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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 109 records · Page 6Linked to original sources
PubMed2000

The efficacy of oral deferiprone in acute iron poisoning.

Due to its high cost and need for parenteral administration, the standard iron chelator deferoxamine is not used in many individuals with acute and chronic iron poisoning worldwide. Deferiprone is the first oral iron chelator to be shown to be effective in chronically iron overloaded thalassemia patients. Its efficacy, by oral administration, in acute iron poisoning has not been tested. Our objective was to determine whether orally administered deferiprone can reduce the mortality of rats following acute, toxic, oral doses of iron. Rats were administered 612 mg/kg elemental iron orally, corresponding to LD50 in the species tested. Two other groups received the same oral dose of iron followed by oral deferiprone: 800 mg/kg and 800 mg/kg, followed by another dose of 800 mg/kg 2 hours later. Coadministration of 800 mg/kg deferiprone with the iron decreased mortality from 30% to 6.6% after 2 hours (P = .02), from 40% to 16.6% after 12 hours (P = .04), and from 53.3% to 20% after 24 hours (P = 0.007). Mortality was also significantly decreased among animals coadministrated 2 repeated doses of deferiprone of 800 mg/kg with iron, to 0%, 9%, and 18%, and 2, 12, and 24 hours postdrug administration, respectively (P = .04, .05, .04, respectively). Histologically, there was a dose-dependent decrease in iron accumulation in the gastrointestinal tract. Orally administered deferiprone can decrease morbidity and mortality caused by acute iron overdose in rats. Oral deferiprone holds promise in the treatment of iron poisoning in humans.

Acute Disease↗
PubMed2000

Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies.

BACKGROUND: This study was designed to examine whether there is an increased risk for major malformations following the use of fluoxetine during the first trimester of pregnancy. METHODS: Published and unpublished reports were identified through computerized and manual searches of bibliographical databases, reference lists from primary articles, and letters to editors, agencies, foundations and content experts. Meta-analysis was undertaken of prospective controlled and uncontrolled studies on the use of fluoxetine during first trimester of pregnancy. RESULTS: The pooled relative risk and 95% confidence interval for major malformations does not suggest an association between the use of fluoxetine during the first trimester and an increased risk of major malformations. Combination of controlled and uncontrolled studies shows a weighted risk of 26% (95% CI 1-4.2%). The summary odds ratio from the two controlled studies (OR = 1.33, 95% CI 0.49-3.58) was not significant. Homogeneity testing shows that the effect sizes are similar throughout all studies. Power analysis indicates that 26 controlled studies of similar size, would be required, to reverse this finding. CONCLUSIONS: The use of fluoxetine during the first trimester of pregnancy is not associated with measurable teratogenic effects in human.

Abnormalities, Drug-Induced↗
PubMed2000

Fetal response to maternally administered morphine.

OBJECTIVE: We sought to determine the effects of maternally administered morphine on fetal response. STUDY DESIGN: Singleton pregnancies requiring fetal blood sampling were enrolled. Only study patients were given morphine intramuscularly. Maternal vital signs, fetal heart rate, biophysical profile score, and umbilical artery Doppler indices (systolic/diastolic ratio, resistance index, and pulsatility index) were completed before and after fetal blood sampling. Maternal and cord blood morphine concentrations were measured. RESULTS: Ten study and 6 control patients were enrolled. A significantly lower biophysical profile score was observed in study patients (P =.001) as a result of absent fetal breathing movements and nonreactive nonstress tests. Gross and fine fetal movements were unaffected. A significant correlation was measured between the biophase morphine concentration and each of the Doppler indices. CONCLUSION: Morphine administered to the mother causes a significant decrease in the biophysical profile score. Correlation between the biophase morphine concentration and the Doppler indices was calculated. These results suggest that morphine acts as a vasoconstrictor of the placental vasculature but do not support the use of intramuscular morphine to suppress fetal movement.

Analgesics, Opioid↗
PubMed2000

Pregnancy outcome after in utero exposure to itraconazole: a prospective cohort study.

OBJECTIVE: This study was undertaken to determine whether itraconazole use during the first trimester of pregnancy was associated with increased risks of major malformations, spontaneous abortions, premature deliveries, and neonatal complications. STUDY DESIGN: In a prospective cohort study pregnant women exposed to oral itraconazole were matched with control subjects not exposed to any known teratogens. Primary outcome was the rate of major malformations. Secondary outcomes were live birth rate, rates of spontaneous abortion and therapeutic abortion, gestational age at delivery, birth weight, and neonatal complications. RESULTS: A total of 229 women exposed to itraconazole were reported to the manufacturer, 198 of whom used the drug during the first trimester of pregnancy. The rate of major malformations in the study group (156 live births) was 3.2%, compared with 4.8% in the control group (187 live births; relative risk, 0.67; 95% confidence interval, 0. 23-1.95). The rate of any pregnancy loss was higher in the exposed group (relative risk, 1.75; 95% confidence interval, 1.47-2.09). Birth weight was lower in the itraconazole group, although that difference may not be clinically significant. Gestational age at birth, rate of preterm delivery, Apgar scores at 1 and 5 minutes, and neonatal complications were comparable between the groups. CONCLUSION: Our study supports the hypothesis that the use of itraconazole during pregnancy is safe. Further surveillance and reporting of pregnancy outcomes will help to support this conclusion.

Abortion, Spontaneous↗
PubMed2000

Inducible polymorphic ventricular tachyarrhythmias in a transgenic mouse model with a long Q-T phenotype.

We created a mouse model with a prolonged Q-T interval and spontaneous arrhythmias by overexpressing the NH(2) terminus and first transmembrane segment (Kv1.1N206Tag) of a delayed rectifier potassium channel (LQT(+/-) mouse). Analyses were performed using whole cell recordings of cardiac myocytes, surface electrocardiography, and programmed electrical stimulation. Action potential duration (APD) was prolonged to the same extent and was more highly variable in myocytes derived from LQT(+/-) and LQT(+/+) mice than in myocytes derived from wild-type (WT) FVB mice. Under ketamine anesthesia, the Q-T interval of both LQT(+/+) and LQT(+/-) mice was comparably prolonged versus that of WT mice. Stimulation of the right ventricle using an intracardiac catheter induced polymorphic ventricular tachyarrhythmias in 50% of the LQT(+/-) mice and 36% of the LQT(+/+) mice, whereas polymorphic ventricular tachyarrhythmias were not inducible in WT mice. The analyses of LQT(+/-) and LQT(+/+) mice indicate that prolongation of the Q-T interval in LQT mice is associated with prolonged APD, increased dispersion of APD among cardiocytes, and inducibility of polymorphic ventricular tachycardia, providing the substrate for spontaneous arrhythmias in these animals.

Action Potentials↗
PubMed2000

Prospective, controlled, multicentre study of loperamide in pregnancy.

BACKGROUND: Loperamide is a synthetic piperidine derivative used for the treatment of both acute and chronic diarrhea. Little is known about its safety and risk in pregnancy. Human data are limited to one surveillance study of Michigan Medicaid patients, with 108 women exposed in the first trimester. In this study there were six major birth defects, three of which were cardiovascular anomalies. OBJECTIVES: To determine whether loperamide use in pregnancy is associated with an increased risk of major malformations. The secondary end points were rates of minor malformations, spontaneous and therapeutic abortions, and premature births, and mean birth weights. PATIENTS AND METHODS: Women counselled by five teratogen information centres on the safety and risk of loperamide in pregnancy were followed after delivery and compared with a similar group of women matched for age, smoking, alcohol and other exposures. RESULTS: One hundred and five follow-ups were completed; 89 of the women were exposed to loperamide in the first trimester of pregnancy. There were no statistically significant differences between the study group and the control group in any of the end points that were analyzed. However, of women who took loperamide throughout their pregnancy, 21 of 105 had babies who were 200 g smaller than babies in the control group. CONCLUSIONS: The results of this study suggest that the use of loperamide during pregnancy is not associated with an increased risk of major malformations.

Abnormalities, Drug-Induced↗
PubMed2000

Estimation of neonatal exposure after accidental ingestion of lufenuron in a breastfeeding mother.

A case of accidental anti-flea preparation (lufenuron) ingestion by a breastfeeding mother is reported. An estimation of infant exposure level was calculated based on the highest level measured. The breastfed infant was exposed to an average lufenuron dose of 0.032 mg/kg/day, which is only 3% of a reported acute overdose. No adverse effects were reported during 7 months of follow-up. Breastfeeding should be considered cautiously after consultation with a regional poison center in cases of accidental ingestion of this drug by a breastfeeding mother. The infant should be monitored for potential adverse effects.

Adult↗
PubMed2000

Glucose metabolism is elevated and vascular resistance and maternofetal transfer is normal in perfused placental cotyledons from severely growth-restricted fetuses.

We hypothesized that placental resistance was elevated and transfer reduced in cotyledons from intrauterine growth-restricted (IUGR) fetuses. We perfused 10 cotyledons from term, normally grown fetuses, six from preterm, normally grown fetuses with normal umbilical arterial end-diastolic velocities (EDV), and six from preterm IUGR fetuses (<3rd centile) with absent or reversed umbilical arterial EDV. Perfused cotyledons were pressure-fixed, and villi were observed by scanning electron microscopy. The groups did not differ in fetoplacental resistance at baseline; neither did they differ in the change in resistance that followed the administration of nitroglycerin or angiotensin II. The increase in resistance during hypoxia was similar in the two preterm groups but greater in the term than in the preterm normally grown group (p < 0.05). Groups did not differ in net maternofetal transfer of oxygen or glucose, or in clearance of aminoisobutyric acid or antipyrine. However, glucose consumption was doubled in cotyledons of preterm IUGR versus preterm normally grown fetuses (p < 0.05). Terminal villi of perfused cotyledons from preterm IUGR fetuses displayed less terminal villous branching and budding than preterm controls, as anticipated from previous work. IUGR fetuses with absent or reversed umbilical arterial EDV in vivo may have high placental resistance due to a vasoconstrictive rather than anatomic abnormality and an elevated placental glucose consumption that may impair glucose transfer.

Female↗
PubMed2000

Choice of breastfeeding and physicians' advice: a cohort study of women receiving propylthiouracil.

OBJECTIVE: To examine the gap between the current social/medical practice and the evidence-based recommendation in favor of breastfeeding during maternal propylthiouracil (PTU) therapy. DESIGN: Prospective, observational, cohort study. SUBJECTS: Women requiring PTU during pregnancy, and endocrinologists and family physicians in Ontario, Canada. INTERVENTIONS: Questionnaire. MAIN OUTCOME MEASURES: Women were interviewed postpartum regarding their choice of infant feeding method and relevant advice received from physicians. Physicians were questioned about their advice to nursing women receiving PTU. RESULTS: Of 78 women, 66 had live births. Thirty-six required PTU postpartum (group 1), and 30 did not (group 2). Thirty-six healthy women served as controls (group 3). Breastfeeding initiation rates for groups 1, 2, and 3 were 44%, 83%, and 83%, respectively. In group 1, 15 women who breastfed received advice from 22 physicians regarding breastfeeding (20 in favor, 1 against, and 1 equivocal). Eleven who formula fed received advice from 17 physicians (4 in favor, 12 against, and 1 equivocal). A logistic regression analysis of group 1 showed that physicians' advice was the only significant predictor of the woman's choice to breastfeed during PTU therapy (relative risk: 5.48; 95% confidence interval: 1.28-23.40). The physician survey showed that 44% of endocrinologists do not recommend breastfeeding during PTU therapy. CONCLUSIONS: A substantial proportion of the lactating patients on PTU still receive advice against breastfeeding from their physicians. Physicians' advice and attitudes toward breastfeeding during PTU therapy are a major factor in women's final decision to breastfeed. Physicians' compliance with evidence-based data will facilitate breastfeeding in this group.propylthiouracil, breastfeeding, decision-making.

Attitude of Health Personnel↗
PubMed2000

Psychosocial morbidity among women with nausea and vomiting of pregnancy: prevalence and association with anti-emetic therapy.

Unlike severe nausea and vomiting of pregnancy (NVP), it is not known whether milder forms of NVP have been associated with psychosocial morbidity. We undertook the study to explore the prevalence of psychosocial morbidity by severity of NVP, and determine whether, after correction for severity of nausea/vomiting, there is a relationship between psychosocial morbidity and women's decisions to take anti-emetics as a reflection of their distress due to NVP. From 1996-97, an NVP Healthline was advertised. Callers underwent semi-structured interviews about both their NVP and associated psychosocial morbidity in a previous pregnancy. Most of the 3201 callers resided in Canada, worked outside the home, reported on planned pregnancy (a median of) 4 years before, and described severe (> 5 episodes/day of) nausea and vomiting. More severe nausea/vomiting was associated with more frequent feelings of depression, consideration of termination of pregnancy, adverse effects on women's relationships with their partners or their partners' everyday lives, and the perceived likelihood that NVP would harm their baby (p < 0.0001). However, all psychosocial factors were reported by a clinically important proportion of women with mild nausea/vomiting (0-1 episodes/day). The severity of vomiting was most closely related to women's decisions to take anti-emetics, but other psychosocial factors were also independently associated with anti-emetic therapy. We conclude that psychosocial morbidity is evident across the spectrum of severity of nausea and vomiting among women with NVP. The severity of nausea or vomiting does not appear adequately to reflect the distress caused by NVP, as reflected by women's decisions to take anti-emetic therapy.

Adult↗
PubMed2000

Zopiclone use during pregnancy.

QUESTION: One of my patients, whom I had treated with a 2-week course of zopiclone for insomnia, conceived while using the medication. She is concerned. How should I advise her? ANSWER: Based on available, albeit limited, evidence, zopiclone does not appear to be a major human teratogen.

Abnormalities, Drug-Induced↗
PubMed2000

Can we use anxiolytics during pregnancy without anxiety?

QUESTIONOne of my patients suffers from anxiety and was using lorazepam to treat it. When she became pregnant, she stopped the medication immediately, but now she is worried about the potential effect on the baby because she was using the drug just after conception. Is this class of drugs safe during pregnancy? What should she do if she needs antianxiety treatment during the rest of her pregnancy?ANSWEREvidence to date from cohort studies did not identify a notable association between use of benzodiazepines and increased risk of major malformations, including oral cleft. In contrast, data from case-control studies show a slightly increased risk of oral cleft. Hence, level 2 ultrasonography is recommended to rule out visible forms of cleft lip. Using benzodiazepines late in pregnancy could cause withdrawal syndrome in newborns.

Anti-Anxiety Agents↗
PubMed2000

Caffeine during pregnancy? In moderation.

QUESTION: Many of my female patients, those who plan pregnancy or have conceived, are afraid of any intake of caffeine. This often makes their lives miserable during pregnancy. Is this justified scientifically? ANSWER: Motherisk's recent meta-analysis suggests that the risks for miscarriage and fetal growth retardation increase only with daily doses of caffeine above 150 mg/d, equivalent to six typical cups of coffee a day. It is possible that some of this presumed risk is due to confounders, such as cigarette smoking.

Abortion, Spontaneous↗
PubMed2000

Attitudes and practices of physicians and naturopaths toward herbal products, including use during pregnancy and lactation.

BACKGROUND: The popularity of complementary therapies continues to grow, and physicians are asked increasingly by their patients for information regarding these modalities. PURPOSE: To assess the impact of these trends on physicians and medical students, and compare their attitudes and practices with those of the naturopaths and their students, with particular interest in the use of herbal products during pregnancy and breastfeeding. MATERIALS AND METHODS: A detailed questionnaire was distributed by a medical student and a naturopathic student to a randomly selected group of physicians, medical students, naturopaths and naturopathic students. They were asked a variety of questions about their background, attitudes and practices concerning herbal products. RESULTS: Thirty-eight per cent of the questionnaires were returned, with a total of 242 respondents. Fifty-four per cent of physicians discussed complementary therapies with their patients, whereas 100% of naturopaths discussed conventional medicines with their patients. The most popular product recommended by both medical doctors and naturopaths was echinacea, followed by St John's Wort. Eighty-six per cent of physicians, 74% of medical students, 66% of naturopaths and 50% of naturopathic students think that complementary medical education should be incorporated into the standard medical curriculum. Only one physician actually recommended a herbal product to a pregnant patient compared with 49% of the naturopaths who felt comfortable doing so. CONCLUSIONS: Complementary medicine has become a reality, and physicians are recommending herbal products to their patients, although on a smaller scale than are naturopaths. However, the two most popular herbal products are the same in each group. Physicians are less likely to recommend herbal products to pregnant and breastfeeding women than are naturopaths.

Attitude of Health Personnel↗
PubMed2000

Can we use metronidazole during pregnancy and breastfeeding? Putting an end to the controversy.

QUESTION: Two of my patients have been diagnosed with giardiasis, and I would like to treat them with the drug of choice for this infection, metronidazole (Flagyl). One of them is 6 weeks pregnant and the other is breastfeeding a 2-month-old infant, and I have received conflicting information about the safety of this drug during pregnancy and breastfeeding. What should I do? ANSWER: Although metronidazole has been on the market for almost 40 years, its use remains controversial during pregnancy and breastfeeding. Recent evidence has shown, however, that this drug is not associated with adverse effects during either pregnancy or breastfeeding.

Adult↗