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Gideon Koren

Publications and source records attributed to Gideon Koren.

At least 37 records · Page 2Linked to original sources
PubMed2006

Fatty acid ethyl esters (FAEE); comparative accumulation in human and guinea pig hair as a biomarker for prenatal alcohol exposure.

AIMS: To compare the incorporation rate (ICR) of fatty acid ethyl esters (FAEE) in hair between guinea pigs and humans, and to assess the relationship between ethanol exposure and FAEE concentrations in hair. METHODS: Published data from pregnant guinea pigs, including maximum blood ethanol concentration (BEC), dosage regimen, and total hair FAEE concentration, were compared with published data from alcoholic patients, where dose of ethanol consumed and total hair FAEE concentration were reported. Mean values of ethanol Vmax for pregnant guinea pigs and humans were obtained from published data (26.2 and 24 mg/dl/h, respectively). RESULTS: Total and individual FAEE ICRs, defined as the ratio of hair FAEE to the area under the BEC-time curve (total systemic ethanol exposure), were found to be on average an order of magnitude lower in the guinea pig than in the human. The profiles of ester incorporation also differed slightly between species, with ethyl stearate being highly incorporated in guinea pig hair and less so in human hair. The results may reflect in the human greater FAEE production, greater FAEE deposition in hair, slower FAEE catabolism, differential sebum production and composition, or a combination thereof. Also, ethyl oleate was found to correlate with total systemic ethanol exposure for both guinea pigs and humans, correlation coefficients equalling 0.67 (P < 0.05) and 0.49 (P < 0.05), respectively. No other ethyl esters, nor total FAEE, were found to correlate with systemic ethanol exposure. CONCLUSION: When extrapolating FAEE concentrations in hair from guinea pigs to humans, an order of magnitude difference should be considered, with humans incorporating more FAEE per unit of ethanol exposure. Also, the results suggest caution should be taken when interpreting values of single esters because of their differential incorporation among species. Lastly, our findings suggest ethyl oleate may be of keen interest in FAEE hair analysis, particularly across species.

Adult↗
PubMed2006

Pregnancy outcome following gestational exposure to azithromycin.

BACKGROUND: Azithromycin is an azalide antibiotic with an extensive range of indications and has become a common treatment option due to its convenient dosing regimen and therapeutic advantages. Human studies addressing gestational use of azithromycin have primarily focused on antibiotic efficacy rather than fetal safety. Our primary objective was to evaluate the possibility of teratogenic risk following gestational exposure to azithromycin. METHODS: There were 3 groups of pregnant women enrolled in our study: 1) women who took azithromycin, 2) women exposed to non-teratogenic antibiotics for similar indications, and 3) women exposed to non-teratogenic agents. They were matched for gestational age at time of call, maternal age, cigarette and alcohol consumption. Rates of major malformations and other endpoints of interest were compared among the three groups. RESULTS: Pregnancy outcome of 123 women in each group was ascertained. There were no statistically significant differences among the three groups in the rates of major malformations; 3.4% (exposed) versus 2.3% (disease matched) and 3.4% (non teratogen) or any other endpoints that were examined. In the azithromycin group, 88 (71.6%) women took the drug during the first trimester CONCLUSION: Results suggest that gestational exposure to azithromycin is not associated with an increase in the rate of major malformations above the baseline of 1-3%. Our data adds to previous research showing that macrolide antibiotics, as a group, are generally safe in pregnancy and provides an evidence-based option for health professionals caring for populations with chlamydia.

Journal Article↗
PubMed2006

Occurrence and impact of unanticipated variation in intravenous methotrexate dosing.

BACKGROUND: Studies using direct measurement suggest that the doses of up to 65% of drug infusions are outside industry standards. These preparation-associated errors occur despite routine safety procedures. As of April 5, 2006, the clinical impact of these errors had not been evaluated. OBJECTIVE: To measure the occurrence and associated clinical outcomes of variations in intravenous methotrexate dosing. METHODS: A prospective observational study was performed on 47 methotrexate infusions of 800 mg/m2 that were administered to 19 children with acute lymphoblastic leukemia. Serum methotrexate concentrations were measured at the end of the infusions, which were administered over 24 hours. The total methotrexate dose was determined by direct measurement of the concentration and the volume of each infusion. RESULTS: Dosing errors greater than or equal to 10% occurred in 11 (23%) infusions and ranged from -61% to 55% of the ideal dose. Repeated measures regression analysis found the measured total methotrexate dose was not significantly associated with the serum methotrexate concentration (p = 0.58) or with clinical toxicities. The methotrexate dose administered over the last hours of infusion (p = 0.006) and the serum creatinine level at diagnosis (p = 0.05) were the most significant predictors of the methotrexate concentration. High methotrexate concentrations were significantly associated with increased hepatic aminotransferase levels; however, the degree of elevation was of limited clinical relevance. CONCLUSIONS: While unexpected errors in drug dosing are more common than is suggested by other methods, the clinical impact observed in this model of methotrexate infusion was not demonstrably greater than medication errors described by other methods. Subsequent studies in this model of dosing error will require larger sample sizes, and other drugs should be evaluated.

Antimetabolites, Antineoplastic↗
PubMed2006

Nonsteroidal antiinflammatory drugs during third trimester and the risk of premature closure of the ductus arteriosus: a meta-analysis.

BACKGROUND: Nonsteroidal antiinflammatory drugs (NSAIDs) are increasingly being used during pregnancy to treat a variety of conditions. An evaluation of the risk of premature closure of the ductus arteriosus is useful in determining the safety of NSAIDs at different stages of pregnancy. OBJECTIVE: To determine whether NSAID use during the third trimester of pregnancy is associated with an increased risk of premature constriction of the ductus arteriosus. METHODS: A systematic review was conducted of MEDLINE (1966-2004), Embase (1980-2004), and the Cochrane Database of Systematic Reviews (1991-2004). Summary estimates of the odds ratios, comparing ductal outcomes in exposed and unexposed fetuses, and their 95% confidence intervals were calculated assuming a random effects model. RESULTS: Based on 217 patients exposed to indomethacin and 221 to placebo, the risk of ductal closure was 15-fold higher in the group of women exposed to NSAIDs compared with those receiving either placebo or other NSAIDs (8 studies; OR = 15.04, 95% CI 3.29 to 68.68). There was no significant increased risk of ductal closure in the infants of women treated with indomethacin compared with those receiving other drugs (4 studies; OR = 2.12, 95% CI 0.48 to 9.25). Similar results were found when calculating rate differences. CONCLUSIONS: Short-term use of NSAIDs in late pregnancy is associated with a significant increase in the risk of premature ductal closure.

Abnormalities, Drug-Induced↗
PubMed2006

A randomized cross over trial of tolerability and compliance of a micronutrient supplement with low iron separated from calcium vs high iron combined with calcium in pregnant women [ISRCTN56071145].

BACKGROUND: Prenatal micronutrient combinations with high iron content are associated with high rates of gastrointestinal symptoms. This coupled with nausea and vomiting of pregnancy results in women often discontinuing their multivitamins. A new prescription supplement (PregVit) that separates iron from calcium in two tablets--morning and evening, has lower elemental iron content (35 mg), but results in similar extent of iron absorption when compared to another supplement containing (60 mg) of elemental iron (Materna). The objectives of this study were to compare tolerability and compliance with PregVit vs. a supplement with high iron content (Materna), in pregnant women. METHODS: Randomized, crossover open labeled study in 135 pregnant women attending outpatient clinics in Ontario and Quebec. RESULTS: Use of PregVit was associated with a 30% reduction in constipation rate as compared to Materna. Both products demonstrated similar compliance rates. Compliance of Materna was negatively associated with the severity of nausea and vomiting of pregnancy. No such correlation was found for PregVvit. CONCLUSION: PregVit, a supplement with lower iron content (35 mg), has significantly decreased constipation rates as compared to 60 mg iron--Materna and has similar compliance rates. High iron content in multivitamin supplements is associated with adverse effects in pregnancy.

Journal Article↗
PubMed2006

Perfusion studies of glyburide transfer across the human placenta: implications for fetal safety.

OBJECTIVE: Gestational diabetes affects up to 5% of women. Oral hypoglycemics have been avoided because of the assumption that their placental transfer may cause fetal-neonatal hypoglycemia. A recent randomized trial could not show measurable glyburide levels in umbilical blood despite maternal treatment with regular doses of glyburide. The mechanism underlying this phenomenon is not known. The objective of our study was to document, using a human placenta perfusion model, whether glyburide is actively effluxed from the fetal to the maternal circulation. STUDY DESIGN: In vitro perfusion studies of human cotyledon were performed to quantify placental transfer of glyburide. Using close circle experiments and introducing glyburide to both maternal and fetal circulations at 200 ng/mL, we looked for evidence of transport against concentration gradient from the fetus to the mother. In parallel experiments, the P-glycoprotein inhibitor verapamil was used in an attempt to inhibit transplacental glyburide movement. RESULTS: There was highly significant transfer of glyburide against concentration gradient from the fetal to the maternal circulation. Fetal-to-maternal concentration ratio was 0.92 +/- 0.23 at the start of the experimental period and 0.31 +/- 0.47 3 hours later (P = .01) (n = 5). Verapamil did not modify glyburide transport. CONCLUSION: This is the first direct evidence of active glyburide transport from the fetus to the mother and, in general, of any medicinal drug used during pregnancy. These experiments suggest that glyburide is actively efflux by a transporter other than P-glycoprotein. Alternatively, it is possible that a minority of glyburide is carried by P-glycoprotein, but most of the fetal load is pumped to the mother by a yet-unidentified placental transport system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Drugs of abuse testing in meconium.

Prenatal substance abuse is an ongoing concern with significant impact on neonatal health and development across socioeconomic lines. Meconium, passed by neonates during their first post-natal bowel movements, is a matrix unique to the developing fetus and contains a long history of prenatal metabolism. Over the last two decades, the use of meconium as a matrix for assessing prenatal exposure to drugs of abuse has yielded methods exhibiting higher sensitivity, easier collection, and a larger window of detection than traditional matrices. Recently, a method has been developed for the analysis of fatty acid ethyl esters in meconium as a biomarker of fetal alcohol exposure, potentially facilitating the future diagnosis of Fetal Alcohol Spectrum Disorder in situations where gestational alcohol consumption history is unknown. Screening for prenatal exposure to illicit and abused licit drugs in meconium is possible by use of a variety of immunoassay methods with conformational analysis usually occurring by GCMS or LCMS. In spite of increased sample preparation time relative to blood and urine, the long metabolic history, coupled with the ease and wide window of collection of meconium make it the ideal matrix for determining fetal drug exposure.

Female↗
PubMed2006

Enantioselective metabolism of ifosfamide by the kidney.

Ifosfamide (IF), a potent chemotherapeutic agent for solid tumors, is known to cause high rates of nephrotoxicity, which is most likely due to the renal production of the metabolite chloroacetaldehyde. Enantioselective oxidation of IF has been shown in the liver but has never been reported in the kidney. Using porcine and human kidney samples, as well as the renal porcine cell line LLCPK-1, we document enantioselective metabolism of IF with prevalent production of the N-dechloroethylifosfamide (DCEIF) metabolites from the (S)-IF enantiomer compared to the amount of N-DCEIF metabolites produced from the (R)-IF enantiomers. Since IF enantiomers appear to be equally effective in chemotherapy, these results suggest that replacing the clinically standard racemic mixture of IF with (R)-IF may decrease renal metabolism of the drug and hence may decrease nephrotoxicity.

Adolescent↗
PubMed2006

Medication errors in children.

Medication error is a major source of iatrogenic injuries in children. Dosing errors are the most common type of medication errors in pediatrics. Sicker patients in intensive care units and emergency departments are more often harmed by such errors. Strategies that have been found to be effective in reducing medication errors include the use of computerized physician order entry systems, preprinted order forms, and color-coded systems. Adopting the "systems approach" to medication errors is crucial to every health system where practitioners seek to enhance patient safety.

Child↗
PubMed2006

Diagnostic radiation in pregnancy: perception versus true risks.

Significant numbers of therapeutic abortions are performed for radiation-exposed pregnant women because of concerns about the teratogenic risk. However, available data suggest that current diagnostic radiation procedures are not teratogenic.

Abnormalities, Radiation-Induced↗
PubMed2006

Can venlafaxine in breast milk attenuate the norepinephrine and serotonin reuptake neonatal withdrawal syndrome.

A newborn infant whose mother had used venlafaxine, a selective inhibitor of both norepinephrine and serotonin reuptake, throughout pregnancy exhibited signs consistent with the norepinephrine and serotonin reuptake withdrawal syndrome. Is it possible that mother's milk can help mitigate the effects of norepinephrine and serotonin reuptake withdrawal? Pharmacokinetic analysis and review of the only published case with active treatment of a baby with venlafaxine suggest that breastfeeding may mitigate the neonatal withdrawal syndrome.

Breast Feeding↗
PubMed2006

Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis.

BACKGROUND: The use of folic acid-fortified multivitamin supplements has long been associated with decreasing the risk of neural tube defects. Several studies have also proposed the effectiveness of these supplements in preventing other birth defects; however, such effects have never been systematically examined. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the protective effect of folic acid-fortified multivitamin supplements on other congenital anomalies. METHODS: We searched Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases for studies describing the outcome of pregnancies in women using multivitamin supplements that were published in all languages from January 1966 to July 2005. The references from all collected articles were reviewed for additional articles. Two independent reviewers who were blinded to the source and identity of the articles extracted data based on predetermined inclusion and exclusion criteria. Using a random effects model, rates of congenital anomalies in babies born to women who were taking multivitamin supplements were compared with rates in the offspring of controls who were not. RESULTS: From the initial search, 92 studies were identified; 41 of these met the inclusion criteria. Use of multivitamin supplements provided consistent protection against neural tube defects (random effects odds ratio[OR] 0.67, 95% confidence intervals [95% CI] 0.58-0.77 in case control studies; OR 0.52, 95% CI 0.39-0.69 in cohort and randomized controlled studies), cardiovascular defects (OR 0.78, 95% CI 0.67-0.92 in case control studies; OR 0.61, 95% CI 0.40-0.92 in cohort and randomized controlled studies), and limb defects (OR 0.48, 95% CI 0.30-0.76 in case control studies; OR 0.57, 95% CI 0.38-0.85 in cohort and randomized controlled studies). For cleft palate, case control studies showed OR 0.76 (95% CI 0.62-0.93), and cohort and randomized controlled studies showed OR 0.42 (95% CI 0.06-2.84); for oral cleft with or without cleft palate, case control studies showed OR 0.63 (95% CI 0.54-0.73), and cohort and randomized controlled studies showed OR 0.58 (95% CI 0.28-1.19); for urinary tract anomalies, case control studies showed OR 0.48 (95% CI 0.30-0.76), and cohort and randomized controlled studies showed OR 0.68 (95% CI 0.35-1.31); and for congenital hydrocephalus case control studies showed OR 0.37 (95% CI 0.24-0.56), and cohort and randomized controlled studies showed OR 1.54 (95% CI 0.53-4.50). No effects were shown in preventing Down syndrome, pyloric stenosis, undescended testis, or hypospadias. CONCLUSION: Maternal consumption of folic acid-containing prenatal multivitamins is associated with decreased risk for several congenital anomalies, not only neural tube defects. These data have major public health implications, because until now fortification of only folic acid has been encouraged. This approach should be reconsidered.

Adult↗
PubMed2006

Fetal outcome following roxithromycin exposure in early pregnancy.

OBJECTIVE: Because very little information exists on the fetal safety of roxithromycin, we aimed to extend the knowledge on fetal outcome in pregnant women who were exposed to roxithromycin in early pregnancy. METHODS: Twenty pregnant women inadvertently exposed to roxithromycin during early pregnancy were identified and prospectively followed-up. For comparison, 170 pregnant women matched by age and gravidity, not being exposed to any potential teratogenic agent during pregnancy, were recruited as controls. All gestations were confirmed by ultrasound examination, and participants were followed-up until delivery. Newborns were examined by a neonatologist. RESULTS: Of 20 pregnant women exposed to roxithromycin during early pregnancy, information was obtained from 17 cases. The median dose of roxithromycin to which pregnant women were exposed was 300 mg/day (range 300-450 mg/day) and exposure occurred at a mean of 4.0 (range 2.8-17.6) weeks. Mean gestational age at delivery was 39.2 weeks in the exposed group and 39.4 in the controls (p = 0.6). Birth weight of babies exposed in utero to roxithromycin was not different to controls. We did not observe any major malformation in the exposed group whereas three (1.8%) occurred in the control group. CONCLUSIONS: . Despite the limitations of the study due to the small sample size, roxithromycin appears not to be a major teratogen.

Adult↗
PubMed2006

Therapeutic drug monitoring of antithyroid drugs in pregnancy: the knowledge gaps.

Despite being a common condition in pregnancy, and despite propylthiouracil (PTU) being perceived as safer than methimazole, there are virtually no epidemiological controlled studies on malformation rate an neurobehavioral outcomes with the former. This knowledge gap must be filled to ensure fetal safety.

Abnormalities, Drug-Induced↗
PubMed2006

Contact dermatitis and bradycardia in a preterm infant given tetracaine 4% gel.

The use of analgesics for procedural pain management in the newborn infant has been steadily increasing during the past decade. With this trend of increased analgesic utilization, there is the potential for infants to suffer from drug-induced side effects. There also is the potential to wrongfully blame drugs for all adverse events that occur during analgesic use. Two adverse events that occurred in a neonate exposed to tetracaine gel and the probability that the adverse events were caused by the drug are presented. During administration of the topical local anesthetic tetracaine for analgesia during percutaneous central venous catheter placement, a preterm infant experienced bradycardia. Several hours later, a local cutaneous reaction that progressed to skin desquamation occurred at the site. The authors assessed the probability that tetracaine caused 2 adverse events using a validated adverse drug reaction probability scale by Naranjo et al. According to the algorithm developed by Naranjo et al, it was determined that bradycardia was unlikely caused by the drug; however, the dermal reaction was probably the result of the drug.The authors determined that tetracaine caused a serious local skin reaction, but not bradycardia, in a preterm infant. This is the first report of a serious skin reaction in a neonate treated with tetracaine. Based on these findings, tetracaine gel can continue to be used to treat pain in neonates with careful evaluation of the skin.

Administration, Topical↗