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Biomedical subjects

Gideon Koren

Publications and source records attributed to Gideon Koren.

263 records · Page 15Linked to original sources

Influenza vaccination during pregnancy.

QUESTION: A 27-year-old patient of mine recently learned she is pregnant. She took the influenza vaccine offered at work when she was 7 weeks pregnant. Is her fetus at risk of malformations? ANSWER: No evidence indicates that killed influenza vaccine is teratogenic, even if given during the first trimester. Since 1996, Health Canada's Centre for Disease Control and Prevention has recommended that pregnant women in their second and third trimesters be vaccinated. This should not be interpreted as evidence that the vaccine is teratogenic in the first trimester because such evidence does not exist.

Adult↗

A prospective-controlled study of pregnant veterinary staff exposed to inhaled anesthetics and x-rays.

Most veterinary staff are women of reproductive age. They are exposed to "waste" anesthetic gas and ionizing radiation in their workplace, which may endanger fetal safety. Presently, exposure of female veterinary staff to these health hazards has not been adequately addressed in the medical literature. Our primary objective was to investigate the incidence of major malformations associated with occupational exposure to inhaled anesthetics and/or radiation among pregnant veterinary staff. The secondary objective was to determine the rates of other adverse outcomes. We prospectively collected data on and followed-up women occupationally exposed to inhaled anesthetics and/or radiation in veterinary practices in Ontario, and compared them to controls matched for maternal age and gestational age at the time of call to the Motherisk Program. A total of 95 women were prospectively enrolled and followed-up. Among the participants there were 87 (93.5%) and 88 (92.8%) livebirths in the study and control groups, respectively. There were 4 (4.8%) major birth defects in the study group and 3 (3.4%) in the control group. The rates of spontaneous abortion were also similar, 6 (6.4%) cases in the study group and 7 (7.4%) cases in the control group. These results suggest that Ontario female veterinary staff exposed to inhaled anesthetics and/or radiation do not seem to be at an increased risk for major malformations above baseline risk.

Adult↗

Evaluating the efficacy of EMLA in alleviating pain associated with lumbar puncture; comparison of open and double-blinded protocols in children.

Potential benefit of the topical anesthetic EMLA prior to lumbar puncture was studied in children with cancer. Comparison was made between 2 types of study: the first one involved 10 children who were enrolled in a double-blind placebo-controlled study and in the second, 18 children in an open crossover study. Although both studies suggested the favourable effects of EMLA in alleviating pain associated with LP, they illustrated the need to perform such studies in a controlled blinded fashion; the effect in the double-blind study was not apparent in some cases, whereas it was clear cut in all open cases.

Adolescent↗

Determinants of women's decision making on whether to treat nausea and vomiting of pregnancy pharmacologically.

Nausea and vomiting of pregnancy (NVP) affects up to 80% of all women to some degree during their pregnancies. Diclectin (doxylamine and pyridoxine [vitamin B6]) has been on the Canadian market for many years and is indicated as the drug of choice for the treatment of NVP. However, some women choose not to treat NVP with pharmacologic measures, perhaps due to a persistent fear of teratogenic risk. The objective of this study was to determine the factors that influence a woman's decision not to treat NVP with pharmacologic measures. Fifty-nine women recruited from the Motherisk Nausea and Vomiting Helpline completed a questionnaire. All were informed that Diclectin was considered safe for use during pregnancy. At a follow-up telephone call, 34% were not using any pharmacologic treatment, and of those who were taking the drug, 26% were using less than the recommended dose. Reasons cited for not using the medication were insufficient safety data, preference for non-pharmacologic methods, and being made to feel uncomfortable by the physician. Of the women who did use Diclectin, the most convincing reassuring information that it was safe to use came from friends and family. Many other factors play a large role in a women's decision making.

Adult↗

Pregnancy outcome following high doses of Vitamin E supplementation.

The recommended dose of Vitamin E in human pregnancy is 22-30 mg/day. High doses of Vitamin E (>or=400 IU/day) have been shown to attenuate or even prevent the damaging effect of ethanol and diabetes on the fetus in experimental animal models. The Motherisk program prospectively enrolled, and followed-up on, 82 pregnant women exposed to high doses (>or=400 IU/day) of Vitamin E during the first trimester of pregnancy. Pregnancy outcome was compared to a matched control group. The study group (n=82) was exposed to Vitamin E at doses ranging from 400-1200 IU/day. There was one pregnancy with major malformation (omphalocele) in study group. There was an apparent decrease in mean birth weight (3173+/-467 g) in Vitamin E group as compare to control (3417+/-565 g; P=0.0015); however, there were no significant differences in rates of live births, preterm deliveries, miscarriages and stillbirths. Therefore, it is concluded that consumption of high doses of Vitamin E during the first trimester of pregnancy does not appear to be associated with an increased risk for major malformations, but may be associated with decrease in birth weight.

Adult↗

Pregnancy outcome of women who failed appointments at a teratogen information service clinic.

The effect of failed appointments at a teratogen information service (TIS) clinic on pregnancy outcome is not known. The objectives of our study were 1) to identify predictors of failed appointments and 2) to evaluate if failed appointments were associated with a higher rate of adverse pregnancy outcome among women booked for counseling at a TIS clinic over 5 consecutive months. Of 242 patients scheduled to come to clinic, 154 were followed-up at 20 weeks gestational age. Women who were pregnant at 20 weeks were more likely to have attended the clinic (81% attendance rate), than women who had a spontaneous abortion, a therapeutic abortion, or an ectopic pregnancy (54% attendance rate) (P = 0.003). Independent predictors of failed appointments included exposure to illicit drugs, history of previous spontaneous abortion, and a main concern that was a nonmedication exposure. In conclusion, pregnant women who failed appointments at a TIS clinic are at greater risk for not being pregnant at 20 weeks gestational age than those who attended the clinic. Telephone counseling should be considered in selected cases to ensure that all women get relevant information at the time of appointment booking.

Abortion, Spontaneous↗

Antioxidants and fetal protection against ethanol teratogenicity. I. Review of the experimental data and implications to humans.

Ethanol is the most common human teratogen, and heavy drinking during pregnancy can result in serious adverse outcomes to the fetus. The cellular mechanisms by which ethanol induces damage in utero are not well understood, while induction of oxidative stress is believed to be one putative mechanism. Our objective is to review the data of antioxidant effects in experimental models of fetal alcohol syndrome. Prior to the description of the available experimental data, we will briefly review the mechanisms leading to ethanol-induced oxidative stress. Ethanol-induced oxidative damage to the fetus could be attenuated by a variety of antioxidants as was documented in whole animal and tissue culture studies. Experiments, retrieved from the literature search, are described and criticized. Although experimental data are still limited, the application of a treatment strategy that includes antioxidants is justified since antioxidant treatment in human pregnancy for pre-eclampsia was demonstrated to be safe and effective. The available experimental evidence and the safety of vitamins C and E in pregnancy suggest that experimental use of antioxidants in alcohol-consuming mothers should be seriously considered to reduce fetal alcohol damage.

Alcohol-Induced Disorders, Nervous System↗

Binding of acetaldehyde to human and Guinea pig placentae in vitro.

BACKGROUND: Significant interindividual variability exists following maternal alcohol consumption; not all children born to alcoholic women manifest the symptoms associated with foetal alcohol spectrum disorder (FASD). OBJECTIVE: To investigate the potential role of the placenta as a source of variability by determining if interindividual variability exists in the binding of acetaldehyde to human placenta. METHODS: Acetaldehyde was added to ten different human placental homogenates and subjected to equilibrium dialysis. Homogenates of placentae obtained from guinea pigs chronically exposed to ethanol throughout gestation were also dialysed in the presence of acetaldehyde to look for alterations in binding after chronic alcohol exposure. Nonlinear least-squares regression analysis was used to characterize the binding system involved. RESULTS: It was found that the amount of acetaldehyde bound to human placentae varied by as much as 3-fold among placentae. The binding profile of acetaldehyde was characterized as a two site binding system (Ka(1)=9.8 x 10(5)+/-0.7 x 10(5)l/mol, N(1)=1.1 x 10(-8)+/-0.7 x 10(-8)mol/g tissue; Ka(2)=1.6 x 10(4)+/-0.9 x 10(4)l/mol, N(2)=1.7 x 10(-7)+/-0.4 x 10(-7)mol/g tissue). Chronic alcohol exposure had no effect on the degree of acetaldehyde binding. CONCLUSION: This previously unidentified source of variability may partially explain why some foetuses are adversely affected by prenatal alcohol exposure while others are not.

Acetaldehyde↗

Paternal alcohol exposure and Turner syndrome.

AIMS: Turner syndrome (TS) is a sex chromosome aneuploidy that occurs as a result of a non-disjunctional error in meiosis I or anaphase lag; however, the aetiology of this disorder remains unknown. Anecdotal evidence suggests that paternal alcoholism may play an unidentified role in the aetiology of TS. Accordingly, the primary objective of this study was to determine the potential association between paternal alcohol exposure and TS. METHODS: The questionnaire was designed to solicit information about the parents' health and lifestyle habits occurring 1 year prior to and throughout the pregnancy of their daughter with TS. Alcohol dependence was assessed by the Brief Michigan Alcohol Screening Test (BMAST). The study population was solicited from the Turner's Syndrome Society of Canada and included any parent(s) having a child with TS who was of any age. Two hundred and twelve families completed and returned the survey. RESULTS: This provided a response rate of 86.5%. Six of the fathers (3.6%; n = 166) and six of the mothers (3.6%; n = 165) had scores of 5 or more on the BMAST (scores of 5+ are considered to be in the 'alcoholic range'). This is considerably lower than the population norm of 9.5%. CONCLUSIONS: Our study has suggested there is no association between paternal or maternal alcohol consumption and TS.

Adolescent↗

Pharmacokinetics of high doses of cyanocobalamin administered by intravenous injection for 26 weeks in rats.

1. High doses of vitamin B12 (cyanocobalamin) may be therapeutically effective to treat neurological alterations secondary to a wide range of disease states. The aim of the present study was to evaluate the effect of dose and repeated administration on the pharmacokinetics of cyanocobalamin in rats. 2. Forty-eight rats were randomly assigned to receive 1, 5, 25 or 100 mg/kg cyanocobalamin for 182 days (26 weeks). Cyanocobalamin plasma levels were quantified by HPLC on days 1, 85 and 182 of treatment and were analysed by means of non-compartment pharmacokinetic (PK) analysis. In addition, population PK analysis was used to fit cyanocobalamin plasma concentrations to time by means of a two-compartment model for intravascular administration. 3. The half-life of cyanocobalamin ranged from approximately 20 to 50 min, clearance ranged from 4.5 to 9 mL/min and the volume of distribution at steady state ranged from 140 to 470 mL. A statistically significant negative relationship existed between the dose of cyanocobalamin and the normalized area under the plasma concentration-time curve (AUC). This non-linearity was not exhibited in population PK analysis. No evidence of toxicity was observed. 4. At very high and prolonged doses (up to 100 mg/kg for 26 weeks), intravascular administration of cyanocobalamin in rats follows a two-compartment kinetic model and cyanocobalamin undergoes extensive extravascular distribution. The negative relationship between dose and normalized AUC is compatible with possible saturation of tubular reabsorption, thus increasing renal clearance at higher doses.

Algorithms↗