12 results on '"Zelner I"'
Search Results
2. Acute Poisoning During Pregnancy: Observations from the Toxicology Investigators Consortium.
- Author
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Zelner I, Matlow J, Hutson JR, Wax P, Koren G, Brent J, and Finkelstein Y
- Subjects
- Acute Disease, Emergency Medical Services, Female, Humans, Nonprescription Drugs poisoning, Poisoning diagnosis, Poisoning epidemiology, Pregnancy, Pregnancy Complications diagnosis, Pregnancy Complications epidemiology, Psychotropic Drugs poisoning, Registries, Risk Assessment, Risk Factors, Treatment Outcome, United States epidemiology, Antidotes therapeutic use, Poisoning therapy, Pregnancy Complications therapy
- Abstract
Acute poisonings during pregnancy pose a particular challenge to health care providers because of the potential for an immediate life threat or possible life-long implications for both the mother and fetus, including teratogenicity of the poison or its antidote. We describe recent consequential exposures among pregnant women in the USA. We identified all poisoning cases involving pregnant women that were catalogued by the medical toxicology services across the 37 sites of the Toxicology Investigators Consortium (ToxIC) Registry of the American College of Medical Toxicology between January 2010 and December 2012. Of 17,529 exposure cases reported in the ToxIC Registry, 103 (0.6 %) involved pregnant women, 80 % of whom were symptomatic and about a quarter displayed a specific toxidrome. The majority of cases (n = 53; 51.5 %) involved intentional exposures, most commonly to pharmaceutical agents, followed by unintentional pharmaceutical exposures (10 %) and withdrawal syndromes (9 %). Non-opioid analgesics were the most common class of agents encountered (31 %), followed by sedative-hypnotics/muscle relaxants (18 %), opioids (17 %), anti-convulsants (10 %), and anti-depressants (10 %). Over a third of cases involved exposure to multiple substances, and 32 % involved exposure to more than one drug class. The most commonly administered antidotes were N-acetylcysteine (23 %), sodium bicarbonate (10 %), flumazenil (4 %), and physostigmine (4 %). About half of acute poisoning cases among pregnant women presenting for emergency care involved intentional exposures, mostly with over-the-counter analgesics and psychoactive medications. Clinicians should be cognizant of the unique circumstances, maternal and fetal risks, and management principles of the acutely poisoned pregnant woman.
- Published
- 2015
- Full Text
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3. Foetal alcohol spectrum disorder: identifying the neurobehavioural phenotype and effective interventions.
- Author
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Koren G, Zelner I, Nash K, and Koren G
- Subjects
- Adolescent, Child, Child Behavior Disorders psychology, Developmental Disabilities diagnosis, Developmental Disabilities psychology, Fetal Alcohol Spectrum Disorders psychology, Humans, Reproducibility of Results, Sensitivity and Specificity, Child Behavior Disorders diagnosis, Fetal Alcohol Spectrum Disorders diagnosis, Neuropsychological Tests
- Abstract
Purpose of Review: Since the first description of the foetal damage of alcohol in 1967, numerous studies have outlined different aspects of neurodevelopmental dysfunction, adversely affecting the lives of children worldwide. Although the cause of the syndrome is sorted out, the pathogenesis of brain damage is far from being clear. In contrast to children exhibiting the full facial dysmorphology, who are relatively easy to diagnose, in those presenting only with alcohol-related neurodevelopmental damage diagnosis is much more challenging due to poor specificity of the brain dysfunction. Hence, identifying the neurodevelopmental phenotype of foetal alcohol spectrum disorder (FASD) is a major challenge., Recent Findings: Recently, a behavioural phenotype of FASD has been described and validated using items from the Child Behaviour Checklist. This tool has high sensitivity and specificity in separating children with FASD from those with ADHD and from healthy controls. In parallel, a number of intervention studies show promise in improving the abilities of children and adolescents with the syndrome to cope with daily tasks and improve their quality of life., Summary: The neurobehavioural screening test can facilitate screening for FASD and is an official screening tool in the FASD toolkit of the Public Health Agency of Canada. Promising new interventions may attenuate the long-term outcome of these children.
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- 2014
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4. Synthesis of fatty acid ethyl esters in mammalian tissues after ethanol exposure: a systematic review of the literature.
- Author
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Zelner I, Matlow JN, Natekar A, and Koren G
- Subjects
- Animals, Esters metabolism, Ethyl Ethers metabolism, Fatty Acids metabolism, Humans, Mammals metabolism, Oxidation-Reduction, Acyltransferases metabolism, Ethanol metabolism, Fatty Acids biosynthesis
- Abstract
The ability to undergo non-oxidative metabolism from ethanol to fatty acid ethyl esters (FAEEs) varies greatly among tissues and organs. To gain a greater understanding of non-oxidative ethanol metabolism to FAEE, we aimed to collect all published data on FAEE synthesis in mammalian organs and tissues to identify all tissues, organs, and enzymes that are known to, or likely possess FAEE-synthetic activity. A systematic search for relevant papers was performed and two independent reviewers examined potentially relevant abstracts (articles on FAEEs that pertain to ethanol exposure) to determine whether they met the inclusion criteria. Information on FAEE synthesis was retrieved from papers meeting the inclusion/exclusion criteria and summarized by organ/tissue/matrix examined. The systematic search through four databases yielded 78 articles that investigated FAEE synthesis by tissues, tissue fractions and cell lines, and 29 articles that attempted to purify and/or characterize the enzymes involved in FAEE synthesis. Two enzyme activities have been studied: FAEE synthase (FAEES, which conjugates ethanol and free fatty acid) and acyl-CoA: ethanol O-acyltransferase (AEAT, which conjugates ethanol and fatty acyl-CoA). Both activities are expressed by a variety of different enzymes. FAEES activity is the most widely studied and has been purified from several tissues and shown to be associated with several well-known enzymes, while the identity of enzymes possessing AEAT activity remains unknown. The organs and tissues that have been shown to synthesize FAEEs are discussed, with special emphasis on the studies that attempted to elucidate the enzymology of FAEE synthesis in those tissues.
- Published
- 2013
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5. Alcohol consumption among women.
- Author
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Zelner I and Koren G
- Subjects
- Alcohol Drinking adverse effects, Female, Global Health, Humans, Pregnancy, Risk Factors, Sex Factors, Alcohol Drinking epidemiology, Fetal Alcohol Spectrum Disorders epidemiology
- Abstract
Alcohol (ethanol) consumption in pregnancy is the etiology of fetal alcohol spectrum disorder (FASD), a leading cause of congenital disability worldwide. Hence, any attempt to prevent or manage FASD must start from comprehensive understanding of alcohol consumption by women in general, and by women of reproductive years in particular. This review presents and synthesizes studies conducted worldwide on alcohol consumption by pregnant women, risk factors associated with gestational drinking, as well as doses and definitions of drinking behaviours.
- Published
- 2013
6. Meconium fatty acid ethyl esters as biomarkers of late gestational ethanol exposure and indicator of ethanol-induced multi-organ injury in fetal sheep.
- Author
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Zelner I, Kenna K, Brien JF, Bocking A, Harding R, Walker D, and Koren G
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- Animals, Female, Pregnancy, Sheep, Sheep, Domestic, Biomarkers metabolism, Esters metabolism, Ethanol toxicity, Fatty Acids metabolism, Fetal Alcohol Spectrum Disorders metabolism, Meconium metabolism
- Abstract
Background: Meconium fatty acid ethyl esters (FAEE) constitute a biomarker of heavy fetal ethanol exposure. Our objective was to measure meconium FAEE in fetal sheep following daily, relatively moderate-dose ethanol exposure in late gestation, and to evaluate their utility in identifying fetal organ-system injury., Methods: Pregnant ewes received ethanol (0.75 g/kg; n = 14) or saline (n = 8) via 1-h i.v. infusion daily during the third trimester equivalent, while additional pregnant sheep served as untreated controls (n = 6). The daily ethanol regimen produced similar maximal maternal and fetal plasma ethanol concentrations of 0.11-0.12 g/dL. Ewes and fetuses were euthanized shortly before term, and meconium was collected and analyzed for FAEE (ethyl palmitate, stearate, linoleate, and oleate)., Results: Meconium total FAEE concentration was significantly higher in ethanol-exposed fetuses compared with controls, and a positive cut-off of 0.0285 nmol total FAEE/g meconium had 93.3% sensitivity and specificity for detecting fetal ethanol exposure. When the studied animals (ethanol-exposed and controls) were classified according to meconium FAEE concentration, FAEE-positive and FAEE-negative groups frequently differed with respect to previously examined pathological endpoints, including nephron endowment, lung collagen deposition, cardiomyocyte maturation, and tropoelastin gene expression in cerebral vessels. Furthermore, in all studied animals as a group (ethanol-exposed and controls combined), meconium FAEE concentration was correlated with many of these pathological endpoints in fetal organs., Conclusions: We conclude that, in fetal sheep, meconium FAEE could serve as a biomarker of daily ethanol exposure in late gestation and could identify fetuses with subtle ethanol-induced toxic effects in various organs. This study illustrates the potential for using meconium FAEE to identify neonates at risk for dysfunction of major organs following in-utero ethanol exposure that does not result in overt physical signs of ethanol teratogenicity.
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- 2013
- Full Text
- View/download PDF
7. Pharmacokinetics of ethanol in the maternal-fetal unit.
- Author
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Zelner I and Koren G
- Subjects
- Animals, Ethanol adverse effects, Female, Humans, Pregnancy, Ethanol pharmacokinetics, Fetus drug effects, Fetus metabolism, Maternal-Fetal Exchange drug effects, Maternal-Fetal Exchange physiology
- Abstract
Due to its wide range of deleterious effects on the unborn baby, knowledge on the disposition of ethanol in the maternal-fetal unit is critical. This review summarizes and updates the existing evidence on ethanol disposition in the mother, the placenta and the fetus, and relates them to their potential fetal effects.
- Published
- 2013
8. False-positive meconium test results for fatty acid ethyl esters secondary to delayed sample collection.
- Author
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Zelner I, Hutson JR, Kapur BM, Feig DS, and Koren G
- Subjects
- Adult, Carbohydrates chemistry, Esters analysis, False Positive Reactions, Feces chemistry, Feces microbiology, Female, Fetal Alcohol Spectrum Disorders, Gas Chromatography-Mass Spectrometry, Glucose chemistry, Humans, Infant, Newborn, Lipase analysis, Pregnancy, Prospective Studies, Solid Phase Microextraction, Central Nervous System Depressants metabolism, Ethanol metabolism, Fatty Acids analysis, Meconium chemistry
- Abstract
Background: Meconium analysis for fatty acid ethyl esters (FAEEs) is a validated method for identifying heavy prenatal ethanol (EtOH) exposure. This study investigated whether delayed sample collection can result in false-positive test results for FAEEs because of collection of samples potentially contaminated with postnatally produced stool., Methods: Serial excretions were prospectively collected from neonates born to nondrinking mothers to capture the transition from meconium to postnatal stool. These were analyzed for FAEEs using headspace-solid phase microextraction and gas chromatography-mass spectrometry. Experiments involving incubation of samples with glucose or EtOH were performed to explore a potential mechanism of FAEE elevation., Results: A total of 136 samples were collected from 30 neonates during their first few days of life (median of 4 samples/baby over a mean period of 68.5 hours postpartum). Although the first-collected meconium sample tested negative for FAEEs in all babies, later samples tested above the 2 nmol/g positive cutoff in 19 of 30 babies. Median time to appearance of FAEE-positive samples was 59.2 hours postpartum. In vitro experiments demonstrated that FAEE levels can be further increased in late samples (likely containing postnatal stool) after incubation with glucose, and that FAEEs are readily formed in meconium in the presence of EtOH., Conclusions: Collection of samples excreted later in the postpartum period can lead to false-positive test results for FAEEs, which could be because of contamination with dietary components of postnatally produced stool and EtOH-producing microorganisms. Clinically, it is critical to collect the earliest possible excretion for determination of FAEEs to ensure that the FAEE content is representative of in utero EtOH exposure., (Copyright © 2012 by the Research Society on Alcoholism.)
- Published
- 2012
- Full Text
- View/download PDF
9. P2X₇-mediated calcium influx triggers a sustained, PI3K-dependent increase in metabolic acid production by osteoblast-like cells.
- Author
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Grol MW, Zelner I, and Dixon SJ
- Subjects
- Adenosine Triphosphate metabolism, Animals, Bone Remodeling drug effects, Cell Line, Cell Survival drug effects, Clone Cells, Enzyme Inhibitors pharmacology, Glucose metabolism, Hydrogen-Ion Concentration, Kinetics, Lactic Acid metabolism, Ligands, Mice, Osteoblasts metabolism, Osteoblasts pathology, Phosphoinositide-3 Kinase Inhibitors, Purinergic P2X Receptor Agonists chemistry, Purinergic P2X Receptor Agonists metabolism, Purinergic P2X Receptor Antagonists pharmacology, Receptors, Purinergic P2X7 chemistry, Uridine Triphosphate metabolism, Calcium Signaling drug effects, Osteoblasts drug effects, Phosphatidylinositol 3-Kinases metabolism, Purinergic P2X Receptor Agonists pharmacology, Receptors, Purinergic P2X7 metabolism
- Abstract
The P2X₇ receptor is an ATP-gated cation channel expressed by a number of cell types, including osteoblasts. Genetically modified mice with loss of P2X₇ function exhibit altered bone formation. Moreover, activation of P2X₇ in vitro stimulates osteoblast differentiation and matrix mineralization, although the underlying mechanisms remain unclear. Because osteogenesis is associated with enhanced cellular metabolism, our goal was to characterize the effects of nucleotides on metabolic acid production (proton efflux) by osteoblasts. The P2X₇ agonist 2',3'-O-(4-benzoylbenzoyl)ATP (BzATP; 300 μM) induced dynamic membrane blebbing in MC3T3-E1 osteoblast-like cells (consistent with activation of P2X₇ receptors) but did not induce cell death. Using a Cytosensor microphysiometer, we found that 9-min exposure to BzATP (300 μM) caused a dramatic increase in proton efflux from MC3T3-E1 cells (∼2-fold), which was sustained for at least 1 h. In contrast, ATP or UTP (100 μM), which activate P2 receptors other than P2X₇, failed to elicit a sustained increase in proton efflux. Specific P2X₇ receptor antagonists A 438079 and A 740003 inhibited the sustained phase of the BzATP-induced response. Extracellular Ca²⁺ was required during P2X₇ receptor stimulation for initiation of sustained proton efflux, and removal of extracellular glucose within the sustained phase abolished the elevation elicited by BzATP. In addition, inhibition of phosphatidylinositol 3-kinase blocked the maintenance but not initiation of the sustained phase. Taken together, we conclude that brief activation of P2X₇ receptors on osteoblast-like cells triggers a dramatic, Ca²⁺-dependent stimulation of metabolic acid production. This increase in proton efflux is sustained and dependent on glucose and phosphatidylinositol 3-kinase activity.
- Published
- 2012
- Full Text
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10. Clinical use of meconium fatty acid ethyl esters for identifying children at risk for alcohol-related disabilities: the first reported case.
- Author
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Zelner I, Shor S, Lynn H, Roukema H, Lum L, Eisinga K, and Koren G
- Subjects
- Alcohol Drinking adverse effects, Alcohol Drinking metabolism, Biomarkers analysis, Biomarkers metabolism, Fatty Acids metabolism, Female, Fetal Alcohol Spectrum Disorders metabolism, Humans, Infant, Infant, Newborn, Meconium metabolism, Neonatal Screening methods, Pregnancy, Fatty Acids analysis, Fetal Alcohol Spectrum Disorders diagnosis, Meconium chemistry
- Abstract
Fatty acid ethyl esters (FAEEs) in meconium are validated biomarkers of heavy fetal alcohol exposure that may potentially be used clinically for identifying children at risk for alcohol-related disabilities. However, until now, FAEEs have been largely used anonymously in epidemiological studies, and by child protection authorities in need for verification of heavy alcohol use in pregnancy. Here we describe the first case of a neonate identified as part of a research study on a pilot neonatal screening program for prenatal alcohol exposure. The neonate's meconium tested high for FAEEs (52 nmol/g; positive cut-off ≥ 2 nmol/g), which prompted active follow-up of the infant's development, identifying early neurocognitive problems and allowing initiation of a remedial program.
- Published
- 2012
11. Universal screening for prenatal alcohol exposure: a progress report of a pilot study in the region of Grey Bruce, Ontario.
- Author
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Zelner I, Shor S, Gareri J, Lynn H, Roukema H, Lum L, Eisinga K, Nulman I, and Koren G
- Subjects
- Esters analysis, Fatty Acids analysis, Female, Fetal Alcohol Spectrum Disorders metabolism, Gas Chromatography-Mass Spectrometry, Hospital Units, Humans, Infant, Infant, Newborn, London, Meconium metabolism, Ontario, Pilot Projects, Pregnancy, Prenatal Care legislation & jurisprudence, Program Development, Alcoholism metabolism, Ethanol toxicity, Fetal Alcohol Spectrum Disorders etiology, Fetus drug effects, Mass Screening methods
- Abstract
The main objective of this study is to evaluate the clinical utility of meconium analysis for fatty acid ethyl esters as a universal screening tool intended for the detection of newborns at risk for fetal alcohol spectrum disorder. This will be accomplished by assessing the rate of voluntary participation in a nonanonymous neonatal screening program and by determining the logistics of implementing the necessary follow-up and interventions as part of routine care. Additionally, this study will determine the predictive value of fatty acid ethyl ester-positive meconium with regard to neurodevelopmental delays. This is an ongoing prospective cohort study. Written informed consent is sought from all Grey Bruce women delivering at participating birthing sites. Collected meconium samples are tested for fatty acid ethyl esters by headspace-solid-phase microextraction followed by gas chromatography-mass spectrometry. Children with positive results are followed up through an existing public health program involving regular home visits and assessments of developmental milestones by a public health nurse. These children and matched control subjects also undergo neurodevelopmental testing at 3 and 18 months of age by a clinical psychologist using Bayley Scales of Infant and Toddler Development. If delays are detected, the child is referred to diagnostic services and appropriate intervention programs. This study has been granted ethics approval and enrollment began in November 2008 at St. Joseph's Health Care in London, Ontario. The first positive case has been identified and the follow-up is currently being conducted by the public health unit. The successful completing of this study will reveal the population's willingness to participate in a neonatal screening program for prenatal alcohol exposure and determine the costs, feasibility, and utility of implementing such programs in clinical practice.
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- 2010
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12. Universal or targeted screening for fetal alcohol exposure: a cost-effectiveness analysis.
- Author
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Zelner I and Koren G
- Subjects
- Cost-Benefit Analysis, Ethanol adverse effects, Female, Fetal Alcohol Spectrum Disorders diagnosis, Humans, Infant, Newborn, Pregnancy, Prenatal Exposure Delayed Effects diagnosis, Risk Factors, Fetal Alcohol Spectrum Disorders economics, Mass Screening economics, Neonatal Screening economics
- Abstract
Very rarely therapeutic drug monitoring is evaluated for its ability to provide cost savings. A new article describes the cost-effectiveness of meconium analysis for fatty acid ethyl esters in the management of fetal alcohol spectrum disorder. This article is a summary and a critical appraisal of the article by Hopkins et al.
- Published
- 2009
- Full Text
- View/download PDF
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