Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
J Neurooncol ; 136(2): 413-419, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29273890

RESUMO

We aimed to assess the efficacy of stereotactic irradiation for patients with recurrent high-grade glioma (HGG) and identify predictive factors of progression-free survival (PFS) and overall survival (OS) following reirradiation. We identified 32 patients with recurrent brain HGG who had been treated with either single-dose (stereotactic radiosurgery) or fractionated stereotactic radiotherapy between April 2008 and October 2015. Median follow up was 21.4 months (range 12.9-23.2) and median PFS was and 3.3 months (95% CI [2.3-4.7]), respectively. OS was 90.40% (95% CI [73.09-96.80]) at 6 months and 79.55% (95% CI [59.9-90.29]) at 12 months. Univariate analysis showed that biological effective dose at isocenter ≤ 76 Gy was a poor prognostic factor for both OS (83.33 vs. 100% at 6 months, p = 0.032) and median PFS (2.7 vs. 4.7 months, p = 0.025), as was gross tumor volume (GTV) above 1 cm3 for OS (86.15 vs. 94.12% at 6 months, p = 0.043). Contact with the subventricular zone (SVZ) was also a poor prognostic factor for median PFS (2.3 vs. 4.7 months, p = 0.002). Multivariate analysis showed that SVZ contact remained a poor prognostic factor for PFS (hazard ratio = 3.44, 95% CI [1.21-9.82], p = 0.021). Results suggest that reirradiation is a safe and effective treatment option for recurrent HGG in patients with a good Karnosfsky Performance Scale score, a long progression-free interval since first radiation and limited GTV, and that contact to SVZ is a strong prognostic factor for PFS.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/radioterapia , Glioma/diagnóstico , Glioma/radioterapia , Ventrículos Laterais/efeitos da radiação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/radioterapia , Reirradiação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Intervalo Livre de Progressão , Radiocirurgia , Adulto Jovem
2.
Ann Dermatol Venereol ; 141(2): 111-21, 2014 Feb.
Artigo em Francês | MEDLINE | ID: mdl-24507205

RESUMO

BACKGROUND: Recent years have seen the emergence of new molecules for the treatment of patients with metastatic cutaneous melanoma, with significant benefits in terms of survival and the opening of new therapeutic perspectives. In addition, many techniques are currently being developed for locoregional treatment of metastatic sites. Management of metastatic melanoma is thus fast-changing and is marked by innovative therapeutic approaches. However, the availability of these new treatments has prompted debate among healthcare professionals concerning their use and their place in therapeutic strategy. AIMS: Since 2008, the French National Cancer Institute (INCa) has been leading a project to define and diffuse national clinical practice guidelines. It has performed a review of these treatment methods, which it aims to circulate, and it is seeking to develop recommendations in order to allow nationwide implementation of innovative approaches while promoting good use thereof. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts within a multidisciplinary working group, with feedback from specialists in cancer care delivery. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. RESULTS: This article presents the national recommendations for first- and second-line systemic treatment and for locoregional treatment of metastatic sites in patients presenting metastatic cutaneous melanoma.


Assuntos
Melanoma/secundário , Melanoma/terapia , Neoplasias Cutâneas/secundário , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/cirurgia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Terapia Combinada , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Gerenciamento Clínico , França , Humanos , Indóis/uso terapêutico , Ipilimumab , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Melanoma/epidemiologia , Melanoma/genética , Terapia de Alvo Molecular , Estadiamento de Neoplasias , Compostos de Nitrosoureia/uso terapêutico , Oncogenes , Compostos Organofosforados/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Sulfonamidas/uso terapêutico , Temozolomida , Vemurafenib
3.
Eur Ann Otorhinolaryngol Head Neck Dis ; 137(6): 477-481, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31727477

RESUMO

INTRODUCTION: In old and frail patients, oncologic anterior skull-base surgery through an endonasal endoscopic approach avoids the morbidity incurred by transfacial and transcranial approaches, sometimes considered unreasonable, although surgery remains the gold standard treatment for sinonasal cancer. OBJECTIVES: To assess the functional and oncologic results of this surgery in over-70 year-olds. MATERIAL AND METHODS: A single-center retrospective study included all patients aged over 70 years at surgery, who underwent endonasal endoscopic oncologic resection and reconstruction of the anterior skull base, between October 2008 and October 2018. RESULTS: Fifteen procedures in 13 patients met the inclusion criteria. Mean hospital stay was 7 days. All resections were considered R0, apart from one case with positive dura-mater margins (6.7%). All patients had complete radio-surgical treatment, in accordance with the REFCOR recommendations. Two cases of meningitis were reported (13.3%). At a median follow-up of 27 months, 4 patients presented local recurrence, 1 of whom also had lung metastases. Two patients died of disease-related or treatment-related causes. CONCLUSION: This technique is a feasible treatment in patients aged over 70 years, providing good functional results, and acceptable oncologic outcome.


Assuntos
Melanoma , Cavidade Nasal , Neoplasias Nasais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Base do Crânio/cirurgia , Cirurgia Endoscópica Transanal/métodos , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Estesioneuroblastoma Olfatório/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Masculino , Melanoma/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Cuidados Pós-Operatórios/métodos , Estudos Retrospectivos
4.
Cancer Radiother ; 23(2): 147-150, 2019 Apr.
Artigo em Francês | MEDLINE | ID: mdl-30904418

RESUMO

Whereas immune checkpoint inhibitors of serine/threonine protein kinase B-raf therapy dramatically changed metastatic outcomes of patients with melanoma, they remain at high risk of brain extension. Additional local treatment can be offered in this situation such as surgery and or stereotactic radiotherapy. In this review article, we describe the different options with published data and their optimal timing.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Melanoma/secundário , Melanoma/terapia , Antineoplásicos Imunológicos/uso terapêutico , Encéfalo/patologia , Neoplasias Encefálicas/patologia , Antígeno CTLA-4/antagonistas & inibidores , Fracionamento da Dose de Radiação , Humanos , Melanoma/patologia , Mutação , Necrose/etiologia , Necrose/prevenção & controle , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Radiocirurgia , Neoplasias Cutâneas/patologia
5.
Mutat Res ; 637(1-2): 16-22, 2008 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-17681554

RESUMO

An adequate folate intake minimizes the risk of various cancers and other disorders such as vascular diseases and neural tube defects. However, meta-analyses revealed difficulties in supporting the relationship between folate intake and the risk of cancer. Interestingly, there have been no reports to date on the potential ability of folate to modulate xenobiotic metabolising enzymes (XMEs), the inhibition of bioactivating Phase-I XMEs and/or induction of detoxifying Phase-II XMEs being one of the most evoked cancer chemopreventive strategies. Here, several CYP-dependent oxidations were studied in liver sub-cellular preparations from Sprague-Dawley rats receiving rodent chow supplemented with folic acid daily, for 1 or 2 consecutive months. Using either specific substrates as probes of different CYP isoforms or the regio- and stereo-selective metabolism of testosterone as a multibiomarker, we found that folic acid markedly inactivated most of the Phase-I XME analysed; up to 54% for the CYP1A1-linked deethylation of ethoxyresorufin in males, and up to 86% for the testosterone 2alpha-hydroxylase (CYP2C11) in females, after 2 months treatment. The Phase-II marker glutathione S-transferase significantly increased (~107%) after 1 month of supplementation in females only. These changes, if reproduced in humans might have public health implications. These data suggest caution in performing folate chemoprevention trials before its overall toxicological characterization has been fully addressed.


Assuntos
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Suplementos Nutricionais , Ácido Fólico/toxicidade , Glutationa Transferase/metabolismo , Microssomos Hepáticos/metabolismo , Animais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Família 2 do Citocromo P450 , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Ratos , Ratos Sprague-Dawley , Esteroide 16-alfa-Hidroxilase , Esteroide Hidroxilases/metabolismo , Xenobióticos/metabolismo
6.
Acta Neurochir (Wien) ; 149(11): 1109-16; discussion 1116, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17712516

RESUMO

Although the majority of people worldwide are bilingual, the brain representation of language in bilingual persons is still a matter of debate. Since the beginning of the studies conducted on bilinguals, most authors denied that learning a new language requires a new semantic processing or the involvement of new cortical areas. In this paper, we review neurosurgical studies using direct electrocortical or subcortical stimulation techniques for brain mapping in bilingual subjects and compare this data with that obtained from other brain mapping methods. The authors focused on the most controversial issue whether multiple languages are represented in common or distinct cerebral areas. Seven direct brain mapping studies from different teams focused on bilingualism and multilingualism. All these studies showed that even if cerebral representation of language in multilingual patients could be grossly located in the same cortical region, it was possible to individualise distinct language-specific areas by direct cortical stimulation in the dominant frontal and temporo-parietal regions. Task- and language-specific sites were also described, demonstrating an important specialisation of some cortical areas. Using subcortical stimulation, some authors were able to find specific white matter tracts for different languages. Finally, all authors recommend in bilingual patients who need brain mapping for neurosurgical purpose to test all languages in which the subjects are fluent.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiologia , Eletroencefalografia , Multilinguismo , Dominância Cerebral/fisiologia , Estimulação Elétrica , Lobo Frontal/fisiologia , Humanos , Fibras Nervosas Mielinizadas/fisiologia , Rede Nervosa/fisiologia , Lobo Parietal/fisiologia , Lobo Temporal/fisiologia
7.
Radiat Oncol ; 12(1): 67, 2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28424082

RESUMO

BACKGROUND: We aimed to identify subventricular zone (SVZ)-related prognostic factors of survival and patterns of recurrence among patients with glioblastoma. METHODS: Forty-three patients with primary diagnosed glioblastoma treated in our Cancer Center between 2006 and 2010 were identified. All patients received surgical resection, followed by temozolomide-based chemoradiation. Ipsilateral (iSVZ), contralateral (cSVZ) and bilateral (bSVZ) SVZs were retrospectively segmented and radiation dose-volume histograms were generated. Multivariate analysis using the Cox proportional hazards model was assessed to examine the relationship between prognostic factors and time to progression (TTP) or overall survival (OS). RESULTS: Median age was 59 years (range: 25-85). Median follow-up, OS and TTP were 22.7 months (range 7.5-69.7 months), 22.7 months (95% CI 14.5-26.2 months) and 6.4 months (95% CI 4.4-9.3 months), respectively. On univariate analysis, initial contact to SVZ was a poor prognostic factor for OS (18.7 vs 41.7 months, p = 0.014) and TTP (4.6 vs 12.9 months, p = 0.002). Patients whose bSVZ volume receiving at least 20 Gy (V20Gy) was greater than 84% had a significantly improved TTP (17.7 months vs 5.2 months, p = 0.017). This radiation dose coverage was compatible with an hippocampal sparing. On multivariate analysis, initial contact to SVZ and V20 Gy to bSVZ lesser than 84% remained poor prognostic factors for TTP (HR = 3.07, p = 0.012 and HR = 2.67, p = 0.047, respectively). CONCLUSION: Our results suggest that contact to SVZ, as well as insufficient bSVZ radiation dose coverage (V20Gy <84%), might be independent poor prognostic factors for TTP. Therefore, targeting SVZ could be of crucial interest for optimizing glioblastoma treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Ventrículos Laterais/efeitos da radiação , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Terapia Combinada , Feminino , Seguimentos , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida
8.
Clin Exp Med ; 6(2): 84-8, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16820996

RESUMO

Superoxide dismutase (SOD) is reported to be the major enzymatic defence against free radicals and common oxidants. EC-SOD is the only extracellular form of SOD present at a high concentration in vascular intima. The aims of the present study were to elucidate the role of EC-SOD in patients with coronary artery disease (CAD) and evaluate its association with free radicals, inflammation and with the severity of the disease. The study included 36 consecutive subjects with CAD being treated in the Institute of Clinical Physiology (33 males, 3 females) and 19 controls (16 males, 2 females). Each subject, after cardiac catheterisation and coronariography, was evaluated for serum EC-SOD activity, peroxy radicals, high-sensitive interleukin-6 (hs-IL-6), high-sensitive tumour necrosis factor (hs-TNFa) and high-sensitive C-reactive protein (hs-CRP) serum levels. The analysis of EC-SOD serum activity did not show any particular difference between patients and controls, while the serum levels of peroxy radicals, hs-IL-6 and hs-CRP showed a significant difference between the two groups (respectively: P<0.01, P<0.001, P<0.01). Moreover, enhancement of hs-IL-6 serum levels was also observed in severe disease (involvement of 3, 4 coronary arteries; P<0.05), while EC-SOD activity showed a slight increment in association with the number of arteries involved. hs-IL-6 concentrations were statistically significantly associated with peroxy radicals and CRP levels (respectively: P<0.05, r2=0.1; P<0.05, r2=0.14). The present study suggests a low effectiveness of EC-SOD activity in prevention against CAD and further confirms hs-IL-6 as a useful marker in diagnostic prevention and in clinical characterisation of CAD.


Assuntos
Doença da Artéria Coronariana/enzimologia , Superóxido Dismutase/metabolismo , Vasculite/enzimologia , Idoso , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fator de Necrose Tumoral alfa/metabolismo
10.
Naunyn Schmiedebergs Arch Pharmacol ; 372(1): 79-87, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16080005

RESUMO

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. In clinical settings, proton pump inhibitors have proven to be effective in preventing and healing NSAID-induced gastroduodenal lesions. The present study investigates the mechanisms of protection afforded by pantoprazole against gastric injury induced by different NSAIDs in rats. Animals were orally treated with indomethacin (100 micromol/kg), diclofenac (60 micromol/kg), piroxicam (150 micromol/kg) or ketoprofen (150 micromol/kg). Thirty minutes before NSAIDs, animals received pantoprazole 6 or 60 micromol/kg orally. Four hours after NSAIDs, the following parameters were assessed: histomorphometric evaluation of gastric mucosal damage; gastric mucosal levels of myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione as an index of non-proteic sulfhydryl compounds (GSH), and prostaglandin E2 (PGE2); mucosal cyclooxygenase-1 and -2 (COX-1, COX-2) mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). Separate experiments were carried out to assay the effects of pantoprazole on gastric acid secretion in pylorus-ligated rats. The in vitro influence of pantoprazole (1-10 microM) on the oxidation of low density lipoproteins (LDLs) induced by copper sulphate was also examined. All NSAIDs elicited mucosal necrotic lesions associated with neutrophil infiltration and reduction of PGE2 levels. Increments of MPO and MDA contents, as well as a decrease in GSH levels, were detected in the gastric mucosa of indomethacin-, piroxicam- or ketoprofen-treated animals. Indomethacin enhanced mucosal COX-2 expression, while not affecting COX-1. At the oral dose of 6 micromol/kg pantoprazole did not affect NSAID-induced mucosal damage, whereas at 60 micromol/kg it markedly reduced injuries provoked by all test NSAIDs. Pantoprazole 60 micromol/kg also reversed the effects of NSAIDs on MPO, MDA, and GSH mucosal contents, without interfering with the decrease in PGE2 levels or indomethacin-induced COX-2 expression. However, at both doses, pantoprazole inhibited acid secretion in pylorus-ligated rats. Furthermore, pantoprazole concentration dependently reduced the in vitro oxidation of LDLs. Our results suggest that besides inhibiting acid secretion, the protection afforded by pantoprazole against NSAID-induced gastric damage depends on a reduction in mucosal oxidative injury, which may also account for an increment of sulfhydryl radical mucosal bioavailability. It is also suggested that pantoprazole does not influence the down-regulation of gastric prostaglandin production associated with NSAID treatment.


Assuntos
Antiulcerosos/farmacologia , Benzimidazóis/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Omeprazol/análogos & derivados , Inibidores da Bomba de Prótons , Sulfóxidos/farmacologia , 2-Piridinilmetilsulfinilbenzimidazóis , Animais , Anti-Inflamatórios não Esteroides , Diclofenaco , Relação Dose-Resposta a Droga , Ácido Gástrico/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Glutationa/metabolismo , Indometacina , Ligadura , Lipoproteínas LDL/química , Lipoproteínas LDL/metabolismo , Masculino , Malondialdeído/metabolismo , Omeprazol/farmacologia , Oxirredução , Pantoprazol , Peroxidase/metabolismo , Piroxicam , Piloro/cirurgia , Ratos , Ratos Wistar
12.
Neurochirurgie ; 61(6): 371-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24647149

RESUMO

OBJECTIVES: Giant intracranial aneurysms represent a major therapeutic challenge for each surgical team. The aim of our study was to extensively review the French contemporary experience in treating giant intracranial aneurysms in order to assess the current management. PATIENTS AND METHODS: This retrospective multicenter study concerned consecutive patients treated for giant intracranial aneurysms (2004-2008) in different French university hospitals (Bordeaux, Caen, Clermont-Ferrand, Lille, Lyon, Nice, Paris-Lariboisière, Rouen et Toulouse). Different variables were analyzed: the diagnostic circumstances, the initial clinical status based on the WFNS scale, aneurysmal features and exclusion procedure. At 6 months, the outcome was evaluated according to the modified Rankin Scale (mRS): favorable (mRS 0-2) and unfavorable (mRS 3-6). A multivariate logistic regression model included all the independent variables with P<0.25 in the univariate analysis (P<0.05). RESULTS: A total of 79 patients with a mean age of 51.5 ± 1.6 years (median: 52 years; range: 16-79) were divided into two groups, with the ruptured group (n=26, 32.9%) significantly younger (P<0.05, Student's-t-test) than the unruptured group (n=53, 67.1%). After SAH, the initial clinical status was good in 12 patients (46.2%), and in the unruptured group, the predominant diagnosis circumstance was a pseudo-tumor syndrome occurring in 22 (41.5%). The first procedure of aneurysm treatment in the global population was endovascular in 42 patients (53.1%), microsurgical in 29 (36.7%) and conservative in 8 (10.2). An immediate neurological deterioration was reported in 38 patients (48.1%) after endovascular treatment in 19 (45.2% of endovascular procedures), after miscrosurgical in 15 (51.7% of microsurgical procedures) and after conservative in 4 (the half). At 6 months, the outcome was favorable in 45 patients (57%) and after multivariate analysis, the predictive factors of favorable outcome after management of giant cerebral aneurysm were the initial good clinical status in cases of SAH (P<0.002), the endovascular treatment (P<0.005), and the absence of neurological deterioration (P<0.006). The endovascular procedure was obtained as a predictive factor because of the low risk efficacy of indirect procedures, in particular a parent vessel occlusion. CONCLUSION: The overall favorable outcome rate concerned 57% of patients at 6 months despite 53.8% of poor initial clinical status in cases of rupture. The predictive factors for favorable outcome were good clinical status, endovascular treatment and the absence of postoperative neurological deterioration. Endovascular treatment should be integrated into the therapeutic armenmatarium against giant cerebral aneurysms but the durability of exclusion should be taken into account during the multidisciplinary discussion by the neurovascular team.


Assuntos
Aneurisma Intracraniano/cirurgia , Adolescente , Adulto , Idoso , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Environ Mol Mutagen ; 31(3): 218-27, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9585260

RESUMO

The influence of several methodological factors on mean values of sister chromatid exchanges (SCEs) and micronuclei (MN) in peripheral lymphocytes of 1,650 subjects was analyzed. Donors belonged to a general healthy population living in Pisa and in two nearby small cities: Cascina and Navacchio (Ca-Na). Blood samples were collected over a period of 29 months and processed in three different laboratories of the some institute. Slides were analyzed by several scorers. Our data showed that lymphocyte proliferation indexes (PIs) and baseline mean values of SCEs were affected mainly by sampling period. This factor accounted for a percentage ranging from roughly 10% (Pisa) to 20% (Ca-Na) of total SCE variance and from roughly 10% (Pisa) to 13% (Ca-Na) of total PIs variance. A marginal effect was attributable to the different laboratories involved (maximum 3% for SCEs and 7% for PIs). The sampling period variable included many sources of variability such as culture media batches, fetal calf serum, PHA, BrdUrd, and seasonality. MN counts revealed a more marked dependence on processing laboratories. This factor accounted for a percentage of roughly 10% (Pisa and Ca-Na) of total variance, while the sampling period was marginally effective (about 1-4% of total variability). Because laboratories were equipped and supplied with the same materials and consumables and technicians were rotated constantly, the only variable ascertained was represented by the three different models of CO2 incubators used for lymphocyte culturing. When "month" and "incubator" variables were considered jointly, experimental variability accounted for 15-20% of total variance, both for PIs and mean values SCEs and MN. The variability due to slide scoring was reduced by assigning each slide to five different scorers and matching low with high scorers in each group. Present data show that when the study is performed under these controlled conditions, about 20% of total interdonor variability can be explained by experimental or seasonal factors.


Assuntos
Linfócitos/ultraestrutura , Testes para Micronúcleos , Troca de Cromátide Irmã , Adolescente , Adulto , Idoso , Doadores de Sangue , Preservação de Sangue , Divisão Celular , Células Cultivadas , Criança , Meios de Cultura , Citogenética/métodos , Feminino , Variação Genética , Humanos , Itália , Estilo de Vida , Masculino , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Valores de Referência , Estações do Ano , Fumar , Fatores Socioeconômicos , Manejo de Espécimes , Inquéritos e Questionários
14.
J Am Soc Echocardiogr ; 11(2): 169-80, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9517556

RESUMO

The purpose of this study was to detect myocardial perfusion defects as a result of coronary occlusion and myocardial reperfusion after thrombolysis with intravenous (i.v.) administration of the echo contrast agent BR1 (Bracco Research, Switzerland), which consists of microbubbles (median diameter 2.5 microm) containing sulfur exafluoride in a phospholipidic shell. To generate a coronary thrombosis, a copper coil was advanced into the left circumflex coronary artery in eight anesthetized dogs with opened chest cavities. Coronary occlusion occurred 18 +/- 10 minutes after the insertion of the coil and was documented both by an electromagnetic flow meter (as zero blood flow) and by radiolabeled microspheres (as myocardial perfusion defect). After 2 hours of occlusion, streptokinase was infused i.v.; reperfusion was documented by both the flow-meter and microspheres. Left ventricular cavity enhancement was apparent after all contrast injections. Peak cavity intensity did not increase with dose and was not affected by signal processing (suggesting signal saturation), whereas the duration of contrast effect significantly increased with the dose (from 26 +/- 16 to 147 +/- 74 seconds). Myocardial contrast intensity also increased after contrast (from 15 +/- 12 to 21 +/- 18 gray level/pixel, p < 0.001). Contrast echo detected myocardial perfusion defects (corresponding to 17% +/- 11% of LV cross-sectional area) in all the injections performed during coronary occlusion and detected myocardial reperfusion with a sensitivity of 50% versus microspheres. The extent of perfusion defects by contrast echo showed a good correlation with microspheres (r = 0.73). Myocardial reperfusion was not detected by changes in heart rate, aortic pressure, pulmonary arterial pressure, cardiac output, left ventricular fractional area change, or wall-motion score index. Hemodynamic parameters were not affected by contrast injections. Thus, the i.v. administration of BR1 allows us to accurately detect myocardial perfusion defects during coronary occlusion and, to a lesser extent, myocardial reperfusion after thrombolysis.


Assuntos
Meios de Contraste/administração & dosagem , Ecocardiografia , Reperfusão Miocárdica , Hexafluoreto de Enxofre , Terapia Trombolítica , Animais , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/tratamento farmacológico , Cães , Feminino , Hemodinâmica/efeitos dos fármacos , Masculino , Hexafluoreto de Enxofre/administração & dosagem , Hexafluoreto de Enxofre/farmacologia
15.
Free Radic Res ; 48(8): 841-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24886290

RESUMO

Lectin-like oxidized low-density lipoprotein (LOX-1) has been identified in endothelial cells as the main receptor of oxidized low-density lipoprotein (OxLDL). LOX-1 is upregulated in the presence of pathological conditions including atherosclerosis, hypertension, and diabetes because it acts as a mediator of "endothelial dysfunction". It promotes the generation of superoxide anion (O2(-)), the inhibition of nitric oxide (NO) production and the increment of endothelial adhesiveness to monocytes. Recently, it was reported that OxLDL, binding to LOX-1, determined a significant increase in the generation of reactive oxygen species (ROS), suggesting the involvement of signaling pathways such as mitogen-activated protein kinases (MAPKs). It is now generally accepted that ROS act indirectly on the modulation of LOX-1 expression because ROS oxidize native LDL. Moreover, LOX-1 activation per se may stimulate ROS generation. Accordingly, our findings showed that high levels of ROS can directly increase LOX-1 production in microvascular endothelial cells (HMEC-1). It has been reported that OxLDL, usually > 20 µg protein/ml, induced apoptosis in a variety of cell types. At low concentrations (< 5 µg protein/ml) OxLDL appears to be associated with cell proliferation and low levels of ROS-induced capillary tube formation in endothelial cells. Our data and those of the literature indicate the existence of a direct control of LOX-1 by ROS. Although ROS in large amounts clearly have detrimental effects on cell biology, small amounts of ROS could have a beneficial effect, suggesting its therapeutic potential for reducing ischemic tissue.


Assuntos
Lipoproteínas LDL/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores Depuradores Classe E/metabolismo , Animais , Células Endoteliais/metabolismo , Radicais Livres/metabolismo , Humanos , Estresse Oxidativo/fisiologia , Transdução de Sinais/efeitos dos fármacos
16.
Cell Death Dis ; 5: e1543, 2014 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-25429620

RESUMO

Glioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover, recent studies showed that differentiated tumor cells may have the ability to dedifferentiate and acquire a stem-like phenotype, a phenomenon also called plasticity, in response to microenvironment stresses such as hypoxia. We hypothesized that GBM cells could be subjected to a similar dedifferentiation process after ionizing radiations (IRs), then supporting the GBM rapid recurrence after radiotherapy. In the present study we demonstrated that subtoxic IR exposure of differentiated GBM cells isolated from patient resections potentiated the long-term reacquisition of stem-associated properties such as the ability to generate primary and secondary neurospheres, the expression of stemness markers and an increased tumorigenicity. We also identified during this process an upregulation of the anti-apoptotic protein survivin and we showed that its specific downregulation led to the blockade of the IR-induced plasticity. Altogether, these results demonstrated that irradiation could regulate GBM cell dedifferentiation via a survivin-dependent pathway. Targeting the mechanisms associated with IR-induced plasticity will likely contribute to the development of some innovating pharmacological strategies for an improved radiosensitization of these aggressive brain cancers.


Assuntos
Desdiferenciação Celular/efeitos da radiação , Glioblastoma/metabolismo , Glioblastoma/patologia , Proteínas Inibidoras de Apoptose/metabolismo , Células-Tronco Neoplásicas/patologia , Tolerância a Radiação/efeitos da radiação , Radiação Ionizante , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Regulação para Baixo/efeitos da radiação , Humanos , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Fenótipo , Survivina
17.
Neurochirurgie ; 60(6): 269-75, 2014 Dec.
Artigo em Francês | MEDLINE | ID: mdl-25241016

RESUMO

INTRODUCTION: The management of metastatic cutaneous melanoma is changing, marked by innovative therapies. However, their respective use and place in the therapeutic strategy continue to be debated by healthcare professionals. OBJECTIVE: The French national cancer institute has led a national clinical practice guideline project since 2008. It has carried out a review of these modalities of treatment and established recommendations. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. RESULTS: This article presents the results of bibliographic search, the conclusions of the literature and the recommendations concerning locoregional treatments of brain metastases for patients with metastatic cutaneous melanoma.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Melanoma/secundário , Humanos , Neoplasias Cutâneas , Melanoma Maligno Cutâneo
18.
Neurochirurgie ; 59(4-5): 142-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23953035

RESUMO

The operating room (OR) is a high-risk complex setting, where patient safety relies on the coordinated efforts of multiple team members. However, little attention has been paid to evaluating the strategies employed by OR practitioners to prevent and correct incidents that inevitably occur during surgery. Therefore, we were prompted to investigate human factor (HF) engineering methods that have been used in an innovative way in order to systematically observe and analyze the management of incidents in the neurosurgical OR of a French university hospital. A technical case report illustrates our approach that associates the following procedures: the recording of OR team member activities and behaviour by video cameras and direct observation of a HF researcher, with the description and the explicit demonstration of safety related procedures in self- and cross-confrontation interviews of OR team members. This technical report emphasizes complementary aspects of clinical performance related to safety skills. Moreover, individual and team performances rely on complementary abilities that associate practical knowledge, skills, and attitudes, which are engaged at various degrees to prevent and manage incidents. This report also enlightens new quality-improvement opportunities as well as further objectives for future studies.


Assuntos
Neoplasias Encefálicas/cirurgia , Salas Cirúrgicas , Gravação em Vídeo , Idoso , Feminino , Hospitais Universitários , Humanos , Equipe de Assistência ao Paciente , Estudos Prospectivos , Gravação em Vídeo/métodos
19.
Neurochirurgie ; 58(4): 230-4, 2012 Aug.
Artigo em Francês | MEDLINE | ID: mdl-22626817

RESUMO

BACKGROUND AND PURPOSE: Seizures can occur in patients who have surgery for a chronic subdural hematoma. However, the incidence of seizures and their impact on the clinical course of patients in the perioperative period is not well known. METHODS: In this retrospective study, we reviewed 161 cases of patients treated for chronic subdural hematoma in our institution. The surgical procedures consisted in trephine craniotomy in 156 cases, burr-hole craniotomy in three cases, and bone flap craniotomy in two cases. All the patients had systematic antiepileptic drug prophylaxis. RESULTS: In our patients' population, the incidence of seizures was 10.6% before surgery and 14.9% after surgery. Low initial score on the Glasgow Coma Scale (P<0.001) and preoperative cognitive impairment (P=0.005) were associated with a higher rate of postoperative seizures. In our study, the mortality rate was 14.9%. Low initial score on the Glasgow Coma Scale (P=0.068) and postoperative seizures (P=0.002) were associated with a higher mortality rate. CONCLUSIONS: We have shown that patients suffering from seizures may have worse outcome. The benefit of a systematic perioperative prophylaxis using antiepileptic drugs has to be evaluated.


Assuntos
Hematoma Subdural Crônico/cirurgia , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Convulsões/epidemiologia , Convulsões/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Craniotomia , Feminino , Escala de Coma de Glasgow , Hematoma Subdural Crônico/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Radiografia , Recidiva , Estudos Retrospectivos , Convulsões/mortalidade
20.
Food Chem Toxicol ; 49(1): 233-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20971153

RESUMO

The protective effect of a powder of grain (Lisosan G) against cisplatin-induced toxicity in rats was studied. Male rats were fed with Lisosan G before injection of cisplatin and four days later they were killed and blood was collected along with hepatic, renal and testicular tissues. The results showed that cisplatin treatment increased plasma blood urea nitrogen, creatinine and hydrogen peroxide and decreased cytochrome P450 content in renal and hepatic tissues. It also reduced the plasmatic testosterone level and caused a depletion of testicular 17α-progesterone hydroxylase activity. In the group fed with Lisosan G and treated with cisplatin blood urea nitrogen and creatinine returned to the control level indicating a protective effect of Lisosan G. It was also observed that the ones fed with Lisosan G were able to attenuate the decrease in the P450-dependent activities and the activities of antioxidant enzymes as well. Lisosan G protected the testicular 17α-progesterone hydroxylase activity and increased the plasma testosterone level compared to animals treated only with cisplatin. Our results showed a protective effect of Lisosan G against the cisplatin induced toxicity. The protective effect of Lisosan G could be associated mainly with the attenuation of the oxidative stress and the preservation in antioxidant enzymes.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Extratos Vegetais/farmacologia , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Peróxido de Hidrogênio/metabolismo , Rim/efeitos dos fármacos , Rim/enzimologia , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Preparações de Plantas , Ratos , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA