Showing 78177–78190 of 78,293 results for "PensoAssathiany Dominique"

Journals 2009 EN

A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematological malignancies

Michel Moreau · J. Klastersky · Alexandre Vargas Schwarzbold +12 more

Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia (FN). The objective of this study is to validate a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle.

Elsevier BV
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Journals 2009 EN

2008 SOR guidelines for the prevention and treatment of thrombosis associated with central venous catheters in patients with cancer: report from the working group

P. Debourdeau · D. Kassab Chahmi · Grégoire Le Gal +11 more

In view of the lack of recommendations on central venous catheter (CVC)-associated thrombosis in cancer patients, we established guidelines according to the well-standardized Standards, Options and Recommendations methodology.

Elsevier BV
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Journals 2009 EN

Pilocytic astrocytoma of the optic pathway: a tumour deriving from radial glia cells with a specific gene signature

Aurélie Tchoghandjian · C. Fernandez · Carole Colin +9 more

Pilocytic astrocytomas are WHO grade I gliomas that occur predominantly in childhood. They share features of both astroglial and oligodendroglial lineages. These tumours affect preferentially the cerebellum (benign clinical course) and the optic pathway, especially the hypothalamo-chiasmatic region (poor prognosis). Understanding the molecular basis responsible for the aggressive behaviour of hypothalamo-chiasmatic pilocytic astrocytomas is a prerequisite to setting up new molecular targeted therapies. We used the microarray technique to compare the transcriptional profiles of five hypothalamo-chiasmatic and six cerebellar pilocytic astrocytomas. Validation of the microarray results and comparison of the tumours with normal developing tissue was done by quantitative real-time PCR and immunohistochemistry. Results demonstrate that cerebellar and hypothalamo-chiasmatic pilocytic astrocytomas are two genetically distinct and topography-dependent entities. Numerous genes upregulated in hypothalamo-chiasmatic pilocytic astrocytomas also increased in the developing chiasm, suggesting that developmental genes mirror the cell of origin whereas migrative, adhesive and proliferative genes reflect infiltrative properties of these tumours. Of particular interest, NOTCH2, a gene expressed in radial glia and involved in gliomagenesis, was upregulated in hypothalamo-chiasmatic pilocytic astrocytomas. In order to find progenitor cells that could give rise to hypothalamo-chiasmatic pilocytic astrocytomas, we performed a morphological study of the hypothalamo-chiasmatic region and identified, in the floor of the third ventricle, a unique population of vimentin- and glial fibrillary acidic protein-positive cells highly suggestive of radial glia cells. Therefore, pilocytic astrocytomas of the hypothalamo-chiasmatic region should be considered as a distinct entity which probably originates from a unique population of cells with radial glia phenotype.

Oxford University Press
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Journals 2009 EN

CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5

Cyril Goizet · A. Boukhris · A. Dürr +23 more

Thirty-four different loci for hereditary spastic paraplegias have been mapped, and 16 responsible genes have been identified. Autosomal recessive forms of spastic paraplegias usually have clinically complex phenotypes but the SPG5, SPG24 and SPG28 loci are considered to be associated with 'pure' forms of the disease. Very recently, five mutations in the CYP7B1 gene, encoding a cytochrome P450 oxysterol 7-alpha hydroxylase and expressed in brain and liver, have been found in SPG5 families. We analysed the coding region and exon-intron boundaries of the CYP7B1 gene by direct sequencing in a series of 82 unrelated autosomal recessive hereditary spastic paraplegia index patients, manifesting either a pure (n = 52) or a complex form (n = 30) of the disease, and in 90 unrelated index patients with sporadic pure hereditary spastic paraplegia. We identified eight, including six novel, mutations in CYP7B1 segregating in nine families. Three of these mutations were nonsense (p.R63X, p.R112X, p.Y275X) and five were missense mutations (p.T297A, p.R417H, p.R417C, p.F470I, p.R486C), the last four clustering in exon 6 at the C-terminal end of the protein. Residue R417 appeared as a mutational hot-spot. The mean age at onset in 16 patients was 16.4 +/- 12.1 years (range 4-47 years). After a mean disease duration of 28.3 +/- 13.4 years (10-58), spasticity and functional handicap were moderate to severe in all cases. Interestingly, hereditary spastic paraplegia was pure in seven SPG5 families but complex in two. In addition, white matter hyperintensities were observed on brain magnetic resonance imaging in three patients issued from two of the seven pure families. Lastly, the index case of one family had a chronic autoimmune hepatitis while his eldest brother died from cirrhosis and liver failure. Whether this association is fortuitous remains unsolved, however. The frequency of CYP7B1 mutations were 7.3% (n = 6/82) in our series of autosomal recessive hereditary spastic paraplegia families and 3.3% (n = 3/90) in our series of sporadic pure spastic paraplegia. The recent identification of CYP7B1 as the gene responsible for SPG5 highlights a novel molecular mechanism involved in hereditary spastic paraplegia determinism.

Oxford University Press
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Journals 2009 EN

Local and remote epileptogenicity in focal cortical dysplasias and neurodevelopmental tumours

Sandrine Aubert · Fabrice Wendling · Jean Régis +6 more

During the pre-surgical evaluation of drug-resistant epilepsy, the assessment of the extent of the epileptogenic zone and its organization is a crucial objective. Indeed, the epileptogenic zone may be organized as a simple focal lesional site or as a more complex network (often referred to as the 'epileptogenic network') extending beyond the lesion. This distinction is particularly relevant in developmental lesions such as focal cortical dysplasias or dysembryoplastic neuroepithelial tumours and may determine both the surgical strategy and the prognosis. In this study, we have quantified the epileptogenic characteristic of brain structures explored by depth electrodes in 36 patients investigated by stereoelectroencephalography and suffering from focal drug-resistant epilepsy associated with focal cortical dysplasias or dysembryoplastic neuroepithelial tumours. This quantification was performed using the 'Epileptogenicity Index' method that accounts for both the propensity of a brain area to generate rapid discharges and the time for this area to get involved in the seizure. Epileptogenicity Index values range from 0 (no epileptogenicity) to 1 (maximal epileptogenicity). We determined Epileptogenicity Index from signals recorded in distinct brain structures including the lesional site. We studied the type of epileptogenic zone organization (focal versus network) and looked for a correlation with clinical data and post-surgical outcome. Mean Epileptogenicity Index in lesional regions was 0.87 (+/-0.25), and 0.29 (+/-0.30) in 'non-lesional' structures. The number of highly epileptogenic structures (defined by Epileptogenicity Index value >or=0.4) was 3.14 (+/-1.87) in the whole population. We found that 31% of patients had only one epileptogenic structure (N(EI>or=0.4) = 1), therefore disclosing a strictly focal epileptogenic zone organization while 25 patients had more than one epileptogenic region, disclosing a network (61%) or bilateral (8%) epileptogenic zone organization. We observed a trend for a difference in seizure outcome according to the type of epileptogenic zone organization. Indeed, 57% of patients with network organization and 87% with focal organization were seizure-free while none of those with bilateral organization became seizure-free. The determination of Epileptogenicity Index computed from electrophysiological signals recorded according to the stereoelectroencephalography technique is a novel tool. Results suggest that it can help in the delineation of the epileptogenic zone associated with brain lesions and that it could be used in the definition of the subsequent surgical resection.

Oxford University Press
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Journals 2009 EN

Mapping interictal oscillations greater than 200 Hz recorded with intracranial macroelectrodes in human epilepsy

Benoît Crépon · Vincent Navarro · Dominique Hasboun +5 more

Interictal high-frequency oscillations over 200 Hz have been recorded with microelectrodes in the seizure onset zone of epileptic patients suffering from mesial temporal lobe epilepsy. Recent work suggests that similar high-frequency oscillations can be detected in the seizure onset zone using standard diagnostic macroelectrodes. However, only a few channels were examined in these studies, so little information is available on the spatial extent of high-frequency oscillations. Here, we present data on high-frequency oscillations recorded from a larger number of intracerebral contacts spatial (mean 38) in 16 patients. Data were obtained from 1 h of interictal recording sampled at 1024 Hz and was analysed using a new semi-automatic detection procedure based on a wavelet decomposition. A detailed frequency analysis permitted a rapid and reliable discrimination of high-frequency oscillations from other high-frequency events. A total of 1932 high-frequency oscillations were detected with an average frequency of 261 +/- 53 Hz, amplitude of 11.9 +/- 6.7 microV and duration of 22.7 +/- 11.6 ms. Records from a patient often showed several different high-frequency oscillation patterns. We classified 24 patterns from 11 patients. Usually (20/24 patterns) high-frequency oscillations were nested in an epileptic paroxysm, such as a spike or a sharp wave, and typically high-frequency oscillations (19/24) were recorded from just one recording contact. Unexpectedly in other cases, high-frequency oscillations (5/24) were detected simultaneously on two or three contacts, sometimes separated by large distances. This large spatial extent suggests that high-frequency oscillations may sometimes result from a neuronal synchrony manifest on a scale of centimetres. High-frequency oscillations were almost always recorded in seizure-generating structures of patients suffering from mesial (9/9) or polar (1/3) temporal lobe epilepsy. They were never found in the epileptic or healthy basal, lateral temporal or extra temporal neocortex nor in the healthy amygdalo-hippocampal complex. These findings confirm that the generation of oscillations at frequencies higher that 200 Hz is, at this scale, a specific, intrinsic property of seizure-generating networks in medial and polar temporal lobes, which have a common archaic phylogenetic origin. We show that this activity can be detected and its spatial extent determined with conventional intracranial electroencephalography electrodes in records from patients with temporal lobe epilepsy. It is a reliable marker of the seizure onset zone that should be considered in decisions on surgical treatment.

Oxford University Press
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Journals 2009 EN

c-Met activation in medulloblastoma induces tissue factor expression and activity: effects on cell migration

Provençal Mathieu · Labbé David · Veitch Ryan +6 more

Met, the receptor for hepatocyte growth factor (HGF), is a receptor tyrosine kinase that has recently emerged as an important contributor to human neoplasia. In physiological and pathological conditions, Met triggers various cellular functions related to cell proliferation, cell migration and the inhibition of apoptosis, and also regulates a genetic program leading to coagulation. Since medulloblastomas (MBs) express high levels of tissue factor (TF), the main initiator of blood coagulation, we therefore examined the link between Met and TF expression in these pediatric tumors. We observed that stimulation of the MB cell line DAOY with HGF led to a marked increase of TF expression and procoagulant activity, in agreement with analysis of clinical MB tumor specimens, in which tumors expressing high levels of Met also showed high levels of TF. The HGF-dependent increase in TF expression and activity required Src family kinases and led to the translocation of TF to actin-rich structures at the cell periphery, suggesting a role of the protein in cell migration. Accordingly, addition of physiological concentrations of the TF activator factor VIIa (FVII) to HGF-stimulated DAOY cells promoted a marked increase in the migratory potential of these cells. Overall, these results suggest that HGF-induced activation of the Met receptor results in TF expression by MB cells and that this event probably contribute to tumor proliferation by enabling the formation of a provisional fibrin matrix. In addition, TF-mediated non-hemostatic functions, such as migration toward FVIIa, may also play a central role in MB aggressiveness.

Oxford University Press
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