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IntroductionAlthough aircraft noise is known to impact human health, the biological pathway is still unclear. One of the possible pathway is that aircraft noise exposure may induce a modification o...

Resume Introduction Les recommandations internationales pour l’administration de la vitamine D (25-OH) chez les prematures sont divergentes (800–1000 UI/jour en Europe, 200 UI/kg sans depasser 400 UI/j aux Etats-Unis). Les nouveau-nes prematures de faible poids de naissance sont a risque de carence, mais egalement de surdosage en 25-OH. Methode Entre 2013 et 2015, 16 anciens prematures ( Resultats L’âge gestationnel etait de 27 (24–35) SA pour un poids de 810 (560–2120) grammes. Le signe d’appel du surdosage en 25-OH avait ete une nephrocalcinose (37 %), une hypercalcemie (44 %) ou une hypercalciurie (19 %). L’âge le jour du signe d’appel etait de 36,6 (27,6–47,6) SA. Un dosage de 25-OH avait ete realise 13 (0–281) jours apres le signe d’appel ; la concentration en 25-OH etait alors de 210 (119–350) nmol/L et celle en 1-25(OH), lorsqu’elle avait ete mesuree (n = 10), de 370 (245–718) pmol/L. Apres arret de la supplementation, la 25-OH s’etait normalisee chez 10 patients dans un delai de 10 (3–32) mois. Conclusion Le diagnostic de surdosage en 25-OH chez les anciens prematures doit etre envisage devant l’existence d’une nephrocalcinose, d’une hypercalcemie ou d’une hypercalciurie. Il justifie la realisation d’un dosage de la 25-OH. La supplementation en vitamine D est essentielle pour une formation osseuse optimale mais les objectifs cibles superieurs ne devraient probablement pas exceder 120 nmol/L.

Preterm neonates are particularly at risk of vitamin D (25-D) deficiency. To prevent rickets and osteopenia in this population, international guidelines vary between 800 and 1000IU per day of vitamin D in Europe and recommend 400IU per day in the USA. Target levels of circulating 25-D are not well identified, with the lower target level 50-75nmol/L and the upper target level probably 120nmol/L.Between 2013 and 2015, 16 premature infants (born35WG) were referred to pediatric nephrology clinics because of symptoms secondary to 25-D overdose during the neonatal period. Clinical and biological data were retrospectively reviewed to better define this population. The results are presented as the median (range).Gestational age was 27 (24-35)WG with a birth weight of 810 (560-2120)g. Nephrocalcinosis was the initial symptom in 37% of cases, hypercalcemia in 44%, and hypercalciuria in 19%. Daily vitamin D doses were 333 (35-676)IU. Age and body weight at initial symptom were 36.6 (27.6-47.6)WG and 2300 (640-3760)g, respectively. The 25-D level at the time of the first dosage was 210 (119-350)nmol/L and the 1-25 vitamin D level was 370 (245-718)pmol/L (local normal values for age240). During follow-up, 12 patients displayed nephrocalcinosis, ten hypercalciuria, and three hypercalcemia. The 25-D level normalized in ten patients within 10 (3-32)months after vitamin D withdrawal. Nephrocalcinosis improved in ten of 12 patients, within 12 (3-30)months. Vitamin D could be readministered in ten patients. When searched (n=3), no CYP24A1 mutation was identified in two patients, but was identified in the heterozygous state in one.A 25-D overdose should be systematically ruled out in the presence of nephrocalcinosis, hypercalcemia, and/or hypercalciuria during infancy in children born preterm. Studies are required to assess the exact frequency of 25-D deficiency and overdose in this population, as well as to evaluate the potential deleterious effects of this imbalance on bone, kidney, and brain development.

Osteocalcin is a hormone secreted by osteoblasts, which regulates energy metabolism by increasing β-cell proliferation, insulin secretion, insulin sensitivity, and energy expenditure. This has been demonstrated in mice, but to date, the evidence implicating osteocalcin in the regulation of energy metabolism in humans are indirect. To address this question more directly, we asked whether a benign osteoblastic tumor, such as osteoma osteoid in young adults, may secrete osteocalcin. The study was designed to assess the effect of surgical resection of osteoid osteoma on osteocalcin and blood glucose levels in comparison with patients undergoing knee surgery and healthy volunteers. Blood collections were performed the day of surgery and the following morning after overnight fasting. Patients and controls were recruited in the orthopedic surgery department of New York Presbiterian Hospital, NY-USA and Hospices Civils de Lyon, France. Seven young males were included in the study: two had osteoid osteoma, two underwent knee surgery, and three were healthy volunteers. After resection of the osteoid osteomas, we observed a decrease of osteocalcin by 62% and 30% from the initial levels. Simultaneously, blood glucose increased respectively by 32% and 15%. Bone turnover markers were not affected. This case study shows for the first time that osteocalcin in humans affects blood glucose level. This study also suggests that ostoid osteoma may be considered, at least in part, as an osteocalcinoma.

Resume Les tests ELISA et d'inhibition de l'hemagglutination ont ete compares pour la recherche des anticorps Newcastle lors de vaccination par goutte oculaire au moyen de virus type La Sota. Les deux tests sont positifs des le 6eme jour, moment ou seules des IgM specifiques sont observees. Les IgG specifiques apparaissent entre le 7eme et le 8eme jour. On ne trouve pas d'IgA specifiques dans le serum des volailles vaccinees. Une fixation non specifique des IgM sur l'antigene s'observe en methode ELISA. Le test d'inhibition de l'hemagglutination est aussi sensible et plus specifique que le test ELISA pour la recherche des anticorps Newcastle. Zusammenfassung Serologische Diagnostik der Newcastle Disease durch Hamagglutinationshemmungstests und ELISA Kinetik der verschiedenen vakzinalen Antikorperklassen Die ELISA- und Hamagglutinationshemmungstests wurden, um die Newcastle-Antikorper bei der Vakzinierung durch Augentropfen mittels Virus des Types La Sota zu untersuchen, verglichen. Die beiden Tests sind ab dem 6. Tag, wenn nur die spezifischen IgM beobachtet werden, positiv. Die spezifischen IgG erscheinen zwischen dem 7. und 8. Tag. Es gibt keine spezifischen IgA im Serum des vakzinierten Geflugels. Eine unspezifische Verbindung der IgM am Antigen wird mit dem ELISA beobachtet. Um die Newcastle-Antikorper zu untersuchen, ist der Hamagglutinationshemmungstest gleich sensible und spezifischer als der ELISA-Test. Summary Serological diagnosis of Newcastle Disease by haemagglutination inhibition and ELISA tests Kinetics of different classes of vaccinal antibodies The ELISA and HI tests were compared in investigating the antibody response following eyedrop vaccination with La Sota types of Newcastle Disease virus. Both were positive from day 6, when only specific IgM was detected. Specific IgG in the serum of vaccinated fowls appeared between days 7 and 8. No specific IgA was detected in the serum of vaccinated birds. A non-specific binding of IgM to the antigen was revealed by the ELISA test. For the study of ND antibodies the HI test is just as sensitive and more specific than the ELISA test. Resumen El diagnostico de la enfermedad de Newcastle por las pruebas de inhibicion de la hemaglutinacion y ELISA Se compararon las pruebas ELISA y de inhibicion de la hemaglutinacion para examinar los anticuerpos Newcastle en la vacunacion por gota ocular mediante virus tipo La Sota. Ambas pruebas son positivas a partir del dia 6°, si solo se tienen en cuenta las IgM especificas. Las IgG especificas aparecen entre el dia 7° y 8°. No hay ninguna IgA especifica en el suero sanguineo de las aves vacunadas. Se observa con la ELISA una fijacion inespecifica de las IgM als antigeno. Para estudiar los anticuerpos Newcastle, la prueba de inhibicion de la hemaglutinacion es mas sensible y especifica que la prueba ELISA.

International audience; We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients. INTRODUCTION: Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients. METHODS: Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above). RESULTS: In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results. CONCLUSIONS: Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients.

Adrenal insufficiency is a rare but life-threatening disease. Replacement therapy sometimes fails to prevent an acute adrenal crisis and most often does not lead to restoration of well-being. We report here the 1-year outcome of the first simultaneous kidney-adrenal gland-pancreas transplantation in a 33-year-old patient with type 1 diabetes and concomitant autoimmune adrenal insufficiency. En bloc left adrenal gland and kidney grafts were anastomosed on the left iliac vessels in normal vascular conditions and the pancreas graft was anastomosed on the right iliac vessels. The immunosuppressive regimen was not modified by the addition of the adrenal gland. We observed no additional morbidity due to the adrenal gland transplantation, as there were no surgical complications. One-year kidney and pancreas graft functions were satisfactory (estimated glomerular filtration rate: 55 mL/min/1.73 m(2) and HbA1c: 4.8%). The adrenal graft functioned well at 12 months with a normalization of cortisol and aldosterone baseline levels. Functional imaging at 3 months showed good uptake of [(123) I]-metaiodobenzylguanidine by the adrenal graft. Transplantation of the adrenal gland en bloc with the left kidney appears to be a good therapeutic option in patients with adrenal insufficiency awaiting kidney or kidney-pancreas transplantation.

Since 2005, international guidelines propose a stadification for chronic renal failure based on the glomerular filtration rate (GFR) value. The performance of the creatinine-based equations allowing the estimation of GFR and the bias of the creatinine measurements is, more than ever, a crucial issue. The consequences for the clinical biologists are of importance. First, the Cockcroft-Gault formula must be replaced by the four variable-MDRD equation. Second, the biologists must chose from the "175" and the "186" versions of the MDRD equation. The first one fits the creatinine methods which are traceable to the reference method (liquid or gas chromatography coupled to mass spectrometry). The second equation must be used for creatinine methods, which are not traceable to the reference method. Today, only some enzymatic methods can prove that they are traceable to the reference method. For the colorimetric methods, future is inclear.

The National Kidney Foundation/Kidney-Dialysis Outcome Quality Initiative guidelines recommend to maintain the serum intact parathyroid hormone (PTH) concentration between 150 and 300 ng/l in chronic kidney disease (CKD) stage 5 patients. As these limits were derived from studies that used the Allegro intact PTH assay, we aimed to evaluate whether they were applicable to other PTH assays. We compared the PTH concentrations measured with 15 commercial immunoassays in 47 serum pools from dialysis patients, using the Allegro intact PTH assay as the reference. We also evaluated the recovery of graded amounts of synthetic 1–84 and 7–84 PTH added separately to a serum pool. Although the assays were highly correlated, the concentrations differed from one assay to another. The median bias between the tested assays and the Allegro intact PTH assay ranged from -44.9 to 123.0%. When the PTH concentrations were 150 or 300 ng/l with the Allegro intact PTH assay, they ranged with other assays from 83 to 323 ng/l and from 160 to 638 ng/l, respectively. The tested assays recognized 7–84 PTH with various cross-reactivities, whereas a given amount of 1–84 PTH was recovered differently by these assays. We found important inter-method variability in PTH results owing to both antibody specificity and standardization reasons. The unacceptable consequence is that opposite therapeutic attitudes may be reached in a single patient depending on the PTH assay used. We propose to use assay-specific decision limits for CKD patients, or to apply a correcting factor to the PTH results obtained with a given assay.

To assess inter-assay variation and accuracy of blood creatinine measurements as well as the effect of the standardization of the calibration procedures on inter-assay variation.Inter-assay variation and accuracy were assessed using 30 frozen human sera and 3 certified reference materials, which were analysed by 17 creatinine assays (colorimetric: 12, enzymatic: 4, HPLC: 1). Usual calibration procedure was compared with two common calibration procedures using either a reference material (404.1 micromol/L), or secondary sera calibrators (69, 115 et 180 micromol/L).Most of the commercially available methods display inaccuracy,10% for creatininemia150 micromol/L in most cases. For this concentration range, the mean creatininemia was statistically significantly different as a function of the assay used (p0.001). Enzymatic assays produced lower results than colorimetric ones for low creatinine levels but higher results for high creatinine levels. Assays being calibrated according to the manufacturer's recommendations, the median dispersion factor was 14% for the 20 samples between 45 and 150 micromol/L, and 8% for the 10 samples between 250 and 350 micromol/L. The calibration procedure modified inter-assay variation significantly (p0.001) but we gained little advantage from both common calibration procedures. A significant decrease of inter-assay variation occurred within each technical group (colorimetric or enzymatic) when a common calibration was performed using calibrators which concentration(s) was(were) close to the concentrations to be measured.Inter-assay variation is too high to allow prediction of glomerular filtration rate (GFR) or creatinine clearance from serum creatinine level. Our results highlight the interest of a calibration procedure using several concentrations with at least one between 90 and 150 micromol/L. The marketing of such a calibrator should be considered in order to decrease inter-assay variation in the range of creatinine levels which defines a mild chronic renal failure. Such an approach will certainly reduce inter-assay variation only within each technical group but could allow to include technical group as a co-variable in the algorithms developed for predicting GFR or creatinine clearance. A global transferability will certainly need the correlation of all types of creatinine assays versus a definitive method, whom definition remains uncertain.

Biochemical markers of bone turnover have for several years been considered as valuable parameters in research clinical studies, but their use in individual patients is still debated. Recently several position papers have proposed guidelines for their use in clinical practice in patients with post menopausal osteoporosis. In the present article, we report the results of a survey which aims at comparing the actual modalities of prescription of French physicians with the above-mentioned recommendations. We contacted by phone clinical chemists from 158 different hospitals and asked them to transmit to the concerned physicians of their hospital a detailed questionnaire for assessing which bone marker(s) is (are) prescribed and for which purpose (s), and if not prescribed, the reason of non prescription. We were able to analyze 309 questionnaires from 89 hospitals including 5 specialties, rheumatology (35.9%), endocrinology (18.1%), gynecology (11.0%), internal medicine (22.0%) and geriatry (12.9%). The results showed large discrepancies between the mode of prescription of a subset of physicians and the guidelines. The most often evoked reason for non prescription was a lack of information about bone markers suggesting a need for teaching courses. This survey has also shown that many physicians do not know exactly which parameters are effectively measured in their hospital and which are addressed to specialized laboratories underlining the importance of the dialogue between clinicians and clinical chemists. We propose that in a given hospital, the present article may serve as a basis for a discussion between clinicians and biologists about the development and/or the optimization of the measurements of these markers of bone turnover.

Biochemical markers of bone turnover have been developed over the past 20 years that are more specific for bone tissue than conventional ones such as total alkaline phosphatase and urinary hydroxyproline. They have been widely used in clinical research and in clinical trials of new therapies as secondary end points of treatment efficacy. Most of the interest has been devoted to their use in postmenopausal osteoporosis, a condition characterized by subtle modifications of bone metabolism that cannot be detected readily by conventional markers of bone turnover. Although several recent studies have suggested that biochemical markers may be used for the management of the individual patient in routine clinical practice, this has not been clearly defined and is a matter of debate. Because of the crucial importance to clarify this issue, the Société Francaise de Biologie Clinique prompted an expert committee to summarize the available data and to make recommendations. The following paper includes a review on the biochemical and analytical aspects of the markers of bone formation and resorption and on the sources of variability such as sex, age, menstrual cycle, pregnancy and lactation, physical activity, seasonal variation and effects of diseases and treatments. We will also describe the effects of pre-analytical factors on the measurements of the different markers. Finally based on that review, we will make practical recommendations for the use of these markers in order to minimize the variability of the measurements and improve the clinical interpretation of the data.

BACKGROUND YKL-40 is a 40 kDa glycoprotein secreted by chondrocytes and synoviocytes. It has been suggested that it is a surrogate marker of synovial inflammation and joint destruction in rheumatoid arthritis (RA) and osteoarthritis (OA) and related to C reactive protein (CRP) serum levels in RA. OBJECTIVE To study serum levels of YKL-40 in patients with hip OA and its relation with CRP. METHODS YKL-40 and CRP were assayed in serum samples from 45 patients (24 women, 21 men, mean age 65) with symptomatic OA of the hip and 33 healthy controls. YKL-40 was assayed by immunoassay and CRP by ultrasensitive immunonephelometry. OA severity was assessed by the measurement of joint space width with a computer analysis system of digitised hip radiographs. Statistical analysis was performed to determine correlations between serum markers and radiological joint space width. RESULTS The mean (standard error) YKL-40 level was 90.3 (8.2) ng/ml in patients with hip OA and 66.9 (8.2) ng/ml in controls (p=0.03). The mean CRP level was 2.93 (3.03) mg/l in OA and 1.40 (1.61) mg/l in controls (p=0.006). The serum levels of YKL-40 and CRP increased with age and were significantly correlated (Spearman test: r s =0.42, p=0.005) in patients but not in controls. Neither YKL-40 nor CRP correlated with radiographic joint space width. CONCLUSIONS Serum YKL-40 was significantly increased in patients with hip OA. The correlation between YKL-40 and CRP suggests that YKL-40 may be a marker of joint inflammation in OA. Longitudinal studies are required to assess the usefulness of YKL-40 in the monitoring of patients with hip OA.

Introduction Il est actuellement decrit de nombreux roles extra-osseux de la vitamine D. Elle pourrait notamment etre impliquee dans la physiopathologie du diabete de type 2. L’obesite, facteur de risque majeur d’insulinoresistance, est egalement associee a des deficits en vitamine D parfois tres severes. Cette etude a pour but d’etudier les liens entre statut vitaminique D et insulinoresistance chez le sujet obese. Patients et methodes Il s’agit d’une etude observationnelle retrospective portant sur 943 patients avec un IMC median de 38,9 kg/m2. L’insulinoresistance est evaluee par le HOMA-IR. L’exposition de la population aux UVB est egalement prise en compte. Les liens entre 25 (OH) D, IMC, exposition theorique aux UVB et insulinoresistance ont ete etudies en analyses categorielles et lineaires. Resultats L’IMC (r = − 0,38, p Le niveau d’insulinoresistance est inversement correle a l’exposition theorique aux UVB de la population. Il existe une relation lineaire inverse entre 25 (OH) D et insulinoresistance et cette relation est independante des parametres anthropometriques (IMC, leptine) et du niveau d’exposition aux UVB. Discussion Ces resultats, mis en perspectives avec les donnees physiopathologiques de la litterature retrouvant une action moleculaire de la vitamine D sur les voies de signalisation insulinique, nous permettent d’evoquer un role direct du deficit en vitamine D dans l’insulinoresistance des sujets obeses faisant de cette vitamine l’un des mediateurs potentiels des variations saisonnieres de l’insulinoresistance. Ainsi, le deficit en vitamine D est en theorie une cause reversible d’insulinoresistance chez le sujet obese. Une etude prospective d’intervention visant a evaluer l’efficacite d’une supplementation vitaminique D dans le traitement de l’insulinoresistance du sujet obese est en preparation.

To cover the need in paediatric organ transplantation, every potential donor should be considered as a multi-organ donor. Successful transplantation may be performed with kidneys retrieved from very young infants, even anencephalic neonates if the en-bloc technique using both kidneys is used. Regarding the liver, paediatric donors can be accepted from one month of age while livers harvested from older children and even young adults can be transplanted into small children after ex-vivo reduction of the size of the graft. Multi-organ procurement from the same donor provides valuable organs if the anaesthetic management of the donor is appropriate. Active transplant programs needs international cooperation which is made possible by the organ exchange organizations.

Individual variations in serological response to avian influenza virus infection were demonstrated after experimental infection of specific-pathogen-free chickens with H6N2 influenza virus. Homologous antibodies were detected from the 6th to the 157th day after infection using hemagglutination-inhibition or enzyme-linked immunosorbent assay and from the 11th to the 157th day by agar gel precipitation test.

Antigenic variants of the Italian strain of NDV were selected using monoclonal antibodies directed against the HN and F proteins of Italian virus. Antigenic mapping of the HN and F proteins using variant viruses in cross neutralization tests revealed the presence of at least two different epitopes on HN and four epitopes on F protein. Immunoselected variant viruses were demonstrated to have different intravenous pathogenicity index than the parental Italian virus.

Individual variations in serological response to avian influenza virus infection were demonstrated after experimental infection of specific-pathogen-free chickens with H6N2 influenza virus. Homologous antibodies were detected from the 6th to the 157th day after infection using hemagglutination-inhibition or enzyme-linked immunosorbent assay and from the 11th to the 157th day by agar gel precipitation test.