David Guez - Academia.edu (original) (raw)

Papers by David Guez

The American Journal of Cardiology, 1996

Left ventricular hyperuophy is a major risk factor for cardi-lar morbidity and mortality. Angiote... more Left ventricular hyperuophy is a major risk factor for cardi-lar morbidity and mortality. Angiotensinconverting enxyme inhibitors, calcium antagonists, and b-blockers prevent, and cause regression of, left ventricubr hype&o&y after short-term therapy. The abilii of diuretics to do the same is unclear. We have performed a meta-analysis of studies documenting the effect on left ventricular mass of 6 months' treatment with 2.5 mg indapamide daify. Six studies comprising 197 patients, aged 20-75 years, were included. There was an overall mean reduction in left ventricular mass index of 13.3?, which was principally due to a reduction in left ventricular wall thickness rather than internal diameter.

Teknologi Kejuruan, 2009

Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut ... more Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut harus disesuaikan dengan kemampuan tubuh saluran untuk menahan gerusan. Tujuan penelitian ini adalah untuk menentukan model matematika superelevasi di sisi karamba dengan ...

Teknologi Kejuruan, 2009

Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut ... more Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut harus disesuaikan dengan kemampuan tubuh saluran untuk menahan gerusan. Tujuan penelitian ini adalah untuk menentukan model matematika superelevasi di sisi karamba dengan ...

Behavioural processes, 2014

Behavioural innovations have become central to our thinking about how animals adjust to changing ... more Behavioural innovations have become central to our thinking about how animals adjust to changing environments. It is now well established that animals vary in their ability to innovate, but understanding why remains a challenge. This is because innovations are rare, so studying innovation requires alternative experimental assays that create opportunities for animals to express their ability to invent new behaviours, or use pre-existing ones in new contexts. Problem solving of extractive foraging tasks has been put forward as a suitable experimental assay. We review the rapidly expanding literature on problem solving of extractive foraging tasks in order to better understand to what extent the processes underpinning problem solving, and the factors influencing problem solving, are in line with those predicted, and found, to underpin and influence innovation in the wild. Our aim is to determine whether problem solving can be used as an experimental proxy of innovation. We find that in...

Journal of Cerebral Blood Flow & Metabolism, 2015

Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme ... more Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme patients, in part due to poor penetration of most drugs across the blood-brain barrier (BBB). We propose a minimal-invasive combined treatment approach consisting of local BBB disruption in the tumor in parallel to systemic drug administration. Local BBB disruption is obtained by convection-enhanced delivery of a novel BBB disruption agent, enabling efficient/targeted delivery of the systemically administered drug by the tumors own vasculature. Various human serum albumin (HSA) analogs were synthesized and screened for BBB disruption efficacy in custom in vitro systems. The candidate analogs were then delivered into naïve rat brains by convection-enhanced delivery and screened for maximal BBB disruption and minimal brain toxicity. These studies found a noncationized/neutralized analog, ethylamine (EA)-HSA, to be the optimal BBB-opening agent. Immunocytochemical studies suggested that BBB disruption by EA-HSA may be explained by alterations in occludin expression. Finally, an efficacy study in rats bearing intracranial gliomas was performed. The rats were treated by convection-enhanced delivery of EA-HSA in parallel to systemic administration of Methotrexate, showing significant antineoplastic effects of the combined approached reflected in suppressed tumor growth and significantly (~x3) prolonged survival.Journal of Cerebral Blood Flow & Metabolism advance online publication, 11 February 2015; doi:10.1038/jcbfm.2015.6.

Molecular and cellular biochemistry, 1998

The aim of these experiments was to investigate the radical scavenging properties of three diuret... more The aim of these experiments was to investigate the radical scavenging properties of three diuretics: indapamide (IND) and its major metabolite, 5-OH indapamide (5-OH IND), compared to a reference diuretic, hydrochlorothiazide (HTZ). Electron Paramagnetic Resonance (EPR) was used to determine the scavenging abilities of these compounds on enzymatically produced superoxide radical anion, with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) used as a spin-trap. These experiments revealed that IND and specially 5-OH IND were effective superoxide radical anion scavengers at 0.2 mg/ml. In the second part of these studies, allophycocyanin was used as an indicator of free radical mediated protein damage. In the assay, 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) was used as a peroxyl radical generator, Trolox (a water-soluble analogue of vitamin E) as a control standard, and the loss of allophycocyanin fluorescence was monitored. The antioxidant effects of the diuretics were expressed in...

Neuro-Oncology, 2014

Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing... more Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients. One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist. Histological validation confirmed that regions of contrast agent clearance in the TRAMs >1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P < .0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated. The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan >1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

PLoS ONE, 2012

Electroporation, is known to induce cell membrane permeabilization in the reversible (RE) mode an... more Electroporation, is known to induce cell membrane permeabilization in the reversible (RE) mode and cell death in the irreversible (IRE) mode. Using an experimental system designed to produce a continuum of IRE followed by RE around a single electrode we used MRI to study the effects of electroporation on the brain. Fifty-four rats were injected with Gd-DOTA and treated with a G25 electrode implanted 5.5 mm deep into the striata. MRI was acquired immediately after treatment, 10 min, 20 min, 30 min, and up to three weeks following the treatment using: T1W, T2W, Gradient echo (GE), serial SPGR (DCE-MRI) with flip angles ranging over 5-25u, and diffusion-weighted MRI (DWMRI). Blood brain barrier (BBB) disruption was depicted as clear enhancement on T1W images. The average signal intensity in the regions of T1-enhancement, representing BBB disruption, increased from 1887683 (arbitrary units) immediately post treatment to 2246694 20 min post treatment, then reached a plateau towards the 30 min scan where it reached 2289687. DWMRI at 30 min showed no significant effects. Early treatment effects and late irreversible damage were clearly depicted on T2W. The enhancing volume on T2W has increased by an average of 2.2760.27 in the first 24-48 hours post treatment, suggesting an inflammatory tissue response. The permanent tissue damage, depicted as an enhancing region on T2W, 3 weeks post treatment, decreased to an average of 50610% of the T2W enhancing volumes on the day of the treatment which was 3365% of the BBB disruption volume. Permanent tissue damage was significantly smaller than the volume of BBB disruption, suggesting, that BBB disruption is associated with RE while tissue damage with IRE. These results demonstrate the feasibility of applying reversible and irreversible electroporation for transient BBB disruption or permanent damage, respectively, and applying MRI for planning/monitoring disruption volume/shape by optimizing electrode positions and treatment parameters.

Unravelling the role of neuromessenger processes in learning and memory has long interested resea... more Unravelling the role of neuromessenger processes in learning and memory has long interested researchers. We investigated the effects of an acetylcholinesterase blocker, Methyl Parathion (MeP), on honeybee learning. We used visual and olfactory tasks to test whether MeP had a detrimental effect on the acquisition of new knowledge when this new knowledge contradicts previously acquired one. Our results indicate that treatment with MeP prior to conditioning was significantly detrimental to the acquisition of incongruous (but not irrelevant or congruous) new knowledge due to improved recall. The neurobiological and ecotoxicological consequences of these results are discussed.

Chirurgie, 1998

... cadre de lischkmie critique* J Marzelle, R Raffoul, T Mekouar, D Laridon, F Cormier, JM Fiche... more ... cadre de lischkmie critique* J Marzelle, R Raffoul, T Mekouar, D Laridon, F Cormier, JM Fichelle, D Guez, JM Cormier Clinique de ... Simpson@), un atherotome rotationnel a vitesse lente (Transluminal Extraction catheter, TEC@) ou des fi-bres transmettant les ultrasons (Baxter). ...

Annals of Vascular Surgery, 1995

This report describes the results of 96 infrainguinal endovascular revascularization procedures p... more This report describes the results of 96 infrainguinal endovascular revascularization procedures performed in 86 patients with limb-threatening ischemia over a 3-year period. There were 41 women and 45 men (mean age 72.9 +/- 11.9 years) including 47 patients (51.1%) with diabetes and 13 (15.1%) with renal insufficiency. All patients had severe ischemia characterized by rest pain (18.8%), ulceration (12.5%), or gangrene (68.8%). Twelve procedures were carried out in association with conventional surgical reconstruction and in eight patients with mixed ulcers a venous procedure was performed during the same session. A total of 143 arterial lesions were treated including 61 occlusions (mean length 5.9 +/- 3.5 cm) and 82 stenoses (mean length 4.6 +/- 3 cm). The following techniques were used: transluminal angioplasty in 99 cases, laser in five cases, Rotablator in 24 cases, and aspiration thrombectomy in 15 cases. Nine patients (10.5%) died in the hospital. Initial failure was observed in 32 patients, of whom 18 underwent subsequent surgical revascularization and 14 required amputation of the extremity within 2 months. Analysis of variance was used to assess the following 12 risk factors for initial failure of endovascular revascularization: sex, age, diabetes, renal insufficiency, associated surgery, treatment of multiple lesions, artery treated, type of lesion, length of lesion, quality of runoff, use of an atherotome, and stent placement. Results showed a significant correlation between initial failure and both quality of runoff (12.9% in patients with two or more patent leg arteries vs. 36.5% in patients with one or fewer patent leg arteries; p < 0.05) and type of lesion (14.5% for stenosis vs. 45.9% for occlusion). Mean follow-up was 9.98 +/- 9.9 months and 4.7% of patients were lost. Restenosis was observed during follow-up of 16 of the 74 initially successful procedures. ANOVA was used to assess the same 12 risk factors for restenosis. Results showed a significant correlation between restenosis and both sex (10.8% in women vs. 32.4% in men; p < 0.05) and age (8% for patients > 80 years of age vs. 28.6% for patients < 80 years; p < 0.05). Primary patency, secondary patency and limb salvage rates calculated according to the actuarial method were 65%, 75%, and 84%, respectively, at 6 months and 47%, 67%, and 81%, respectively, at 1 year. Limb salvage rates for the endoluminal techniques used in this study were satisfactory, especially in elderly patients with either segmental lesions or contraindications for distal bypass.

Bioelectrochemistry, 2014

Keywords: Blood brain barrier Electroporation Brain Tumor MRI In spite of aggressive therapy, exi... more Keywords: Blood brain barrier Electroporation Brain Tumor MRI In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r 2 = 0.99, p b 0.001) and the number of treatment pulses (r 2 = 0.94, p b 0.002). Blood-brain barrier disruption depicted 3.2 ± 0.3 times larger volumes than the final permanent damage volumes (p b 0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors.

Cardiovascular Surgery, 1995

Progress in Biophysics and Molecular Biology, 2005

A large amount of data demonstrating the stochastic nature of gene expression and cell differenti... more A large amount of data demonstrating the stochastic nature of gene expression and cell differentiation has accumulated during the last 40 years. These data suggest that a gene in a cell always has a certain probability of being activated at any time and that instead of leading to on and off switches in an all-or-nothing fashion, the concentration of transcriptional regulators increases or decreases this probability. In order to integrate these data in an appropriate theoretical frame, we have tested the relevance of the selective model of cell differentiation by computer simulation experiments. This model is based on stochastic gene expression controlled by cellular interactions. Our results show that it is readily able to produce tissue organization. A model involving only two cells generated a bi-layer cellular structure of finite growth. Cell death was not a drawback but an advantage because it improved the viability of this bi-layer structure. However, our results also show that cellular interactions cannot be simply based on raw selection between cells. Instead, tissue coordination includes at least two basic components: phenotypic autostabilization (differentiated cells stabilize their own phenotype) and interdependence for proliferation (differentiated cells stimulate the proliferation of alien phenotypes). In this modified autostabilization-selection model, cellular organization and growth arrest result from a quantitative equilibrium between the parameters controlling these two processes. An imbalance leads to tissue disorganization and invasive cancer-like growth. These findings suggest that cancer does not result solely from mutations in the cancerous cell but from the progressive addition of several small alterations of the equilibrium between autostabilization and interdependence for proliferation. In this frame, it is not solely the cancerous cell that is abnormal. The whole organism is involved. Tumor growth is a local effect of an imbalance between all the factors involved in tissue organization.

PLoS ONE, 2013

Behavioural innovations are increasingly thought to provide a rich source of phenotypic plasticit... more Behavioural innovations are increasingly thought to provide a rich source of phenotypic plasticity and evolutionary change. Innovation propensity shows substantial variation across avian taxa and provides an adaptive mechanism by which behaviour is flexibly adjusted to changing environmental conditions. Here, we tested for the first time the prediction that inter-individual variation in innovation propensity is equally a measure of behavioural flexibility. We used Indian mynas, Sturnus tristis, a highly successful worldwide invader. Results revealed that mynas that solved an extractive foraging task more quickly learnt to discriminate between a cue that predicted food, and one that did not more quickly. However, fast innovators were slower to change their behaviour when the significance of the food cues changed. This unexpected finding appears at odds with the well-established view that avian taxa with larger brains relative to their body size, and therefore greater neural processing power, are both faster, and more flexible learners. We speculate that the existence of this relationship across taxa can be reconciled with its absence within species by assuming that fast, innovative learners and non innovative, slow, flexible learners constitute two separate individual strategies, which are both underpinned by enhanced neural processing power. This idea is consistent with the recent proposal that individuals may differ consistently in 'cognitive style', differentially trading off speed against accuracy in cognitive tasks.

Pharmacology Biochemistry and Behavior, 2003

Habituation of the proboscis extension reflex (PER) in honeybees (Apis mellifera) is age-dependen... more Habituation of the proboscis extension reflex (PER) in honeybees (Apis mellifera) is age-dependent. Very young bees ( 7 days old) require significantly less trials to abolish the response to multiple sucrose stimulations than older bees (!8 days old). A nicotinic agonist, imidacloprid, modifies this behaviour by increasing the number of trials in 7-day-old bees and by decreasing it in older bees [Neurobiol. Learn. Mem. 76 (2001) 183.]. Here we tested our hypothesis that this effect is associated with a differential expression of two subtypes of nicotinic acetylcholine receptors (nAChRs). By testing the effects of six metabolites of imidacloprid, we show that two of them, olefin and 5hydroxy-imidacloprid, modify the number of trials needed to habituate the PER in a contrasting manner. Olefin increases the number of trials in both age groups, whereas 5-hydroxy-imidacloprid decreases the number of trials, but only in 8-day-old individuals. We conclude that olefin and 5-hydroxy-imidacloprid are specific agonists of two subtypes of an nAChR that are differentially expressed during adult maturation of young honeybees. Olefin is the agonist of an nAChR expressed in both age groups, whereas 5-hydroxy-imidacloprid is the agonist of a late-onset nAChR that is activated in 8-day-old bees. The implications of this finding for the honeybee biology are discussed. D

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2007

Molecular imaging using PET in small rodents requires commonly the knowledge of the input functio... more Molecular imaging using PET in small rodents requires commonly the knowledge of the input function of the tracer (quantitative and kinetic studies of the metabolism, development of new drugs or new tracers, etc.). In this paper, we report the status and the performances of the prototype of a counting system that is under development at DAPNIA a in collaboration with SHFJ b . The detection device is made of silicon diodes of 0.3 mm thickness proper to measure the positrons emitted by the radiotracer contained in arterial blood flowing in a thin-wall microtube. Such diodes are poorly efficient for the 511 keV gammas from the rodent and thus require a rather light lead shielding and allow operating very close by to the animal. The detectors, the front-end electronics (for signal preamplification, shaping, and discrimination) and the acquisition circuits are mounted on a single card. The device is connected directly to a portable computer via an USB port.

The American Journal of Cardiology, 1996

Left ventricular hyperuophy is a major risk factor for cardi-lar morbidity and mortality. Angiote... more Left ventricular hyperuophy is a major risk factor for cardi-lar morbidity and mortality. Angiotensinconverting enxyme inhibitors, calcium antagonists, and b-blockers prevent, and cause regression of, left ventricubr hype&o&y after short-term therapy. The abilii of diuretics to do the same is unclear. We have performed a meta-analysis of studies documenting the effect on left ventricular mass of 6 months' treatment with 2.5 mg indapamide daify. Six studies comprising 197 patients, aged 20-75 years, were included. There was an overall mean reduction in left ventricular mass index of 13.3?, which was principally due to a reduction in left ventricular wall thickness rather than internal diameter.

Teknologi Kejuruan, 2009

Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut ... more Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut harus disesuaikan dengan kemampuan tubuh saluran untuk menahan gerusan. Tujuan penelitian ini adalah untuk menentukan model matematika superelevasi di sisi karamba dengan ...

Teknologi Kejuruan, 2009

Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut ... more Besar aliran sekunder di sisi karamba yang ditandai oleh besar superelevasi pada tempat tersebut harus disesuaikan dengan kemampuan tubuh saluran untuk menahan gerusan. Tujuan penelitian ini adalah untuk menentukan model matematika superelevasi di sisi karamba dengan ...

Behavioural processes, 2014

Behavioural innovations have become central to our thinking about how animals adjust to changing ... more Behavioural innovations have become central to our thinking about how animals adjust to changing environments. It is now well established that animals vary in their ability to innovate, but understanding why remains a challenge. This is because innovations are rare, so studying innovation requires alternative experimental assays that create opportunities for animals to express their ability to invent new behaviours, or use pre-existing ones in new contexts. Problem solving of extractive foraging tasks has been put forward as a suitable experimental assay. We review the rapidly expanding literature on problem solving of extractive foraging tasks in order to better understand to what extent the processes underpinning problem solving, and the factors influencing problem solving, are in line with those predicted, and found, to underpin and influence innovation in the wild. Our aim is to determine whether problem solving can be used as an experimental proxy of innovation. We find that in...

Journal of Cerebral Blood Flow & Metabolism, 2015

Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme ... more Despite aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme patients, in part due to poor penetration of most drugs across the blood-brain barrier (BBB). We propose a minimal-invasive combined treatment approach consisting of local BBB disruption in the tumor in parallel to systemic drug administration. Local BBB disruption is obtained by convection-enhanced delivery of a novel BBB disruption agent, enabling efficient/targeted delivery of the systemically administered drug by the tumors own vasculature. Various human serum albumin (HSA) analogs were synthesized and screened for BBB disruption efficacy in custom in vitro systems. The candidate analogs were then delivered into naïve rat brains by convection-enhanced delivery and screened for maximal BBB disruption and minimal brain toxicity. These studies found a noncationized/neutralized analog, ethylamine (EA)-HSA, to be the optimal BBB-opening agent. Immunocytochemical studies suggested that BBB disruption by EA-HSA may be explained by alterations in occludin expression. Finally, an efficacy study in rats bearing intracranial gliomas was performed. The rats were treated by convection-enhanced delivery of EA-HSA in parallel to systemic administration of Methotrexate, showing significant antineoplastic effects of the combined approached reflected in suppressed tumor growth and significantly (~x3) prolonged survival.Journal of Cerebral Blood Flow & Metabolism advance online publication, 11 February 2015; doi:10.1038/jcbfm.2015.6.

Molecular and cellular biochemistry, 1998

The aim of these experiments was to investigate the radical scavenging properties of three diuret... more The aim of these experiments was to investigate the radical scavenging properties of three diuretics: indapamide (IND) and its major metabolite, 5-OH indapamide (5-OH IND), compared to a reference diuretic, hydrochlorothiazide (HTZ). Electron Paramagnetic Resonance (EPR) was used to determine the scavenging abilities of these compounds on enzymatically produced superoxide radical anion, with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) used as a spin-trap. These experiments revealed that IND and specially 5-OH IND were effective superoxide radical anion scavengers at 0.2 mg/ml. In the second part of these studies, allophycocyanin was used as an indicator of free radical mediated protein damage. In the assay, 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) was used as a peroxyl radical generator, Trolox (a water-soluble analogue of vitamin E) as a control standard, and the loss of allophycocyanin fluorescence was monitored. The antioxidant effects of the diuretics were expressed in...

Neuro-Oncology, 2014

Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing... more Conventional magnetic resonance imaging (MRI) is unable to differentiate tumor/nontumor enhancing tissues. We have applied delayed-contrast MRI for calculating high resolution treatment response assessment maps (TRAMs) clearly differentiating tumor/nontumor tissues in brain tumor patients. One hundred and fifty patients with primary/metastatic tumors were recruited and scanned by delayed-contrast MRI and perfusion MRI. Of those, 47 patients underwent resection during their participation in the study. Region of interest/threshold analysis was performed on the TRAMs and on relative cerebral blood volume maps, and correlation with histology was studied. Relative cerebral blood volume was also assessed by the study neuroradiologist. Histological validation confirmed that regions of contrast agent clearance in the TRAMs >1 h post contrast injection represent active tumor, while regions of contrast accumulation represent nontumor tissues with 100% sensitivity and 92% positive predictive value to active tumor. Significant correlation was found between tumor burden in the TRAMs and histology in a subgroup of lesions resected en bloc (r(2) = 0.90, P < .0001). Relative cerebral blood volume yielded sensitivity/positive predictive values of 51%/96% and there was no correlation with tumor burden. The feasibility of applying the TRAMs for differentiating progression from treatment effects, depicting tumor within hemorrhages, and detecting residual tumor postsurgery is demonstrated. The TRAMs present a novel model-independent approach providing efficient separation between tumor/nontumor tissues by adding a short MRI scan >1 h post contrast injection. The methodology uses robust acquisition sequences, providing high resolution and easy to interpret maps with minimal sensitivity to susceptibility artifacts. The presented results provide histological validation of the TRAMs and demonstrate their potential contribution to the management of brain tumor patients.

PLoS ONE, 2012

Electroporation, is known to induce cell membrane permeabilization in the reversible (RE) mode an... more Electroporation, is known to induce cell membrane permeabilization in the reversible (RE) mode and cell death in the irreversible (IRE) mode. Using an experimental system designed to produce a continuum of IRE followed by RE around a single electrode we used MRI to study the effects of electroporation on the brain. Fifty-four rats were injected with Gd-DOTA and treated with a G25 electrode implanted 5.5 mm deep into the striata. MRI was acquired immediately after treatment, 10 min, 20 min, 30 min, and up to three weeks following the treatment using: T1W, T2W, Gradient echo (GE), serial SPGR (DCE-MRI) with flip angles ranging over 5-25u, and diffusion-weighted MRI (DWMRI). Blood brain barrier (BBB) disruption was depicted as clear enhancement on T1W images. The average signal intensity in the regions of T1-enhancement, representing BBB disruption, increased from 1887683 (arbitrary units) immediately post treatment to 2246694 20 min post treatment, then reached a plateau towards the 30 min scan where it reached 2289687. DWMRI at 30 min showed no significant effects. Early treatment effects and late irreversible damage were clearly depicted on T2W. The enhancing volume on T2W has increased by an average of 2.2760.27 in the first 24-48 hours post treatment, suggesting an inflammatory tissue response. The permanent tissue damage, depicted as an enhancing region on T2W, 3 weeks post treatment, decreased to an average of 50610% of the T2W enhancing volumes on the day of the treatment which was 3365% of the BBB disruption volume. Permanent tissue damage was significantly smaller than the volume of BBB disruption, suggesting, that BBB disruption is associated with RE while tissue damage with IRE. These results demonstrate the feasibility of applying reversible and irreversible electroporation for transient BBB disruption or permanent damage, respectively, and applying MRI for planning/monitoring disruption volume/shape by optimizing electrode positions and treatment parameters.

Unravelling the role of neuromessenger processes in learning and memory has long interested resea... more Unravelling the role of neuromessenger processes in learning and memory has long interested researchers. We investigated the effects of an acetylcholinesterase blocker, Methyl Parathion (MeP), on honeybee learning. We used visual and olfactory tasks to test whether MeP had a detrimental effect on the acquisition of new knowledge when this new knowledge contradicts previously acquired one. Our results indicate that treatment with MeP prior to conditioning was significantly detrimental to the acquisition of incongruous (but not irrelevant or congruous) new knowledge due to improved recall. The neurobiological and ecotoxicological consequences of these results are discussed.

Chirurgie, 1998

... cadre de lischkmie critique* J Marzelle, R Raffoul, T Mekouar, D Laridon, F Cormier, JM Fiche... more ... cadre de lischkmie critique* J Marzelle, R Raffoul, T Mekouar, D Laridon, F Cormier, JM Fichelle, D Guez, JM Cormier Clinique de ... Simpson@), un atherotome rotationnel a vitesse lente (Transluminal Extraction catheter, TEC@) ou des fi-bres transmettant les ultrasons (Baxter). ...

Annals of Vascular Surgery, 1995

This report describes the results of 96 infrainguinal endovascular revascularization procedures p... more This report describes the results of 96 infrainguinal endovascular revascularization procedures performed in 86 patients with limb-threatening ischemia over a 3-year period. There were 41 women and 45 men (mean age 72.9 +/- 11.9 years) including 47 patients (51.1%) with diabetes and 13 (15.1%) with renal insufficiency. All patients had severe ischemia characterized by rest pain (18.8%), ulceration (12.5%), or gangrene (68.8%). Twelve procedures were carried out in association with conventional surgical reconstruction and in eight patients with mixed ulcers a venous procedure was performed during the same session. A total of 143 arterial lesions were treated including 61 occlusions (mean length 5.9 +/- 3.5 cm) and 82 stenoses (mean length 4.6 +/- 3 cm). The following techniques were used: transluminal angioplasty in 99 cases, laser in five cases, Rotablator in 24 cases, and aspiration thrombectomy in 15 cases. Nine patients (10.5%) died in the hospital. Initial failure was observed in 32 patients, of whom 18 underwent subsequent surgical revascularization and 14 required amputation of the extremity within 2 months. Analysis of variance was used to assess the following 12 risk factors for initial failure of endovascular revascularization: sex, age, diabetes, renal insufficiency, associated surgery, treatment of multiple lesions, artery treated, type of lesion, length of lesion, quality of runoff, use of an atherotome, and stent placement. Results showed a significant correlation between initial failure and both quality of runoff (12.9% in patients with two or more patent leg arteries vs. 36.5% in patients with one or fewer patent leg arteries; p < 0.05) and type of lesion (14.5% for stenosis vs. 45.9% for occlusion). Mean follow-up was 9.98 +/- 9.9 months and 4.7% of patients were lost. Restenosis was observed during follow-up of 16 of the 74 initially successful procedures. ANOVA was used to assess the same 12 risk factors for restenosis. Results showed a significant correlation between restenosis and both sex (10.8% in women vs. 32.4% in men; p < 0.05) and age (8% for patients > 80 years of age vs. 28.6% for patients < 80 years; p < 0.05). Primary patency, secondary patency and limb salvage rates calculated according to the actuarial method were 65%, 75%, and 84%, respectively, at 6 months and 47%, 67%, and 81%, respectively, at 1 year. Limb salvage rates for the endoluminal techniques used in this study were satisfactory, especially in elderly patients with either segmental lesions or contraindications for distal bypass.

Bioelectrochemistry, 2014

Keywords: Blood brain barrier Electroporation Brain Tumor MRI In spite of aggressive therapy, exi... more Keywords: Blood brain barrier Electroporation Brain Tumor MRI In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r 2 = 0.99, p b 0.001) and the number of treatment pulses (r 2 = 0.94, p b 0.002). Blood-brain barrier disruption depicted 3.2 ± 0.3 times larger volumes than the final permanent damage volumes (p b 0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors.

Cardiovascular Surgery, 1995

Progress in Biophysics and Molecular Biology, 2005

A large amount of data demonstrating the stochastic nature of gene expression and cell differenti... more A large amount of data demonstrating the stochastic nature of gene expression and cell differentiation has accumulated during the last 40 years. These data suggest that a gene in a cell always has a certain probability of being activated at any time and that instead of leading to on and off switches in an all-or-nothing fashion, the concentration of transcriptional regulators increases or decreases this probability. In order to integrate these data in an appropriate theoretical frame, we have tested the relevance of the selective model of cell differentiation by computer simulation experiments. This model is based on stochastic gene expression controlled by cellular interactions. Our results show that it is readily able to produce tissue organization. A model involving only two cells generated a bi-layer cellular structure of finite growth. Cell death was not a drawback but an advantage because it improved the viability of this bi-layer structure. However, our results also show that cellular interactions cannot be simply based on raw selection between cells. Instead, tissue coordination includes at least two basic components: phenotypic autostabilization (differentiated cells stabilize their own phenotype) and interdependence for proliferation (differentiated cells stimulate the proliferation of alien phenotypes). In this modified autostabilization-selection model, cellular organization and growth arrest result from a quantitative equilibrium between the parameters controlling these two processes. An imbalance leads to tissue disorganization and invasive cancer-like growth. These findings suggest that cancer does not result solely from mutations in the cancerous cell but from the progressive addition of several small alterations of the equilibrium between autostabilization and interdependence for proliferation. In this frame, it is not solely the cancerous cell that is abnormal. The whole organism is involved. Tumor growth is a local effect of an imbalance between all the factors involved in tissue organization.

PLoS ONE, 2013

Behavioural innovations are increasingly thought to provide a rich source of phenotypic plasticit... more Behavioural innovations are increasingly thought to provide a rich source of phenotypic plasticity and evolutionary change. Innovation propensity shows substantial variation across avian taxa and provides an adaptive mechanism by which behaviour is flexibly adjusted to changing environmental conditions. Here, we tested for the first time the prediction that inter-individual variation in innovation propensity is equally a measure of behavioural flexibility. We used Indian mynas, Sturnus tristis, a highly successful worldwide invader. Results revealed that mynas that solved an extractive foraging task more quickly learnt to discriminate between a cue that predicted food, and one that did not more quickly. However, fast innovators were slower to change their behaviour when the significance of the food cues changed. This unexpected finding appears at odds with the well-established view that avian taxa with larger brains relative to their body size, and therefore greater neural processing power, are both faster, and more flexible learners. We speculate that the existence of this relationship across taxa can be reconciled with its absence within species by assuming that fast, innovative learners and non innovative, slow, flexible learners constitute two separate individual strategies, which are both underpinned by enhanced neural processing power. This idea is consistent with the recent proposal that individuals may differ consistently in 'cognitive style', differentially trading off speed against accuracy in cognitive tasks.

Pharmacology Biochemistry and Behavior, 2003

Habituation of the proboscis extension reflex (PER) in honeybees (Apis mellifera) is age-dependen... more Habituation of the proboscis extension reflex (PER) in honeybees (Apis mellifera) is age-dependent. Very young bees ( 7 days old) require significantly less trials to abolish the response to multiple sucrose stimulations than older bees (!8 days old). A nicotinic agonist, imidacloprid, modifies this behaviour by increasing the number of trials in 7-day-old bees and by decreasing it in older bees [Neurobiol. Learn. Mem. 76 (2001) 183.]. Here we tested our hypothesis that this effect is associated with a differential expression of two subtypes of nicotinic acetylcholine receptors (nAChRs). By testing the effects of six metabolites of imidacloprid, we show that two of them, olefin and 5hydroxy-imidacloprid, modify the number of trials needed to habituate the PER in a contrasting manner. Olefin increases the number of trials in both age groups, whereas 5-hydroxy-imidacloprid decreases the number of trials, but only in 8-day-old individuals. We conclude that olefin and 5-hydroxy-imidacloprid are specific agonists of two subtypes of an nAChR that are differentially expressed during adult maturation of young honeybees. Olefin is the agonist of an nAChR expressed in both age groups, whereas 5-hydroxy-imidacloprid is the agonist of a late-onset nAChR that is activated in 8-day-old bees. The implications of this finding for the honeybee biology are discussed. D

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2007

Molecular imaging using PET in small rodents requires commonly the knowledge of the input functio... more Molecular imaging using PET in small rodents requires commonly the knowledge of the input function of the tracer (quantitative and kinetic studies of the metabolism, development of new drugs or new tracers, etc.). In this paper, we report the status and the performances of the prototype of a counting system that is under development at DAPNIA a in collaboration with SHFJ b . The detection device is made of silicon diodes of 0.3 mm thickness proper to measure the positrons emitted by the radiotracer contained in arterial blood flowing in a thin-wall microtube. Such diodes are poorly efficient for the 511 keV gammas from the rodent and thus require a rather light lead shielding and allow operating very close by to the animal. The detectors, the front-end electronics (for signal preamplification, shaping, and discrimination) and the acquisition circuits are mounted on a single card. The device is connected directly to a portable computer via an USB port.