Browsing by Author "Amorim, J"
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- Casos clínicosPublication . Morais, N; Moreira da Costa, JA; Valle, JM; Amorim, J; Serviço de Neurocirurgia, Hospital de Braga; Serviço de Neurocirurgia, Hospital de Braga
- Casos clínicos IIPublication . Morais, N; Moreira da Costa, JA; Valle, JM; Amorim, J
- Clinical, imagiological and etiological spectrum of posterior reversible encephalopathy syndromePublication . Pereira, PR; Pinho, J; Rodrigues, M; Rocha, J; Sousa, F; Amorim, J; Ribeiro, M; Rocha, J; Ferreira, CObjective Analyze the cases of posterior reversible encephalopathy syndrome (PRES) admitted in a Neurology Department during an 8-year period. Method Retrospective observational study in a central hospital in the north of Portugal. Results 14 patients were identified, mean age 52.3 years. Precipitating factors included: eclampsia, isolated arterial hypertension, spinal trauma and autonomic dysreflexia, Guillain-Barré syndrome, sepsis, sarcoidosis and pulmonary cryptococcosis and drugs. Most patients presented posterior-predominant vasogenic edema lesions, however 64.2% presented frontal lesions and in 42.8% cerebellum was involved. Four patients also had acute ischemic lesions and 1 had hemorrhagic lesions. During follow-up 10 patients recovered fully, 2 recovered partially, 1 suffered a recurrence and 2 died in hospital. Conclusion PRES has many etiological factors. The terms posterior and reversible should be revised because PRES frequently involves other brain regions and it is not always reversible. PRES patients may develop life-threatening complications and mortality is not negligible.
- Dramatic recovery after IV thrombolysis in anterior circulation ischemic stroke: Predictive factors and prognosisPublication . Rocha, J; Pinho, J; Varanda, S; Amorim, J; Rocha, JR; Maré, R; Ferreira, CBACKGROUND AND PURPOSE: Dramatic recovery (DR) after thrombolysis is dependent of vessel recanalization and is predictive of favorable clinical outcome. Successful recanalization is not equivalent to DR. Our objective was to assess its frequency and evaluate clinical and biochemical predictors and their prognosis. METHODS: We analyzed prospectively registered data from January 2007 to September 2012. All patients with anterior circulation stroke and NIHSS≥10 were included. Improvement of ≥10 or a score ≤3 24h after thrombolysis was defined as DR. RESULTS: In the 230 patients included, DR frequency was 23% (53 patients). DR group had lower admission NIHSS (14 vs 17, p=0.024), less total anterior circulation infarcts (p=0.009), more partial anterior circulation infarcts (p=0.003) and lower blood glucose on admission (118 vs 128mg/dL, p=0.013). All patients with DR had an Alberta Stroke Program Early CT Score (ASPECTS) ≥7, vs 89.3% without DR (p=0.013). Arterial recanalization, defined as hyperdense middle cerebral artery sign disappearance on control CT, was more frequent in the DR group (68.4% vs 14.1%, p<0.001). Intracranial hemorrhage on 24h-control CT scan was less frequent in the DR group (p<0.001). Multinomial logistic regression analysis showed that ASPECTS score was an independent predictor of DR (OR=2.35, 95%CI=1.32-4.16, p=0.003) and CT evidence of recanalization was independently associated with DR (OR=11.60, 95%CI, 3.02-44.53, p<0.001). CONCLUSION: DR is a frequent occurrence. ASPECTS score is an independent predictor of DR, which is also independently associated with CT evidence of middle cerebral artery recanalization.
- Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in glioma susceptibility and patient prognosisPublication . Xavier-Magalhães, A; Oliveira, AI; Vieira de Castro, J; Pojo, M; Gonçalves, CS; Lourenço, T; Viana-Pereira, M; Costa, S; Linhares, P; Vaz, R; Nabiço, R; Amorim, J; Pinto, AA; Reis, RM; Costa, BMAbnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is oncogenic in several human cancers, including gliomas. The HOTAIR single nucleotide polymorphisms (SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of HOTAIR, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor types. However, the relevance of these HOTAIR SNPs has not been studied in glioma. Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.
- Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomasPublication . Martinho, O; Longatto-Filho, A; Lambros, MB; Martins, A; Pinheiro, C; Silva, AI; Pardal, F; Amorim, J; Mackay, A; Milanezi, F; Tamber, N; Fenwick, K; Ashworth, A; Reis-Filho, J; Lopes, JM; Reis, RMBACKGROUND: Malignant gliomas are the most prevalent type of primary brain tumours but the therapeutic armamentarium for these tumours is limited. Platelet-derived growth factor (PDGF) signalling has been shown to be a key regulator of glioma development. Clinical trials evaluating the efficacy of anti-PDGFRA therapies on gliomas are ongoing. In this study, we intended to analyse the expression of PDGFA and its receptor PDGFRA, as well as the underlying genetic (mutations and amplification) mechanisms driving their expression in a large series of human gliomas. METHODS: PDGFA and PDGFRA expression was evaluated by immunohistochemistry in a series of 160 gliomas of distinct World Health Organization (WHO) malignancy grade. PDGFRA-activating gene mutations (exons 12, 18 and 23) were assessed in a subset of 86 cases by PCR-single-strand conformational polymorphism (PCR-SSCP), followed by direct sequencing. PDGFRA gene amplification analysis was performed in 57 cases by quantitative real-time PCR (QPCR) and further validated in a subset of cases by chromogenic in situ hybridisation (CISH) and microarray-based comparative genomic hybridisation (aCGH). RESULTS: PDGFA and PDGFRA expression was found in 81.2% (130 out of 160) and 29.6% (48 out of 160) of gliomas, respectively. Its expression was significantly correlated with histological type of the tumours; however, no significant association between the expression of the ligand and its receptor was observed. The absence of PDGFA expression was significantly associated with the age of patients and with poor prognosis. Although PDGFRA gene-activating mutations were not found, PDGFRA gene amplification was observed in 21.1% (12 out of 57) of gliomas. No association was found between the presence of PDGFRA gene amplification and expression, excepting for grade II diffuse astrocytomas. CONCLUSION: The concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas. Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas.
- Immunoglobulin genes implicated in glioma riskPublication . Pandey, JP; Kaur, N; Costa, N; Amorim, J; Nabico, R; Linhares, P; Vaz, R; Viana-Pereira, M; Reis, RMBoth genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, a pathogen implicated as a promoter of gliomagenesis, has lead us to hypothesize that these determinants are risk factors for glioma. To test this hypothesis, we genotyped the IGHG locus comprising the GM alleles, specifically GM alleles 3 and 17, of 120 glioma patients and 133 controls via TaqMan® genotyping assay. To assess the associations between GM genotypes and the risk of glioma, we applied an unconditional multivariate logistic regression analysis adjusted for potential confounding variables. In comparison to subjects who were homozygous for the GM 17 allele, the GM 3 homozygotes were over twice as likely, and the GM 3/17 heterozygotes were over three times as likely, to develop glioma. Similar results were achieved when analyzed by combining the data corresponding to alleles GM 3 and GM 3/17 in a dominant model. The GM 3/17 genotype and the combination of GM 3 and GM 3/17 were found to be further associated with over 3 times increased risk for high-grade astrocytoma (grades III-IV). Allele frequency analyses also showed an increased risk for gliomas and high-grade astrocytoma in association with GM 3. Our findings support the premise that the GM 3 allele may present risk for the development of glioma, possibly by modulating immunity to cytomegalovirus.
- Impact of EGFR genetic variants on glioma risk and patient outcomePublication . Costa, BM; Viana-Pereira, M; Fernandes, R; Costa, S; Linhares, P; Vaz, R; Pinheiro, C; Lima, J; Soares, P; Silva, A; Pardal, F; Amorim, J; Nabiço, R; Almeida, R; Alegria, C; Pires, MM; Pinheiro, C; Carvalho, E; Oliveira, P; Lopes, JM; Reis, RMBACKGROUND: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, -216G/T and -191C/A, and a polymorphic (CA)(n) microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. METHODS: We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. RESULTS: None of the EGFR -216G/T variants was significantly associated with glioma risk. The -191C/A genotype was associated with higher risk for glioma when the (CA)(n) alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)(n) repeat cutoff point used, shorter (CA)(n) repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)(n) cutoff points, only -191C/A genotype was consistently associated with improved survival of patients with glioblastoma. CONCLUSIONS: Our findings implicate EGFR -191C/A and the (CA)(n) repeat polymorphisms as risk factors for gliomas, and suggest -191C/A as a prognostic marker in glioblastoma. IMPACT: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies
- Molecular alterations of PDGA and PDGFRA in GliomasPublication . Martinho, O; Longatto-Filho, A; Lambros, MB; Martins, A; Pinheiro, C; Silva, AI; Pardal, F; Amorim, J; Mackay, A; Milanezi, F; Tamber, N; Fenwick, K; Ashworth, A; Reis-Filho, JS; Lopes, JM; Reis, RM
- Mucormicose rinocerebrorbitária e diabetes mellitus – a propósito de um caso clínico.Publication . Matta-Coelho, C; Amorim, J; Carvalho, SD; Silva, D; Monteiro, AM; Souto, SB; Marques, O