Browsing by Author "Carvalho, D"
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- Agonistas dos Receptores do GLP-1 no Tratamento da Diabetes Tipo 2Publication . Carvalho, D; Silva Nunes, J; Raposo, J; Medina, J; Jácome de Castro, J; Carrilho, FA Diabetes Mellitus tipo 2 é um flagelo individual, social e económico, em particular nas sociedades ocidentais. A metformina surge como fármaco de primeira linha na terapêutica farmacológica desta patologia, mas na impossibilidade de controlo metabólico adequado sob esta em monoterapia, as recomendações colocam as restantes classes de fármacos ao mesmo nível, reflectindo uma mudança de paradigma para a individualização da terapêutica. A partir de 2007 foram disponibilizadas três novas classes de fármacos antidiabéticos: inibidores da dipeptidil peptidase 4, agonistas dos receptores do glucagon-like peptide-1, e inibidores do co-transportador 2 de sódio e glicose. Destas três, os agonistas dos receptores do glucagon-like peptide-1 são a classe considerada mais eficaz no controlo glicémico. Este artigo debruça-se sobre as mais recentes evidências científicas sobre os agonistas dos receptores do glucagon-like peptide-1, concluindo que, para além da eficácia no controlo glicémico, são bem tolerados, com a vantagem de reduzirem o peso e apresentarem benefícios cardiovasculares. No entanto, devido às actuais condições económicas e à impossibilidade de prescrever estes fármacos indiscriminadamente, propomos as características dos doentes que mais poderão beneficiar da terapêutica com esta classe, bem como um sistema de controlo de reembolso que permita que esta seja utilizada nos doentes que mais beneficiam.
- Anatomical and Physiological Basis of Continuous Spike-Wave of Sleep Syndrome after Early Thalamic LesionsPublication . Leal, A; Calado, E; Vieira, JP; Mendonça, C; Ferreira, JC; Ferreira, H; Carvalho, D; Furtado, F; Gomes, R; Monteiro, JPOBJECTIVE: Early neonatal thalamic lesions account for about 14% of continuous spike-wave of sleep (CSWS) syndrome, representing the most common etiology in this epileptic encephalopathy in children, and promise useful insights into the pathophysiology of the disease. METHODS: We describe nine patients with unilateral neonatal thalamic lesions which progressed to CSWS. Longitudinal whole-night and high-density electroencephalograms (EEGs) were performed, as well as detailed imaging and clinical evaluation. Visual evoked potentials were used to probe cortical excitability. RESULTS: Thalamic volume loss ranged from 19% to 94%, predominantly on medial and dorsal nuclei and sparing the ventral thalamus. Lesions produced white matter loss and ventricle enlargement on the same hemisphere, which in four patients was associated with selective loss of thalamic-cortical fibers. Cortical thickness quantification failed to reveal hemispheric asymmetries. Impact on EEG rhythms was mild, with a volume-loss-related decrease in alpha power and preservation of sleep spindles. The sleep continuous spiking was lateralized to the hemisphere with the lesion. Visual cortex stimulation in five patients with posterior cortex spiking revealed an abnormal frequency-dependent excitability at 10-20Hz on the side of the lesion. SIGNIFICANCE: Unilateral selective thalamic-cortical disconnection is a common feature in our patients and is associated with both a focal pattern of CSWS and a pathological type of frequency-dependent excitability (peak: 10-20Hz). We propose that this excitability represents an abnormal synaptic plasticity previously described as the augmenting response. This synaptic plasticity has been described as absent in the corticocortical interactions in healthy experimental animals, emerging after ablation of the thalamus and producing a frequency-dependent potentiation with a peak at 10-20Hz. Because this response is potentiated by sleep states of reduced brainstem activation and by appropriate stimulating rhythms, such as sleep spindles, the simultaneous occurrence of these two factors in nonrapid-eye-movement sleep is proposed as an explanation for CSWS in our patients.
- Caffeine Consumption and Mortality in Diabetes: An Analysis of NHANES 1999-2010Publication . Neves, JS; Leitão, L; Magriço, R; Bigotte Vieira, M; Viegas Dias, C; Oliveira, A; Carvalho, D; Claggett, BAim: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the effect of coffee consumption in diabetes remains unclear. We aimed to evaluate the association of caffeine consumption and caffeine source with mortality among patients with diabetes. Methods: We examined the association of caffeine consumption with mortality among 1974 women and 1974 men with diabetes, using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Caffeine consumption was assessed at baseline using 24 h dietary recalls. Cox proportional hazard models were fitted to estimate hazard ratios (HR) for all-cause, cardiovascular, and cancer-related mortality according to caffeine consumption and its source, adjusting for potential confounders. Results: A dose-dependent inverse association between caffeine and all-cause mortality was observed in women with diabetes. Adjusted HR for death among women who consumed caffeine, as compared with non-consumers, were: 0.57 (95% CI, 0.40-0.82) for <100 mg of caffeine/day, 0.50 (95% CI, 0.32-0.78) for 100 to <200 mg of caffeine/day, and 0.39 (95% CI, 0.23-0.64) for ≥200 mg of caffeine/day (p = 0.005 for trend). This association was not observed in men. There was a significant interaction between sex and caffeine consumption (p = 0.015). No significant association between total caffeine consumption and cardiovascular or cancer mortality was observed. Women who consumed more caffeine from coffee had reduced risk of all-cause mortality (p = 0.004 for trend). Conclusion: Our study showed a dose-dependent protective effect of caffeine consumption on mortality among women with diabetes.
- Citometria com Esferas na Abordagem do Transplante Renal Precoce. Estudo ProspectivoPublication . Ferreira, AC; Viana, H; Cabrita, A; Carvalho, D; Ferreira, A; Remédio, F; Lima, A; Sancho, R; Trindade, H; Carvalho, F; Nolasco, F
- Collapsing Glomerulopathy in Portugal: a Review of the Histological and Clinical Findings in HIV and Non-HIV PatientsPublication . Ferreira, AC; Carvalho, D; Carvalho, F; Galvão, MJ; Nolasco, FBACKGROUND: Collapsing glomerulopathy (CG) is a glomerulonephritis seen in association with human immunodeficiency virus (HIV) infection, known as HIV-associated nephropathy (HIVAN), and less frequently observed in non-HIV-infected patients. Method. The aim of this study was to review the histological and clinical findings of all CG diagnosed since 1981 in our laboratory. Result. Since 1981, 18 kidney biopsies with collapsing features were diagnosed among 6130 biopsies performed: 72.2% (n = 13) males, mean age 33.8 ± 9.7 years, 61.1% (n = 11) of black ethnic origin. HIV infection was present in 10 patients. Mean serum creatinine (Scr) was 4.7 ± 2.5 mg/dL, and mean proteinuria was 6.1 ± 5 g/24 h. Both HIVAN and non-HIVAN patients were similar in terms of age, gender and dialysis requirement. In the HIVAN population, African origin was predominant and more frequent than in the non-HIVAN population, Scr was higher and proteinuria was less severe. Interstitial infiltrate, interstitial fibrosis and tubular atrophy were severe, and the presence of microcystic dilatation of renal tubules was more common. Immunofluorescence was positive in six patients. In the non-HIVAN population, this histological lesion was related to an infectious illness in 6/8 patients and to the use of illegal oral drugs in one patient. Interstitial infiltrate, interstitial fibrosis and tubular atrophy presented as moderate to severe, and tubular atrophy correlated with dialysis requirement. Mesangial proliferation was present in 3/8 patients, with C3 and IgA deposits. CONCLUSION: CG is a rare podocytopathy. In this study, the association between infection and CG is evident, and we may suggest that infections could, in a direct or indirect manner, be a trigger of podocyte injury.
- Collapsing Glomerulopathy. A Biopsy ReviewPublication . Ferreira, AC; Carvalho, D; Carvalho, F; Nolasco, F; Ribeiro Santos, J
- Collapsing Glomerulopathy. A Treatable Disease?Publication . Ferreira, AC; Carvalho, D; Carvalho, F; Nolasco, F; Ribeiro dos Santos, JRenal disease is a relatively common complication in human immunodeficiency virus (HIV) infected patients and has become the fourth leading cause of death in AIDS individuals, immediately following septicaemia, pneumonia and hepatic disease. HIV associated nephropathy, HIV associated immune complex renal disease and HIV associated thrombotic microangiopathy are the main causes of chronic renal failure in this population. The authors report a case of a 44 year-old black male, HIV 1 infected with low CD4 count, admitted to the nephrology department with non nephrotic proteinuria and renal failure. Renal biopsy revealed a focal segmental glomerulosclerosis collapsing variant. The patient was treated with highly active antiretroviral therapy and an ACE inhibitor and, at 3 months of follow-up, has recovered his renal function. This case illustrates the efficacy of highly active antiretroviral therapy (HAART) on HIV associated nephropathy. Prospective studies are needed to evaluate HAART in the treatment of HIV associated nephropathies.
- A Common Variant in the CDK8 Gene Is Associated with Sporadic Pituitary Adenomas in the Portuguese Population: a Case-Control StudyPublication . Gaspar, L; Gonçalves, C; Fonseca, F; Carvalho, D; Cortez, L; Palha, A; Barros, I; Nobre, E; Duarte, J; Amaral, C; Bugalho, MJ; Marques, O; Pereira, B; Lemos, MThe majority of pituitary adenomas occur in a sporadic context, and in the absence of known genetic predisposition. Three common variants at the NEBL (rs2359536), PCDH15 (rs10763170) and CDK8 (rs17083838) loci were previously associated with sporadic pituitary adenomas in the Han Chinese population, but these findings have not yet been replicated in any other population. The aim of this case-control study was to assess if these variants are associated with susceptibility to sporadic pituitary adenomas in the Portuguese population. Genotype and allele frequencies were determined in 570 cases and in 546 controls. The CDK8 rs17083838 minor allele (A allele) was significantly associated with sporadic pituitary adenomas, under an additive (odds ratio (OR) 1.73, 95% confidence interval (CI) 1.19-2.50, p = 0.004) and dominant (OR 1.82, 95% CI 1.24-2.68, p = 0.002) inheritance model. The NEBL rs2359536 and PCDH15 rs10763170 variants were not associated with the overall risk for the disease, although a borderline significant association was observed between the PCDH15 rs10763170 minor allele (T allele) and somatotrophinomas (dominant model, OR 1.55, 95% CI 1.02-2.35, p = 0.035). These findings suggest that the CDK8 rs17083838 variant, and possibly the PCDH15 rs10763170 variant, may increase susceptibility to sporadic pituitary adenomas in the Portuguese population.
- Composite Outcomes in Observational Studies of Ulcerative Colitis: a Systematic Review and Meta‐AnalysisPublication . Magro, F; Alves, C; Santiago, M; Ministro, P; Lago, P; Correia, L; Gonçalves, R; Carvalho, D; Portela, F; Dias, C; Dignass, A; Danese, S; Peyrin‐Biroulet, L; Estevinho, MM; Moreira, PBackground: Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes. Objective: This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes. Methods: A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest. Results: A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased. Conclusion: The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes.
- Demographic and Clinical Characteristics of Human Immunodeficiency Virus-Infected Patients Receiving Dialysis in Portugal: a Nationwide Multicentre SurveyPublication . Lopes, JA; Abreu, F; Almeida, E; Carvalho, B; Carmo, C; Carvalho, D; Barber, E; Costa, F; Silva, G; Boquinhas, H; Graça Silva, J; Inchaustegui, L; Dias, L; Batista, M; Neves, P; Mendes, TBackground: Data on human immunodeficiency virus (HIV) infected patients receiving dialysis in Portugal is scarce. Methods: This nationwide epidemiological survey retrospectively evaluates HIV-infected patients on chronic dialysis in Portugal between 1997 and 2002. Results: Sixty-six patients were evaluated (mean age: 39.1±1.6 years, 47 men, 35 black African). Sixty-two patients started dialysis and 4 patients who were receiving dialysis had HIV seroconversion. Eighty-five percent of patients were treated in Lisbon. The annual incidence of HIV-infected patients on chronic dialysis was 0.5% in 1997 and 0.9% in 2002. Seventy-eight percent of patients were HIV-1 infected , 13% had hepatitis B and 31% hepatitis C. Sexual contact was the mode of transmission of HIV in 53% of cases. Four patients had biopsy-proved HIV-associated nephropathy. Ninety-five percent of patients were on chronic hemodialysis. Fifty percent of patients had acquired immunodeficiency syndrome. At follow-up, 12 patients died. HIV-infected CKD patient survival after starting dialysis was 80% at 3 years. Conclusion: The incidence of HIV-infected patients on chronic dialysis in Portugal has almost doubled. Widespread use of highly active antiretroviral therapy and the increasing number of black Africans from former overseas Portuguese colonies now living in Portugal are possible reasons for this large increase.