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Boulogne S.,Hospices civils de Lyon | Ryvlin P.,CHU Vaudois | Rheims S.,Hospices civils de Lyon
Revue neurologique | Year: 2016

Invasive EEG recordings are frequently required during the presurgical exploration of patients with drug-resistant focal epilepsy in order to clarify the epileptic zone location. Intracranial direct electrical stimulations (DES) induce EEG and/or clinical responses that participate in this evaluation. Clinical DES protocols (1Hz and/or 50Hz) trigger massive cortical activation that can elicit seizures, after-discharges or complex clinical signs. In contrast, low-energy (<1Hz) protocols activate more localized cortical regions using single-pulse electrical stimulations (SPES). SPES can elicit two main types of responses. Cortico-cortical evoked potentials (CCEPs) correspond to highly consistent early responses, appearing before 100ms after stimulation, with fixed latency; they are considered physiological and assess the effective connectivity between the recorded regions. Late responses appear after 100ms; they are rare, inconsistent with variable latency and are suggestive of an underlying epileptogenic cortex. Paired-pulse stimulation paradigm associates a conditioning and a test stimulation to induce intracortical inhibition or facilitation by modifying the response amplitude. Largely used in transcranial magnetic stimulation, it has rarely been applied to CCEP although the mechanisms put in place seem highly similar. Low frequency intracerebral stimulations allow analysing brain connectivity and cortical excitability with a high temporal and spatial resolution. The development of new stimulation protocols and the combination with imaging or statistical techniques recently offered promising results. Copyright © 2016 Elsevier Masson SAS. All rights reserved.


Lammer J.,Medical University of Vienna | Malagari K.,National and Kapodistrian University of Athens | Vogl T.,Goethe University Frankfurt | Pilleul F.,Lyon University Hospital Center | And 16 more authors.
CardioVascular and Interventional Radiology | Year: 2010

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead ®) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease. © 2009 Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).


Wade K.A.,Hopital principal de Dakar | Sene B.E.J.,CHU Vaudois | Niang E.M.,Hopital principal de Dakar | Diallo A.,Hopital principal de Dakar | Diatta B.,Hopital principal de Dakar
Medecine et Sante Tropicales | Year: 2012

We report the results of a retrospective study in the medical intensive care unit of the Principal Military Teaching Hospital of Dakar. The objectives were to determine the epidemiological and clinical aspects of severe malaria and to evaluate the prognostic values of the failure of different organs. Eighty-seven patients were admitted for severe malaria. Their average age was 35 ± 18.53 with a sex-ratio of 1.71 for men. Mortality was 33.3% and concerned mainly young adults. Neurological failure was the most frequent (79.3%). Hemodynamic failure was the most relevant prognostic factor for mortality, followed by hypoglycemia, respiratory and renal failure. The Simplified Acute Physiology Score II (SAPS II) was reliable in predicting mortality. The mean SAPS II was 44.85, with an expected mortality of 32.6%.


Lauwerys B.R.,Catholic University of Leuven | Hachulla E.,Hopital Claude Huriez | Spertini F.,CHU Vaudois | Lazaro E.,Bordeaux University Hospital Center | And 8 more authors.
Arthritis and Rheumatism | Year: 2013

Objective We developed interferon-α-kinoid (IFN-K), a drug composed of inactivated IFNα coupled to a carrier protein, keyhole limpet hemocyanin. In human IFNα-transgenic mice, IFN-K induces polyclonal antibodies that neutralize all 13 subtypes of human IFNα. We also previously demonstrated that IFN-K slows disease progression in a mouse model of systemic lupus erythematosus (SLE). This study was undertaken to examine the safety, immunogenicity, and biologic effects of active immunization with IFN-K in patients with SLE. Methods We performed a randomized, double-blind, placebo-controlled, phase I/II dose-escalation study comparing 3 or 4 doses of 30 μg, 60 μg, 120 μg, or 240 μg of IFN-K or placebo in 28 women with mild to moderate SLE. Results IFN-K was well tolerated. Two SLE flares were reported as serious adverse events, one in the placebo group and the other in a patient who concomitantly stopped corticosteroids 2 days after the first IFN-K dose, due to mild fever not related to infection. Transcriptome analysis was used to separate patients at baseline into IFN signature-positive and -negative groups, based on the spontaneous expression of IFN-induced genes. IFN-K induced anti-IFNα antibodies in all immunized patients. Notably, significantly higher anti-IFNα titers were found in signature-positive patients than in signature-negative patients. In IFN signature-positive patients, IFN-K significantly reduced the expression of IFN-induced genes. The decrease in IFN score correlated with the anti-IFNα antibody titer. Serum complement C3 levels were significantly increased in patients with high anti-IFNα antibody titers. Conclusion These results show that IFN-K is well tolerated, immunogenic, and significantly improves disease biomarkers in SLE patients, indicating that further studies of its clinical efficacy are warranted. Copyright © 2013 by the American College of Rheumatology.


Snape K.,Institute of Cancer Research | Hanks S.,Institute of Cancer Research | Ruark E.,Institute of Cancer Research | Barros-Nunez P.,Instituto Mexicano Del Seguro Social | And 17 more authors.
Nature Genetics | Year: 2011

Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division. © 2011 Nature America, Inc. All rights reserved.


Grouzmann E.,CHU Vaudois | Bigliardi P.,CHU Vaudois | Appenzeller M.,CHU Vaudois | Pannatier A.,Service de Pharmacie | Buclin T.,CHU Vaudois
Biological Chemistry | Year: 2011

Substance P (SP), an undecapeptide belonging to the tachykinin family, is released during the activation of sensory nerves, and causes vasodilation, edema and pain through activation of tissular Neurokinin 1 receptors. SP proinflammatory effects are terminated by angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), while the aminopeptidase dipeptidylpeptidase IV (DPPIV) can also play a role. The aim of this randomized, crossover, doubleblind study was to assess the cutaneous vasoreactivity (flare and wheal reaction, burning pain sensation) to intradermal injection of ascending doses of SP in six volunteers receiving a single therapeutic dose of the DPPIV inhibitor sitagliptin or a matching placebo. Cutaneous SP challenges produced the expected, dose-dependent flare and wheal response, while eliciting mild to moderate local pain sensation with little dose dependency. However, no differences were shown in the responses observed under sitagliptin compared with placebo, while the study would have been sufficiently powered to detect a clinically relevant increase in sensitivity to SP. The results of this pilot study are in line with proteolytic cleavage of SP by ACE and NEP compensating the blockade of DPPIV to prevent an augmentation of its proinflammatory action. Copyright © by Walter de Gruyter.


PubMed | CHU Vaudois and French Institute of Health and Medical Research
Type: Journal Article | Journal: Revue neurologique | Year: 2016

Invasive EEG recordings are frequently required during the presurgical exploration of patients with drug-resistant focal epilepsy in order to clarify the epileptic zone location. Intracranial direct electrical stimulations (DES) induce EEG and/or clinical responses that participate in this evaluation. Clinical DES protocols (1Hz and/or 50Hz) trigger massive cortical activation that can elicit seizures, after-discharges or complex clinical signs. In contrast, low-energy (<1Hz) protocols activate more localized cortical regions using single-pulse electrical stimulations (SPES). SPES can elicit two main types of responses. Cortico-cortical evoked potentials (CCEPs) correspond to highly consistent early responses, appearing before 100ms after stimulation, with fixed latency; they are considered physiological and assess the effective connectivity between the recorded regions. Late responses appear after 100ms; they are rare, inconsistent with variable latency and are suggestive of an underlying epileptogenic cortex. Paired-pulse stimulation paradigm associates a conditioning and a test stimulation to induce intracortical inhibition or facilitation by modifying the response amplitude. Largely used in transcranial magnetic stimulation, it has rarely been applied to CCEP although the mechanisms put in place seem highly similar. Low frequency intracerebral stimulations allow analysing brain connectivity and cortical excitability with a high temporal and spatial resolution. The development of new stimulation protocols and the combination with imaging or statistical techniques recently offered promising results.


PubMed | CHU Vaudois, French Institute of Health and Medical Research and unite digestif
Type: Journal Article | Journal: Diagnostic and interventional imaging | Year: 2015

The availability of intra-arterial hepatic therapies (radio and/or chemo-embolisation, intra-arterial hepatic chemotherapy) has convinced radiologists to perfect their knowledge of the anatomy of the liver arteries. These sometimes, complex procedures most often require selective arterial catheterization. Knowledge of the different arteries in the liver and the peripheral organs is therefore essential to optimize the procedure and avoid eventual complications. This paper aims to describe the anatomy of the liver arteries and the variants, applying it to angiography images, and to understand the implications of such variations in interventional radiological procedures.


PubMed | CHU Vaudois, Rennes University Hospital Center and University Rennes2
Type: | Journal: Annals of physical and rehabilitation medicine | Year: 2016

In children with hemiplegic cerebral palsy (HCP), some studies have shown an improvement in manual function following a self-rehabilitation program by mirror therapy. However, adherence to this protocol has not been reported. So, we studied the feasibility and compliance of this self-rehabilitation program in the hemiplegic child.The aim of this study was to evaluate the effect of mirror therapy on the upper limb of children with HCP. Twenty-eight children (11.92.7 years) went through a self-rehabilitation program by mirror therapy at home. This program was developed by the Swiss team of Newman and Gigax. It consists of 7 exercises, for a total of 15min, repeated 5 days per week for 5 weeks. A diary was given to each child to note the daily time spent on the protocol and the number of series actually done for each exercise. Adherence was assessed by the number of series performed. Difficulties and adverse events that occurred during this period were also collected.All the children have achieved the 5 week protocol and all were satisfied with their participation. The global observance of the protocol is good with 86.3% of the exercises performed on the average of five weeks (SD12.6). There is no significant difference between the observance of the first week and that of the fifth week (87% vs. 81%) (P=0.22). It exists a significant decrease in the average length of time spent on the protocol between the first and the fifth week (18min 24 vs. 12min 42) (P<0.05). No event or significant adverse effects was detected during the protocol.This self-rehabilitation protocol by mirror therapy shows good feasibility and good compliance. Self-rehabilitation seems to be an interesting tool easy to implement and well accepted by the children with HCP.


PubMed | CHU Vaudois, French Institute of Health and Medical Research and unite digestif
Type: Journal Article | Journal: Diagnostic and interventional imaging | Year: 2014

The liver segmentation system, described by Couinaud, is based on the identification of the three hepatic veins and the plane passing by the portal vein bifurcation. Nowadays, Couinauds description is the most widely used classification since it is better suited for surgery and more accurate for the localisation and monitoring of intra-parenchymal lesions. Knowledge of the anatomy of the portal and venous system is therefore essential, as is knowledge of the variants resulting from changes occurring during the embryological development of the vitelline and umbilical veins. In this paper, the authors propose a straightforward systematisation of the liver in six steps using several additional anatomical points of reference. These points of reference are simple and quickly identifiable in any radiological examination with section imaging, in order to avoid any mistakes in daily practice. In fact, accurate description impacts on many diagnostic and therapeutic applications in interventional radiology and surgery. This description will allow better preparation for biopsy, portal vein embolisation, transjugular intrahepatic portosystemic shunt, tumour resection or partial hepatectomy for transplantation. Such advance planning will reduce intra- and postoperative difficulties and complications.

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