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Steichen O.,University Pierre and Marie Curie | Grateau G.,University Pierre and Marie Curie | Girot R.,University Pierre and Marie Curie | Lefevre G.,Service de Biochimie et Hormonologie
Infection | Year: 2011

Fever is often present during painful vaso-occlusive crisis (VOC) in sickle-cell disease (SCD), but does not always indicate infection. The aim of our study was to test procalcitonin as a marker of invasive bacterial infection in VOC. Consecutive SCD adults hospitalized for VOC were included. Data were collected at admission and within 24 h after the onset of fever. We distinguished patients with clinically defined and microbiologically documented invasive bacterial infection from patients with no evidence of invasive bacterial infection and who fared well without antibiotics. One hundred and twelve patients were enrolled (61% females, median age 23 years, 88% homozygous SCD). All patients with procalcitonin (PCT) level ≥1 μg/L had an invasive bacterial infection, but two patients (33%) with an invasive bacterial infection had a PCT level <1 μg/L. High levels of PCT indicate invasive bacterial infection. However, a single low PCT level without follow-up measurement cannot rule out an invasive bacterial infection and should not withhold the prescription of antibiotics. © 2010 Urban & Vogel.


Hertig A.,French Institute of Health and Medical Research | Hertig A.,University Pierre and Marie Curie | Liere P.,University Paris - Sud | Chabbert-Buffet N.,Service dObsttrique et Gyncologie | And 14 more authors.
American Journal of Obstetrics and Gynecology | Year: 2010

Objective: Experimental data have revealed the critical role played by 2-methoxy-estradiol, a metabolite of 17β-estradiol, in the pathophysiology of preeclampsia. We used gas chromatography/mass spectrometry to measure a whole panel of hormonal steroids in the plasma from women during the third trimester of their pregnancy. Study Design: The population study consists of 24 pregnant patients with different outcomes: normal, or complicated by isolated preeclampsia or by severe preeclampsia with Hemolysis Enzyme Liver Low Platelets (HELLP) syndrome. Results: 17β-estradiol was reduced by 50% in isolated preeclampsia, and by 70% in severe preeclampsia with HELLP syndrome (normal: 8.54 ± 0.9 ng/mL; isolated preeclampsia: 4.65 ± 1.0 ng/mL; severe preeclampsia with HELLP syndrome: 2.64 ± 0.4 ng/mL), as is estrone. Downstream, 2-methoxy-estradiol was decreased only in severe preeclampsia with HELLP syndrome. The concentrations of estrone and 17β-estradiol precursors were comparable between groups, suggesting that placental aromatase is deficient in preeclampsia. Conclusion: The gradual decrease of estrogen levels with increasing severity of preeclampsia suggests an impairment of placental steroidogenesis. © 2010 Mosby, Inc.


PubMed | Service de biochimie et hormonologie, Sahlgrenska Academy East Hospital, University Paris Diderot and King's College London
Type: | Journal: Brain, behavior, and immunity | Year: 2014

Preterm birth is very strongly associated with maternal/foetal inflammation and leads to permanent neurological deficits. These deficits correlate with the severity of white matter injury, including maturational arrest of oligodendrocytes and hypomyelination. Preterm birth and exposure to inflammation causes hypothyroxinemia. As such, supplementation with thyroxine (T4) seems a good candidate therapy for reducing white matter damage in preterm infants as oligodendrocyte maturation and myelination is regulated by thyroid hormones. We report on a model of preterm inflammation-induced white matter damage, in which induction of systemic inflammation by exposure from P1 to P5 to interleukin-1 (IL-1) causes oligodendrocyte maturational arrest and hypomyelination. This model identified transient hypothyroidism and wide-ranging dysfunction in thyroid hormone signalling pathways. To test whether a clinically relevant dose of T4 could reduce inflammation-induced white matter damage we concurrently treated mice exposed to IL-1 from P1 to P5 with T4 (20 g/kg/day). At P10, we isolated O4-positive pre-oligodendrocytes and gene expression analysis revealed that T4 treatment did not recover the IL-1-induced blockade of oligodendrocyte maturation. Moreover, at P10 and P30 immunohistochemistry for markers of oligodendrocyte lineage (NG2, PDGFR and APC) and myelin (MBP) similarly indicated that T4 treatment did not recover IL-1-induced deficits in the white matter. In summary, in this model of preterm inflammation-induced white matter injury, a clinical dose of T4 had no therapeutic efficacy. We suggest that additional pre-clinical trials with T4 covering the breadth and scope of causes and outcomes of perinatal brain injury are required before we can correctly evaluate clinical trials data and understand the potential for thyroid hormone as a widely implementable clinical therapy.


Hertig A.,French Institute of Health and Medical Research | Hertig A.,University Pierre and Marie Curie | Fort J.,Service de Gynecologie Obstetrique | Lefevre G.,Service de Biochimie et Hormonologie | And 5 more authors.
American Journal of Obstetrics and Gynecology | Year: 2010

Objective: The pathogenesis of the HELLP (hemolysis, enzyme liver, low platelets) syndrome is unknown. Recently soluble endoglin (sEng) was identified as a cause of the appearance of schistocytes and liver pathology in an animal model of preeclampsia (PE). Study Design: We explored the value of sEng in 82 women who delivered in a context of normal pregnancy (NP, n = 10), PE (n = 49), or HELLP (n = 23). Results: sEng was elevated in pathological pregnancies (66.7 ± 62 and 75.7 ± 48 pg/mL in PE and HELLP, respectively, vs 5.29 ± 1.25 in NP, P < .001 for both comparisons) and was correlated with an increase in transaminases (r2 = 0.17; P = .05), but it was not statistically different between PE and HELLP. Conclusion: Although recent literature findings demonstrated a role of sEng in the pathophysiology of HELLP syndrome in animal models, we found that, at the time of delivery, sEng was not specifically elevated in preeclamptic patients with HELLP. © 2010 Mosby, Inc. All rights reserved.


Milovanovic I.,French Institute of Health and Medical Research | Njuieyon F.,French Institute of Health and Medical Research | Deghmoun S.,French Institute of Health and Medical Research | Chevenne D.,Service de Biochimie et Hormonologie | And 4 more authors.
PLoS ONE | Year: 2014

Background: Being born small for gestational age (SGA) is a risk factor for later development of type 2 diabetes. The development of glucose tolerance disorders in adults involves insulin resistance and impaired insulin secretion. Objective: To evaluate insulin secretion and insulin sensitivity in a 4-yr old cohort of SGA. Methods: 85 children were prospectively followed from mid-gestation to 4 years of age. Fetal growth velocity (FGV) was measured using ultrasound measurements. Body composition and hormonal profile were measured at birth, 1 and 4 years. Results: 23 SGA babies had lower birth weight compared to 62 AGA (-1.9±0.3 vs. -0.6±0.8 z-score; p<0.0001) and they were thinner at birth (ponderal index 24.8±1.8 vs. 26.3±3.1 kg/m3; p = 0.01 and fat mass 11±2.6 vs. 12.9±3.1%; p = 0.01). No significant differences in other measured metabolic and hormonal parameters were observed between two groups at birth. SGA infants experienced an early catch-up growth in weight (mean gain of 1.1±0.6 SD) during the first year of life. At 4 years, SGA children remain lighter than AGA, but with weight z-score in the normal range (-0.1±1.3 vs. 0.5±1.3 z-score; p = 0.05). No excess of fat mass was observed (19±4.8 vs. 19.7±4.1%; p = 0.45). 120-min plasma glucose was significantly higher (6.2±1.1 vs. 5.6±0.9 mmol/l; p = 0.006) and insulinogenic index was significantly lower (0.28±0.15 vs. 0.40±2.4; p = 0.02) in the SGA group at 4-yrs of life contrasting with a preserved insulin sensitivity (QUICKI 0.47±0.09 vs. 0.43±0.05; p = 0.06). Conclusion: SGA children with compensatory catch-up growth in first year of life show mild disturbances of glucose tolerance associated to a lower insulinogenic index at 4-yrs of age suggesting impairment of β-cell function. © 2014 Milovanovic et al.


Bastard J.-P.,Service de biochimie et hormonologie | Bastard J.-P.,French Institute of Health and Medical Research | Bastard J.-P.,University Pierre and Marie Curie | Lavoie M.-E.,University of Montréal | And 6 more authors.
Diabetes and Metabolism | Year: 2012

Aim: The study evaluated and compared, with other surrogate indices of insulin sensitivity/resistance (IS/R), the relevance of the TyG index, a product of fasting glucose and triglyceride (TG) levels, and the EGIR index, which includes TG, high-density lipoprotein cholesterol (HDL-c) and waist circumference in its formula to estimate IS/R, in non-diabetic postmenopausal women. Methods: A secondary analysis was performed using the baseline data for 163 non-diabetic postmenopausal women from the Montreal-Ottawa New Emerging Team (MONET) population database. The subjects participated in hyperinsulinaemic-euglycaemic (HIEG) clamp and oral glucose tolerance (OGTT) tests. Correlations and comparisons between surrogate indices were performed in addition to inter-rater agreement tests. The optimal value of surrogate indices for diagnosis of IS/R was established on a receiver operating characteristic (ROC) scatter plot. Results: A significant correlation was found between the HIEG clamp and all IS/R surrogate indices tested [r = -0.370 (TyG index) to 0.608 (SIisOGTT index); P< 0.001]. On ROC curve analysis, a higher AUROC was found for SIisOGTT (0.791) than for TyG and EGIR (0.706 and 0.675, respectively; P= 0.07 and P< 0.05, respectively). Conclusion: The TyG and EGIR IS/R indices were only relatively modestly related to the HIEG clamp. In contrast, both fasting- and OGTT-derived IS/R surrogate indices, which include insulin values in their formulae, appeared to be more accurate in estimating IS/R in our study population. Thus, the TyG and EGIR IS/R indices need to be tested and validated more extensively in different populations before being put to large-scale clinical use. © 2012 Elsevier Masson SAS.


Milovanovic I.,Institute National Of La Santeet Of La Recherche Medicale | Njuieyon F.,Institute National Of La Santeet Of La Recherche Medicale | Deghmoun S.,Institute National Of La Santeet Of La Recherche Medicale | Chevenne D.,Service de Biochimie et Hormonologie | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Background: Being born small for gestational age (SGA) is regarded as a risk factor for later metabolic complications. The SGA is defined as a birth weight below -2 SD of the distribution for sex and gestational age. However, the definition of SGA does not distinguish between those born after fetal growth restriction and innate SGA (iSGA). Objective: Our objective was to test whether innate SGA infants show any metabolic complications at the age of 2 yr in comparison with infants born appropriate for gestational age (AGA). Methods: Fifty-eight infants with family SGA risk factors (SGA in a previous pregnancy or among parents, maternal height less than -2 SD for adult height in French women, and small fetal size at second-trimester ultrasound examination) were prospectively followed from midgestation to 2 yr of age. Fetal growth velocity was measured from ultrasound measurements. Body composition and hormonal profile were measured at birth and 1 and 2 yr. Results: Fetal growth velocity was not significantly different between iSGA and AGA (-0.17 ± 0.2 vs. -0.17 ± 0.3 percentiles/d of gestation; P = 0.96). iSGA infants were significantly lighter at birth (-1.7 ± 0.45 vs. 0.46 ± 0.77 SD; P < 0.0001) and at 4 months of age (-0.85 ± 0.88 vs. 0.29 ± 1 SD; P < 0.0001), and they remain so over follow-up (-0.73 ± 1.08 vs. 0.2 ± 1.02 SD; P = 0.0014 at 2 yr). Height z-scores and percent fat time courses followed a similar pattern. No differences in any of the metabolic and hormonal parameters were observed between iSGA and AGA up to 2 yr (insulin at birth, 5.1 ± 6.8 vs. 5.2 ± 4.6 mIU/liter, P = 0.2; at 2 yr, 2 ± 1.6 vs. 2 ± 1.5 mIU/liter, P = 0.66). Conclusion: Infants born iSGA do not experience severe fetal growth restriction and do not show any evidence of metabolic risk either at birth or in the first 2 yr of life. Copyright © 2012 by The Endocrine Society.


PubMed | Nancy University Hospital Center, Pole de biochimie et biologie moleculaire, Service de biochimie et hormonologie, Lyon University Hospital Center and Laboratoire Of Biochimie
Type: Journal Article | Journal: Annales de biologie clinique | Year: 2015

Hemolysis should lead to changes in test results. Our study evaluated the impact of hemolysis on 26 blood measurements of stat biochemistry markers (sodium, potassium, chloride, urea, creatinine, glucose, total protein, calcium, magnesium, inorganic phosphorus, uric acid, C-reactive protein, total bilirubin, ASAT, ALAT, LDH, creatine kinase, alkaline phosphatase, glutamyl-transferase, lipase, alcohol, iron, hCG, troponins, natriuretic peptides) determined with 13 different types of instruments in 17 hospital laboratories. Four pools of samples (collected from lithium heparin or EDTA or sodium fluoride tubes, according to the measured parameters) were overloaded with five increasing concentrations of whole blood lysate (final concentration from 0 to 2.000 mg/dL). Replication was performed for each assay, average values were calculated and differences between results with and without lysate were analyzed. A difference exceeding the square root of the sum of both squared analytic and biologic imprecisions for each analyte, was judged to be significant. Except homogeneous and expected impact of hemolysis on certain parameters like potassium, LDH... (due to their intra-erythrocyte concentration) a heterogeneous effect was found for other parameters, according to the analyzer and/or to the methodology. In summary, this study confirms the importance of mastering the measurement of the hemolysis and leads to several recommendations: (i) biologists should have a good knowledge of the impact of hemolysis on the measurements they perform, depending on their chosen analyzers; (ii) if an interference is noticed, it is recommended to add to the result a relevant comment and to check that the comment is properly edited in the laboratory computer software and appears on printed and transmitted results.


PubMed | Service de biochimie et hormonologie and French Institute of Health and Medical Research
Type: Journal Article | Journal: PloS one | Year: 2014

Being born small for gestational age (SGA) is a risk factor for later development of type 2 diabetes. The development of glucose tolerance disorders in adults involves insulin resistance and impaired insulin secretion.To evaluate insulin secretion and insulin sensitivity in a 4-yr old cohort of SGA.85 children were prospectively followed from mid-gestation to 4 years of age. Fetal growth velocity (FGV) was measured using ultrasound measurements. Body composition and hormonal profile were measured at birth, 1 and 4 years.23 SGA babies had lower birth weight compared to 62 AGA (-1.90.3 vs. -0.60.8 z-score; p<0.0001) and they were thinner at birth (ponderal index 24.81.8 vs. 26.33.1 kg/m3; p=0.01 and fat mass 112.6 vs. 12.93.1%; p=0.01). No significant differences in other measured metabolic and hormonal parameters were observed between two groups at birth. SGA infants experienced an early catch-up growth in weight (mean gain of 1.10.6 SD) during the first year of life. At 4 years, SGA children remain lighter than AGA, but with weight z-score in the normal range (-0.11.3 vs. 0.51.3 z-score; p=0.05). No excess of fat mass was observed (194.8 vs. 19.74.1%; p=0.45). 120-min plasma glucose was significantly higher (6.21.1 vs. 5.60.9 mmol/l; p=0.006) and insulinogenic index was significantly lower (0.280.15 vs. 0.402.4; p=0.02) in the SGA group at 4-yrs of life contrasting with a preserved insulin sensitivity (QUICKI 0.470.09 vs. 0.430.05; p=0.06).SGA children with compensatory catch-up growth in first year of life show mild disturbances of glucose tolerance associated to a lower insulinogenic index at 4-yrs of age suggesting impairment of -cell function.


PubMed | Service de Biochimie et Hormonologie
Type: Evaluation Studies | Journal: Diabetes & metabolism | Year: 2012

The study evaluated and compared, with other surrogate indices of insulin sensitivity/resistance (IS/R), the relevance of the TyG index, a product of fasting glucose and triglyceride (TG) levels, and the EGIR index, which includes TG, high-density lipoprotein cholesterol (HDL-c) and waist circumference in its formula to estimate IS/R, in non-diabetic postmenopausal women.A secondary analysis was performed using the baseline data for 163 non-diabetic postmenopausal women from the Montreal-Ottawa New Emerging Team (MONET) population database. The subjects participated in hyperinsulinaemic-euglycaemic (HIEG) clamp and oral glucose tolerance (OGTT) tests. Correlations and comparisons between surrogate indices were performed in addition to inter-rater agreement tests. The optimal value of surrogate indices for diagnosis of IS/R was established on a receiver operating characteristic (ROC) scatter plot.A significant correlation was found between the HIEG clamp and all IS/R surrogate indices tested [r=-0.370 (TyG index) to 0.608 (SIisOGTT index); P<0.001]. On ROC curve analysis, a higher AUROC was found for SIisOGTT (0.791) than for TyG and EGIR (0.706 and 0.675, respectively; P=0.07 and P<0.05, respectively).The TyG and EGIR IS/R indices were only relatively modestly related to the HIEG clamp. In contrast, both fasting- and OGTT-derived IS/R surrogate indices, which include insulin values in their formulae, appeared to be more accurate in estimating IS/R in our study population. Thus, the TyG and EGIR IS/R indices need to be tested and validated more extensively in different populations before being put to large-scale clinical use.

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