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Biomedical subjects

Gideon Koren

Publications and source records attributed to Gideon Koren.

At least 73 records · Page 4Linked to original sources
PubMed2005

Chickenpox in pregnancy: revisited.

Varicella infection during the first and second trimester of pregnancy may increase the risk for congenital varicella syndrome 0.5-1.5% above the baseline risk for major malformation. Third trimester infection may lead to maternal pneumonia which can be life threatening if not treated appropriately. Varicella-zoster immune globulin (VZIG) should be administered as soon as possible preferably within 96 h from exposure to prevent maternal infection or subsequent complications. Later than 96 h, the effectiveness of VZIG has not been evaluated. Neonatal varicella is more severe if maternal rash appears 5 days prior to or 2 days after delivery. The newborn should be given VZIG immediately. Intravenous acyclovir is recommended for maternal pneumonia and severely affected neonate. No controlled study has yet evaluated the effectiveness of acyclovir or valacyclovir for postexposure prophylaxis to pregnant women or neonates. Unlike primary varicella infection in pregnancy, herpes zoster has not been documented to cause complications unless in the disseminated form. The advent of advanced imaging techniques and molecular biotechniques has improved prenatal diagnosis. With increase use of vaccination, the incidence of chickenpox in pregnancy is expected to decline in the future.

Acyclovir↗
PubMed2005

Liposomal lidocaine to improve procedural success rates and reduce procedural pain among children: a randomized controlled trial.

BACKGROUND: Historically, children have been undertreated for their pain, and they continue to undergo painful cutaneous procedures without analgesics. A new topical anesthetic, liposomal lidocaine 4% cream (Maxilene, RGR Pharma, Windsor, Ont.), has become available. It has pharmacologic properties that are superior to other topical anesthetics, including an onset of action of only 30 minutes. We sought to determine the success rate of cannulation, analgesic effectiveness, procedure duration and rate of adverse skin reactions when liposomal lidocaine is used before intravenous cannulation of children. METHODS: In this double-blind randomized controlled trial, children aged 1 month to 17 years received liposomal lidocaine or placebo before cannulation. Success on first cannulation attempt was recorded, and, among children 5 years and older, pain was evaluated before and after the attempt by the child, parents and research assistant using a validated measure (Faces Pain Scale-Revised). For children younger than 5 years, pain was evaluated by the parents and research assistant only. The total duration of the procedure and adverse skin reactions were also recorded. RESULTS: Baseline characteristics did not differ (p > 0.05) between children who received liposomal lidocaine (n = 69) and those who received placebo (n = 73). Cannulation on the first attempt was achieved in 74% of children who received liposomal lidocaine compared with 55% of those who received placebo (p = 0.03). Among children 5 years of age and older (n = 67), lower mean pain scores during cannulation were reported by those receiving liposomal lidocaine (p = 0.01). Similarly, lower mean pain scores during cannulation were reported by the parents and research assistant for all children who received liposomal lidocaine than for all those who received placebo (p < 0.001). The mean total procedure duration was shorter with liposomal lidocaine (6.7 v. 8.5 minutes; p = 0.04). The incidence of transient dermal changes was 23% in both groups (p = 1.0). CONCLUSIONS: Use of liposomal lidocaine was associated with a higher intravenous cannulation success rate, less pain, shorter total procedure time and minor dermal changes among children undergoing cannulation. Its routine use for painful cutaneous procedures should be considered whenever feasible.

Adolescent↗
PubMed2005

Cytochrome P450 3A and 2B6 in the developing kidney: implications for ifosfamide nephrotoxicity.

Repeated administration of agents (e.g., cancer chemotherapy) that can cause drug-induced nephrotoxicity may lead to acute or chronic renal damage. This will adversely affect the health and well-being of children, especially when the developing kidney is exposed to toxic agents that may lead to acute glomerular, tubular or combined toxicity. We have previously shown that the cancer chemotherapeutic ifosfamide (IF) causes serious renal damage substantially more in younger children (less than 3 years of age) than among older children. The mechanism of the age-related IF-induced renal damage is not known. Our major hypothesis is that renal CYP P450 expression and activity are responsible for IF metabolism to the nephrotoxic chloroacetaldehyde. Presently, the ontogeny of these catalytic enzymes in the kidney is sparsely known. The presence of CYP3A4, 3A5 and 2B6 was investigated in human fetal, pediatric and adult kidney as was the metabolism of IF (both R-IF and S-IF enantiomers) by renal microsomes to 2-dechloroethylifosfamide (2-DCEIF) and 3-dechloroethylifosfamide (3-DCEIF). Our analysis shows that CYP 3A4 and 3A5 are present as early as 8 weeks of gestation. IF is metabolized in the kidney to its two enantiomers. This metabolism can be inhibited with CYP 3A4/5 and 2B6 specific monoclonal inhibitory antibodies, whereby the CYP3A4/5 inhibitory antibody decreased the production of R-3-DCEIF by 51%, while the inhibitory CYP2B6 antibody decreased the production of S-2-DCEIF and S-3-DCEIF by 44 and 43%, respectively, in patient samples. Total renal CYP content is approximately six-fold lower than in the liver.

Adolescent↗
PubMed2005

Antidepressant use during pregnancy and the rates of spontaneous abortions: a meta-analysis.

BACKGROUND: Due to the high prevalence of depression in women of childbearing age and coupled with the fact that approximately 50% of the pregnancies are unplanned, there is a high chance that these women have been exposed to antidepressants in early pregnancy. OBJECTIVE: To determine baseline rates of spontaneous abortions (SAs) and whether antidepressants increase those rates. METHODS: Rates of SAs in women taking antidepressants compared with non-depressed women were combined into a relative risk using a random effects model. MEDLINE, EMBASE, Healthstar, Toxline, Psychlit, Cochrane database, and Reprotox were searched for studies published in any language from 1966 to 2003. Key words used to identify articles included pregnancy outcome, abortion, miscarriage, spontaneous, antidepressant, depression, and the generic names of each antidepressant and class. Bibliographies, review articles, and reference lists from studies were also used to identify potential articles expected to provide evidence of safety of antidepressants in pregnancy. RESULTS: Of 15 potential articles, 6 cohort studies of 3567 women (1534 exposed, 2033 nonexposed) provided extractable data. All matched on important confounders. Tests found no heterogeneity (chi2 3.13; p = 0.98), and all quality scores were adequate (>50%). The baseline SA rate (95% CI) was 8.7% (7.5% to 9.9%; n = 2033). For antidepressants, the rate was 12.4% (10.8% to 14.1%; n = 1534), significantly increased by 3.9% (1.9% to 6.0%); RR was 1.45 (1.19 to 1.77; n = 3567). No differences were found among antidepressant classes. CONCLUSIONS: Maternal exposure to antidepressants may be associated with increased risk for SA; however, depression itself cannot be ruled out.

Abortion, Spontaneous↗
PubMed2005

Development of contrast sensitivity in infants with prenatal and neonatal thyroid hormone insufficiencies.

Thyroid hormone is essential for normal brain development including structures critical for visual processing. While chick and rodent models have demonstrated abnormal visual development following prenatal thyroid hormone loss, comparable data do not exist in the human. To determine whether human infants with intrauterine and early postnatal thyroid hormone insufficiencies have compromised visual abilities, we investigated contrast sensitivity and visual acuity development in 13 infant offspring of women with hypothyroidism during pregnancy (HYPO), 16 preterm infants born between 32 and 35 weeks gestation, 12 infants with congenital hypothyroidism (CH), and 20 typically developing infants. All were assessed with the sweep visual evoked potential technique at 3, 4.5, and 6 months (corrected) age. Results showed significantly reduced contrast sensitivity but normal visual acuity in HYPO and CH groups relative to controls (p < 0.003 and p < 0.05 respectively). Stratification of the HYPO group into subgroups based on maternal TSH levels during the first half of pregnancy revealed lower contrast sensitivities for infants whose mothers' TSH values were above than below the median (p < 0.05). In the CH group, those with an absent thyroid gland and/or a newborn TSH value above 200 mIU/L had lower contrast sensitivities than did those with other etiologies or TSH levels below 100 mIU/L (p < 0.05). There were no significant effects involving the preterm group. These results indicate that thyroid hormone is important for human visual development.

Animals↗
PubMed2005

Effects of drugs on the fetus.

Most drugs are not labelled for use in pregnancy. Consequently, large numbers of women expose their fetus to potential risks, either because they do not know that they are pregnant or because they require treatment for gestational pathologies. The present review focuses on drug classes for which the risk:benefit ratio during pregnancy has been discussed recently based on human data. Selective serotonin reuptake inhibitors have gained wide acceptance in the treatment of depression and data on their risk for neonatal adaptation after late exposure are reviewed. Angiotensin converting enzyme inhibitors and angiotensin II receptors antagonists interact with the renin-angiotensin system, although with different mechanisms, and might cause severe fetal tubular dysgenesis. Non-steroidal anti-inflammatory and antiviral drugs and recreational drugs are also presented.

Drug-Related Side Effects and Adverse Reactions↗
PubMed2005

Study on circadian variation in folate pharmacokinetics.

BACKGROUND: In a new preparation of prenatal multivitamins, PregVit, two tablets a day (a.m. and p.m.) are given. Folic acid is separated from iron and zinc and is given in the p.m. tablet to overcome problems due to folic acid interactions with iron or zinc, and frequent presence of nausea and vomiting of pregnancy in the morning. The circadian variation of folate in humans has not been investigated. This is the first study attempting to determine whether circadian variation of folate pharmacokinetics exists in humans. OBJECTIVES: To determine whether circadian rhythm of folate pharmacokinetics exists in humans. METHODS: In a crossover design, six healthy, non-pregnant women were randomized to receive 1 tablet of PregVit p.m., containing 1.1 mg of folic acid, in the morning or evening. Serum folate levels were measured over 10 hours. The area under the concentration-time curve (AUC) was used to compare the extent of absorption between the two time periods. RESULTS: The mean AUC values for serum folate after administration of PregVit p.m. were 334.5+/-119.6 nM*h and 283.1+/-64.3 nM*h for morning and evening, respectively (P = 0.17). The morning and evening peak serum folate concentrations were also similar (135.3+/-41.7 nM and 130.3+/-14.2 nM, respectively) (P = 0.75). Similarly, the time to peak for the morning arm (1 0.5 hour) was similar to evening administration (1+/-0.4 hour). CONCLUSIONS: There is no evidence of circadian variation in folate pharmacokinetics. Thus, the introduction of folate in PregVit p.m. will not affect its effectiveness as compared to its routine administration in the morning.

Adolescent↗
PubMed2005

Screening for children's exposure to environmental tobacco smoke in a pediatric primary care setting.

BACKGROUND: The American Academy of Pediatrics (Elk Grove Village, Ill) has recommended that pediatricians assess their patients' environmental tobacco smoke (ETS) exposure, but the specific questions most likely to identify children with high ETS exposure are not known. Cotinine is a nicotine metabolite, present in hair, that can be used to quantify months of ETS exposure. OBJECTIVE: To develop a brief screening tool that will accurately predict ETS exposure as defined by child hair cotinine level. METHODS: We compared the performance of a series of easily administered screening questions regarding home ETS exposure to child hair cotinine levels. Subjects were a convenience sample of healthy children aged 2 weeks to 3 years of both self-reported smokers and nonsmokers. RESULTS: Hair samples and questionnaire data were obtained from 291 children. Based on clinical applicability and statistical significance, 3 questions ("Does the mother smoke?", "Do others smoke?", and "Do others smoke inside?") were selected as a valid screening tool to determine children's ETS exposure risk. Maternal report of smoking outside only or smoking few cigarettes per day had no impact on child hair cotinine levels. CONCLUSIONS: It was possible to derive a simple, specific, and valid screening tool that can be used in pediatric offices to identify children at risk for ETS exposure. Further research is needed to test this tool prospectively.

Adult↗
PubMed2005

Unintended pregnancies and exposure to potential human teratogens.

BACKGROUND: We aimed to investigate the risk factors associated with unintended pregnancies as well as the association between unintended pregnancies and potential teratogenic exposures. METHODS: A cross-sectional survey was performed among women attending the Maternity School of the Samsung Cheil Hospital and Women's Health Care Center in Seoul, Korea. Demographic data, obstetric history, socioeconomic status, intention to become pregnant, and exposure to potential teratogens were obtained. RESULTS: A total of 1354 women with median age of 29 years and median gestational age of 29 weeks were included. Of these, an educational level above high school was 74.2%, primigravida was 77.3% and unintended pregnancy was 48%. In the logistic regression analysis, women younger than 24 years of age had a relative risk (RR) of 2.5 (95% confidence interval [CI], 1.3-4.7) of having an unintended pregnancy and women with lower household monthly income level had a RR of 1.3 (95% CI, 1.0-1.6). Women with unintended pregnancies had an RR of 1.9 (95% CI, 1.5-2.5), 3.0 (95% CI, 2.0-4.5), 1.5 (95% CI, 1.0-2.3), 2.9 (95% CI, 1.1-7.2), and 2.0 (95% CI, 1.62.4) of being exposed to alcohol, medications, cigarette smoking, X-rays, or to any of these, respectively, during the first trimester of pregnancy. CONCLUSIONS: Unintended pregnancies are more likely to occur among young women with a lower household monthly income level. Prenatal counseling should be especially recommended for women with unintended pregnancies in order to evaluate whether they have been exposed to potential teratogenic agents.

Adult↗
PubMed2005

A survey of pregnant women using isotretinoin.

BACKGROUND: Isotretinoin is a known human teratogen, causing birth defects and/or subnormal cognitive performance in prenatally-exposed children. METHODS: A survey was conducted among women who called teratology information services throughout North America. Using a structured questionnaire, women with an isotretinoin-exposed pregnancy were prospectively interviewed before the outcome of the pregnancy was known. RESULTS: Almost 1/4 of the women surveyed (24%; 8/34) did not recall having contraception counseling before starting their medications. Once therapy was initiated, 62% (21/34) recalled using a birth control method, but only 29% (6/21) recalled using 2 forms of birth control, as specified by the voluntary pregnancy prevention programs. Monthly pregnancy tests were not always conducted during treatment, as recalled by the surveyed women (56%; 19/34). As many as 24% (8/34) of the women surveyed recalled that they were not screened using 2 pregnancy tests before receiving a prescription, another recommendation of the programs. Only a small number of the women (30%; 6/20) in the United States recalled being enrolled in any manufacturers' voluntary pregnancy prevention survey. CONCLUSIONS: Results demonstrate that essential components of voluntary pregnancy prevention programs were not consistently followed, which resulted in fetal exposures.

Abnormalities, Drug-Induced↗
PubMed2005

Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study.

OBJECTIVE: Bupropion was developed for the treatment of depression, but subsequently was found to be effective for smoking cessation. To date, there are no prospective comparative studies examining its safety in pregnancy. The primary objective was to determine whether bupropion increases the risks for major malformations above baseline. The secondary objective was to examine the rates of live births, stillbirths, spontaneous and therapeutic abortions, mean birth weight, and gestational age at birth. STUDY DESIGN: Women who were pregnant or planning a pregnancy and taking bupropion were enrolled in the study. Follow-up of pregnancy outcome was carried out between 4 months and 1 year after delivery. Three comparisons were carried out: 1) women exposed to bupropion vs a nonteratogen group; 2) those taking for depression vs other antidepressants, vs a nonteratogen group; 3) spontaneous abortions were compared between those taking for depression, vs another antidepressant group vs a nonteratogen group. RESULTS: We completed follow-up on 136 women exposed to bupropion during the first trimester of pregnancy. There were (105) live births, no major malformations, the mean birth weight was (3450g), the mean gestational age at delivery was (40 weeks), the number of spontaneous abortions was 20, there were 10 therapeutic abortions, there was 1 stillbirth, and 1 neonatal death. There were no statistically significant differences between any of the end points we examined between the exposed and comparison groups, with the exception of significantly more spontaneous abortions in the bupropion group (P = .009). CONCLUSION: These results suggest that bupropion does not increase the rates of major malformation above baseline. The higher rates of spontaneous abortions are similar to other studies examining the safety of antidepressants during pregnancy.

Abnormalities, Drug-Induced↗
PubMed2005

Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome.

OBJECTIVE: Citalopram is a selective serotonin reuptake inhibitor indicated for depression. The safety of this medication in pregnancy has not been fully established. The purpose of this study was to investigate whether citalopram is associated with an increased incidence of adverse pregnancy outcomes. STUDY DESIGN: Pregnant women who contacted the Motherisk Program, a Teratogen Information Center in Toronto, Ontario, with regard to the safety of citalopram in pregnancy were enrolled in the study. The exposed women were matched to a disease-matched group of women and a nonteratogenic group. All women were matched for age (+/- 2 years) and gestational age at time of first call to the Motherisk (+/- 2 weeks). A structured telephone follow-up interview was conducted following the expected date of confinement. RESULTS: The total number of pregnant women enrolled in this study was 396 (132 women in each group). A total of 125 women took citalopram at least in the first trimester. Seventy-one (54%) women continued to take the drug throughout pregnancy. One hundred fourteen women (86%) had live births, 14 (11%) had spontaneous abortions, 2 (1.5%) had elective terminations, and 2 (1.5%) experienced stillbirths. Fetal survival rates, mean birth weights, and duration of pregnancy were not statistically different among the 3 groups. Of 108 live-born infants whose mothers were exposed to citalopram in the first trimester, there was 1 (0.9%) male infant born with a major malformation. There was a relative risk of 4.2 (95% confidence interval 1.71-10.26) in neonates exposed to citalopram close to term to be admitted to special-care nurseries as compared with the unexposed infants. CONCLUSION: Citalopram use during the period of embryogenesis in pregnancy is not associated with an apparent major teratogenic risk. Late pregnancy use of citalopram is associated with increased risk of poor neonatal adaptation syndrome, recently described with other selective serotonin reuptake inhibitors.

Antidepressive Agents, Second-Generation↗
PubMed2005

Pregnancy outcome following non-obstetric surgical intervention.

OBJECTIVE: To evaluate the effects of non-obstetric surgical procedures on maternal and fetal outcome. METHODS: A systematic review of all English language literature. RESULTS: Fifty-four papers met the inclusion criteria. The overall number of patients reported was 12,452. Reported maternal death was rare at .006%. The miscarriage rate was 5.8%; however, this number is difficult to interpret since matched controls were not available. The rate of elective termination of pregnancy following non-obstetric surgery was 1.3%. The rate of premature labor induced by non-obstetric surgical intervention was 3.5% and this was noted specifically following appendectomy versus other types of interventions (P<.001). A total of 2.5% of pregnancies resulted in fetal loss. The prematurity rate was 8.2%. The rate of major birth defects among women who underwent non-obstetric surgical intervention in the first trimester was 3.9%. Sub-analysis of papers reporting on appendectomy during pregnancy revealed a high rate (4.6%) of surgery-induced labor. Fetal loss associated with appendectomy was 2.6%; however, this rate was increased when peritonitis was present (10.9%). CONCLUSIONS: Modern surgical and anesthesia techniques appear to diminish the rate of maternal death. Surgery in the first trimester does not appear to increase major birth defects and should not be delayed when indicated. Acute appendicitis with peritonitis is associated with higher risk to the mother and fetus.

Appendectomy↗