Gisèle Pickering

University of Auvergne, Clermont-Ferrand, Auvergne, France

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Publications (56)146.23 Total impact

  • Gisèle Pickering
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    ABSTRACT: Post-herpetic neuralgia is a painful condition and its prevalence increases with age. It is a burden for older patients and the association of age-related pharmacokinetic and pharmacodynamic changes, high co-morbidity and polypharmacy leads to the risk of adverse drug reactions and interactions. This type of neuropathic pain is particularly difficult to treat and guidelines recommend the use of gabapentinoids and some antidepressants, the utility of which may be hampered by adverse effects such as sedation, dizziness and impaired age-related renal function. Re-formulations of antiepileptics (anticonvulsants) are being developed and/or marketed and suggest interesting innovative profiles with improved bioavailability, low drug-drug interactions and better tolerability that need to be confirmed in future studies. However, there are no new antiepileptics being developed for post-herpetic neuralgia, and prospective studies specifically focused on the older population are still missing, while this age group is particularly at risk of developing shingles and chronic neuropathic pain with a deleterious impact on quality of life.
    Drugs & Aging 09/2014; · 2.50 Impact Factor
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    ABSTRACT: N-methyl-D-aspartate receptor antagonists are potential therapies for neuropathic pain, and memantine has a good tolerance profile. A preclinical study recently reported that presurgery memantine may prevent neuropathic pain development and cognition dysfunction. Considering the high prevalence of breast cancer and of post-mastectomy neuropathic pain, a clinical trial is carried out to evaluate if memantine may prevent neuropathic pain development and maintain cognitive function and quality of life in cancer patients. Methods/design: A randomized clinical trial (NCT01536314) includes 40 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Memantine (5 to 20 mg/day; n = 20) or placebo (n = 20) is administered for 4 weeks starting 2 weeks before surgery. Intensity of pain, cognitive function, quality of life and of sleep, anxiety and depression are evaluated with questionnaires. The primary endpoint is pain intensity on a 0 to 10) numerical scale at 3 months post-mastectomy. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at alpha = 0.05.
    Trials. 08/2014; 15(1):331.
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    ABSTRACT: The N-methyl-D-aspartate receptor plays an important role in central sensitization of neuropathic pain and N-methyl-D-aspartate receptor antagonists, such as ketamine, memantine and dextromethorphan may be used for persistent pain. However, ketamine cannot be repeated too often because of its adverse events. A drug relay would be helpful in the outpatient to postpone or even cancel the next ketamine infusion. This clinical trial evaluates if memantine and/or dextromethorphan given as a relay to ketamine responders may maintain or induce a decrease of pain intensity and have a beneficial impact on cognition and quality of life. This trial is a multi-center, randomized, controlled and single-blind clinical study (NCT01602185). It includes 60 ketamine responder patients suffering from neuropathic pain. They are randomly allocated to memantine, dextromethorphan or placebo. After ketamine infusion, 60 patients received either memantine (maximal dose 20mg/day), or dextromethorphan (maximal dose 90mg/day), or placebo for 12weeks. The primary endpoint is pain measured on a (0-10) Numeric Rating Scale 1month after inclusion. Secondary outcomes include assessment of neuropathic pain, sleep, quality of life, anxiety/depression and cognitive function at 2 and 3months. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α=0.05. This study will explore if oral memantine and/or dextromethorphan may be a beneficial relay in ketamine responders and may diminish ketamine infusion frequency. Preservation of cognitive function and quality of life is also a central issue that will be analyzed in these vulnerable patients.
    Contemporary clinical trials. 06/2014;
  • G. Pickering
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    ABSTRACT: La médecine basée sur les preuves concernant les opioïdes chez le sujet âgé est encore très pauvre, mais les recommandations actuelles vont vers une utilisation individualisée des opioïdes et une adaptation du traitement en fonction des comorbidités et des autres médicaments. Considérant la forte augmentation de la prescription et de la consommation d’opioïdes chez le sujet âgé, une surveillance du risque de mésusage, de surdosage et d’abus doit être complétée par une éducation thérapeutique adaptée.
    Les cahiers de l année gérontologique 04/2014; 6(1).
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    ABSTRACT: Pain management in the elderly remains insufficient, be it at home, in nursing homes or hospitals. Inadequate evaluation and/or misinterpretation of the clinical signs present probably explain this poor management and are linked to the particularities of the old patient. Thus, recommendations to improve evaluation of pain in the elderly were formulated. However, these guidelines are rarely implemented in daily practice, most likely because they markedly increase the workload of the geriatric healthcare workers already required to perform multiple evaluations. Unfortunately, the dysfunctions observed are detrimental to the quality of life of these patients, and their morbidity and mortality. To improve pain management in the elderly, it is important to simplify the tasks of the different actors involved by proposing evaluation algorithms taking advantage of the complementarity of self-report and behavioral scales.
    Douleurs Evaluation - Diagnostic - Traitement 04/2014;
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    ABSTRACT: The efficiency of inhibitory pain descending pathways (evaluated using conditioned pain modulation [CPM]) has not been studied in postherpetic neuralgia (PHN). To compare CPM in PHN patients with healthy controls. Nine PHN patients and nine control individuals were matched according to age and sex. Amplitudes of cortical thermal-evoked potentials were recorded on the surface of the scalp; clinical pain and thermal pain were evaluated on a 0 to 10 numerical rating scale, at baseline and at intervals during the 6 min after CPM (elicited by a cold pressor test, 8°C). A battery of cognitive tests was performed. Amplitude differences, percentages and related areas under the curve (AUC CPM<⁄span>) were calculated and all data were compared between both groups; P<0.05 was considered to be statistically significant. AUC CPM0-6 min<⁄span> was significantly lower in PHN patients compared with controls (-39±51 µV⁄min versus -144±66 µV⁄min; P=0.0012) and correlated (P=0.04) with clinical pain intensity. Pain ratings before CPM were similar in both groups but were significantly lower in the control group 3 min after the cold pressor test. Cognitive test results were not significantly different. Psychophysical and electrophysiological approaches have shown that patients with PHN exhibit a deficiency of pain inhibition modulation, which could signal a predisposing factor to developing chronic pain. This deficiency was not linked to the cognitive performance but rather to subtle in situ cognitivoemotional adaptations, which remain to be investigated.
    Pain research & management : the journal of the Canadian Pain Society = journal de la societe canadienne pour le traitement de la douleur. 01/2014;
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    ABSTRACT: Acetaminophen (APAP) by oral or intravenous (iv) routes is used for mild to moderate pain but may take time to be effective. When fast relief is required and/or oral or iv routes are not available because of the patient's condition, the transmucosal route may be an alternative.
    Drug Design, Development and Therapy 01/2014; 8:1621-7. · 3.49 Impact Factor
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    ABSTRACT: N-methyl-D-aspartate (NMDA) receptor antagonists are used for post-surgery neuropathic pain but severe side-effects limit their clinical use. Memantine, when given after surgery, shows conflicting results as regard neuropathic pain alleviation. Memantine is here administered in animals before or after spinal nerve ligation (SNL) in order to evaluate the induced antinociceptive/cognitive effects and associated molecular events, including the phosphorylation of several tyrosine (pTyr(1336), pTyr(1472)) and serine (pSer(1303)) residues in the NR2B subunit of the NMDA receptor. Spinal nerve ligated and sham animals received memantine (20mg/kg/day) or vehicle (1ml/kg/day) by intraperitoneal route. Pre-emptive protocol started 4 days before surgery and continued for 2 days post-surgery. In the post-operative protocol, the 7 day-treatment began on the day of surgery. Tests were done before and after surgery. Tactile allodynia, mechanical hyperalgesia and spatial memory were respectively evaluated by von Frey, Randall & Selitto and Y-maze-tests, and molecular events by western-blot analysis. Spinal nerve ligated animals displayed nociception, impaired memory and increased expression of the three phosphorylated residues. Post-operative memantine had no beneficial effect. Pre-emptive memantine prevented the development of post-surgical nociception, impairment of spatial memory and did not increase the expression of pTyr(1472)NR2B at spinal, insular and hippocampal levels. Memantine administered a few days before surgery is a promising strategy to alleviate neuropathic pain development and impairment of cognitive function in animals. The pivotal role of pTyr(1472)NR2B must be studied further, and these findings will now be challenged in patients for the prevention of postsurgical neuropathic pain.
    European journal of pharmacology 06/2013; · 2.59 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: Neuropathic pain has been shown to be accompanied by cognitive impairment, but the specific impact of postherpetic neuropathic pain on cognitive processes has not been explored. This study aims to evaluate the impact of pain on several domains of cognition in older patients with postherpetic neuralgia (PHN). METHODS: This cross-sectional study (clinicaltrial.gov NCT 00989040) included 84 individuals after signature of informed consent. Participants: 42 patients with PHN and 42 healthy volunteers. Of the 42 PHN patients, 21 received systemic treatment (antidepressants, anticonvulsants, opiates) and 21 had topical treatment with the 5% lidocaine medicated plaster. All participants performed a panel of four cognitive tests: reaction time, semantic memory, decision-making, and visual memory (Cantab(®) , Cambridge). RESULTS: Forty men and 44 women with a mean age of 72 ± 8 years participated. Each PHN patient was matched by age and gender with a healthy volunteer. Vigilance, decision-making, and semantic memory were significantly impaired (P < 0.05) in patients on systemic treatment, especially with antidepressants, while no significant changes were noted between the lidocaine plaster group and their matched controls of healthy volunteers. CONCLUSION: This study shows the deleterious effect of systemic PHN treatment on several domains of cognition. Cognitive impairment associated with pain and antidepressants may be reversed by topical pain management. Topical treatment with 5% lidocaine medicated plaster is a valuable alternative for pain alleviation and maintains cognitive integrity in this vulnerable population.
    Pain Practice 05/2013; · 2.61 Impact Factor
  • Gisèle Pickering
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    ABSTRACT: To summarize developments in analgesic use in the older person. Observational studies, reviews and a few randomized trials dealing with analgesic use in the older person have been published during the past year. Recent trials examine also pharmacological/nonpharmacological interventions, and education of older patients as well as clinicians in pain management. Under-treatment of pain remains a major concern in community-dwelling or institutionalized older persons, especially with dementia. An increased awareness of pain and palliative pain management in the older person is present throughout the literature. Age-related factors affect the safety and efficacy of the analgesic treatment and pharmacological aspects are often underlined, especially when impaired cognition and frailty are present. The use of topical analgesics, well tolerated in older persons, allows reduction of concomitant treatments and of adverse events. Optimizing analgesic use in older patients is carried out by exploring motivations and attitudes of the patients, by analysing barriers and practices of clinicians and by setting up structured educational nursing interventions. Although a larger number of older persons are included in studies, prospective and large-scale trials are needed in this vulnerable population characterized by a high variability and heterogeneity.
    Current opinion in supportive and palliative care 03/2012; 6(2):207-12.
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    ABSTRACT: The role of the gut microbiota in patho-physiology of irritable bowel syndrome (IBS) is suggested by several studies. However, standard cultural and molecular methods used to date have not revealed specific and consistent IBS-related groups of microbes. To explore the constipated-IBS (C-IBS) gut microbiota using a function-based approach. The faecal microbiota from 14 C-IBS women and 12 sex-match healthy subjects were examined through a combined strictly anaerobic cultural evaluation of functional groups of microbes and fluorescent in situ hybridisation (16S rDNA gene targeting probes) to quantify main groups of bacteria. Starch fermentation by C-IBS and healthy faecal samples was evaluated in vitro. In C-IBS, the numbers of lactate-producing and lactate-utilising bacteria and the number of H(2) -consuming populations, methanogens and reductive acetogens, were at least 10-fold lower (P < 0.05) compared with control subjects. Concomitantly, the number of lactate- and H(2) -utilising sulphate-reducing population was 10 to 100 fold increased in C-IBS compared with healthy subjects. The butyrate-producing Roseburia - E. rectale group was in lower number (0.01 < P < 0.05) in C-IBS than in control. C-IBS faecal microbiota produced more sulphides and H(2) and less butyrate from starch fermentation than healthy ones. A major functional dysbiosis was observed in constipated-irritable bowel syndrome gut microbiota, reflecting altered intestinal fermentation. Sulphate-reducing population increased in the gut of C-IBS and were accompanied by alterations in other microbial groups. This could be responsible for changes in the metabolic output and enhancement in toxic sulphide production which could in turn influence gut physiology and contribute to IBS pathogenesis.
    Alimentary Pharmacology & Therapeutics 02/2012; 35(7):828-38. · 4.55 Impact Factor
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    ABSTRACT: Previous studies suggest that the antinociceptive action of paracetamol (acetaminophen, APAP) might involve descending inhibitory pain pathways and the opioidergic system: this study explores this issue in humans with naloxone, the opioid antagonist. After ethical approval, 12 healthy male volunteers were included in this randomized, controlled, double-blind, crossover, four-arm study. They were administered intravenous paracetamol (APAP 1 g) or saline (placebo, pl) followed at 100 min with IV naloxone (Nal 8 mg) or saline, every week for 4 weeks. The amplitude of cerebral potentials evoked by thermal/painful stimuli applied on the arm was recorded nine times over 150 min, witnessing of pain integration at central level. Amplitude changes as well as areas under the curve (AUCs) over 150 min were compared for the four treatments by repeated measures anova (significance 0.05). Amplitude changes were significant for APAP/pl vs. pl/pl at t(150) : -44% (95%CI -58 to -30) vs. -27% (95%CI -37 to -17; P < 0.05) but not vs. APAP/Nal. AUC (0-150) of APAP/pl is significantly different from pl/pl (-3452%.min (95%CI -4705 to -2199) vs. -933% min (95%CI -2273 to 407; P = 0.015) but not from APAP/Nal (-1731% min (95%CI -3676 to 214; P = 0.08) and other treatments. AUC (90-150) is not significantly different. This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception, suggesting no significant implication of the opioid system in paracetamol mechanism of action: this needs be confirmed on a larger number of subjects.
    Fundamental and Clinical Pharmacology 11/2011; · 1.99 Impact Factor
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    ABSTRACT: Patients undergoing major surgery represent a good model for the study of the hepatic metabolism of acetaminophen (APAP) after surgery and for the evaluation of how the detoxification process is influenced by aging. Thirty patients received intravenous APAP (1 g/6 h) for 4 days (D1-D4). Daily 24-h urinary metabolites-cysteine-APAP, mercapturate-APAP, APAP, and glucuronide and sulfate conjugates-as well as blood glutathione levels were compared with repeated-measures analysis of variance (significance, P<0.05). Between D1 and D4, cysteine-APAP increased (308±308 mg vs. 570±512 mg, P=0.005), and sulfate and glucuronide conjugates decreased (1,365±1,084 mg vs. 694±600 mg, P<0.0001 and 2,418±817 mg vs. 1,513±1,076 mg, P=0.011, respectively). Blood glutathione decreased (790±125 vs. 623±132 µmol/l, P<0.0001. These changes increased with aging. APAP disposition after major surgery shifts toward the oxidative pathways of metabolism, and this is enhanced with aging. Supplementation with sulfur-containing amino acids should be investigated further as it might minimize the effect on antioxidant defenses, especially in older persons undergoing more extensive surgical procedures.
    Clinical Pharmacology &#38 Therapeutics 11/2011; 90(5):707-11. · 6.85 Impact Factor
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    ABSTRACT: Studies in animals and in patients have suggested that magnesium (Mg), a physiological blocker of N-methyl-D-aspartate receptor, could have an antinociceptive effect in painful situations. This randomised, double-blind, controlled trial in two parallel groups aims at studying oral Mg effects in patients with neuropathic pain. It explores the impact of Mg (6x419 mg Mg chloride/capsule per day for a month), versus placebo (lactose) on pain [Neuropathic Pain Symptom Inventory (NPSI) and numerical scale (NS)], and on quality of life indicators after 4 weeks treatment, in 45 patients suffering from neuropathic pain. After 4 weeks, NPSI, NS and quality of life are not different in the Mg and placebo groups, while the frequency of pain paroxysms diminishes and the emotional component improves in the Mg group compared to baseline. This clinical trial displays a large placebo response and could not demonstrate any significant difference in pain alleviation after a month of oral treatment between Mg and placebo in patients suffering from neuropathic pain. Frequency of pain paroxysms and emotional impact will be explored in future studies as they constitute major aspects of pain alleviation in chronic pain conditions.
    Magnesium research: official organ of the International Society for the Development of Research on Magnesium 06/2011; 24(2):28-35. · 1.38 Impact Factor
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    ABSTRACT: Studies in animals and in healthy volunteers have demonstrated the central serotonergic analgesic mechanism of action of paracetamol involving the inhibition of this analgesia by tropisetron, a 5-HT3 antagonist. This randomized, double-blind, controlled study aims at studying this interaction in post-operative patients after ear surgery. Thirty-six patients are included in two parallel groups with intravenous paracetamol (1 g) and either tropisetron (T, 5 mg/mL) or placebo (c, NaCl 0.9%) administered at the end of surgery. Numerical pain evaluations are performed every 30 min, six times after awakening. The difference between the sums of numerical scales of both groups [9 ± 10 (T) vs. 6 ± 7 (c)] is not significant, but the tropisetron group displays higher pain scores despite additional rescue analgesia. The limits of this trial call for a much larger study to investigate further this pharmacodynamic interaction.
    Fundamental and Clinical Pharmacology 03/2011; 26(3):432 - 437. · 1.99 Impact Factor
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    ABSTRACT: Sulfur amino acids are determinant for the detoxification of paracetamol (N-acetyl-p-aminophenol) through sulfate and glutathione conjugations. Long-term paracetamol treatment is common in the elderly, despite a potential cysteine/glutathione deficiency. Detoxification could occur at the expense of anti-oxidative defenses and whole body protein stores in elderly. We tested how older persons satisfy the extra demand in sulfur amino acids induced by long-term paracetamol treatment, focusing on metabolic and nutritional aspects. Effects of 3 g/day paracetamol for 14 days on fasting blood glutathione, plasma amino acids and sulfate, urinary paracetamol metabolites, and urinary metabolomic were studied in independently living older persons (five women, five men, mean (±SEM) age 74 ± 1 years). Dietary intakes were recorded before and at the end of the treatment and ingested sulfur amino acids were evaluated. Fasting blood glutathione, plasma amino acids, and sulfate were unchanged. Urinary nitrogen excretion supported a preservation of whole body proteins, but large-scale urinary metabolomic analysis revealed an oxidation of some sulfur-containing compounds. Dietary protein intake was 13% higher at the end than before paracetamol treatment. Final sulfur amino acid intake reached 37 mg/kg/day. The increase in sulfur amino acid intake corresponded to half of the sulfur excreted in urinary paracetamol conjugates. In conclusion, older persons accommodated to long-term paracetamol treatment by increasing dietary protein intake without any mobilization of body proteins, but with decreased anti-oxidative defenses. The extra demand in sulfur amino acids led to a consumption far above the corresponding population-safe recommendation.
    Age 02/2011; 34(1):181-93. · 6.28 Impact Factor
  • Lizi Zhao, Gisèle Pickering
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    ABSTRACT: Paracetamol (acetaminophen) is a worldwide used analgesic and antipyretic drug. It is metabolised via several metabolic pathways, including glucuronidation, sulfation, oxidation, hydroxylation, and deacetylation: Hepatic and other organ damage may occur, especially in overdose, because of the accumulation of a toxic metabolite. Intersubject and ethnic differences have been reported in paracetamol metabolism activation, suggesting possible differences in susceptibility to toxicity and in pain alleviation, linked to different pharmacogenetic profiles. This article aims at reviewing, in the literature, the links between paracetamol metabolism and enzyme genotypes in the context of toxic side effects and efficacy of paracetamol in therapeutics.
    Drug Metabolism Reviews 02/2011; 43(1):41-52. · 5.54 Impact Factor
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    ABSTRACT: To compensate for poor acute pain detection in elderly inpatients with inability to communicate verbally (ICV), the Doloplus Collective team devised the 5-item Algoplus behavior-assessment scale specifically aimed at quickly detecting acute pain in these individuals. Algoplus was developed in three successive phases, including expert opinions, caregivers interviews, patient video recordings and statistical procedures. Among the 1500 recorded primary pain behaviors, 48 were selected and clustered into a 5-item scale. This version was validated based on 349 old inpatients (204 with acute pain and 145 without) from different care settings and hospitals. Comparators were objective acute pain clinical situations, experts' clinical judgment on acute pain presence, and self-rating scales (Visual Analog Scale, Numeric Rating Scale and Verbal Descriptor Scale) for a communicative subsample (n=134). Algoplus showed good discriminant validity with adequate internal consistency (Kuder-Richardson-20, 0.712), excellent interrater reliability (intraclass coefficient, 0.812) and high sensitivity to change during specific pain situations and after starting pain management. Excellent correlations were observed between Algoplus and experts' clinical judgment, acute pain clinical situations or each comparator self-rating-pain score. For patients with acute pain conditions, a score ⩾2 out of 5 on the Algoplus scale was retained as the threshold for the presence of acute pain in elderly ICV inpatients, with 87% sensitivity and 80% specificity. In addition, the very brief rating time of ∼1min is particularly relevant in acute-care settings, where repetitive pain-monitoring is required.
    European journal of pain (London, England) 02/2011; 15(2):198.e1-198.e10. · 3.37 Impact Factor
  • Gisèle Pickering, Alain Leplege
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    ABSTRACT: Herpes zoster pain and postherpetic neuralgia (PHN) particularly affect older persons. This literature review presents how quality of life is evaluated and the consequences of shingles and PHN on the quality of life of older persons. Although more than 150 articles have been published on herpes zoster and its consequences, specific studies focusing on the older population are needed, in several domains like epidemiology, preventive medicine, neuropsychology, and pharmacology.
    Pain Practice 12/2010; 11(4):397-402. · 2.61 Impact Factor
  • G. Pickering, R. Salimani, C. Dubray
    European Journal of Pain Supplements 01/2010; 4(1):86-87.

Publication Stats

684 Citations
146.23 Total Impact Points

Institutions

  • 2000–2012
    • University of Auvergne
      • • Faculty of medicine
      • • Faculty of Pharmaceutical Sciences
      Clermont-Ferrand, Auvergne, France
  • 2011
    • Sun Yat-Sen University
      Shengcheng, Guangdong, China
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2002–2011
    • Université Blaise Pascal - Clermont-Ferrand II
      Clermont, Auvergne, France
  • 2003–2009
    • University Hospital Estaing of Clermont-Ferrand
      Clermont, Auvergne, France
  • 2001–2006
    • Centre Hospitalier Universitaire de Clermont-Ferrand
      Clermont, Auvergne, France
  • 2001–2004
    • Centre Hospitalier Universitaire de Nice
      Nice, Provence-Alpes-Côte d'Azur, France