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1.
J Clin Neurophysiol ; 26(4): 218-26, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19602985

ABSTRACT

This paper describes the design and test results of a three-stage automated system for neonatal EEG seizure detection. Stage I of the system is the initial detection stage and identifies overlapping 5-second segments of suspected seizure activity in each EEG channel. In stage II, the detected segments from stage I are spatiotemporally clustered to produce multichannel candidate seizures. In stage III, the candidate seizures are processed further using measures of quality and context-based rules to eliminate false candidates. False candidates because of artifacts and commonly occurring EEG background patterns such as bifrontal delta activity are also rejected. Seizures at least 10 seconds in duration are considered for reporting results. The testing data consisted of recordings of 28 seizure subjects (34 hours of data) and 48 nonseizure subjects (87 hours of data) obtained in the neonatal intensive care unit. The data were not edited to remove artifacts and were identical in every way to data normally processed visually. The system was able to detect seizures of widely varying morphology with an average detection sensitivity of almost 80% and a subject sensitivity of 96%, in comparison with a team of clinical neurophysiologists who had scored the same recordings. The average false detection rate obtained in nonseizure subjects was 0.74 per hour.


Subject(s)
Electroencephalography/methods , Epilepsy/diagnosis , Signal Processing, Computer-Assisted , Algorithms , Artifacts , Epilepsy/complications , Humans , Infant, Newborn , Sensitivity and Specificity
2.
Mol Cancer Ther ; 8(4): 947-58, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19372568

ABSTRACT

Hypoxia inducible factor-1 (HIF-1) promotes tumor cell adaptation to microenvironmental stress. HIF-1 is up-regulated in irradiated tumors and serves as a promising target for radiosensitization. We initially confirmed that the orally bioavailable HIF-1 inhibitor PX-478 reduces HIF-1 protein levels and signaling in vitro in a dose-dependent manner and provides direct radiosensitization of hypoxic cancer cells in clonogenic survival assays using C6 glioma, HN5 and UMSCCa10 squamous cells, and Panc-1 pancreatic adenocarcinoma cell lines. However, PX-478 yields striking in vivo tumor sensitization to single-dose irradiation, which cannot be explained by incremental improvement in direct tumor cell killing. We show that PX-478 prevents postradiation HIF-1 signaling and abrogates downstream stromal adaptation in C6 and HN5 reporter xenografts as measured by serial ultrasound, vascular magnetic resonance imaging, and hypoxia response element-specific micro-positron emission tomography imaging. The primacy of indirect PX-478 in vivo effects was corroborated by our findings that (a) either concurrent or early postradiation sequencing of PX-478 provides roughly equivalent sensitization and (b) constitutive vascular endothelial growth factor expression maintains refractory tumor vessel function and progression following combined radiation and PX-478. These results confirm that disruption of postradiation adaptive HIF-1 signaling by PX-478 imparts increased therapeutic efficacy through blockade of HIF-1-dependent reconstitution of tumor stromal function. Successful translation of targeted HIF-1 radiosensitization to the clinical setting will require specific consideration of tumor microenvironmental effects and mechanisms.


Subject(s)
Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Mustard Compounds/pharmacology , Phenylpropionates/pharmacology , Stromal Cells/radiation effects , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Animals , Blotting, Western , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Cell Hypoxia/radiation effects , Enzyme-Linked Immunosorbent Assay , Glioma/metabolism , Glioma/pathology , Glioma/radiotherapy , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Immunoenzyme Techniques , Magnetic Resonance Imaging , Mice , Mice, Nude , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/radiotherapy , Positron-Emission Tomography , Tumor Cells, Cultured , Tumor Stem Cell Assay , Vascular Endothelial Growth Factor A/metabolism , Whole-Body Irradiation
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