Showing papers by "Gideon Koren published in 2010"
TL;DR: Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed and should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia).
Abstract: Introduction. Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome. Methods. We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included “colchicine” and “poisoning” or “overdose” or “toxicity” or “intoxication.” Toxicokinetics. Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. Therapeutic and toxic doses. The usual adult oral doses for FMF is 1.2–2.4 mg/day;...
414 citations
TL;DR: This review uses emerging evidence to describe the usefulness of hair analysis for cortisol and discusses the current methods used.
308 citations
TL;DR: Diclectin delayed release formulation of doxylamine succinate and pyridoxine hydrochloride is effective and well tolerated in treating nausea and vomiting of pregnancy.
132 citations
TL;DR: National standards of care for the screening and recording of alcohol use and counselling on alcohol use of women of child-bearing age and pregnant women based on the most up-to-date evidence are established.
Abstract: Objective To establish national standards of care for the screening and recording of alcohol use and counselling on alcohol use of women of child-bearing age and pregnant women based on the most up-to-date evidence. Evidence Published literature was retrieved through searches of PubMed, CINAHL, and the Cochrane Library in May 2009 using appropriate controlled vocabulary (e.g., pregnancy complications, alcohol drinking, prenatal care) and key words (e.g., pregnancy, alcohol consumption, risk reduction). Results were restricted to literature published in the last five years with the following research designs: systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no language restrictions. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment (HTA) and HTA-related agencies, national and international medical specialty societies, clinical practice guideline collections, and clinical trial registries. Each simple-article was screened for relevance and the full text acquired if determined to be relevant. The evidence obtained was reviewed and evaluated by the members of the Expert Workgroup established by the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was evaluated and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Values The quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table 1). Sponsor The Public Health Agency of Canada and the Society of Obstetricians and Gynaecologists of Canada. Endorsement These consensus guidelines have been endorsed by the Association of Obstetricians and Gynecologists of Quebec; the Canadian Association of Midwives; the Canadian Association of Perinatal, Women's Health and Neonatal Nurses (CAPWHN); the College of Family Physicians of Canada; the Federation of Medical Women of Canada; the Society of Rural Physicians of Canada; and Motherisk. Summary Statements 1.There is evidence that alcohol consumption in pregnancy can cause fetal harm. (II-2) There is insufficient evidence regarding fetal safety or harm at low levels of alcohol consumption in pregnancy. (III) 2.There is insufficient evidence to define any threshold for low-level drinking in pregnancy. (III) 3.Abstinence is the prudent choice for a woman who is or might become pregnant. (III) 4.Intensive culture-, gender-, and family-appropriate interventions need to be available and accessible for women with problematic drinking and/or alcohol dependence. (II-2) Recommendations 1.Universal screening for alcohol consumption should be done periodically for all pregnant women and women of child-bearing age. Ideally, at-risk drinking could be identified before pregnancy, allowing for change. (II-2B) 2.Health care providers should create a safe environment for women to report alcohol consumption. (III-A) 3.The public should be informed that alcohol screening and support for women at risk is part of routine women's health care. (III-A) 4.Health care providers should be aware of the risk factors associated with alcohol use in women of reproductive age. (III-B) 5.Brief interventions are effective and should be provided by health care providers for women with at-risk drinking. (II-2B) 6.If a woman continues to use alcohol during pregnancy, harm reduction/treatment strategies should be encouraged. (II-2B) 7.Pregnant women should be given priority access to withdrawal management and treatment. (III-A) 8.Health care providers should advise women that low-level consumption of alcohol in early pregnancy is not an indication for termination of pregnancy. (II-2A)
117 citations
TL;DR: Analysis of cortisol levels in hair has the potential to be a valuable short-term dynamic stress indicator that will complement paleopathological and biochemical studies of health and stress, and permit the reconstruction of increasingly detailed life histories.
102 citations
TL;DR: Cortisol concentrations in hair do not predict depressive symptoms in CAD patients attending cardiac rehabilitation, and perceived stress was not associated with long-term cortisol concentrations.
Abstract: Objective Concentrations of cortisol in hair, a novel marker of longer-term cortisol status, were compared in depressed versus nondepressed patients with coronary artery disease (CAD). Methods 20 mg hair samples of 3 cm length were collected from 121 patients attending a cardiac rehabilitation program, 34 of whom suffered from depressive symptoms. Results Controlling for age, gender, coronary artery bypass grafting, history of depression, and time since most recent acute coronary syndrome, cortisol concentrations (P = 0.162) did not predict severity of depression. Younger age (P = 0.003) was a significant predictor of depressive symptoms. Perceived stress was not associated with long-term cortisol concentrations (P = 0.161). Conclusions Cortisol concentrations in hair do not predict depressive symptoms in CAD patients attending cardiac rehabilitation.
86 citations
TL;DR: Although the analysis revealed no evidence that untreated maternal epilepsy was associated with a lower IQ in the child, there may have been confounding factors, such as milder epilepsy, in this group.
Abstract: Background: Results of studies investigating the long-term effects of intrauterine exposure to antiepileptic drugs (AEDs) on cognitive functioning are limited and conflicting. Objective: To estimate intellectual development of children prenatally exposed or unexposed to AEDs by assessing IQ scores in a systematic review and meta-analysis. Methods: A literature search using Pubmed, EMBASE and Google Scholar from inception to 30 April 2009 was performed to identify all original cohort studies that investigated cognitive functioning after in utero exposure to AEDs. Studies had to include at least one group exposed to an AED and one unexposed group. Data from drug exposed and unexposed controls were combined using a random effects model. Results: Eleven studies met the inclusion criteria. Eight studies (three for valproic acid and five for carbamazepine) evaluated IQ as a measure of cognitive development. IQ was assessed by the Wechsler, Bayley or McCarthy intelligence scales, depending on age. One study investigated phenytoin and one study investigated phenobarbital (phenobarbitone). Because one study was reported in two different publications, seven studies were included in the meta-analysis. In total, the seven selected studies included 67 children exposed in utero to valproic acid and 151 exposed to carbamazepine, and 494 unexposed controls born to healthy women or to women with untreated epilepsy. The mean full-scale IQ (FSIQ), verbal IQ (VIQ) and performance IQ (PIQ) scores in children exposed to valproic acid in utero were 83.9 (95% CI 64.2, 103.6), 93.7 (95% CI 72.6, 114.7) and 88.3 (95% CI 69.9, 106.9), respectively. The mean FSIQ, VIQ and PIQ scores in the control group were 102 (95% CI 90, 116), 101 (95% CI 87, 114) and 99 (95% CI 90, 117), respectively. The mean FSIQ, VIQ and PIQ were all significantly lower in the valproic acid group compared with the unexposed group. The FSIQ and VIQ of children exposed to carbamazepine were not statistically different from those of the unexposed control group. In a sub-analysis of carbamazepine exposure in three studies using the Wechsler intelligence scale, PIQ was significantly lower in children exposed to carbamazepine than in unexposed children. Conclusions: Although our analysis revealed no evidence that untreated maternal epilepsy was associated with a lower IQ in the child, there may have been confounding factors, such as milder epilepsy, in this group. Exposure to valproic acid in pregnancy is associated with significantly reduced intelligence in children whose mothers were treated for epilepsy. Exposure to carbamazepine in pregnancy does not appear to be associated with reduced FSIQ and VIQ in children, although PIQ was lower in the sub-analysis. Clinicians should inform families of the potential cognitive adverse effects of valproic acid. More studies are needed to corroborate these findings.
86 citations
TL;DR: Fatal opioid toxicity occurred in a developmentally delayed child aged 5 years 9 months who was inadvertently administered high doses of hydrocodone for a respiratory tract infection, and genetic analysis revealed that the child had a reduced capability to metabolize the drug via the CYP2D6 pathway.
Abstract: Fatal opioid toxicity occurred in a developmentally delayed child aged 5 years 9 months who was inadvertently administered high doses of hydrocodone for a respiratory tract infection. The concentration of hydrocodone in postmortem blood was in the range associated with fatality; however, hydromorphone, a major metabolite catalyzed by cytochrome P450 2D6 (CYP2D6), was not detected when using mass spectrometry. Genetic analysis revealed that the child had a reduced capability to metabolize the drug via the CYP2D6 pathway (CYP2D6*2A/*41). Coadministration of clarithromycin (a potent cytochrome P450 3A4 inhibitor) for an ear infection and valproic acid for seizures since birth further prevented drug elimination from the body. This case highlights the interplay between pharmacogenetic factors, drug-drug interactions, and dose-related toxicity in a child.
79 citations
TL;DR: Investigation of whether insulin glargine crosses the human placenta using the human perfused placental lobule technique found that it is not likely to cross the placente, when used at therapeutic concentrations.
Abstract: OBJECTIVE Insulin glargine (Lantus) is an extended-action insulin analog with greater stability and duration of action than regular human insulin. The long duration of action and decreased incidence of hypoglycemia provide potential advantages for its use in pregnancy. However, the placental pharmacokinetics of insulin glargine have not been studied. Therefore, the objective of this study was to determine whether insulin glargine crosses the human placenta using the human perfused placental lobule technique.
RESEARCH DESIGN AND METHODS Placentae were obtained with informed consent after elective cesarean section delivery of noncomplicated term pregnancies. Insulin glargine, at a therapeutic concentration of 150 pmol/l (20 μU/ml) was added to the maternal circulation. Additional experiments were carried out at insulin glargine concentrations 1,000-fold higher than therapeutic levels (150, 225, and 300 nmol/l). A subsequent perfusion for which the maternal circuit remained open and insulin glargine was continuously infused at 150 pmol/l was completed for further confirmation of findings. The appearance of insulin glargine in the fetal circulation was analyzed by a chemiluminescence immunoassay.
RESULTS Results from perfusions carried out at therapeutic concentrations (150 pmol/l) of insulin glargine showed no detectable insulin glargine in the fetal circuit. After perfusion with very high insulin glargine concentrations of 150, 225, and 300 nmol/l, the rate of transfer remained low at 0.079 ± 0.01, 0.14, and 0.064 pmol · min−1 · g tissue−1, respectively.
CONCLUSIONS Insulin glargine, when used at therapeutic concentrations, is not likely to cross the placenta.
79 citations
TL;DR: The results support clinical pathology data in humans and suggest that HK-2 cells are a suitable model to use in in vitro toxicity studies to determine drug-induced nephrotoxicity in humans.
Abstract: Established cell lines are widely used as in vitro models in toxicology studies. The choice of an appropriate cell line is critical when performing studies to elucidate drug-induced toxicity in humans. The porcine renal proximal tubular cell line LLC-PK1 is routinely used to study the nephrotoxic effects of drugs in humans. However, there are significant interspecies differences in drug pharmacokinetics and pharmacodynamics. The objective of this study was to determine whether the human renal proximal tubular cell line HK-2 is an acceptable model to use when performing in vitro toxicity studies to predict effects in humans. We examined 2 nephrotoxic agents, ifosfamide (IFO) and acyclovir, that exhibit different clinical nephrotoxic patterns. HK-2 cells metabolized IFO to its nephrotoxic metabolite, chloroacetaldehyde (CAA). Acyclovir induced a concentration-dependent decrease in HK-2 cell viability, suggesting that acyclovir may induce direct insult to renal proximal tubular cells. The results support cli...
72 citations
TL;DR: There was no association between in utero exposure to ciclosporin and long-term neurocognitive and behavioral development in children after maternal renal transplantation and Maternal IQ and socioeconomic status were positive and significant predictors for children’s IQ.
Abstract: Background: Immunosuppressant therapy is essential in the prevention of organ transplant rejection.
TL;DR: To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADR and matched control patients.
Abstract: Background: Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high...
TL;DR: Most pregnant women believe that medicines in general are helpful and safe to use, however, they are much more restrictive and unsure about use during pregnancy, and health-care professionals should be aware of such attitudes.
Abstract: Background:Beliefs about medication may impact a woman's decision to take a needed medication during pregnancy. While many women will be faced with decisions regarding medication use during pregnancy, there is a paucity of research on this topic in the literature.Objective:To study pregnant women's beliefs about medication and factors that determine those beliefs.Methods:A questionnaire was posted at the University of Oslo's Web site for Internet surveys for 5 weeks from mid-September 2008 through October 2008. Seven general statements from the “Beliefs about Medicines” questionnaire and 9 pregnancy-specific statements were used to assess pregnant women's attitudes toward medication use during pregnancy. Other information, such as sociodemographic background and personal medication use during pregnancy, was also collected.Results:A total of 866 pregnant women completed the questionnaire. Most women had a positive attitude toward medication in general, but believed pregnant women should be more restrictive...
TL;DR: Compared with conventional methods, this method of detection for opiates is fast, simple, and accurate, with the sensitivity and specificity required in forensic and clinical toxicology.
TL;DR: The results indicate that the Q141K variant of ABCG2 may have the potential to alter the placental pharmacokinetics of glyburide used in pregnancy.
Abstract: The antidiabetic agent glyburide (glibenclamide) is frequently used for the treatment of type II diabetes and is increasingly being used for the treatment of gestational diabetes. Evidence suggests that breast cancer resistance protein/ATP-binding cassette, subfamily G, member 2 (ABCG2) expressed in the placenta protects the fetus against the accumulation of glyburide. A number of studies have investigated the significance of several single-nucleotide polymorphisms (SNPs) in the ABCG2 gene. Associations between the Q141K (C421A) SNP and ABCG2 protein expression, membrane surface translocation, efflux activity, or ATPase activity have been shown. Therefore, alterations in glyburide transport across the placenta, resulting in increased fetal glyburide exposure, may be seen in individuals carrying the C421A allele. The purpose of this study is to investigate whether the Q141K SNP causes alterations in ABCG2-mediated glyburide transport. Glyburide accumulation assays were carried out with stably transfected human embryonic kidney (HEK)-293 cells expressing wild-type ABCG2 (Arg482) and polymorphic ABCG2 (Q141K). Glyburide kinetic parameters were determined for comparison of wild-type and SNP ABCG2 activity by simultaneously fitting data for ABCG2-expressing cells (saturable transport) and empty vector-expressing cells (nonsaturable transport) by nonlinear regression analysis. The apparent K(t) and V(max) values for the transfected HEK-293 cells expressing the polymorphic variant (Q141K) of ABCG2 were significantly higher than those values determined for the wild-type ABCG2-expressing cells (p < 0.05). Our results indicate that the Q141K variant of ABCG2 may have the potential to alter the placental pharmacokinetics of glyburide used in pregnancy.
TL;DR: The use of antidepressants in pregnancy appears to be associated with a small, but statistically significant increased rate in the incidence of preterm births, confirming results from several other studies.
Abstract: Objective: To compare the rates of low birth weight, preterm delivery and small for gestational age (SGA), in pregnancy outcomes among women who were exposed and nonexposed to antidepressants during pregnancy. Methods: At The Motherisk Program, we analyzed pregnancy outcomes of 1,243 women in our database who took various antidepressants during their pregnancy. Nine hundred and twenty-eight of these women and 928 nonexposed women who delivered a live born infant were matched for age, (±2 years), smoking and alcohol use and specific pregnancy outcomes were compared between the two groups. Results: There were 82 (8.8%) preterm deliveries in the antidepressant group and 50 (5.4%) in the comparison group. OR: 1.7 (95% CI: 1.18–2.45). There were 89 (9.6%) in the antidepressant group and 76 (8.2%) in the comparison group who delivered babies evaluated as SGA; OR: 1.19 (95% CI: 0.86–1.64). The mean birth weight in the antidepressant group was 3,449±591 g and 3,455±515 g in the comparison group (P=.8). Conclusion: The use of antidepressants in pregnancy appears to be associated with a small, but statistically significant increased rate in the incidence of preterm births, confirming results from several other studies. It is difficult to ascertain whether this small increased rate of preterm births is confounded by depression, antidepressants, or both. However, we did not find a statistically significant difference in the incidence of SGA or lower birth weight. This information adds to limited data available in the literature regarding these outcomes following the use of antidepressants in pregnancy. Depression and Anxiety, 2010. © 2009 Wiley-Liss, Inc.
TL;DR: Using the Organization of Teratology Information Specialists network, pregnant women exposed to MMF during pregnancy were prospectively identified and followed and the absolute risk from MMF may be smaller than originally calculated based on case reports.
Abstract: Mycophenolate mofetil (MMF) has become a major therapeutic option in the management of patients undergoing transplantation, as well as in the treatment of autoimmune conditions. Case reports have suggested that MMF use during pregnancy is associated with a specific pattern of congenital malformations. Because many pregnancies are unplanned, it is imperative to assess the teratogenic risk of MMF. Using the Organization of Teratology Information Specialists network, we prospectively identified and followed pregnant women exposed to MMF during pregnancy to update this teratogenic potential. Ten cases were identified and all received the drug during embryogenesis at the recommended doses (500 to 1500 mg daily). There were four miscarriages and one elective abortion due to fear of teratogenesis. None of the five live births had malformations. It is possible that, similar to other human teratogens discovered first by case reports, the absolute risk from MMF may be smaller than originally calculated based on case reports. Because the major malformations phenotypic of MMF may be visualized in utero (e.g., microtia, cleft palate, congenital diaphragmatic hernia, and cardiac malformation), diagnostic imaging should be performed.
Journal Article•
TL;DR: Commonly prescribed pain medications appear to be relatively safe to use during pregnancy, although caution should be used when prescribing them in late pregnancy.
Abstract: QUESTION My pregnant patients frequently ask about taking pain medications, sometimes for chronic conditions. What is known about the safety of using analgesics in therapeutic doses for acute or chronic pain during pregnancy?
ANSWER Commonly prescribed pain medications appear to be relatively safe to use during pregnancy. None of the analgesics has been found to increase the risk of major malformations, although caution should be used when prescribing them in late pregnancy.
TL;DR: The physiological development of the hair follicle and hair production during fetal life is reviewed to review the mechanisms and timing of hair development in the prenatal period.
TL;DR: An understanding of this genotype-phenotype relationship will allow for prediction of susceptible or favorable genotypes in order to personalize medication choices to minimize fetal exposure to teratogens, or to maximize pharmacological therapy to the fetus.
TL;DR: The occurrence of infra-His blocks in LQT2 rabbits under isoflurane and intra-His block in LqT1 rabbits after dofetilide suggest differential regional sensitivities of the rabbit His-Purkinje system to drugs blocking I(Kr) and I (Ks).
Abstract: We have generated transgenic rabbits lacking cardiac slow delayed-rectifier K+ current [IKs; long QT syndrome type 1 (LQT1)] or rapidly activating delayed-rectifier K+ current [IKr; long QT syndrom...
TL;DR: This study characterizes the incidence of prenatal alcohol exposure in Montevideo, Uruguay, using a novel biomarker, fatty acid ethyl esters, in meconium as well as a survey to mothers, and highlights a 44% incidence.
Abstract: Prenatal alcohol exposure can lead to a wide range of deficits known as fetal alcohol spectrum disorder. Epidemiologic studies regarding alcohol consumption in pregnancy have concentrated on North America, but recent reports have suggested that consumption is significant in many parts of the world. In Uruguay, alcohol consumption has changed into more risky and dangerous patterns and thus has a theoretical risk of having a high rate of prenatal alcohol exposure. This study characterizes the incidence of prenatal alcohol exposure in Montevideo, Uruguay, using a novel biomarker, fatty acid ethyl esters, in meconium as well as a survey to mothers. Nine hundred five meconium samples were collected from Hospital Pereira Rossell and Hospital de Clinicas in Montevideo, Uruguay. A maternal questionnaire was also completed. Meconium was analyzed for fatty acid ethyl esters using liquid-liquid and solid phase extraction with gas chromatography-flame ionization detection. Meconium was also analyzed for other drugs of abuse using enzyme-linked immunosorbent assay. Forty-four percent of meconium samples were above the positive cutoff for fatty acid ethyl esters and represent those newborns with risky prenatal exposure during the final two trimesters of pregnancy. Infants with prenatal alcohol exposure were more likely to have prenatal exposure to tobacco (odds ratio, 1.56; 95% confidence interval, 1.11-2.20) or any illicit drug (odds ratio, 2.29; 95% confidence interval, 0.98-5.31). Ethyl linoleate was a significant predictor of infant birth weight along with prenatal tobacco exposure, maternal body mass index, and infant sex. This study highlights a 44% incidence of prenatal alcohol exposure.
TL;DR: Analysis of hair mercury may be warranted before pregnancy in selected groups of women consuming more than 12 ounces of fish per week, as dietary modification can decrease body burden and ensure fetal safety.
Journal Article•
TL;DR: Pregnancy safety data provided by the FDA pregnancy risk categories and the Compendium of Pharmaceuticals and Specialties are insufficient to guide clinical decisions on how to proceed with a pregnancy following exposure to a category D medication.
Abstract: QUESTION My patient is taking a medication for a chronic condition and has just found out that she is 6 weeks pregnant. The US Food and Drug Administration (FDA) has assigned this medication to pregnancy risk category D, and the Compendium of Pharmaceuticals and Specialties provides no additional data. How should I interpret this information, and how does the Motherisk Program evaluate the safety or risks of drug use in pregnancy? ANSWER Pregnancy safety data provided by the FDA pregnancy risk categories and the Compendium of Pharmaceuticals and Specialties are insufficient to guide clinical decisions on how to proceed with a pregnancy following exposure to a category D medication. The Motherisk Program creates peer-reviewed statements derived from the primary literature, and we examine fetal outcomes as well as the risk-benefit profile of maternal treatment when evaluating the safety of medication use in pregnancy. The FDA announced in May 2008 that it is dropping its pregnancy risk categories and adopting a method similar to the one we use at Motherisk.
TL;DR: If a policy of substituting heparin for warfarin between 6 and 12 weeks' gestation is followed, it is suggested that substitution should begin at a much earlier gestational age, as it is too late to avoid embryopathy.
Abstract: Anticoagulation therapy during pregnancy in women with prosthetic cardiac valves is a therapeutic challenge. The use of vitamin K antagonists such as warfarin during pregnancy carries the potential for serious risks to the fetus, especially if these drugs are administered during the first trimester or at term. Between 6 and 12 weeks' gestation, fetal synthesis of proteins crucial for bone and cartilage formation may be impaired by warfarin, resulting in the well-defined "warfarin embryopathy." One of the most commonly suggested regimens involves the substitution of heparin for warfarin between 6 and 12 weeks' gestation to minimize the risk of warfarin embryopathy. Warfarin has a long half-life; following a single dose, the terminal elimination half-life is about one week, with a mean effective half-life of 40 hours. To date, all existing guidelines have ignored this long elimination half-life. If a policy of substituting heparin for warfarin between 6 and 12 weeks' gestation is followed, we suggest that substitution should begin at a much earlier gestational age. Substitution starting at 6 weeks' gestation may be too late to avoid embryopathy.
TL;DR: An in vitro model system consistent with the in vivo reciprocal downregulation of repolarizing currents seen in transgenic rabbit models is presented, illustrating the importance of the transfection method when studying heterologous ion channel expression and trafficking and suggesting that interactions between KvLQT1 and HERG are mediated through COOH-termini.
Abstract: We previously reported a transgenic rabbit model of long QT syndrome based on overexpression of pore mutants of repolarizing K+ channels KvLQT1 (LQT1) and HERG (LQT2).The transgenes in these rabbit...
TL;DR: The results indicate that infants born in the high-risk obstetric unit had a 12-fold higher risk of screening positive for second and third trimester alcohol exposure compared with infantsBorn in the general population of Grey-Bruce (relative risk=12.04, 95% confidence interval=6.40-22.65, P<.0001).
TL;DR: In-utero exposure to labetalol does not appear to adversely affect the neurocognitive development of young children, and reassuring results may aid disease management for pregnant women with hypertension.
Abstract: Objective: To identify the effect of prenatal labetalol exposure on children's long-term neurodevelopment. Design: A cohort study with matched controls using a prospectively collected database. Methods: Participants were women counseled for hypertension in pregnancy at the Motherisk Program at The Hospital for Sick Children, and The Sunnybrook Health Sciences Centre, Toronto, Canada and their children. Mother-child pairs were divided into groups based on in-utero exposure to labetalol (n = 32), non-teratogenic substances (n = 42), and methyldopa (n = 25). The main outcome measures were children's Full-Scale IQ, Performance IQ and Verbal IQ assessed with the Wechsler Preschool and Primary Scale of Intelligence. Results: There were no statistically significant differences in scores on Full-Scale IQ, Performance IQ, or Verbal IQ between children exposed in utero to labetalol and to non-teratogenic substances (Full-Scale IQ: 109.60 ± 8.20 vs. 111.90 ± 11.39, p = 0.647; Performance IQ: 104.80 ± 8.69 vs. 110.19...
TL;DR: Exposure to H2‐blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores, and no such association was found when therapeutic pregnancy terminations were included in the analysis.
Abstract: Little data exist on the safety of H(2)-blockers during pregnancy. A computerized database of medications dispensed from 1998 to 2007 to all women registered in the "Clalit" health maintenance organization, in the Southern District of Israel, was linked with computerized databases containing maternal and infant hospitalization records from the district hospital. The following confounders were controlled for: parity, maternal age, ethnic group, maternal diabetes, smoking, and peripartum fever. Also, therapeutic pregnancy termination data were analyzed. A total of 117 960 infants were born during the study period, 84 823 of them (72%) to women registered at Clalit; 1148 of the latter were exposed to H(2)-blockers during the first trimester of pregnancy. Exposure to H(2)-blockers was not associated with an increased risk for congenital malformations (adjusted odds ratio [OR] = 1.03, 95% confidence interval [CI]: 0.80-1.32); also, no such association was found when therapeutic pregnancy terminations were included in the analysis (adjusted OR = 1.17, 95% CI: 0.93-1.46). Exposure to H(2)-blockers was not associated with perinatal mortality, premature delivery, low birth weight, or low Apgar scores.
TL;DR: There was a significant correlation between maternal and neonatal hair test results for opioids and understanding the addiction profiles of these women may lead to better clinical and social management and may largely benefit an at-risk population.
Abstract: Identification of maternal opioid abuse in pregnancy is often difficult to ascertain in the absence of a reliable self-report. We aimed to characterize an at-risk neonatal population for opioid exposures as well as other drugs of abuse and alcohol. From June 2007 to January 2009, 563 neonatal hair and 1318 meconium specimens were assessed for opioids and were positive in 11.4% and 17.0%, respectively. Neonates testing positive for opioids in hair or meconium analysis were also more likely to test positive for other licit and illicit substances (odds ratio hair , 1.75; 95% confidence interval, 1.03-2.97 ; odds ratio meconium , 1.61; 95% confidence interval, 1.16-2.22). Specifically, a positive neonatal hair test for opioids also predicted a positive result for oxycodone. In addition, a positive meconium test result for opioids was associated with positive results for cocaine, oxycodone, methadone, benzodiazepines, and fatty acid ethyl esters (alcohol). Finally, there was a significant correlation between maternal and neonatal hair test results for opioids (Spearman rank rho = 0.657, P = 0.03). Understanding the addiction profiles of these women may lead to better clinical and social management and may largely benefit an at-risk population.