Search PubMed⌕ Search

Biomedical subjects

Gideon Koren

Publications and source records attributed to Gideon Koren.

At least 55 records · Page 3Linked to original sources
PubMed2006

Chronic prenatal ethanol exposure and increased concentration of fatty acid ethyl esters in meconium of term fetal Guinea pig.

In humans, the occurrence of prenatal exposure to ethanol is difficult to validate objectively. Increased concentration of fatty acid ethyl esters (FAEE) in the meconium of the newborn may be a biomarker of prenatal ethanol exposure. The validity of this proposed biomarker was tested in pregnant guinea pigs that received chronic oral administration of 4 g ethanol/kg maternal body weight/day (n=8), isocaloric-sucrose/pair-feeding (n=8) or water (n=2) throughout gestation. At gestational day 65 (term, gestational day 66 to 69), each dam and her offspring were euthanized, and meconium was collected from the term fetal large intestine. Eight individual FAEE (lauric, myristic, palmitic, palmitoleic, stearic, oleic, linolenic and arachidonic AEE) were measured by gas chromatography--flame ionization detection and confirmed by gas chromatography--mass spectrometry. The chronic maternal ethanol regimen decreased fetal body weight and brain weight. There was virtually no measurable FAEE in the meconium for the water group (n=3 fetuses). For meconium of the ethanol offspring (n=25 fetuses) compared with the sucrose offspring (n=23 fetuses), the total FAEE concentration was 8-fold higher; and lauric, palmitic, stearic and oleic AEE concentrations were at least 5-fold higher for the ethanol group. The data indicate that fetal meconium FAEE constitute a biomarker of prenatal ethanol exposure for a maternal ethanol regimen that restricts fetal development, with an inverse relationship between meconium total FAEE concentration and both body weight and brain weight.

Animals↗
PubMed2006

A pilot pharmacokinetic and antiangiogenic biomarker study of celecoxib and low-dose metronomic vinblastine or cyclophosphamide in pediatric recurrent solid tumors.

Tumor vasculature is a reasonable target for cancer therapy and lower more frequent doses of traditional chemotherapeutics [low-dose metronomic (LDM) chemotherapy] has been shown to have antiangiogenic efficacy. This study evaluated the safety and pharmacokinetics of celecoxib and LDM vinblastine or cyclophosphamide in children with recurrent, refractory solid tumors. We also investigated whether a subset of circulating plasma proteins are surrogate markers of angiogenic activity. Thirty-three children were enrolled in this pilot study and received celecoxib (250 mg/m(2) PO b.i.d.) and either vinblastine (1 mg/m(2) IV 3 x /wk) or cyclophosphamide (30 mg/m(2) PO daily) continually. Celecoxib alone and with LDM chemotherapy was well tolerated and plasma concentrations were consistent with those shown to have antiangiogenic activity. Four patients (13%) had durable stable disease (28 to 78 wk) although no complete or partial responses were observed. The surrogate markers measured (vascular endothelial growth factor, basic fibroblast growth factor, soluble vascular cell adhesion molecule, soluble intercellular cell adhesion molecule, endostatin, and thrombospondin-1) were highly variable and no statistically significant relationship between them and disease progression or maintenance of stable disease was observed. We concluded that this regimen is well tolerated hence supporting the use of this form of therapy in pediatric patients. However, future studies should include more homogenous patient populations and focus on validating surrogate markers to monitor treatment activity.

Adolescent↗
PubMed2006

The K+ channel gene, Kcnb1: genomic structure and characterization of its 5'-regulatory region as part of an overlapping gene group.

Kcnb1 expression is down-regulated in certain types of cardiomyopathy. As a first step towards understanding Kcnb1 regulation, we determined its genomic structure and characterized its 5'-regulatory region. Two species of Kcnb1 mRNA were found to arise from alternative usage of two highly GC-rich promoters (P1, P2). While transcripts arising from P1 were mainly detected in brain, P2 transcripts were highly expressed in heart and brain. Core regulatory regions were characterized for P1 and P2. The mutation of a potential Nur77/Nurr1/NOR-1 binding site, NBRE(Kcnb1), conserved in both human and mouse, resulted in a significant decrease in basal P2 promoter activity. Luciferase activities of the longest promoter-reporter construct reflected the level of endogenous Kcnb1 mRNA in myoblast, smooth muscle, and pituitary cell lines. Hyperosmolarity increased Kcnb1 mRNA concentration two-fold, mainly at the transcriptional level in clonal pituitary cells. These findings provide a basis for future studies of (post)transcriptional mechanism(s) down-regulating Kcnb1 expression in a variety of cardiomyopathies and point towards a possible involvement of Kcnb1 in pituitary cell excitability and secretory activity regulated by osmolarity.

Animals↗
PubMed2006

The effect of detection approaches on the reported incidence of tenfold errors.

BACKGROUND: Tenfold errors in calculation of paediatric drug doses are often life threatening. The magnitude and characteristics of this phenomenon have not been fully described. OBJECTIVES: The objective of this study was to describe the incidence and nature of paediatric tenfold errors and to describe the effect of different detection approaches on the detection of such errors. METHODS: To evaluate the incidence of tenfold errors, data were collected from three different studies on medication errors all conducted at a large tertiary care paediatric hospital: (i) a study investigating medication event reports to the hospital's Medication Incident Committee; (ii) a study auditing the charts of 1532 patients in the emergency department (ED) and; (iii) a prospective study of medication errors occurring during mock code resuscitations in the ED. RESULTS: In the first study, 20 tenfold errors were reported during the surveyed period. Almost all errors were prescribing errors. The calculated incidence was 1 per 22 500 doses prescribed. In chart auditing study in the ED, two tenfold errors where found in 1678 orders. In the prospective study, four tenfold errors were identified in eight mock resuscitations (125 orders for drugs). CONCLUSION: The incidence of tenfold errors in paediatrics varies dramatically when different detection approaches are used. The rate of tenfold errors may be especially high in resuscitation situations and is underestimated by spontaneous reporting.

Child↗
PubMed2006

Exposure to mirtazapine during pregnancy: a prospective, comparative study of birth outcomes.

BACKGROUND: Mirtazapine is a novel piperazinoazepine antidepressant, unrelated to any known class of antidepressants. Currently, apart from a few case reports and case series in the literature, there are no studies evaluating the safety of this drug during pregnancy. OBJECTIVE: To determine whether mirtazapine increases the risk for major malformations in newborns when used by pregnant women. METHOD: The study design was prospective, with 2 comparison groups: disease-matched pregnant women diagnosed with depression taking other antidepressants and pregnant women exposed to nonteratogens. The primary outcome was major malformations in neonates; secondary endpoints included spontaneous abortions, therapeutic abortions, gestational age at birth, and mean birth weight. Women were recruited from 5 teratogen information services in Toronto, Canada; Farmington, Conn., U.S.A.; Jerusalem, Israel; Rome, Italy; Sydney, Australia; and from the Drug Safety Research Unit in Southampton, United Kingdom. Women were recruited into the study from June 2002 to August 2005. RESULTS: We were able to follow 104 pregnancy outcomes in each drug group. There were 77 live births, 1 stillbirth, 20 spontaneous abortions, 6 therapeutic abortions, and 2 major malformations in the mirtazapine group. The mean +/- SD birth weight was 3335 +/- 654 g and the mean +/- SD gestational age at delivery was 38.9 +/- 2.5 weeks. Most (95%) of the women took mirtazapine in the first trimester, but only 25% of the women took it throughout pregnancy. The differences among the 3 groups were in the rate of spontaneous abortions, which was higher in both antidepressant groups (19% in the mirtazapine group and 17% in the other antidepressant group) than in the nonteratogen group (11%), but none of the differences were statistically significant. The rate of preterm births (prior to 37 weeks' gestation) was also higher in the mirtazapine group (10%) and in the other antidepressant group (7%) than in the nonteratogen group (2%). The difference was statistically significant between the mirtazapine group and the nonteratogen group (p = .04). CONCLUSION: Mirtazapine does not appear to increase the baseline rate of major malformations of 1% to 3%. However, the higher number of spontaneous abortions in the antidepressant groups confirms the higher rates of spontaneous abortions in pregnant women taking antidepressant medications found in previous studies.

Abnormalities, Drug-Induced↗
PubMed2006

Toxoplasmosis during pregnancy.

QUESTION: One of my female patients was tested for Toxoplasma and found positive for immunoglobulin G (IgG). She is planning to get pregnant soon. What are the risks for her and her baby? ANSWER: Up to 25% of Canadians are IgG-positive for Toxoplasma due to past exposure. Immunoglobulin M (IgM) titres indicate current infection. Toxoplasma gondii is an obligate intracellular protozoan that has several forms during its life cycle: oocyte, tachyzoite, and cyst.

Coccidiostats↗
PubMed2006

Metformin use during the first trimester of pregnancy. Is it safe?

QUESTION: A pregnant patient with polycystic ovary syndrome asked me whether continuing metformin, which she was taking to treat infertility before her pregnancy, is safe for her fetus. She has heard that metformin is a "drug for diabetes." How safe is it to take metformin during the first trimester of pregnancy and beyond? ANSWER: Despite the traditional response that all oral hypoglycemic agents are absolutely contraindicated during pregnancy, evidence that metformin is probably safe during the first trimester of pregnancy and beyond is accumulating. Results of a recent meta-analysis by the Motherisk Program showed no increase in incidence of major malformations and a potential protective effect in this patient population.

Female↗
PubMed2006

Safety of gadolinium during pregnancy.

QUESTION: A pregnant patient who underwent magnetic resonance imaging (MRI) because of an acute abdomen, was told that MRI contrast agents (ie, gadolinium-based contrast agents) are contraindicated during pregnancy. What is the risk to her baby? ANSWER: Current radiology practices and recommendations discourage the use of gadolinium-based contrast agents during pregnancy because their safety for the fetus has not yet been proven. In line, however, with the European Society of Radiology guidelines and based on the available evidence, gadolinium-based contrast agents appear to be safe in pregnancy. Gadolinium use should be considered when the diagnostic study is important for the health of the mother.

Abdomen, Acute↗
PubMed2006

Major malformations with valproic acid.

QUESTION: Increasing numbers of pregnant patients are treated with valproic acid, not just for epilepsy, but also for psychiatric conditions. Are there teratogenic risks other than the risk of spina bifida? ANSWER: It has now become evident that valproic acid might cause more than just neural tube defects (NTDs). In a systematic review of all cohort studies intended to answer this question, higher rates of major malformations (and not just NTDs) were found in most studies. The calculated relative risk was 2.59 when compared with other antiepileptic drugs and was 3.77 when compared with risk in the general population. There is compelling evidence that the risk is dose dependent. The risks appear to begin increasing at doses of 600 mg/d and to become more prominent at doses above 1000 mg/d.

Abnormalities, Drug-Induced↗
PubMed2006

Counseling pregnant women treated with paroxetine. Concern about cardiac malformations.

QUESTION: I have always reassured my patients that taking selective serotonin reuptake inhibitors (SSRIs) during pregnancy would not increase their risk of having children with major malformations. A recent warning from Health Canada, based on results of a study from GlaxoSmithKline, stated that infants exposed to paroxetine might be at higher risk of congenital malformations, specifically cardiovascular defects. Some of my pregnant patients who are taking paroxetine heard the warning and asked me whether they should stop taking it. What should I tell them? ANSWER: The new warning is based on unpublished, non-peer-reviewed studies. It ignored 2 published studies that failed to show any association between exposure to paroxetine and cardiovascular malformations, and no association with cardiovascular malformations has been shown by SSRIs as a class. Even if there is risk, it is minimal, and the warning does not disclose details of the cardiovascular malformations. Many cases of ventricular septal defect, the most common cardiac malformation, resolve spontaneously. Concerned pregnant women should know that, if taken after the first trimester, drugs cannot cause cardiac malformations. Failure to treat depression during pregnancy can have severe consequences for both mothers and babies and is the strongest predictor of postpartum depression.

Canada↗
PubMed2006

Diagnosis of fetal alcohol spectrum disorder (FASD): fatty acid ethyl esters and neonatal hair analysis.

Measuring levels of fatty acid ethyl esters (FAEE) in hair has been recently shown to discriminate between adult heavy and non-drinkers. Here, we review the potential of neonatal FAEE measurement in detecting infants exposed to alcohol in utero by outlining current progress in the development of a neonatal hair test for the diagnosis of fetal alcohol spectrum disorder (FASD). Developing a reproducible, accurate and predictable hair test for FAEE measurements in neonatal hair may prove to be a powerful tool in the detection of in utero alcohol exposure which is needed for the diagnosis of FASD. Such a neonatal hair test can revolutionize current FASD diagnostic methodology by providing early diagnosis, allowing intervention and treatment at stages where the adverse effects of alcohol can still be mitigated.

Adult↗
PubMed2006

Does vitamin K prophylaxis prevent bleeding in neonates exposed to enzyme-inducing antiepileptic drugs in utero?

QUESTION: One of my epileptic patients takes carbamazepine. She is 36 weeks pregnant and has asked me whether she should start vitamin K to prevent neonatal bleeding. Does current evidence support this practice? ANSWER: Recent evidence does not support the notion that newborns of women treated with enzyme-inducing anticonvulsant drugs are at increased risk of hemorrhagic disease. Antenatal vitamin K can be prescribed on an individualized basis in certain circumstances, such as imminent premature delivery.

Anticonvulsants↗
PubMed2006

Use of proton pump inhibitors during pregnancy and breastfeeding.

QUESTION: A 36-year-old pregnant patient has symptoms of peptic disease. Treatment with diet and lifestyle modifications and also antacids has given her little relief. If she were not pregnant, I would prescribe a proton pump inhibitor (PPI) for her. She is now 4 weeks pregnant, and I need to determine whether PPIs are safe during pregnancy. ANSWER: Data currently available suggest that omeprazole is not teratogenic in humans. While information on other PPIs is limited, a systematic review of the evidence suggests that they are also not teratogenic.

Anti-Ulcer Agents↗
PubMed2005

Ontogeny of drug elimination by the human kidney.

Renal clearance is an important route of drug elimination. While during the neonatal period there is minimal glomerular filtration and active tubular secretion of drugs, there is a well-described rapid development in these processes in the post-neonatal period. A less appreciated fact is that during toddlerhood, there is an "overshoot" of the glomerular filtration rate (GFR) well above the levels encountered in older children and adults, and there is an early achievement of adult levels in active drug secretion, which stays at a plateau throughout childhood and adulthood with an "overshoot" in toddlers due to specific transport mechanisms. This phenomenon leads to dose requirements for renally excreted drugs in this age group being, on a per-kilogram basis, much larger than in adults. This review discusses the mechanisms related to renal ontogeny in drug handling.

Animals↗
PubMed2005

Human milk biomonitoring data: interpretation and risk assessment issues.

Biomonitoring data can, under certain conditions, be used to describe potential risks to human health (for example, blood lead levels used to determine children's neurodevelopmental risk). At present, there are very few chemical exposures at low levels for which sufficient data exist to state with confidence the link between levels of environmental chemicals in a person's body and his or her risk of adverse health effects. Human milk biomonitoring presents additional complications. Human milk can be used to obtain information on both the levels of environmental chemicals in the mother and her infant's exposure to an environmental chemical. However, in terms of the health of the mother, there are little to no extant data that can be used to link levels of most environmental chemicals in human milk to a particular health outcome in the mother. This is because, traditionally, risks are estimated based on dose, rather than on levels of environmental chemicals in the body, and the relationship between dose and human tissue levels is complex. On the other hand, for the infant, some information on dose is available because the infant is exposed to environmental chemicals in milk as a "dose" from which risk estimates can be derived. However, the traditional risk assessment approach is not designed to consider the benefits to the infant associated with breastfeeding and is complicated by the relatively short-term exposures to the infant from breastfeeding. A further complexity derives from the addition of in utero exposures, which complicates interpretation of epidemiological research on health outcomes of breastfeeding infants. Thus, the concept of "risk assessment" as it applies to human milk biomonitoring is not straightforward, and methodologies for undertaking this type of assessment have not yet been fully developed. This article describes the deliberations of the panel convened for the Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States, held at the Hershey Medical Center, Pennsylvania State College of Medicine, on several issues related to risk assessment and human milk biomonitoring. Discussion of these topics and the thoughts and conclusions of the panel are described in this article.

Adult↗
PubMed2005

Pregnancy outcome after exposure to injectable ribavirin during embryogenesis.

We describe normal pregnancy outcome in a case of first trimester exposure to injectable ribavirin in a 36-year-old pregnant woman who received three intramuscular injections of ribavirin for suspected SARS. She delivered at 40 weeks of gestation a healthy baby girl. In pediatric follow up at 8 month of age, physical examination and neurodevelopmental milestones were normal.

Adult↗