C Oliver

Assistance Publique Hôpitaux de Marseille, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (277)746.37 Total impact

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    ABSTRACT: Aging is associated with changes in thyroid function at several levels of regulation. Thyroid hormones levels are usually within the lower part of normal values reported in the general population. Two changes in aging are of clinical importance: a shift in the distribution of TSH levels, the 97.5th percentile of the TSH distribution being within 6μUI/ml after 70 years and within 7.5μUI/ml in subjects older than 80 instead of 4.5μU/ml in the general population, and an increased prevalence of thyroid nodularity, requiring reliable and non-invasive methods of investigation in older people. Lastly, aging may be associated with comorbidities, high risk of drug interactions and under nutrition, which may make difficult the interpretation of laboratory data and in some cases induce iatrogenic thyroid diseases. Considering the high prevalence of the thyroid diseases in older patients and a better understanding of the physiopathological hormonal variations with the ageing, it seemed useful to propose a review to help the clinician in the care of these situations.
    La Revue de Médecine Interne 01/2013; · 0.90 Impact Factor
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    ABSTRACT: OBJECTIVES: To evaluate hability of a threshold value in ShearWave™ elastography to rule out malignant thyroid nodules while studying its pertinence in association with morphological signs. EQUIPMENT AND METHODS: 148 patients (110 women and 38 men; 52.5 y.o. 15.8) referred for surgery of thyroid nodules underwent standard ultrasound as well as elastography. Characteristics of the morphological signs and maximum elastographic index were calculated in relation to histology. Association of morphological signs alone and then of elastography was also evaluated. One hundred and fifty one nodules were studied on a double-blind basis. RESULTS: 297 nodules were studied. Thirty-five cancers were detected (11.6%). Elastographic index was higher in malignant nodules (115kPa 60.4) than in benign nodules (41kPa 25.8) (p<0.001, Student's t-test). Cut off value of 66kPa was the best to discriminate malignant nodules with a sensitivity of 80% (CI 95%, 62.5; 90.9) and a specificity of 90.5% (CI 95%, 86.1; 93.6) (p=0.0001). Association of elastography and morphological ultrasound signs presented a sensitivity of 97% (CI 95%, 83.3; 99.8) and a negative predictive value of 99.5% (CI 95%, 95.6; 99.9). Interobserver reproducibility proved to be excellent with an interclass correlation of 0.97 (CI 95%, 0.96; 0.98) (p<0.001). CONCLUSION: The 66kPa threshold in Shear Wave elastography is the best ultrasound sign to rule out malignant thyroid nodules. The method is simple, quantitative, reproducible and usable in the study of nodules larger than 3cm. Progress must still be made in the study of calcified nodules and follicular tumors.
    European journal of radiology 09/2012; · 2.65 Impact Factor
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    ABSTRACT: Today there is a better understanding of the events involved in the initiation and progression of thyroid cancer. It is indeed now known that BRAF and RAS mutations and RET/PTC and PAX8/PPARγ rearrangements account for the majority of molecular alterations detected in differentiated thyroid cancers. Abnormal regulation of microRNAs (miRNAs) is also a promising way of research. The diagnostic utility and prognostic value of detecting these molecular events has been analyzed in several recent studies. BRAF mutation analysis improves the performance of fine-needle aspiration diagnosis by increasing specificity in "indeterminate" cytologies and sensitivity in false negatives. Testing for a "panel of mutations" (BRAF, RAS, RET/PTC and PAX8/PPARγ) improves the performance, detecting papillary carcinomas with non-classic histology. The specificity of these analyzes is excellent but their sensitivity is still insufficient. In the future, specific miRNAs expression profiles in thyroid carcinoma and identification of new mutations might provide interesting information. Several studies have found that BRAF mutations are associated with a more aggressive tumor behavior, a higher risk of recurrence and treatment failure. With regard to the other mutations and rearrangements, current data are conflicting and it seems premature to draw practical conclusions applicable in routine practice. Lastly, targeted therapy with tyrosine kinase inhibitors, based on our understanding of the molecular mechanisms of thyroid oncogenesis, has shown promise in metastatic, progressive, and radioactive iodine-refractory differentiated thyroid carcinomas.
    Annales d Endocrinologie 04/2012; 73(3):155-64. · 1.02 Impact Factor
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    ABSTRACT: The determination of elasticity index by elastography has been recently proposed in the evaluation of thyroid nodules, since malignancy is correlated with stiffness of the nodules. The aim of this report is to give an overview on different techniques and results reported by eleven groups active on the field. Advantages and limitations of elastography are also discussed. In our opinion, further studies, preferentially multicentric, are necessary before being able to conclude about the place of elastography in thyroid nodules evaluation, versus fine-needle aspiration cytology (FNAC), the gold standard. Indeed, elastography could reduce FNAC or at least allow to select nodule's (or nodular zone's) for aspirations.
    Annales d Endocrinologie 04/2011; 72(2):120-4. · 1.02 Impact Factor
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    ABSTRACT: Our objective was to report a single-center experience of the management of pituitary tumor apoplexy. We retrospectively analyzed a series of 44 patients hospitalized for pituitary apoplexy between January 1996 and March 2008 at the Timone Hospital, Marseille, France. Most frequent presenting symptoms were headaches (93%), visual impairment (85%) and vomiting (59%). Hypopituitarism was present at diagnosis in 88% of patients, with a high incidence of corticotroph deficiency (70%). A risk factor was found in 52% of patients, mostly hypertension. Apoplexy occurred in a previously undiagnosed pituitary adenoma in 32/44 cases (73%). The apoplectic event concerned 12 secreting, 27 non-functioning, 4 uncharacterized adenomas and one Rathke's pouch cyst. Nineteen patients underwent surgery within the first month, and one patient had conventional radiotherapy. Twenty-four patients, who had no ophthalmic or neurological signs, were conservatively treated in first intention; among them, 6 received high dose corticosteroids. After a median follow-up of 21 months, there was no significant difference in terms of endocrine or visual recovery between the operated and the conservatively treated groups, nor between patients treated with corticosteroids or not. Panhypopituitarism was observed in 52% of patients, but partial or complete visual recovery was present in the majority of patients (91%), whatever the therapeutic approach. The outcome of patients treated with or without surgery for pituitary apoplexy without severe neuro-ophthalmic deficits seems to be identical, pleading for a conservative management of pituitary apoplexy in the absence of visual emergency.
    Journal of endocrinological investigation 01/2011; 34(7):502-9. · 1.65 Impact Factor
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    ABSTRACT: Introduction L’élastographie utilise les ultrasons pour évaluer l’élasticité des tissus. L’EOC est une nouvelle technique qui permet d’estimer la dureté des tissus de manière focale. Elle a l’avantage d’être quantitative, en temps réel et indépendante de l’opérateur. Le but de cette étude est d’évaluer l’efficacité de l’EOC pour prédire la malignité et de la comparer avec les caractéristiques échographiques usuelles. Patients et Méthodes 93 patients et 39 sujets témoins ont été inclus. La valeur prédictive de l’EOC a été établie par des corrélations entre l’élasticité, les paramètres échographiques et l’histologie. L’index d’élasticité (IE) a été analysé dans un premier temps seul. Puis des scores ont été construits avec les paramètres échographiques : vascularisation intranodulaire, hypo-échogénicité et microcalcifications (score1 = score Echo), et avec les mêmes paramètres échographiques plus l’IE (score2 = score Echo+ IE). Pour l’analyse statistique, des études uni et multivariées ont été menées et des courbes ROC ont été réalisées. Résultats 146 nodules ont été analysés chez 93 patients. Vingt neuf nodules étaient malins (19,9 %). L’IE moyen était de 150 KPa ± 95 (30-356) pour les nodules malins vs 36 KPa ± 30 (0-200) pour les bénins (p < 0,001, test T de Student). Pour une valeur prédictive positive > 80 % : les caractéristiques de l’index d’élasticité (IE) (cut off: 65 kPa) étaient : sensibilité = 85,2 %, spécificité = 93,9 %. Les caractéristiques du score Echo étaient : sensibilité = 51,9 % [33,1 ; 70,7] % et spécificité = 97 % [93,6 ; 1] %, et pour le score Echo+ IE : sensibilité = 81,5 % [66,9 ; 96,1] % et spécificité = 97,0 % [93,6 ; 1] %. Conclusions L’élastographie par ondes de cisaillement (EOC) donnent des résultats encourageants. Une étude prospective plus importante devrait être entreprise pour confirmer ces résultats et définir la place respective de l’EOC, de l’échographie classique et de la cytoponction.
    Ultrasound in Medicine and Biology - ULTRASOUND MED BIOL. 09/2010; 147(4):4-5.
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    ABSTRACT: Elastography uses ultrasound (US) to assess elasticity. Shear wave elastography (SWE) is a new technique that estimates tissue stiffness in real time and is quantitative and user independent. The aim of the study was to assess the efficiency of SWE in predicting malignancy and to compare SWE with US. Ninety-three patients and 39 control subjects were included in the study. Predictive value of SWE was assessed by correlation between elasticity, US parameters, and histology. Elasticity index (EI) was first analyzed alone. Scores have been constructed with echographic parameters, i.e. vascularity, hypoechogenicity, and microcalcifications (Score 1=US Score), and with the same parameters plus EI (Score 2=US+SWE Score). For statistical analysis, univariate and multivariate analysis and receiver operating characteristic curves were used. A total of 146 nodules from 93 patients were analyzed. Twenty-nine nodules (19.9%) were malignant. Mean (±sd) EI was 150±95 kPa (range, 30-356) in malignant nodules vs. 36±30 (range, 0-200) kPa in benign nodules (P<0.001, Student's t test). For a positive predictive value of at least 80%, characteristics of tissue elasticity (cutoff, 65 kPa) were: sensitivity=85.2%, and specificity=93.9%. Characteristics of the US Score were: sensitivity=51.9% [95% confidence interval (CI), 33.1; 70.7], and specificity=97% (95% CI, 93.6; 1). Characteristics of the US+SWE Score were: sensitivity=81.5% (95% CI, 66.9; 96.1), and specificity=97.0% (95% CI, 93.6; 1). Promising results have been obtained with SWE. This technique may be applied to multinodular goiters. Larger prospective studies are needed to confirm these results and to define the respective places of SWE, US, and FNA.
    The Journal of Clinical Endocrinology and Metabolism 09/2010; 95(12):5281-8. · 6.31 Impact Factor
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    ABSTRACT: Adrenal insufficiency is caused by primary adrenal failure or by impairment of the corticotropic axis. In both situations, cortisol secretion is deficient, and hydrocortisone is a logical replacement therapy. However, no consensus guideline for dosing has been published, and clinicians adapt the dose empirically after only a clinical evaluation. Under this regimen, some patients receiving an inappropriately high dose of cortisol feel comfortable and also have an increased risk of adverse effects. We performed a pharmacokinetic study of cortisol in patients with adrenal insufficiency to evaluate plasma concentrations when the dosing was based on clinical examination and to develop a model allowing optimization of drug dosing. This was a prospective, open-label study in two endocrinology departments and a clinical investigation centre (Assistance Publique Hôpitaux de Marseille, Marseille, France). Fifty patients with primary (n = 20) or secondary (n = 30) adrenal insufficiency were recruited. All patients were given their usual hydrocortisone replacement regimen. Blood samples for cortisol measurements were drawn at 0600, 0800, 1000, 1200, 1400, 1600, 1800, 2000, 2200 and 0000 h. The observed values were compared with the known physiological range throughout the day (0800, 1600 and 0000 h). A population pharmacokinetic analysis was performed using nonlinear mixed-effects modelling software (NONMEM). The final pharmacokinetic model was then used to simulate several hydrocortisone dosing scenarios. Thirteen different treatment regimens for 50 patients were observed. The cortisol plasma concentrations were compared with the physiological range and showed that 79%, 55% and 45% of patients were over- or under-treated at 0800, 1600 and 2400 h, respectively. The cortisol concentrations showed wide variability and were best described using a one-compartment model with zero-order input and first-order elimination. The pharmacokinetic parameters (intersubject variability) were the following: duration of absorption 0.54 hour, volume of distribution 38.7 L (39.7%) and clearance 12.1 L/h (23.2%). The proportional residual error was 32.3%. This final model was then used to simulate 18 different dosing regimens. The regimen with the highest proportion of simulated patients within the physiological targets was 10 + 5 + 5 mg at 0730, 1200 and 1630 h, respectively. However, even with this regimen, about 54%, 44% and 32% of patients would remain over- or under-treated at 0800, 1600 and 2400 h, respectively. Most patients with adrenal insufficiency are imperfectly treated with hydrocortisone relative to their plasma cortisol concentrations. Using simulation, a standard dosing regimen is suggested, which increases the proportion of patients within the physiological target concentrations. However, an individualized dose adjustment would be more accurate.
    Clinical Pharmacokinetics 07/2010; 49(7):455-63. · 5.49 Impact Factor
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    ABSTRACT: AimSporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI.MethodsEvery patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded.ResultsThe ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7–120 mm (mean 30.3 mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up.ConclusionAggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.RésuméIntroductionLes insulinomes malins sporadiques sont une pathologie rare. Le manque d’informations sur cette pathologie dans la littérature et le développement de traitements agressifs sur les métastases hépatiques nous ont conduit à analyser de façon rétrospective une série de 12 cas d’insulinome malin sporadique.Patients et MéthodesTous les patients d’une métropole régionale présentant un insulinome malin selon les critères de l’OMS de 2004, hors néoplasie endocrinienne multiple de type 1 et tumeurs à risque d’évoluer vers la malignité, avec confirmation anatomopathologique entre 1970 et juin 2005 ont été inclus.RésultatsLe sex-ratio était de 4H/8F avec un âge moyen au diagnostic de 52,5 ans. L’épreuve de jeûne a pu être effectuée chez dix patients et a été interrompue chez neuf d’entre eux après une durée moyenne de 12 heures 45 minutes. La taille moyenne des tumeurs réséquées était de 7 à 120 mm (moyenne 30,3 mm). Les 12 patients ont été opérés. Six patients avaient une ou des métastases hépatiques et une patiente avait un envahissement ganglionnaire adjacent au pancréas. Après la chirurgie, six patients avaient une maladie persistante (suivi moyen de 1,8 ans) appelant d’autres traitements (chimioembolisation, radiofréquence, transplantation hépatique, analogues de la somatostatine…), un patient a récidivé 8,5 ans après la chirurgie, six patients sont en rémission complète (suivi moyen de 5,8 ans). Seulement une patiente est décédée après 24 mois de traitement.ConclusionCette étude rétrospective illustre la grande variabilité du pronostic des insulinomes malins sporadiques. Leur habituel bas grade de malignité et leur évolution lente conduit à permettre des traitements agressifs sur les métastases hépatiques. La prise en charge de ces patients demande une collaboration multidisciplinaire pour pouvoir améliorer leur survie.
    Diabetes & Metabolism 01/2008; · 2.39 Impact Factor
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    ABSTRACT: Data on effects of statins on resting oxidant-antioxidant status are contradictory and no study has been published on the effects of statins on exercise-induced oxidative stress. We carried out a 6-month longitudinal study in 10 dyslipidemic patients receiving 10 mg/day atorvastatin and 13 healthy sedentary subjects. Thiobarbituric acid reactive substances (TBARS) and reduced ascorbic acid (RAA) were measured in plasma at rest and every 5 minutes after submaximal isometric thumb adduction and handgrip sustained until exhaustion. At inclusion, resting TBARS and RAA levels in controls and patients did not differ and exercise increased TBARS and decreased RAA. Atorvastatin reduced resting TBARS and RAA levels in a time-dependent but lipid-independent manner. The main effect was a post-exercise increase in TBARS, without affecting the post-exercise RAA levels. The reduction in oxidative stress occurred earlier in oxidative muscles involved in thumb adduction. In conclusion, atorvastatin lowers resting oxidant-antioxidant activity: exercise-induced oxidative stress occurs mainly in muscles having a high oxidative capacity.
    International journal of clinical pharmacology and therapeutics 05/2007; 45(4):244-52. · 1.20 Impact Factor
  • Annals of the New York Academy of Sciences 12/2006; 553(1):567 - 568. · 4.38 Impact Factor
  • Annals of the New York Academy of Sciences 12/2006; 553(1):479 - 482. · 4.38 Impact Factor
  • Annales d Endocrinologie 10/2006; 67(5):526-526. · 1.02 Impact Factor
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    ABSTRACT: To study alterations in muscle function combining physiological, electrophysiological and metabolic measurements in patients receiving a statin at various dosages during long-term therapy. A 3-month (D0, D30 and D90) longitudinal physiological and electrophysiological muscle study was performed in 26 patients receiving 10, 40 or 80 mg/day atorvastatin. All subjects performed maximal (MVC) and submaximal (60% MVC) isometric thumb adduction, handgrip and knee extension exercises during the recording of surface electromyograms (EMG) of the adductor pollicis (AP), flexor digitorum (FD) and vastus lateralis (VL). The compound muscle potential (M-wave) evoked by direct muscle stimulation was measured at rest and after 60% MVCs and the EMG power spectrum was analyzed during sustained effort. Blood was sampled from an antecubital vein for measurements of pH, lactate and potassium levels after thumb adduction and handgrip exercises. The measurements were repeated on Day 0 (D0), D30 and D90. Atorvastatin did not affect the MVC and endurance time to fatigue. Post-exercise M-wave alterations in the AP began at D30 with the 80 mg/day treatment and there was a reduced or suppressed leftward shift in the EMG power spectrum in the AP and VL with all 3 dosages. In the AP, the EMG changes appeared earlier (D30) with 80 mg/day whereas they only occurred at D90 on the lower dosages. Atorvastatin had no effect on the maximal postexercise variations in pHv and lactate but it significantly reduced the maximal increase in plasma potassium concentration after thumb adduction and handgrip exercise, the effects being only present at D90 on 10 mg/day but occurring as early as D30 with higher dosages. A 3-month atorvastatin treatment did not affect the maximal performance of skeletal muscle during voluntary efforts but EMG analysis revealed a reduced muscle excitability and an attenuated adaptation to fatigue. These effects prevailed in muscles containing the largest proportion of slow-oxidative fibers and were associated with a reduced outward flow of potassium.
    International journal of clinical pharmacology and therapeutics 07/2006; 44(6):251-61. · 1.20 Impact Factor
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    ABSTRACT: Overweight and obesity correspond to excess fat, defined and assessed in clinical practice by the body mass index (BMI: ratio of weight in kilograms to height in meters squared). Obesity has numerous negative health consequences: metabolic, cardiovascular, and mechanical complications, predisposition to some cancers, and psychosocial repercussions. In France in 2003, 30% of adults were overweight and 11% obese. The increase in fat reserves that characterizes obesity results from an energy imbalance, which in turn arises from complex interactions. This explains the clinical and biological heterogeneity of human obesity. Control of this epidemic in the years to come probably depends more on the implementation of activities coordinated by various social actors than on the development of a specific drug.
    La Presse Médicale 03/2006; 35(2 Pt 2):270-6. · 0.87 Impact Factor
  • Annals of the New York Academy of Sciences 02/2006; 839(1):249 - 253. · 4.38 Impact Factor
  • Presse Medicale. 01/2006; 35(2):270-276.
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    ABSTRACT: Several indicators of corticotropic axis hyperactivity have been observed in common abdominal obesity, which is clinically similar to the obesity found in Cushing's syndrome. Corticotropic axis hyperactivity may be involved in the development and metabolic and cardiovascular complications of abdominal obesity. Several mechanisms may be responsible for this hormonal dysregulation: genetic, lifestyle, and nutritional factors, and chronic stress. We note the necessity of methodologically-impeccable clinical studies for an objective evaluation of the role of stress in obesity.
    La Presse Médicale 01/2006; 34(21):1646-53. · 0.87 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 10/2005; 132:266-267. · 0.60 Impact Factor
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    ABSTRACT: The efficacy of a low-protein diet in the secondary prevention of diabetic nephropathy is not established in patients with type 1 or type 2 diabetes mellitus. To determine whether a low-protein diet slows the decrease in glomerular filtration rate (GFR) and decreases the albumin excretion rate (AER) in diabetic patients with incipient and overt nephropathy, we performed a 2-year prospective, randomized controlled trial comparing the effects of a low-protein diet (0.8 g/kg/day) with a usual-protein diet. The study was conducted in a University hospital and included 63 type 1 and type 2 diabetic patients with either incipient or overt nephropathy and mild renal failure (prestudy GFR, 80 +/- 20 mL/min). The primary outcome measures were decreased in GFR and 24-hour AER. In the low-protein-diet group, patients were younger (52 +/- 12 versus 63 +/- 9 years old) and more often were type 2 diabetic. During the follow-up period, according to dietary records the low-protein-diet group consumed 16% +/- 3% of total caloric intakes as compared with 19% +/- 4% in the usual-protein-diet group (P < .02), but 24-hour urinary urea excretions did not differ between the two groups. The 2-year GFR decrease was 7 +/- 11 mL/min in the low-protein-diet group and 5 +/- 15 mL/min in the usual-protein-diet group (P = not significant). AER did not increase significantly in the two diet groups during the follow-up period. Blood pressure and glycemic control were similar in the two groups all along the study. The decrease in GFR and AER were also similar in 6 compliant patients according to dietary records and to 24-hour urinary urea excretions from the low-protein-diet group and in 12 patients from the usual-protein-diet group. A 2-year low-protein diet did not alter the course of GFR or of AER in diabetic patients with incipient or overt nephropathy receiving renin-angiotensin blockers with strict blood pressure control.
    Journal of Renal Nutrition 10/2005; 15(4):398-406. · 1.75 Impact Factor

Publication Stats

3k Citations
746.37 Total Impact Points

Institutions

  • 2003–2012
    • Assistance Publique Hôpitaux de Marseille
      • Service d'endocrinologie, nutrition et maladies métaboliques
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 1989–2007
    • Aix-Marseille Université
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2006
    • Observatoire de la Côte d'Azur
      Grasse, Provence-Alpes-Côte d'Azur, France
  • 1993–2005
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • Faculté des Sciences Ain Chock - Casablanca
      Anfa, Grand Casablanca, Morocco
  • 1987–2002
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1999
    • University of Crete
      • Laboratory of Experimental Endocrinology
      Retimo, Crete, Greece
  • 1992–1998
    • University of Naples Federico II
      • Department of Molecular Medicine and Health Biotechnology
      Napoli, Campania, Italy
  • 1994–1995
    • Slovak Academy of Sciences
      • Institute of Experimental Endocrinology
      Bratislava, Bratislavsky Kraj, Slovakia
  • 1980
    • University of Texas at Dallas
      Richardson, Texas, United States
  • 1974
    • University of Texas Southwestern Medical Center
      • Department of Pharmacology
      Dallas, Texas, United States