Showing papers by "Gideon Koren published in 2003"

Fetal Alcohol Spectrum Disorder

Abstract: One of the most tragic outcomes of a woman’s addiction to or abuse of alcohol is the effects on the unborn child. Fetal Alcohol Spectrum Disorder (FASD) is common and preventable. Western estimates suggest that FASD affects 1% of the population, and in some communities, the frequency is much higher. FASD is caused by a mother’s use of alcohol with or without other substances of abuse that can result in permanent physical and neurodevelopmental impairments to her unborn child. In addition to the primary effects of FASD, affected children are at risk of developing secondary disabilities, including drug and alcohol addictions. It is uncertain what factors, genetic and/or environmental, lead to this addiction. The individual, social, and financial costs are enormous. Multidisciplinary teams have been developed to improve ascertainment of, and standardized approaches to, FASD diagnosis. Strategies and mentorship programs have been developed to better recognize and support women at risk for having FASD children. We discuss issues specific to the treatment and management of FASD adolescents and adults who are struggling with addiction to alcohol and other substances.

DEET-based insect repellents: safety implications for children and pregnant and lactating women

Abstract: Reducing the risk of mosquito bites is currently the only way to reduce the risk of West Nile virus infection. Methods for avoiding mosquito bites include limiting the time spent outdoors at dawn and dusk, wearing protective clothing and using an insect repellent. Repellents containing DEET (N,N-diethyl-m-toluamide, also known as N,N-diethyl-3-methylbenzamide) are the most effective and most widely used. However, concerns have been raised over the risk of adverse toxic effects, especially in young children and pregnant and lactating women. In this article, we review the available evidence on the effectiveness and safety of DEET-based products. The evidence does not support increased risk in young children.

Observation of magnetic flux generated spontaneously during a rapid quench of superconducting films.

Abstract: We report observations of spontaneous formation of magnetic flux lines during a rapid quench of ${\mathrm{Y}\mathrm{B}\mathrm{a}}_{2}{\mathrm{C}\mathrm{u}}_{3}{\mathrm{O}}_{7\ensuremath{-}\ensuremath{\delta}}$ films through ${T}_{c}$. This effect is predicted according to the Kibble-Zurek mechanism of creation of topological defects of the order parameter during a symmetry-breaking phase transition. Our previous experiment, at a quench rate of $20\text{ }\mathrm{K}/\mathrm{s}$, gave null results. In the present experiment, the quench rate was increased to $g{10}^{8}\text{ }\mathrm{K}/\mathrm{s}$. The amount of spontaneous flux increases weakly with the cooling rate.

Cyclosporine excretion into breast milk.

Abstract: Although many female patients of childbearing age who are receiving cyclosporine have successful pregnancies, these women may be advised not to breast-feed. During recent years, cases of uneventful pregnancies and subsequent successful breast-feeding have been reported in the literature. The infant's blood cyclosporine concentration was usually very low. Based on these findings and the lack of detectable adverse effects, some investigators have suggested that women on cyclosporine may breast-feed, challenging the conventional view that cyclosporine is contraindicated during breast-feeding. Here, we report our experience with cyclosporine use during breast-feeding in five mother-infant pairs. We show a wide range of infant exposures to the drug in milk, noting that one of the infants had therapeutic blood concentrations of cyclosporine despite relatively low concentrations of the drug in milk.

Folic acid food fortification is associated with a decline in neuroblastoma.

Abstract: Background Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known. Methods We investigated the rates of neuroblastoma (<1 year), acute lymphoblastic leukemia, and hepatoblastoma registered by the Pediatric Oncology Group of Ontario, which captures 95% of all pediatric cancers in Ontario, before and after the introduction of folate fortification. Results An interventional time series analysis showed that the incidence of neuroblastoma declined from 1.57 cases per 10,000 births before to 0.62 case per 10,000 births after folic acid fortification (P < .0001). The crude incidence rate ratio (0.40; 95% confidence interval, 0.25-0.64) remained significant after adjustment for both age and disease stage at diagnosis (adjusted incidence rate ratio, 0.38; 95% confidence interval, 0.23-0.62). In contrast, there was no significant change in the rate of infant acute lymphoblastic leukemia (incidence rate ratio, 0.97; 95% confidence interval, 0.41-2.27) or hepatoblastoma (incidence rate ratio, 0.81; 95% confidence interval, 0.35-1.89). Conclusions Folic acid fortification was associated with a 60% reduction in neuroblastoma but was not associated with any change in the rate of infant acute lymphoblastic leukemia or hepatoblastoma. Further investigation is needed into the role of metabolism in the formation and prevention of neuroblastoma and other embryonically determined cancers. Clinical Pharmacology & Therapeutics (2003) 74, 288–294; doi: 10.1016/S0009-9236(03)00200-5

Population baseline of meconium fatty acid ethyl esters among infants of nondrinking women in Jerusalem and Toronto.

Abstract: The detection of fatty acid ethyl esters (FAEE) in meconium may provide an objective estimate of prenatal alcohol exposure independent of maternal history. The authors report the results of the first population-based study conducted to investigate basal FAEE levels in the meconium of neonates not exposed to alcohol. Two hundred seven nondrinking women and their neonates were recruited from Toronto and Jerusalem. FAEE were extracted from meconium by solid-phase extraction and analyzed by GC/FID. Similar procedures were conducted in six neonates born to confirmed heavy drinkers. Low levels of meconium FAEE were detected from both cohorts (mean, 1.37 nmol/g vs. 2.08 nmol/g, Toronto vs. Jerusalem). Ethyl stearate, oleate, and linoleate were below the limit of detection in >80% of all samples, whereas ethyl laurate and palmitate were detected in >50% of the samples. Ethyl myristate was the FAEE most commonly detected (>80%). All six meconium samples with confirmed maternal drinking histories tested positive for FAEE at significantly higher levels (mean, 11.08 nmol/g). The use of 2 nmol total FAEE/g meconium as the positive cutoff, when lauric and myristic acid ethyl esters were excluded, yielded the greatest sensitivity (100%) and specificity (98.4%). The authors conclude that certain FAEE are present at measurable levels in the meconium of neonates not exposed to maternal drinking, and correction is needed to allow high specificity.

Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse

Abstract: Background: Meconium and hair are two biological markers of in utero exposure to illicit drugs. Objective: To compare the sensitivity of the two tests for different drugs. Setting: Motherisk laboratory which tests in utero drug exposure in Toronto. Methods: Cocaine, benzoylecgonine, opiates, cannabis, benzodiazepines, methadone, and barbiturates were measured in pairs of hair and meconium samples from the same neonates. Results: Meconium was marginally more sensitive than neonatal hair for detection of cocaine and cannabis, possibly because it may detect second trimester exposure whereas hair grows only during the third trimester of pregnancy. There was a significant correlation between hair and meconium concentrations of cocaine, cannabis, and opiates. Conclusion: In cases of clinical suspicion and a negative neonatal urine test, both meconium and hair are effective biological markers of in utero illicit drug exposure. Meconium may be more sensitive, but neonatal hair is available for three months whereas meconium is available for only one or two days. In contrast, the use of meconium, being a discarded material, is more acceptable to some parents than hair testing, which entails cutting scalp hair from the newborn.

A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy.

Abstract: Objectives: Trazodone and nefazodone are phenylpiperazine antidepressants. Currently, there are no adequate, well-controlled studies on the fetal safety of these drugs. Our primary objective was to determine whether the use of trazodone or nefazodone during pregnancy is associated with an increased risk for major malformations. Secondary outcomes of interest included rates of spontaneous and therapeutic abortions, rates of premature labour, and birth weight. Methods: Pregnant women from 5 centres who had been exposed to these drugs (n = 147) were enrolled in the study during their first trimester. We compared the women with 2 groups of women who took either other antidepressant drugs (n = 147) or nonteratogenic drugs (n = 147). All the women were followed up after delivery to ascertain pregnancy outcome and the health of the baby Results: We have completed 147 follow-ups. There were 121 (82.4%) live births, 20 (13.6%) spontaneous abortions, and 6 (4%) therapeutic abortions. Of the live births, there were 2 (1.6%) major malformations. In all cases, drug exposure occurred during the first trimester, with 52 (35%) of the women using these drugs throughout pregnancy. The mean gestational age at birth was 38 weeks (SD 4.2), and the mean birth weight was 3306.34 g (SD 655). We found no statistically significant differences among the 3 groups in any of the endpoints of interest that we examined. Of the sample, 58 women were exposed to trazodone, and 89 were exposed to nefazodone. Conclusion: Our results suggest that these drugs do not increase the rates of major malformations above the baseline rate of 1% to 3%. (Can J Psychiatry 2003;48:106–110) Information on funding support and author affiliations appears at the end of the article.

Transfer of insulin lispro across the human placenta: in vitro perfusion studies.

Abstract: OBJECTIVE —Insulin lispro (Humalog), a human insulin analog, has a more rapid onset, earlier peak, and shorter duration of glucose lowering activity than regular human insulin. However, it is not known whether insulin lispro crosses the human placenta and reaches the fetus. Therefore, the objective of the present study was to examine whether insulin lispro crosses the placenta using the technique of perfusing a human placental lobule in vitro. RESEARCH DESIGN AND METHODS —Term human placentae from uncomplicated pregnancies were obtained immediately after delivery. Insulin lispro, at concentrations ranging from 100 to 1000 μU/ml, was introduced into the maternal reservoir. The maternal side of the placenta was perfused with constant concentration of lispro insulin; the fetal circulation was closed. Samples were drawn from both the maternal and fetal circulations at regular intervals. The appearance of insulin lispro in the fetal circulation was analyzed by a specific radioimmunoassay. RESULTS —No placental transfer of lispro could be detected during perfusion with 100 and 200 μU/ml. In contrast, there was a small concentration-dependent transfer to the fetus at concentrations of 580 μU/ml and higher, detectable after at least an hour of constant concentration of insulin lispro during perfusion. The rate of placental transfer was 0.019 μU · min −1 · g tissue −1 at maternal levels of 580 μU/ml and 0.045 μU · min −1 · g −1 tissue at maternal levels of 1000 μU/ml. Measuring lispro levels in 11 pregnant women revealed that a dose of 50 units may achieve serum concentrations >200 μU/ml with apparent linear correlation between dose and levels. CONCLUSIONS —Insulin lispro is not likely to cross the placenta at a single standard dose. This study suggests that insulin lispro is unlikely to reach or harm the unborn baby.

Ribavirin in the treatment of SARS: A new trick for an old drug?

Abstract: The dramatic outbreak of severe acute respiratory syndrome (SARS) has led to the use of high-dose intravenous and oral ribavirin in patients affected with this disorder. Ribavirin, a nucleoside analogue with broad antiviral activity, was discovered in 1970 by ICN Pharmaceuticals. In Canada, ribavirin is licensed for the treatment of respiratory syncytial virus (RSV) infection in infants and, in combination with interferon α2b, hepatitis C. In view of the limited circumstances in which it is prescribed, most physicians are not familiar with its pharmacology, dosing and safety. In this article we summarize this information for the benefit of health care professionals who may be involved with patients receiving ribavirin for treatment or prevention of SARS. We also review emerging data on the potential efficacy of ribavirin against the SARS virus, a new mutant of coronavirus.

Maternal-fetal transport of hypoglycaemic drugs.

Abstract: Due to legal, ethical and monetary problems, drug studies in pregnancy are rare. Numerous pharmacokinetic and pharmacodynamic changes occur in pregnancy that can affect the efficacy and safety of drugs, and these are difficult to predict without appropriate studies. Drugs potentially useful and safe in pregnancy have to either not cross the placenta and/or be harmless to the fetus at clinically relevant concentrations. The first characteristic can be predicted using in vitro models such as the placenta perfusion model. In the case of glibenclamide (glyburide), in vitro experiments showed minimal maternal-fetal transfer, leading to completion of a successful clinical trial of this drug in gestational diabetes. Insulin, the main drug used in diabetes during pregnancy, has also been shown not to cross the placenta in vitro, as has insulin lispro. Animal insulin may cross the placenta when complexed with anti-insulin antibodies. Other sulphonylurea drugs (tolbutamide and chlorpropamide) have been shown to cross the placenta both in vitro and in vivo and to produce toxicity in the fetus. This review summarises the pharmacokinetic data available for hypoglycaemic drugs during pregnancy, as well as the potential role for the in vitro placenta perfusion model in the preclinical evaluation of drugs with potential usefulness in pregnancy.

Discrepancies between ordered and delivered concentrations of opiate infusions in critical care.

Abstract: ObjectivesWe sought to test the assumption that the measured concentrations of medication infusions are within pharmaceutical standards (±10% of intended concentrations) and whether, at the time the infusion was mixed, the professional background of persons preparing the infusion or the unit for whi

The safety of oral hypoglycemic agents in the first trimester of pregnancy: a meta-analysis.

Abstract: OBJECTIVE To examine the relationship between first-trimester exposure to oral hypoglycemic agents (OHAs), congenital anomalies and neonatal mortality, accounting for the potential confounding effect of maternal glycemic control. METHOD A meta-analysis was conducted by searching the literature for studies reporting on women with type II diabetes mellitus, first-trimester exposure to OHAs and either major malformations and/or neonatal mortality. Glycemic control monitoring was noted. Studies were reviewed by two reviewers and disagreement was resolved by consensus. Odds ratios and risk differences were calculated to determine the risk of major malformations and neonatal mortality between those exposed and those not exposed to OHAs. RESULTS Ten studies met the inclusion criteria. There was no significant difference in the rates of major malformations between those exposed and those not exposed to OHAs; the odds ratio was 1.05 (95% CI 0.65 to 1.70) and the risk difference was 0.00 (95% CI -0.03 to 0.03). For studies reporting glycemic control, the odds ratio for major malformations between those exposed and those not exposed to OHAs was 1.06 (95% CI 0.62 to 1.81). For neonatal death, the odds ratio was 1.16 (95% CI 0.67 to 2.00) and the risk difference was -0.03 (95% CI -0.17 to 0.12). The studies did not provide sufficient detail to determine which OHA(s) were associated with adverse neonatal outcomes. CONCLUSIONS First-trimester exposure to OHAs did not significantly increase rates of major malformations or neonatal death. However, the studies were heterogeneous and care must be taken in interpreting the results. Further studies are needed to address the safety of OHAs in the first trimester with concomitant good glycemic control.

Systemic exposure to morphine and the risk of acute chest syndrome in sickle cell disease

Abstract: Background The etiology of acute chest syndrome, the most severe complication of the sickle cell crisis, is unknown. Objective Our objective was to assess exposure to morphine as an etiologic factor for acute chest syndrome in sickle cell disease. Methods A post hoc analysis of a randomized controlled trial comparing oral with continuous infusion of morphine was performed. Children (aged 5–17 years) with sickle cell crisis were randomized to receive oral sustained-release morphine, 1.9 mg · kg−1 · 12 h−1, or a continuous intravenous infusion of morphine at 0.04 mg · kg−1 · h−1 by use of a double-blind, placebo-controlled design. In a subgroup of 15 patients, the pharmacokinetics of morphine and its active metabolite morphine-6-glucuronide were also studied. Results At baseline, demographic and physiologic characteristics were similar between groups. There were no differences in the number of previous rescue doses per day, painful sites per episode, physician contacts per year, and hospitalizations per year between treatment arms. There was a 2-fold higher morphine area under the concentration-time curve at steady state (AUCss) and a 3-fold higher morphine-6-glucuronide AUCss with oral morphine than with a continuous intravenous infusion of morphine (P < .001 and P < .006, respectively). New onset of acute chest syndrome was 3-fold more prevalent in the oral group (57%) versus the continuous intravenous infusion group (17%) (P < .001). Conclusions The risk of acute chest syndrome is significantly associated with high systemic exposure to morphine and its active metabolite morphine-6-glucuronide after oral administration of slow-release morphine. Morphine may facilitate respiratory deterioration by eliciting a decrease in oxygen saturation, by inducing histamine release, or through an as-yet-unidentified mechanism. The safe systemic exposure to morphine in terms of area under the concentration-time curve should be further studied in children with sickle cell disease. Clinical Pharmacology & Therapeutics (2004) 75, 140–146; doi: 10.1016/j.clpt.2003.10.007

Milk Transfer and Neonatal Safety of Tacrolimus

Abstract: OBJECTIVE:To report the first case of tacrolimus measurement in human milk following maternal dosing in a woman who breast-fed while taking the medication.CASE REPORT:A 32-year-old white woman who had taken tacrolimus 0.1 mg/kg/d throughout pregnancy contacted the Motherisk Program at 35 weeks' gestation inquiring about the safety of breast-feeding during maternal tacrolimus therapy. After benefit–risk assessment, the mother decided to breast-feed the baby.METHODS:Manually expressed milk samples were collected over 12 hours following the first tacrolimus dose of the day; pre-dosing and 1-hour post-dosing blood concentrations were also determined. The samples were analyzed for tacrolimus by tandem-mass spectrometry. Breast milk and blood samples were collected at steady-state.RESULTS:The highest and mean concentrations of tacrolimus in milk were 0.57 and 0.429 ng/mL, respectively. From these measurements, the exclusively breast-fed infant would ingest, on average, 0.06 μg/kg/d, which corresponds to 0.06% o...

Effects of aspirin consumption during pregnancy on pregnancy outcomes: meta-analysis.

Abstract: BACKGROUND: We assessed the effects and safety of aspirin treatment during pregnancy on fetal and neonatal outcomes. METHODS: We searched MEDLINE (1966–2001), EMBASE (1980–2000), TOXLINE (1994–2000), EBM Cochrane Database of Systematic Reviews (1991–2000), Reproductive Toxicology (2001), teratology texts, and bibliographies of all the included studies. We looked for published randomized controlled studies reporting aspirin treatment to improve outcomes of moderate- and high-risk pregnancies. The key words used to search for articles about exposure to aspirin were salicylic acid, pregnancy, and pregnancy complications; key words used to search for outcome were neonatal diseases and abnormalities. Based on our search strategy, 1904 citations were identified; their titles and abstracts were reviewed by one reviewer. Of these citations, 182 papers were selected for detailed review. Two reviewers independently determined whether a study should be included in the final analysis. In cases of disagreement, the decision was based on the assessment of a third reviewer. RESULTS: Data were extracted independently by each reviewer. We calculated the pooled relative risk (RR) or weighted mean difference and 95% confidence intervals (CI), assuming a random-effect model. Thirty-eight studies met the inclusion criteria. The risk for miscarriage did not differ between women treated with aspirin and placebo (seven studies; RR, 0.92; 95% CI, 0.71–119). Women who took aspirin had a significantly lower risk of preterm delivery than did those treated with placebo (22 studies; RR, 0.92; 95% CI, 0.86–0.98). There was no significant difference in perinatal mortality (20 studies; RR, 0.92; 95% CI, 0.81–1.05) and in the rate of small-for-gestational-age infants (12 studies; RR, 0.96; 95% CI, 0.87–1.07) among offspring of mothers treated with aspirin and those of mothers treated with a placebo. CONCLUSION: For women with moderate- and high-risk pregnancies, aspirin treatment seemed to have a small but significant effect on reducing the rate of preterm deliveries, but did not reduce the rate of perinatal death. Birth Defects Research (Part B) 68:70–84, 2003. © 2003 Wiley-Liss, Inc.

Fetal safety of loratadine use in the first trimester of pregnancy: A multicenter study

Abstract: Background: Women in their childbearing years often require drug therapy for allergic conditions. Loratadine, a newer nonsedating antihistamine, is often used because of its preferred side effect profile. To date no published data exist on the safety of loratadine use in pregnancy. Objective: We sought to determine whether the use of loratadine in the first trimester of pregnancy was associated with an increased risk for major malformations. Secondary outcomes included rates of miscarriage, birth weights, and gestational age at delivery. Methods: All women were prospectively enrolled from 4 participating centers. Detailed maternal medical history and drug exposures were collected at intake, whereas pregnancy complications and outcomes were collected at follow-up. A group of unexposed control subjects were recruited and followed up in a similar manner. Results: This report includes follow-up on 161 loratadine exposed pregnancies and an equal number of unexposed control subjects. Maternal characteristics (age, pregnancy history, alcohol consumption, and smoking habits) were not different between the 2 groups. There were 5 malformations observed in the exposed group and 6 in the control group, which was not significantly different ( P = .9) Similarly, the live birth rate, gestational age at delivery, and birth weights were not different between the 2 groups. Conclusion: These results suggest that loratadine use in pregnancy is not associated with a large risk for major malformations. Further studies are warranted to confirm these findings and to increase study power. (J Allergy Clin Immunol 2003;111:479-83.)

Prediction of milk/plasma concentration ratio of drugs.

Abstract: OBJECTIVE:The milk to plasma (m/p) concentration ratio of drugs is used to estimate the amount of drug offered to the suckling infant. Published literature was reviewed to identify drugs for which sufficient data exist for calculation of m/p ratio and to examine whether the existing empiric data agree with the published method of Atkinson for mathematical prediction of m/p ratios based on physiochemical characteristics.METHODS:Using a comprehensive reference text, we identified studies reporting sufficient data to calculate m/p ratio based on the AUC for milk and plasma. Subsequently, we calculated the m/p ratio with Atkinson's formula based on pKa, lipophilicity, and protein binding. We then correlated the empiric versus predicted (calculated) m/p ratios.RESULTS:Of 192 drugs of which at least some data on milk accumulation have been published, there were sufficient data to quantify m/p ratios for only 69 medications (78 studies). There was no significant correlation between the empiric m/p ratios and the...

Effect of methotrexate on male fertility.

Abstract: QUESTION: Several men with psoriatic arthritis have asked whether the methotrexate they take for rheumatoid arthritis will affect their fertility or the outcome of any of their partners' future pregnancies. What is known regarding risks to fertility and to fetuses? ANSWER: To date, there are no reports of adverse pregnancy outcomes among men exposed to methotrexate before conception. Opinions in the literature differ on the effects of methotrexate on male fertility. Several case reports and studies report no effect; others report reversible sterility. One limitation to several of these studies is the concurrent administration of other chemotherapeutic agents. Small studies reporting on methotrexate use with no other agents suggest no increased infertility. Motherisk is currently following men who are taking methotrexate alone for psoriatic arthritis to see whether it affects fertility.

Monitoring lithium in breast milk: an individualized approach for breast-feeding mothers.

Abstract: Lithium is a drug of choice for the management of bipolar disorder, a disease frequently affecting women in their childbearing years. Unfortunately, this drug has typically been contraindicated in nursing women. Data in humans are limited with respect to the use of this drug in lactating women, and early reports suggest high excretion into milk. The purpose of this report was to verify the excretion of lithium into human milk and to assess infant safety after breast-feeding. The authors found wide interpatient variability in lithium dose offered to the infant through breast milk (from 0% to 30% of maternal weight-adjusted dose), indicating that therapeutic drug monitoring of lithium in milk and/or in infant's blood, coupled with close monitoring of adverse effects, is a rational approach. Since therapeutic drug monitoring of lithium is routine, physicians caring for these women and infants should be encouraged to individualize their recommendations.

In vivo gene transfer of Kv1.5 normalizes action potential duration and shortens QT interval in mice with long QT phenotype.

Abstract: Mutations in cardiac voltage-gated K+ channels cause long QT syndrome (LQTS) and sudden death. We created a transgenic mouse with a long QT phenotype (Kv1DN) by overexpression of a truncated K+ channel in the heart and investigated whether the dominant negative effect of the transgene would be overcome by the direct injection of adenoviral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. End points at 3-10 days included electrophysiology in isolated cardiomyocytes, surface ECG, programmed stimulation of the right ventricle, and in vivo optical mapping of action potentials and repolarization gradients in Langendorff-perfused hearts. Overexpression of Kv1.5 reconstituted a 4-aminopyridine-sensitive outward K+ current, shortened the action potential duration, eliminated early afterdepolarizations, shortened the QT interval, decreased dispersion of repolarization, and increased the heart rate. Each of these changes is consistent with a physiologically significant primary effect of adenoviral expression of Kv1.5 on ventricular repolarization of Kv1DN mice.

Nausea and vomiting in pregnancy: results of a survey that identified interventions used by women to alleviate their symptoms

Abstract: Nausea and vomiting of pregnancy (NVP) affects most pregnant women. There are safe and effective treatments available; however, most women choose to avoid pharmacological therapies and try lifestyle and dietary changes to treat their condition. To date, no attempt has been made to quantify women's experience with a variety of interventions. This study aims to identify factors commonly reported by women that alleviate their symptoms of NVP. Five hundred women with NVP, calling a pregnancy healthline between February 1996 and July 1999, completed a questionnaire where they were asked to rate which of 21 factors helped and to what extent each factor helped to improve their NVP symptoms. For each item, the 'frequency' (percentage of women who indicated that item as an improvement) and 'mean importance' (mean importance score of women who indicated that item as an improvement) were multiplied to give the 'overall impact' score. All 500 women reported that dietary and lifestyle changes helped to improve their NVP symptoms. However, most items were rated low and only 31% of women reported benefit from the use of pharmacological treatment. In conclusion, this study has identified that NVP is a multifaceted condition. Lifestyle changes including validation, supportive counseling and dietary adjustments are important components, that can be used to counsel women with NVP, concomitantly with safe and effective treatment.

Evaluation of eutectic lidocaine/prilocaine cream (EMLA) for steroid joint injection in children with juvenile rheumatoid arthritis: a double blind, randomized, placebo controlled trial.

Abstract: OBJECTIVE: To evaluate the efficacy of eutectic lidocaine/prilocaine cream (EMLA) in reducing the pain associated with steroid joint injection in children with juvenile arthritis. METHODS: A randomized, double blind, placebo controlled parallel group trial. Thirty-one children (ages 8-18 yrs) scheduled for steroid injection into a knee were randomized into groups having either 2.5 g lidocaine/prilocaine cream or placebo cream applied to the injection site 60-90 min before the procedure. Patients assessed the pain associated with initial needle insertion and subsequent steroid injection using a 10 cm visual analog scale. RESULTS: No significant difference was found in the pain reported after needle insertion or steroid injection between the lidocaine/prilocaine cream group (n = 17) and the placebo group (n = 14). There was a trend toward an association of lower median scores with the pain of steroid injection in the lidocaine/prilocaine group (6 mm) compared with the placebo group (22 mm). CONCLUSION: Application of 2.5 g lidocaine/prilocaine cream for 60-90 min had no statistically significant analgesic effect on pain associated with injections of steroids into the knees of children with juvenile arthritis.

Seroprevalence of Toxoplasma gondii infection among veterinary staff in Ontario, Canada (2002): implications for teratogenic risk.

Abstract: Toxoplasma gondii infection is embryotoxic in humans. It is mainly transmitted through raw/undercooked meat and ingestion of oocysts in cat feces. There remains controversy about the actual risk of cats transmitting the disease to humans. Our primary objective was to determine the seroprevalence of T. gondii antibody among veterinary staff, to ascertain whether they have an increased risk through occupational exposure. Our secondary objective was to examine their practices regarding cats, toxoplasma infection, and pregnancy. Veterinary staff attending the 2002 Annual Ontario Veterinary Medical Association Conference were invited to discuss their toxoplasma seroprevalence. Interested attendees completed a questionnaire and a physician drew blood samples to determine T. gondii titres using the ELISA IgG test. We collected 161 completed questionnaires, and 141 blood samples. There were 20 (14.2%, CI95%:8.4–19.9%) reactive titres among the veterinarian staff (80% females aged 30–45). All were regularly exposed to cats, washed their hands when in contact and few wore gloves routinely. These findings of low positive rates may be used to reassure veterinary staff that their exposure to cats does not appear to increase their risk of contracting toxoplasma infection and that pregnant women are not at an increased risk by owning a cat.

Assessment of Visual Functions Following Prenatal Exposure to Organic Solvents

Abstract: Prenatal exposure to organic solvents has been previously associated with increased risk of color vision deficits and reduced visual acuity in young children. These findings prompted us to evaluate visual functioning in solvent-exposed infants using more sensitive non-invasive visual evoked potential (VEP) techniques. VEP techniques are described in the context of an ongoing prospective longitudinal cohort study of infants exposed to organic solvents in utero. VEPs are recorded via three active electrodes fitted over the occipital cortex while infants view changing visual stimuli. The sweep VEP is used to assess contrast detection and visual acuity by presenting sinusoidal gratings that “sweep” across a range of contrasts and spatial frequencies. Transient VEPs are used to assess responses to equiluminant chromatic- and luminance-modulated sinusoidal gratings presented in pattern onset–offset format. A single case study is presented showing abnormal chromatic responses and reduced contrast sensitivity in a 2.5-year-old boy following prenatal exposure to perchloroethylene (PCE). These VEP techniques therefore appear promising for the clinical assessment of visual toxicity in pediatric populations.

Vitamin E: the evidence for multiple roles in cancer.

Abstract: There is accumulating evidence that vitamin E may have different roles in the prevention and treatment of cancer. The purpose of this review is to summarize and evaluate this evidence and to suggest future avenues of research. A comprehensive literature review of vitamin E and cancer was conducted. Articles were organized into the following categories: 1) cancer prevention, 2) direct antineoplastic activity, 3) augmentation of chemotherapy effects, and 4) attenuation or treatment of chemotherapy toxicity. The evidence was systematically evaluated using guidelines developed by the U.S. Preventative Services Task Force. There is evidence to suggest that those individuals with higher serum vitamin E levels and those receiving vitamin E supplementation have a decreased risk of some cancers, including lung, prostate, stomach, and gastrointestinal carcinoma. However, these results differed depending on the study design and the population studied. There is insufficient evidence to support anticancer activity and attenuation of chemotherapy toxicity by vitamin E. Vitamin E is likely to be important in the prevention of some cancers. The therapeutic role of vitamin E is poorly understood. Further research will be required before routine use of vitamin E in patients with cancer can be advocated in the clinical setting.