILR implantation from November 2007 to 2014. For each patient the indication for implantation, baseline characteristics, previous study, complications, recorded tracing and interventions were evaluated. Results: A total of 62 patients were included, 50% men, with a mean age of 62.5±18.8 years old. Previously to ILR implantation 88.7% of patients had performed Holter, 17.7% external events recorder, 33.9% Tilt test and 29% an electrophysiological study. The implantation indications were recurrent syncope in 90.3%, palpitations 8.1% and ischemic stroke in one patient. Mean follow-up time was 17.1±16.3 months. Symptoms were reported in 66.1% of the patients, 46.8% of those yielding a diagnostic finding. In all cases of palpitation complaints with diagnosis we found atrial fibrillation (AF). In patients with syncope atrioventricular conduction disturbance was demonstrated in 19.6%, sinus node dysfunction in 16.1%, paroxysmal supra-ventricular tachycardia 7.1% and AF in 1.8%. These finding resulted in 19 pacemaker and one CRT-D implantation, introduction of anticoagulation in five patients and one ablation of accessory pathway. There were no major complications. Conclusion: ILR proved to be safe and efficient. It has enabled the identification or exclusion of serious rhythm disturbances in more than half of patients and provided a targeted therapeutic intervention.
- Estabilidade de amostras de soro para o doseamento de vitamina B12 e de ácido fólicoPublication . Rocha, L.; Henriques, M.G.; Sousa, M.
- Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin GenePublication . Gonçalves, A.; Oliveira, J.; Coelho, T.; Taipa, R.; Melo-Pires, M.; Sousa, M.; Santos, R.A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD, adding to the diversity of mutational events that give rise to D/BMD.
- A good excuse for skipping the test: electrical storm in a teenagerPublication . Rodrigues, P.; Pinheiro-Vieira, A.; Loureiro, M.; Álvares, S.; Anjo, D.; Roque, C.; Sousa, M.; Torres, S.We describe the case of a teenager with a structurally normal heart that presented with torsades de pointes and cardiac arrest. He had a history of epilepsy in childhood, mild cognitive impairment and cognitive visual dysfunction. The baseline electrocardiogram had prominent J waves and a marked early repolarization pattern in all the leads, with normal QT interval. We discuss the differential diagnosis for this interesting case, as well as the patient's management.