Transcription analysis of TIMP-1 and NM23 genes in glioma cell invasion

Universidade Federal de São Paulo (UNIFESP) EPMUNIFESP, EPMSciEL

Deep brain stimulation of subthalamic nucleous in Parkinson's disease

We present the preliminary results in patients well selected to be implanted by deep brain stimulation (DBS) for Parkinsons's disease (PD). METHODS: 8 PD patients with disabled tremor, akinetic/bradikinetic and rigidity, in spite of best therapeutic assay with poor response were referred to surgery. It was implanted DBS Itrell 2. Theses patients were evaluated by the following scales: UPDRS, Schwab and England. RESULTS: The preliminary results in 6 months showed significant improvement of motor performance and it is shown by the scores. There were no complications so far with these procedures. CONCLUSION: The preliminary results indicate that DBS is highly effective, with benefit to those patients and it is according to literature.OBJETIVO: Apresentamos os resultados preliminares da estimulação cerebral profunda crônica no núcleo subtalâmico para os sintomas motores da doença de Parkinson. MÉTODO: 8 pacientes com doença de Parkinson há mais de 5 anos, apresentando tremor incapacitante, oligocinesia e rigidez acentuada com predomínio unilateral, 3 à direita e um à esquerda, refratários à medicação adequada, foram submetidos ao implante bilateral de eletrodo cerebral profundo permanente subtalâmico, Itrell 2. Estes pacientes foram avaliados segundo as escalas: UPDRS, Schwab e England. RESULTADOS: Os resultados preliminares (6 meses), mostraram melhora significativa dos sinais e sintomas avaliados pelas escalas acima. Não houve complicações com os procedimentos. CONCLUSÃO: Os resultados preliminares indicam que a estimulação subtalâmica é uma boa opção terapêutica, estando de acordo com os resultados da literatura.Universidade Estácio de Sá Departamento de Neurocirurgia Centro de Investigação NeurológicaHospital Pró-Cardíaco Serviço de NeurocirurgiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Análise transcricional dos genes TIMP-1 e NM23-H1 na invasão celular em astrocitoma difuso e glioblastoma multiforme

PURPOSE: To evaluate using transcription analysis the presence and importance of two genes: NM23-H1 and TIMP-1 on control of tumor cell invasion in diffuse astrocytomas (WHO II) and glioblastoma multiforme (WHO IV). METHOD: Northern blot analysis of NM23-H1 and TIMP-1 was performed. Eight diffuse astrocytomas and 19 glioblastomas (WHO IV) were analyzed to determine if TIMP-1 and NM23-H1 were candidates to inhibition of tumor cell invasion quantitated RNA levels. The samples were collected directly from operating room. Total cellular RNA was extracted from frozen tissue samples using guanidinium-isothiocyanate and cesium chloride gradients. Total RNA (10 mg per sample) from tumor tissue were size fractionated through 1% agarose-formaldehyde gel and transferred to nylon filters and then hybridized to 32P-labeled DNA probes and placed for autoradiography. Levels of specific RNAs were determined by computer-assisted laser densitometry. Blot filters were sequentially hybridized to nm23 and TIMP-1 probes in addition to GAPDH, as a control. Statistical analyses were carried out according to t-test for equality of means. RESULTS: NM23-H1 were detected in each sample, however it did not correlate with malignancy and invasiveness. On the other side TIMP-1 gene expression showed a clear correlation between low expression and invasiveness. CONCLUSION: The data suggest that TIMP-1 is an inhibitor of high grade gliomas invasion. NM23-H1 was present in the entire gliomas sample, but it did not vary in diffuse astrocytomas and glioblastomas.OBJETIVO: Comparar através da análise da expressão dos níveis de RNA, a presença e a relevância dos genes NM23-H1 e TIMP-1 no controle da invasão celular tumoral dentro do tecido cerebral normal em: astrocitoma difuso (OMS II) e glioblastoma multiforme (OMS:IV). MÉTODO: Análise em Northern blot dos genes NM23-H1 e TIMP-1. Oito astrocitomas fibrilares difusos (OMS II) e 19 glioblastomas multiformes foram analisados para determinar se TIMP-1 e NM23-H1 estavam relacinados à inibição da invasão tumoral nas neoplasias do sistema nervoso central, quantificando os níveis de RNA dos respectivos genes extraídos diretamente dos tumores. 10 mg por amostra de RNA total foram fracionados de gel de formaldeído e transferidos para os filmes de hibridação. Níveis específicos de RNAs foram determinados na espectrofotometria. Valores das razões entre NM23-H1/GAPDH e TIMP-1/GAPDH foram submetidos à análise de variabilidade das médias. RESULTADOS: A análise da expressão do gene TIMP-1 mostrou supressão em tumores gliais malignos. CONCLUSÃO: Os resultados indicam que existe relação direta entre níveis baixos de TIMP-1 e malignidade dos gliomas. O gene NM23-H1 foi detectado em todas as amostras, mas não foi possível relacionar sua subexpressão ou superexpressão com algum fenótipo de invasividade.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Estácio de SáUniversidade Caxias do SulColumbia University College of Physicians and Surgeons Department of NeurosurgeryUNIFESP, EPMSciEL

Fibrinólise com infusão de rtPA e drenagem estereotáxica de hematoma intracerebral espontâneo profundo

PURPOSE: The authors present a prospective study on 10 patients with stereotactic infusion of tissue plasminogen activator (rtPA) intraparenchimal hemorrhage. METHODS: Between 1999 and 2000, 10 patients with deep seated hematomas in the basal ganglia were selected for stereotactic infusion of rtPA and spontaneous clot drainage. RESULTS: All cases had about 80% reduction of the hematoma volume in the CT scan at the third day. The intracranial pressure was normalized by the third day too. There were no local or systemic complications with the use of this trombolitic. The results were shown by the Glasgow Outcome Scale with six patients in V, three in IV and one in III after 3 months. CONCLUSION: Early treatment and drainage with minimally invasive neurosurgery , can make these patients with deep-seated hematomas recover the consciousness and they can be rehabilitated earlier avoiding secondary complications.OBJETIVO: Estudo prospectivo em 10 pacientes com infusão de trombolítico (rtPA) dentro do hematoma cerebral profundo supratentorial e drenagem estereotáxica. MÉTODO: Entre 1999 e 2000 10 pacientes com hematomas de profundidade foram selecionados para infusão de rtPA e drenagem do coágulo espontânea. RESULTADO: Todos os casos obtiveram 80% de redução do volume do hematoma medidos por TC no terceiro dia. A pressão intracraniana estava normalizada no terceiro dia. Não houve complicações locais ou sistêmicas relacionadas com o uso deste trombolítico. Os resultados comparados foram mostrados pela Escala de Prognóstico de Glasgow com 6 pacientes em GrauV, 3 pacientes em Grau IV e 1 paciente em Grau III após três meses. CONCLUSÃO: Tratamento precoce e drenagem com técnica neurocirúrgica minimamente invasiva pode fazer estes pacientes terem uma recuperação da consciência mais rápida e assim serem reabilitados mais precocemente evitando complicações secundárias.Universidade Estácio de Sá Instituto do Sono Estácio de Sá Centro de Investigação NeurológicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Meningioma anaplásico: relato de caso

Intracranial meningiomas continue to challenge our best clinical efforts to eliminate them once discovered and deemed appropriate for treatment. Malignant meningiomas constitute 10% to 15% of all meningiomas and limited information exists regarding adjuvant treatment. The external whole brain irradiation is recommended. Traditional chemotherapy has proven ineffective; thus, new chemotherapeutic agents and new methods of delivery should be developed. Immunotherapy may be considered for patients with malignant meningiomas when all others previous treatment have failed. We report a case of anaplastic papillary meningioma. A 67-year-old man presented with partial complex seizures, headache and aggressiveness. A computerized tomography and magnetic resonance image demonstrated a large left temporo-occipital mass with difuse contrast enhancement and extensive surrounding edema. A left temporo-occipital flap was performed. The tumor and the infiltrated dura were radically removed. Postoperatively, the patient remained neurologically intact. The treatment was complemented by external whole brain radiation.O tratamento adequado para os pacientes com meningiomas intracranianos continua sendo um desafio, principalmente o de sua variante maligna, a qual tem incidência de 10% a 15%, sem uma certeza do melhor tratamento adjuvante. É indicado o uso da radioterapia externa holocraniana. O uso da quimioterapia tradicional se mostra ineficaz, havendo necessidade de estudos para desenvolver outros agentes quimioterápicos e novos métodos de administração desses agentes no tumor cerebral. A imunoterapia pode ser considerada para os casos de refratariedade aos outros tratamentos adjuvantes. Relatamos o caso de um paciente de 67 anos, com história progressiva de cefaléia, crises convulsivas parciais complexas e agressividade. A investigação radiológica com tomografia computadorizada e ressonância magnética evidenciaram um processo expansivo na região temporoccipital esquerda com contrastação difusa e edema peritumoral importante. Foi realizada craniotomia frontoparietotemporal esquerda com remoção radical da dura-máter infiltrada e do tumor. O paciente evoluiu sem déficit neurológico no pós-operatório. O exame anatomopatológico foi compatível com meningioma maligno do tipo papilar. Foi instituído tratamento complementar com radioterapia externa holocraniana.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)Hospital Pró-Cardíaco e Estereolife, Neurocirurgia Estereotáxica e FuncionalFederal University of Rio de JaneiroUNIFESP, EPMSciEL

Species composition and similarities among anuran assemblages of forest sites in southeastern Brazil

As florestas neotropicais apresentam altas riquezas de espécies de anuros, mas algumas formações florestais brasileiras, como o cerradão, as florestas semidecíduas e as restingas, permanecem pouco conhecidas. A composição de espécies de anuros de quatro áreas florestais pertencentes a diferentes biomas do sudeste do Brasil foi determinada com base em duas técnicas complementares (procura visual e investigação nos sítios reprodutivos), aplicadas de forma simultânea. Registramos um total de 60 espécies de anuros, incluídas em oito famílias. A riqueza de espécies e o nível de endemismo foram maiores na área coberta por floresta pluvial atlântica. As áreas localizadas no domínio do Cerrado foram mais similares entre si do que as áreas localizadas no domínio da Mata Atlântica. Os índices de similaridade mostraram-se negativamente relacionados com a distância geográfica entre as áreas, explicando parte das similaridades observadas. Os fatores que influenciam os padrões de ocorrência são discutidos. Uma das espécies (caso sua identidade seja confirmada) é considerada como Deficiente em Dados pela IUCN (The World Conservation Union), mas não está incluída na lista da fauna brasileira ameaçada de extinção. A presença de certas espécies com requisitos especiais de hábitat e microclima (bioindicadores) sugerem que os ecossistemas estão bem-preservados.Neotropical forests show high anuran species richness, but some Brazilian forest formations, like cerradão, semideciduous forests and restingas, remain poorly known. The composition of anuran species were determined for four forest sites belonging to different biomes in southeastern Brazil, based on two complementary techniques (visual encounter survey and survey on breeding sites), both applied simultaneously. A total of 60 anuran species belonging to eight families was recorded. Species richness and levels of endemism were higher in the Atlantic rainforest site. Sites located in the Cerrado domain were more alike than those located in the Atlantic Forest Domain. Similarity in anuran species composition was negatively correlated to the geographical distance among sites, which explains part of similarities in species composition. Factors affecting these occurrence patterns are discussed. One species (if its identity is confirmed) is considered Data Deficient by IUCN (The World Conservation Union), though it is not included in the Brazilian list of threatened amphibians. The presence of certain species with special habitats and microclimate requirements (bioindicators) suggests well-preserved ecosystems

Cranioplasties: surgical reconstruction strategies

INTRODUCTION: Reconstruction of the skull bones can prove challenging. There are three indications for carrying out cranioplasty: (1) recovery of protection against trauma, (2) recovery of the cranial contour, and (3) treatment of the syndrome of the trephined. The objective of this report is to present the experience of the author with cranioplasties, and discuss surgical reconstruction strategies. METHODS: This report presents a retrospective analysis of 16 consecutive cases of cranial reconstruction, which were operated in 2013 and 2014 in the public health service (INTO - RJ) and in the private practice. RESULTS: From January 2013 to January 2014, 16 patients underwent surgery. Thirteen were men. Their age ranged from 10 to 72 years. Twelve patients underwent reconstruction with a parietal graft, two with custom prosthesis, one with fracture reduction and fixation, and one with reconstruction of soft parts . Most of the defects were located in the fronto-orbital region. The customized prostheses were used in defects of 192 cm2 and 22.5 cm2. Complications occurred in five patients: lesion of the sagittal sinus, irregularity in the contour, seroma, failure in graft integration, leakage of cerebrospinal fluid, and extrusion of the prosthesis. All the complications were resolved without impairment to the reconstruction. The follow-up time ranged from 10 to 22 months. All the patients were pleased with the reconstructions, and improvement of the neurological functions was reported. CONCLUSION: Cranioplasty is a primarily restorative surgical procedure that is used to restore the protective function of the skull and to treat the syndrome of the trephined. The autologous parietal graft is the surgeons' first choice. The prosthesis is indicated when there is a major defect or when the harvesting of a parietal graft is not possible

Validating the predictive ability of the 2MACE score for major adverse cardiovascular events in patients with atrial fibrillation:results from phase II/III of the GLORIA-AF registry

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1–3) and 1 (IQR 0–2), respectively (p < 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21–2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641–0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01468701, NCT01671007 and NCT01937377

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation:a post-hoc analysis from the GLORIA-AF Registry

Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II–III (November 2011–December 2014 for Phase II, and January 2014–December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0 ± 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22–0.25] and 0.66 [0.61–0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67–1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76–0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH.</p