Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification:

BACKGROUND: Over the last few decades, new synthetic insulin analogues have been developed. Their measurement is of prime importance in the investigation of hypoglycaemia, but their quantification is hampered by variable cross-reactivity with many insulin assays. For clinical analysis, it has now become essential to know the potential cross-reactivity of analogues of interest. METHODS: In this work, we performed an extensive study of insulin analogue cross-reactivity using numerous human insulin immunoassays. We investigated the cross-reactivity of five analogues (lispro, aspart, glulisine, glargine, detemir) and two glargine metabolites (M1 and M2) with 16 commercial human insulin immunoassays as a function of concentration. RESULTS: The cross-reactivity values for insulin analogues or glargine metabolites ranged from 0% to 264%. Four assays were more specific to human insulin, resulting in negligible cross-reactivity with the analogues. However, none of the 16 assays was completely free of cross-reactivity with analogues or metabolites. The results show that analogue cross-reactivity, which varies to a large degree, is far from negligible, and should not be overlooked in clinical investigations. CONCLUSIONS: This study has established the cross-reactivity of five insulin analogues and two glargine metabolites using 16 immunoassays to facilitate the choice of the immunoassay(s) and to provide sensitive and specific analyses in clinical routine or investigation

Effects of reflux laryngitis on non-nutritive swallowing in newborn lambs

Reflux laryngitis in infants may be involved not only in laryngeal disorders, but also in disorders of cardiorespiratory control through its impact on laryngeal function. Our objective was to study the effect of reflux laryngitis on non-nutritive swallowing (NNS) and NNS-breathing coordination. Two groups of six newborn lambs, randomized into laryngitis and control groups, were surgically instrumented for recording states of alertness, swallowing and cardiorespiratory variables without sedation. A mild to moderate reflux laryngitis was induced in lambs from the experimental group. A significant decrease in the number of NNS bursts and apneas was observed in the laryngitis group in active sleep (p=0.03). In addition, lower heart and respiratory rates, as well as prolonged apnea duration (p<0.0001) were observed. No physiologically significant alterations in NNS-breathing coordination were observed in the laryngitis group. We conclude that a mild to moderate reflux laryngitis alters NNS burst frequency and autonomous control of cardiac activity and respiration in lambs

Effects of postnatal environmental tobacco smoke on non-nutritive swallowing-breathing coordination in newborn lambs

While prenatal environmental tobacco smoke (ETS) exposure is a well-known risk factor for sudden infant death syndrome, the effect of postnatal ETS exposure is less clear. The objective of this study was to investigate the effect of postnatal ETS exposure on non-nutritive swallowing (NNS) and NNS-breathing coordination, which are crucial to prevent aspiration related-cardiorespiratory events. Eighteen newborn lambs (6 per group) were randomly exposed to either 10 cigarettes/day, 20 cigarettes/day or room air for 15 days. Lambs were instrumented for recording states of alertness, swallowing, electrocardiogram and breathing; recordings were performed in non-sedated lambs at the end of ETS exposure. Urinary cotinine/creatinine ratio confirmed relevant real-life exposure. Postnatal ETS exposure had no effect on NNS frequency but tended to decrease inspiratory NNS (p=0.07) during quiet sleep. No effect on respiratory or heart rate (p>0.6), apnea index (p=0.2) or sleep states (p=0.3) was observed. In conclusion, postnatal ETS exposure in lambs had only mild effects on NNS-breathing coordination

Radio telemetry devices to monitor breathing in non-sedated animals

Radio telemetry equipment has significantly improved over the last 10-15 years and is increasingly being used in research for monitoring a variety of physiological parameters in non-sedated animals. The aim of this review is to provide an update on the current state of development of radio telemetry for recording respiration. Our literature review found only rare reports of respiratory studies via radio telemetry. Much of this article will hence report our experience with our custom-built radio telemetry devices designed for recording respiratory signals, together with numerous other physiological signals in lambs. Our current radio telemetry system allows to record 24 simultaneous signals 24h/day for several days. To our knowledge, this is the highest number of physiological signals, which can be recorded wirelessly. Our devices have been invaluable for studying respiration in our ovine models of preterm birth, reflux laryngitis, postnatal exposure to cigarette smoke, respiratory syncytial virus infection and nasal ventilation, all of which are relevant to neonatal respiratory problems

Impact des pesticides perturbateurs endocriniens sur le cancer du sein

International audienceOf the 800 pesticides used worldwide, about 650 can affect the functioning of the endocrine system: endocrine disrupting pesticides (EDPs). Dietary or environmental exposure to EDPs is a concern, as their presence is currently demonstrated in most biological fluids. Some EDPs are prohibited, classified as carcinogenic, others are “probable” or “possible” carcinogens when there is limited evidence of their tumor effect. The impact of EDPs on breasts is not well known to date. However, since most EDPs have a long half-life and are lipophilic, breasts, composed mainly of adipose tissue, are a suitable site for their concentration. The objective of our review was to analyze the impact of EDPs related to our environmental exposure on breast cancer risk, through an analysis of recent literature, including epidemiological and biological data. Our review showed a positive association between the presence of EDPs and breast cancer, especially among women farmers or EDPs users but also in the general population. Studies on breast tumors have found a higher concentration of EDPs in estrogen-sensitive tumors. As for mortality, studies are contradictory, but confirm the dangerousness of some EDPs. The different series analyzed have several limitations, such as the low number of EDPs evaluated, small numbers and insufficient follow up. The potentiating effect of different EDPs used concomitantly and the window of exposure to these substances are parameters to be assessed.Parmi les 800 pesticides utilisés dans le monde, environ 650 peuvent modifier le fonctionnement du système endocrinien : il s’agit des pesticides perturbateurs endocriniens (PPE). L’exposition aux PPE par voie alimentaire ou environnementale est un sujet préoccupant, leur présence étant actuellement démontrée dans la plupart des fluides biologiques. Certains PPE sont interdits, classés cancérigènes « certains », d’autres sont des cancérigènes « probables » ou « possibles » lorsque les preuves de leur effet tumoral sont limitées. L’impact des PPE sur les seins est à ce jour mal connu. Cependant, la plupart des PPE ayant une demi-vie longue et étant lipophiles, les seins, composés principalement de tissu adipeux, constituent un terrain propice à leur concentration. L’objectif de notre mise au point était d’analyser l’impact des PPE liés à notre exposition environnementale sur le risque de cancer du sein, au travers d’une revue de la littérature récente, portant sur des données épidémiologiques et biologiques. Il est difficile à ce jour d’affirmer une réelle association positive entre la présence de PPE et le cancer du sein même si de plus en plus d’études soulignent un rôle possible des PPE sur le risque de survenu d’un cancer du sein notamment chez les femmes agricultrices ou appliquant des PPE, mais également dans la population générale exposée aux PPE. Les études réalisées sur les tumeurs mammaires retrouvent une concentration en PPE plus élevée dans les tumeurs hormonodépendantes. Les différentes séries analysées ont un certain nombre de limites, telles que le faible nombre de PPE évalués, les petits effectifs et le recul insuffisant. L’effet potentialisateur de différents PPE utilisés concomitamment et la fenêtre d’exposition à ces substances restent des paramètres à évaluer

Hyperthyroïdie et cancer du sein : y a-t-il une association ? [Hyperthyroidism and breast cancer: Is there a link?]

The objective of this review was to determine whether there is an association between hyperthyroidism and the risk of developing a breast cancer from the analysis of data in the literature. METHOD: The analyzed articles were extracted from the PUBMED database from 2002 to 2017 using the following keywords "hyperthyroidism AND breast cancer" and "thyroid AND breast cancer". RESULTS: A total of 22 studies were selected, including 8 cohort studies, 12 case-control studies and 2 meta-analyzes. Of these 22 studies, 15 have established a significant epidemiological or biological link between hyperthyroidism and breast cancer. Five of them were particularly interested in Graves' disease, and four demonstrated a positive association between this disease and the onset of breast cancer, especially within three years from the thyropathy diagnosis. These different studies also highlighted the increased risk of breast cancer seen in overweight or postmenopausal women. Contradictions persist over the types of mammary cancers observed and their prognosis. CONCLUSION: This review reveals that women with hyperthyroidism appear to have a moderately high risk of breast cancer (RR<2). These data are corroborated by solid physiopathological hypotheses. Regardless of the type of thyropathy responsible for hyperthyroidism, care should be taken to ensure that these patients receive a clinical examination of the breasts on an annual basis and mammographic screening every 2 years from the age of 50 years

Should functional sensitivity of a new thyroid stimulating hormone immunoassay be monitored routinely? The ADVIA Centaur TSH3-UL assay experience.

International audienceOBJECTIVES: We emphasize the importance of routine follow-up of subnormal TSH concentrations with QC materials. DESIGN AND METHODS: The functional sensitivity (FS) of the ADVIA Centaur system TSH assay was assessed. We report the values yielded for QC materials in two clinical laboratories. RESULTS: The FS was <0.02 mIU/L. The low-TSH QC (a serum pool) showed unacceptable between-lot imprecision (mean 0.0252 mIU/L, CV 22%). CONCLUSION: We do encourage healthcare laboratories to constitute low-TSH serum pools to ensure that the results they report meet 3rd-generation criteria