Poitiers, France
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Reygagne E.,CHU de Poitiers | Du Boisgueheneuc F.,CHU de Poitiers | Berger A.,CHU de Poitiers
Bulletin du Cancer | Year: 2016

Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status and estimated prognostic (DS GPA). Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies (radiation therapy and surgery) with their neuro-cognitive consequences for brain metastases patients and future concerning preservation of cognitive functions. © 2016 Société Française du Cancer.

Feigerlova E.,CHU de Poitiers | Feigerlova E.,University of Poitiers | Battaglia-Hsu S.-F.,Nancy University Hospital Center
Cytokine and Growth Factor Reviews | Year: 2017

Diabetic nephropathy (DN) is a leading cause of chronic kidney disease (CKD). Interleukin-6 (IL-6) signaling participates in inflammation responses central to the progression of DN. Current evidence suggests that these IL-6 responses are mediated via gp130-STAT3 dependent mechanisms which, on one hand, trigger globally the transition from innate to adaptive immune response, and on the other hand act locally for tissue remodeling and immune cell infiltration. In diabetic conditions the role of IL-6 is not well elucidated. Both IL-6 classical signaling pathway via receptor IL-6R (IL-6R) and IL-6 trans-signaling pathway via soluble IL-6R (sIL-6R) were shown to participate in the pathogenesis and progression of DN, and IL-6 appears to influence renal cells also in an autocrine manner. To date, evidence is limited. The goal of this review is to provide an overview of our current understanding on the role of IL-6 signaling in DN and to delineate challenges for future research. Putative sequential events related to IL-6 secretion by different cell populations in diabetic conditions are outlined. Further, we discuss potential applications of anti-IL-6 therapy in the context of DN. © 2017 Elsevier Ltd.

Pambrun T.,CHU de Poitiers | Mercier A.,University of Poitiers | Chatelier A.,University of Poitiers | Patri S.,University of Poitiers | And 6 more authors.
Heart Rhythm | Year: 2014

Background Myotonic dystrophy type 1 (DM1), a muscular dystrophy due to CTG expansion in the DMPK gene, can cause cardiac conduction disorders and sudden death. These cardiac manifestations are similar to those observed in loss-of-function SCN5A mutations, which are also responsible for Brugada syndrome (BrS). Objective The purpose of this study was to investigate DM1 effects on clinical expression of a loss-of-function SCN5A mutation causing BrS. Methods We performed complete clinical evaluation, including ajmaline test, in 1 family combining DM1 and BrS. We screened the known BrS susceptibility genes. We characterized an SCN5A mutation using whole-cell patch-clamp experiments associated with cell surface biotinylation. Results The proband, a 15-year-old female, was a survivor of out-of-hospital cardiac arrest with ventricular fibrillation. She combined a DMPK CTG expansion from the father's side and an SCN5A mutation (S910L) from the mother's side. S910L is a trafficking defective mutant inducing a dominant negative effect when transfected with wild-type Nav1.5. This loss-of-function SCN5A mutation caused a Brugada phenotype during the mother's ajmaline test. Surprisingly, in the father, a DM1 patient without SCN5A mutation, ajmaline also unmasked a Brugada phenotype. Furthermore, association of both genetic abnormalities in the proband exacerbated the response to ajmaline with a massive conduction defect. Conclusion Our study is the first to describe the deleterious effect of DM1 on clinical expression of a loss-of-function SCN5A mutation and to show a provoked BrS phenotype in a DM1 patient. The modification of the ECG pattern by ajmaline supports the hypothesis of a link between DM1 and Nav1.5 loss of -function. © 2014 Heart Rhythm Society. All right sreserved.

Fakhouri F.,Nantes University Hospital Center | Roumenina L.,French Institute of Health and Medical Research | Provot F.,Lille University Hospital Center | Sallee M.,Marseille University Hospital Center | And 8 more authors.
Journal of the American Society of Nephrology | Year: 2010

In contrast to pregnancy-associated thrombotic thrombocytopenic purpura, the pathogenesis and presentation of pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) remain ill-defined. We conducted a retrospective study to assess the presentation and outcomes of patients presenting with P-aHUS and the prevalence of alternative C3 convertase dysregulation. P-aHUS occurred in 21 of the 100 adult female patients with atypical HUS, with 79% presenting postpartum. We detected complement abnormalities in 18 of the 21 patients. The outcomes were poor: 62% reached ESRD by 1 month and 76% by last follow-up. The risk for P-aHUS was highest during a second pregnancy. Thirty-five women, 26 (74%) of whom had complement abnormalities, had at least one pregnancy before the onset of a non-pregnancy-related aHUS. Outcomes did not differ between patients with pregnancy-related and non-pregnancy-related aHUS. Mutations in the SCR19-20 domains of factor H were less frequent in P-aHUS patients compared with non-pregnancy-related aHUS. Pregnancies in female patients with complement abnormalities (n = 44) were complicated by fetal loss and preeclampsia in 4.8% and 7.7%, respectively. Better understanding of complement dysregulation in pregnancy complications is essential, especially to guide development of pharmacologic agents to modulate this system. Copyright © 2010 by the American Society of Nephrology.

Le Quintrec M.,Hopital Foch | Lionet A.,Lille University Hospital Center | Kandel C.,Nantes University Hospital Center | Gnemmi V.,Lille University Hospital Center | And 4 more authors.
American Journal of Kidney Diseases | Year: 2015

C3 glomerulopathy (C3G) is a prototypic complement-mediated kidney disease. Rapidly progressive forms of C3G usually respond poorly to conventional treatments. We report on the efficacy of the terminal complement inhibitor eculizumab in 3 adult patients with rapidly progressive C3G. In all 3 patients, serum creatinine levels had increased by >50% in the 2 months preceding initiation of eculizumab treatment despite the use of conventional immunosuppressive drugs and/or plasma exchanges in 2 of these individuals. Of note, 2 patients had long-standing nephrotic syndrome. Kidney biopsy performed prior to eculizumab treatment disclosed marked glomerular inflammatory changes and increased C5b-9 deposition in all patients. Eculizumab use was associated with significant improvement in kidney function, with estimated glomerular filtration rates of patients increasing 22 to 38 mL/min/1.73 m2. Eculizumab use also was associated with remission of nephrotic syndrome in the 2 affected patients, an effect observed as early as one week after treatment initiation. Repeat kidney biopsy disclosed regression of glomerular inflammatory changes and decreases in glomerular staining for C5b-9 in all patients. These results warrant further assessment of eculizumab for treatment of rapidly progressive forms of C3G with markedly increased glomerular C5b-9 deposits. © 2015 National Kidney Foundation, Inc.

Purpose: We evaluated the use of tamsulosine versus placebo for management of ureteral stent discomfort. Patients and methods: This prospective and randomized study was realized in the Department of Urology of three university hospital. The participation was proposed at all patient having indication to receive an ureteral stent except for cancer. The evaluation of the tolerance used two validate questionnaires: Ureteral Stent Symptom Questionnaire (USSQ) and IPSS completed by each patient the day of the insertion, next day, one week later and the day before and after the removal. The main assessment criterion was the question "global quality of life" one week after the stent insertion. Results: Seventy-nine patients were randomized between June, 2010 and October, 2012. Despite phone reminders only 38 (48.1%) were complete questionnaires. Out of 39, 18 patients in the tamsulosine group and out of 40, 20 in the phloroglucinol group. The majority of the patients (92%) were included for stone disease. There is not significant difference between the 2 groups using the USSQ and IPSS at day. +. 1, day. +. 7, pre-ablation and day. +. 1 ablation. A significant improvement of the scores was noted to day. +. 1 by the ablation of the JJ in 2 groups. Conclusion: Our study did not show superiority of tamsulosine versus placebo in the improvement of the tolerance of ureteral stent. Level of evidence: 2. © 2014 Elsevier Masson SAS.

Sosner P.,CHU de Poitiers | Sosner P.,University of Poitiers | Sosner P.,French Institute of Health and Medical Research | Wangermez M.,CHU de Poitiers | And 4 more authors.
Atherosclerosis | Year: 2012

Background: The influence of hepatitis C virus (HCV) infection on atherosclerosis risk in HIV-infected patients has not been adequately evaluated in real-life situations. Objectives and methods: We compared indexes of early atherosclerosis evaluated by echo-Doppler ultrasound (presence of plaque in carotid or femoral arteries) in 18 HCV-HIV co-infected patients versus 22 HIV mono-infected patients. Results: Prevalence of subclinical carotid plaque was significantly higher in HCV-HIV co-infected patients (p= 0.04), despite of the fact LDL-cholesterol and blood pressure (BP) were lower in the co-infected patients (p= 0.003). HCV chronic infection (OR = 10; IC: 1.5-72; p= 0.02) was an independent risk factor. Conclusion: This cross sectional study suggests that HCV infection might be an independent cardiovascular risk factor in HCV-HIV co-infected patients. HCV infection might be considered as not only a liver infection but also as a metabolic disease in HIV patients, justifying regular cardiovascular surveillance. © 2012 Elsevier Ireland Ltd.

Withdrawal of nutrition/hydration is a legal and ethical decision in adults. It is very rarely practiced in children in France, due to the fear of letting a child die from hunger and thirst. Several pediatric issues make this decision a complex one. The root of the decision should be the best interest of the child, knowing that the subjective feelings of the family should also be addressed. The physiologic dependence of the infant on environment for food and water is indistinctly superimposed on the means involved for sustaining nutrition during a disease. Nutrition/hydration is synonymous to life and the oral character is linked to pleasure. Thus, the wish to withdraw nutrition/hydration can be considered as a decision to deliberately provoke death. Given the child's lack of autonomy and the fact that the child can be harmed with a chronic disease at birth, make the ethical approach to the decision more complex. Death is the unavoidable result of the decision of withdrawal of nutrition/hydration, but the patient may not suffer from hunger and thirst during the remaining days. Particular attention should be devoted to the prevention of pressure ulcers and use of analgesic drugs in the setting of renal failure. The presumption of an important moral suffering of the family and/or the treating team should balance the choice of this option among other end-of-life decisions in children. © 2009 Elsevier Masson SAS. All rights reserved.

Bensadoun R.-J.,CHU de Poitiers | Nair R.G.,Griffith University
Current Opinion in Oncology | Year: 2012

Purpose of review: To discuss the promising state of the art low-level laser therapy (LLLT) for preventive and therapeutic usage in oral mucositis due to cancer therapy. Recent findings: Photomedicine using LLLT is very effective with intraoral and extraoral devices in the management of oral mucositis, based on several studies including randomized control studies. A systematic review identified 33 relevant articles that were subjected to meta-analysis based on which laser parameters in routine practice are being defined. Meta-analysis showed that LLLT reduced risk of oral mucositis with relative risk (RR) 2.45 [confidence interval (CI) 1.85-3.18], reduced duration, severity of oral mucositis and reduced number of days with oral mucositis (4.38 days, P=0.0009). RR was similar between the red (630-670 nm) and infrared (780-830 nm) LLLT. Pain-relieving effect based on the Cohen scale was at 1.22 (CI 0.19-2.25). Summary: No adverse side effects of LLLT were reported; hence, we recommend red or infrared LLLT with diode output between 10-100 mW, dose of 2-3J/cm 2/cm 2 for prophylaxis and 4J/cm 2 (maximum limit) for therapeutic effect, application on single spot rather than scanning motion. Lesions must be evaluated by a trained clinician and therapy should be repeated daily or every other day or a minimum of three times per week until resolution. There is moderate-to-strong evidence in favor of LLLT at optimal doses as a well tolerated, relatively inexpensive intervention for cancer therapy-induced oral mucositis. It is envisaged that LLLT will soon become part of routine oral supportive care in cancer. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Chavant F.,CHU de Poitiers | Favreliere S.,CHU de Poitiers | Lafay-Chebassier C.,CHU de Poitiers | Plazanet C.,CHU de Poitiers | Perault-Pochat M.-C.,CHU de Poitiers
British Journal of Clinical Pharmacology | Year: 2011

Aims: To investigate putative associations of reports of memory disorders and suspected drugs. Methods: We used the case/noncase method in the French PharmacoVigilance Database (FPVD). Cases were reports of memory loss in the FPVD between January 2000 and December 2009. Noncases were all other reports during the same period. To assess the association between memory impairment and drug intake, we calculated an odds ratio with its 95% confidence interval. RESULTS Among the 188284 adverse drug reactions recorded, we identified 519 cases of memory loss. The sex ratio was 0.6 and the median age was 54 years (range 4-93). The maximal number of cases occurred between 40-49 and 50-59 years. Evolution was favourable in 63% of the cases. We found significant odds ratios for benzodiazepines (alprazolam, bromazepam, prazepam, clonazepam etc.), benzodiazepine-like hypnotics (zolpidem and zopiclone), antidepressants (fluoxetine, paroxetine and venlafaxine), analgesics (morphine, nefopam and tramadol), anticonvulsants (topiramate, pregabalin, levetiracetam etc.), antipsychotics (aripiprazole and lithium) and other drugs, such as trihexyphenidyl, ciclosporin and isotretinoin. Conclusions: Our study confirmed an association between memory disorders and some drugs, such as benzodiazepines and anticonvulsants. However, other drugs, such as benzodiazepine-like hypnotics, newer anticonvulsants, serotonin reuptake inhibitor antidepressants, isotretinoin and ciclosporin were significantly associated with memory disorders, although this was not described or poorly described in the literature. Taking account of the limits of this study in the FPVD (under-reporting, notoriety bias etc.), the case/noncase method allows assessment and detection of associations between exposure to drugs and a specific adverse drug reaction, such as memory disorders, and could thus generate signals and orientate us to further prospective studies to confirm such associations. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

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