Coimbra, Portugal
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Diaz S.O.,University of Aveiro | Barros A.S.,University of Aveiro | Goodfellow B.J.,University of Aveiro | Duarte I.F.,University of Aveiro | And 5 more authors.
Journal of Proteome Research | Year: 2013

In this work, untargeted NMR metabonomics was employed to evaluate the effects of pregnancy on the metabolite composition of maternal urine, thus establishing a control excretory trajectory for healthy pregnancies. Urine was collected for independent groups of healthy nonpregnant and pregnant women (in first, second, third trimesters) and multivariate analysis performed on the corresponding NMR spectra. Models were validated through Monte Carlo Cross Validation and permutation tests and metabolite correlations measured through Statistical Total Correlation Spectroscopy. The levels of 21 metabolites were found to change significantly throughout pregnancy, with variations observed for the first time to our knowledge for choline, creatinine, 4-deoxyerythronic acid, 4-deoxythreonic acid, furoylglycine, guanidoacetate, 3-hydroxybutyrate, and lactate. Results confirmed increased aminoaciduria across pregnancy and suggested (a) a particular involvement of isoleucine and threonine in lipid oxidation/ketone body synthesis, (b) a relation of excreted choline, taurine, and guanidoacetate to methionine metabolism and urea cycle regulation, and (c) a possible relationship of furoylglycine and creatinine to pregnancy, based on a tandem study of nonfasting confounding effects. Results demonstrate the usefulness of untargeted metabonomics in finding biomarker metabolic signatures for healthy pregnancies, against which disease-related deviations may be confronted in future studies, as a base for improved diagnostics and prediction. © 2012 American Chemical Society.


David A.,Centro Hospitalar Of Coimbra | Constantino F.,Polytechnic Institute of Coimbra | Santos J.M.D.,Centro Hospitalar Of Coimbra | Paiva T.,University of Lisbon | Paiva T.,and Clinical Neurophysiology Center
Sleep Medicine | Year: 2012

Objective: To evaluate the perception of health-related quality of life (HRQoL) in Portuguese patients with narcolepsy, and to compare the results to normative data. Methods: Fifty-one narcoleptic adults (26M, 25F), aged between 18 and 80. years (mean = 43.35, SD = 15.32), were included in the final analysis of a multicentric cross-sectional study. The Medical Outcome Study - 36 Item Short-Form Survey (SF-36) was used to assess quality of life, and the Beck Depression Inventory (BDI) was used for self-assessment of depression. Results: Several HRQoL domains were significantly lower than National surveys, except physical function and bodily pain (p between 0.000 and 0.006). SF-36 presented the lowest score in vitality (39.93). Deterioration was significantly higher in role physical (p= 0.006), vitality (p= 0.011), and mental health (p= 0.008) in women, and in physical function (p= 0.003) and bodily pain (p= 0.045) in elderly subjects. Those with higher literacy had better physical function (p= 0.046). Conclusion: HRQoL is significantly deteriorated in narcoleptics, affecting all dimensions (except physical function and bodily pain) when compared with the general Portuguese population. The results are consistent with studies of narcolepsy in other countries in demonstrating the profound impact of this disorder on quality of life. © 2011 Elsevier B.V.


Diaz S.O.,University of Aveiro | Pinto J.,University of Aveiro | Graca G.,University of Aveiro | Duarte I.F.,University of Aveiro | And 8 more authors.
Journal of Proteome Research | Year: 2011

This work describes an exploratory NMR metabonomic study of second trimester maternal urine and plasma, in an attempt to characterize the metabolic changes underlying prenatal disorders and identify possible early biomarkers. Fetal malformations have the strongest metabolic impact in both biofluids, suggesting effects due to hypoxia (leading to hypoxanthine increased excretion) and a need for enhanced gluconeogenesis, with higher ketone bodies (acetone and 3-hydroxybutyric acid) production and TCA cycle demand (suggested by glucogenic amino acids and cis-aconitate overproduction). Choline and nucleotide metabolisms also seem affected and a distinct plasma lipids profile is observed for mothers with fetuses affected by central nervous system malformations. Urine from women who subsequently develop gestational diabetes mellitus exhibits higher 3-hydroxyisovalerate and 2-hydroxyisobutyrate levels, probably due to altered biotin status and amino acid and/or gut metabolisms (the latter possibly related to higher BMI values). Other urinary changes suggest choline and nucleotide metabolic alterations, whereas lower plasma betaine and TMAO levels are found. Chromosomal disorders and pre-preterm delivery groups show urinary changes in choline and, in the latter case, in 2-hydroxyisobutyrate. These results show that NMR metabonomics of maternal biofluids enables the noninvasive detection of metabolic changes associated to prenatal disorders, thus unveiling potential disorder biomarkers. © 2011 American Chemical Society.


Manageiro V.,National Institute Of Health Dr Ricardo Jorge | Ferreira E.,National Institute Of Health Dr Ricardo Jorge | Cougnoux A.,Clermont University | Albuquerque L.,Centro Hospitalar Of Coimbra | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2012

The clinical Klebsiella pneumoniae INSRA6884 strain exhibited nonsusceptibility to all penicillins tested (MICs of 64 to >2,048 μg/ml). The MICs of penicillins were weakly reduced by clavulanate (from 2,048 to 512 μg/ml), and tazobactam restored piperacillin susceptibility. Molecular characterization identified the genes blaGES-7 and a new β-lactamase gene, blaSHV-107, which encoded an enzyme that differed from SHV-1 by the amino acid substitutions Leu35Gln and Thr235Ala. The SHV-107-producing Escherichia coli strain exhibited only a β-lactam resistance phenotype with respect to amoxicillin, ticarcillin, and amoxicillin-clavulanate combination. The kinetic parameters of the purified SHV-107 enzyme revealed a high affinity for penicillins. However, catalytic efficiency for these antibiotics was lower for SHV-107 than for SHV-1. No hydrolysis was detected against oxyimino-β-lactams. The 50% inhibitory concentration (IC50) for clavulanic acid was 9-fold higher for SHV-107 than for SHV-1, but the inhibitory effects of tazobactam were unchanged. Molecular dynamics simulation suggested that the Thr235Ala substitution affects the accommodation of clavulanate in the binding site and therefore its inhibitory activity. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Maltez F.,Hospital Of Curry Cabral | Doroana M.,Centro Hospitalar Lisbon Norte | Branco T.,Medical Service | Valente C.,Centro Hospitalar Of Coimbra
Current Opinion in HIV and AIDS | Year: 2011

Purpose of review: To discuss new antiretroviral agents (ARVs) and alternative ARV treatment strategies that are currently being evaluated, and to provide an overview of the most recent advances in HIV vaccine development. RECENT FINDINGS: There is a continuous need for improvements in ARV therapy (ART) and several new ARVs are currently undergoing clinical investigation, including the non-nucleoside reverse transcriptase inhibitor rilpivirine, the integrase inhibitor elvitegravir, the chemokine receptor 5 co-receptor antagonist vicriviroc and the maturation inhibitor bevirimat. Strategies to optimize ART, such as treatment interruption, induction-maintenance and class-sparing regimens, are also being evaluated and have had varying success to date. However, vaccination still remains the optimal solution, and one second-generation preventative HIV vaccine has produced encouraging results in a recent phase III trial. SUMMARY: Global prevention and treatment with ARVs that are effective, well tolerated and have high barriers to the development of HIV resistance are the main strategies to fight HIV/AIDS while we await the development of an effective vaccine. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Pereira B.J.,Centro Hospitalar Of Coimbra
UroToday International Journal | Year: 2012

Primary adult soft tissue sarcomas represent 1% of all cancers and represent a treatment challenge for surgeons and oncologists. Of these sarcomas, 15% are located in the retroperitoneum. Randomized series that have examined both radiation therapy and chemotherapy have not shown a survival benefit. Conversely, radiotherapy may delay the time to local recurrence but not overall survival. Our review presents medical records of 5 consecutive patients undergoing retroperitoneal sarcoma excision from May 2004 through February 2006. Images were obtained from the patients' exams and during their surgical procedures. Surgery is the only potential curative treatment. As "retroperitoneal surgeons," urologists are completely able to approach these kinds of tumors. © 2012 Digital Science Press, Inc.


Nunes J.,Centro Hospitalar Of Coimbra
Acta médica portuguesa | Year: 2012

Selective and bilateral involvement of the limbic system by gliomas is rarely reported. The authors report the case of a 58 years-male complaining of short-term memory loss in the preceding three weeks. The initial MRI revealed areas of hyperintensity on T2 and FLAIR sequences involving both hippocampus, amygdala, parahippocampus gyrus and the fornix, with contrast enhancement in the right mesial temporal region. Limbic encephalitis diagnosis was assumed and steroid therapy was applied. All other evaluation work-up was negative and follow-up imaging was compatible with tumor. The neuropathologic study of the right temporal lesion revealed glioblastoma multiforme. Glioblastoma can crossover through the commissural white matter to the opposite cerebral hemisphere, most often through the corpus callosum. However, selective and bilateral invasion of the limbic system is rare and when it occurs it may mimic limbic encephalitis.


Guimaraes C.,Centro Hospitalar Of Coimbra | Sanches I.,Centro Hospitalar Of Coimbra | Ferreira C.,Centro Hospitalar Of Coimbra
BMJ Case Reports | Year: 2012

Acute fibrinous and organising pneumonia (AFOP) was recently described as an unusual pattern of diffuse lung disease. Particular characteristics make the differential diagnosis with the well recognised clinical patterns of diffuse alveolar damage, cryptogenic organising pneumonia or eosinophilic pneumonia. The lack of hyaline membranes, the presence of intra-alveolar fibrin, absence of noticeable eosinophils and patchy distribution suggests that AFOP define a distinct histological pattern. The authors describe the case of a woman diagnosed with AFOP after surgical lung biopsy, in association with primary biliary cirrhosis. The patient presented dyspnoea, fatigue, dry cough and thoracic pain. The CT scan showed bilateral patchy infiltrates predominantly in the lower lobes. Flexible bronchoscopy and subsidiary techniques were inconclusive and biopsy through video-assisted thoracoscopic surgery led to anatomopathological diagnosis of AFOP. The patient is having a good clinical response to prednisone. Copyright 2012 BMJ Publishing Group. All rights reserved.


Guimaraes C.,Centro Hospitalar Of Coimbra
BMJ case reports | Year: 2012

Acute fibrinous and organising pneumonia (AFOP) was recently described as an unusual pattern of diffuse lung disease. Particular characteristics make the differential diagnosis with the well recognised clinical patterns of diffuse alveolar damage, cryptogenic organising pneumonia or eosinophilic pneumonia. The lack of hyaline membranes, the presence of intra-alveolar fibrin, absence of noticeable eosinophils and patchy distribution suggests that AFOP define a distinct histological pattern. The authors describe the case of a woman diagnosed with AFOP after surgical lung biopsy, in association with primary biliary cirrhosis. The patient presented dyspnoea, fatigue, dry cough and thoracic pain. The CT scan showed bilateral patchy infiltrates predominantly in the lower lobes. Flexible bronchoscopy and subsidiary techniques were inconclusive and biopsy through video-assisted thoracoscopic surgery led to anatomopathological diagnosis of AFOP. The patient is having a good clinical response to prednisone.


Costa Gomes B.,Centro Hospitalar Of Coimbra
Acta médica portuguesa | Year: 2012

Central Nervous System (CNS) infection by Human Immunodeficiency Virus (HIV) occurs early in the course of the disease and is associated with changes that can reach any level of the neuroaxis. Neuroimaging plays an increasingly important role both in diagnosis and in longitudinal monitoring of these complications, which can be divided into three major categories: injuries directly associated with HIV, opportunistic infections and malignancies. To identify and to describe the neuroradiological changes found in a population of HIV positive patients. Retrospective study with analysis of clinical processes and review of neuroimaging studies of HIV positive patients admitted to the Centro Hospitalar de Coimbra - E.P.E. in the period between 1st January 2008 and 31st March 2011. During the study period we identified 337 episodes of hospitalization of patients with HIV infection, accounting for a total of 196 patients. Of these, 88 underwent at least one neuroimaging examination, with a mean age of 47.1 (27-89) years, of which 75% were males. In 12.5% of the examinations we did not find any relevant changes. In 69.3% atrophy was observed, in 31.2% sequelae lesions with different aetiologies (vascular, infectious), and eight cases of HIV encephalitis were identified. In 19.3% of patients it was diagnosed the presence of an opportunistic infection (11 cases of toxoplasmosis, four of progressive multifocal leukoencephalopathy, one case of tuberculosis and one of neurosyphilis). There were also 10 cases with evidence of recent vascular lesions. Although considered in the differential diagnosis in some cases, in our sample we did not identify any case of tumours. Recognition of CNS changes associated with HIV infection and of their imaging patterns is of critical importance to the establishment of the diagnosis and to the appropriate treatment. Advanced techniques of Magnetic Resonance Imaging may have an important role in this context.

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