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Biomedical subjects

Gideon Koren

Publications and source records attributed to Gideon Koren.

At least 217 records · Page 12Linked to original sources
PubMed2003

From bench to bedside: utilization of an in vitro model to predict potential drug-drug interactions in the kidney: the digoxin-mifepristone example.

Drug interactions are a common source of drug-induced toxicity. For drugs with narrow therapeutic windows, such as digoxin, an understanding of the potential mechanisms by which drugs might interact is essential to clinical practice. This article describes the utility of a renal tubular cell culture model in the prediction of drug interactions involving P-glycoprotein. Digoxin is a cardiac glycoside that undergoes active secretion in the renal tubules by the MDR1 (P-glycoprotein) drug efflux pump. Mifepristone (RU486) is a recently introduced abortifacient that is largely unstudied in terms of drug-drug interactions. The authors used an in vitro model to study the effects of mifepristone on the renal tubular secretion and cellular uptake of digoxin by Madin-Darby canine kidney (MDCK) cells. Mifepristone significantly inhibited the renal tubular secretion of digoxin (p = 0.0005), without interfering with its ability to enter the renal tubular cell. Similar results were found with the P-glycoprotein substrate vinblastine. The findings suggest that drug interactions may result if mifepristone is administered with P-glycoprotein substrates, highlighting the usefulness of this model in the study of not only common but also rare combinations of drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Ionizing radiation during pregnancy.

QUESTION: One of my patients had a computed tomography scan of her abdomen a week ago and has just found out she is 7 weeks pregnant. What should I tell her about the pregnancy and the risk to her fetus? ANSWER: Your patient is not at increased risk of miscarriage or major congenital fetal malformations due to radiation exposure. Her risk is similar to that of the general population (ie, 1% to 3%).

Adult↗
PubMed2003

Safety of colchicine therapy during pregnancy.

QUESTION: A 27-year-old patient in our clinic with familial Mediterranean fever (FMF) has been treated with colchicine for the last decade. She is planning her first pregnancy. What recommendations should we give her regarding use of colchicine before and during pregnancy, bearing in mind that discontinuation of colchicine could lead to complications from amyloidosis? ANSWER: Colchicine passes through the placenta in humans, is teratogenic in animals, and raises rates of male and female infertility. Based on several patients with chromosomal anomalies, some authorities recommend that patients who require colchicine therapy during pregnancy undergo amniocentesis with karyotyping. In contrast, an increasing body of evidence suggests that colchicine use throughout pregnancy carries no substantial teratogenic or mutagenic risk when used at recommended doses. Its use prevents febrile attacks of FMF and reduces the frequency of renal complications.

Amyloidosis, Familial↗
PubMed2003

Trimethoprim-sulfonamide combination therapy in early pregnancy.

QUESTION: One of my patients presented with bacteriuria early in her pregnancy. Urine culture was positive for Escherichia coli. I would like to prescribe a trimethoprim-sulfamethoxazole combination because it worked well for her in the past. What is known about the safety of this medication during early pregnancy? ANSWER: Evidence-based studies report an association between trimethoprim-sulfonamide combinations in early pregnancy and several major malformations, such as neural tube defects and cardiovascular defects. If clinically possible, physicians are advised to use alternative antimicrobial medications for treatment of urinary tract infections during early pregnancy.

Abnormalities, Drug-Induced↗
PubMed2003

Taking bisphosphonates during pregnancy.

QUESTION: Several of my female patients take bisphosphonates for low bone mineral density (BMD). Two of them are of reproductive age. Are these drugs safe during pregnancy? ANSWER: Very little is currently known about the effects of bisphosphonates on human pregnancy. There have been only two reports of bisphosphonate use during late pregnancy. Animal studies suggest that biphosphonates cross the placenta and that the effect is an extension of the expected pharmacologic effect of bisphosphonates on both fetus and mother. Risks and benefits should be carefully weighed.

Animals↗
PubMed2003

Risk of varicella infection during late pregnancy.

QUESTION: I have a patient who contracted varicella at 26 weeks' gestation. She is very concerned and would consider termination if it were earlier in the pregnancy. What are the current predictions of risk for her fetus? ANSWER: Based on review of all available studies, we could not detect a single case of congenital varicella syndrome in the third trimester of pregnancy (0/208), as compared with 5/645 (0.78%) in the first and 9/592 (1.52%) in the second trimester (P < .01 third vs first and second). You can reassure your patient.

Adult↗
PubMed2003

Hemophilia during pregnancy.

QUESTION: A patient in my clinic, who is 10 weeks into her first pregnancy and is a known carrier of hemophilia B, is considering the advantages and disadvantages of antenatal tests and is especially worried about a vaginal delivery thatmight cause bleeding. How should I manage her pregnancy? ANSWER: Many female carriers of hemophilia were found to have lower-than-expected levels of plasma factors, which are thought to be due to X chromosome inactivation. Chorionic villous sampling is the preferred test to determine the sex of the fetus and whether a male infant is affected with hemophilia. Vaginal delivery is not contraindicated and has been proven during the last two decades to be as safe as cesarean section. Vacuum extraction should be avoided to minimize risk of intracranial hemolysis and severe cephalhematoma.

Adult↗
PubMed2003

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

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.

Abnormalities, Drug-Induced↗
PubMed2002

A survey of physicians knowledge regarding awareness of maternal alcohol use and the diagnosis of FAS.

BACKGROUND: Alcohol is the most widely used drug in the world that is a human teratogen whose use among women of childbearing age has been steadily increasing. It is also probable that Fetal Alcohol Syndrome is under diagnosed by physicians. The objectives of this study were twofold: 1) to evaluate the experience, knowledge and confidence of family physicians with respect to the diagnosis of FAS and 2) to evaluate physicians awareness of maternal drinking patterns. METHODS AND PARTICIPANTS: A multiple choice anonymous questionnaire was sent to a randomly selected group of family physicians in the Metropolitan Toronto area. RESULTS: There was a 73% (75/103) total response rate; Overall, 6/75 (8%) of family physicians reported that they had actually diagnosed a child with FAS. 17.9% had suspicions but did not make a diagnosis and 12.7% reported making a referral to confirm the diagnosis. Physician rated confidence in the ability to diagnosis FAS was low, with 49% feeling they had very little confidence. 75% reported counselling pregnant women and 60.8% reported counselling childbearing women in general on the use of alcohol. When asked what screening test they used to detect the use of alcohol, 75% described frequency/quantity. Not a single respondent identified using the current accepted screening method for alcohol use (TWEAK) which is recommended by The Centre for Addiction and Mental Health. CONCLUSIONS: Family physicians do not feel confident about diagnosing FAS. None of the physicians were aware of the current screening methods to accurately gage alcohol use in pregnant and childbearing women.

Alcohol Drinking↗
PubMed2002

Perinatal outcome following third trimester exposure to paroxetine.

BACKGROUND: Paroxetine hydrochloride is commonly used for maternal depression, panic disorder, and obsessive-compulsive disorder. The drug readily crosses the human placenta. Although it does not appear to increase teratogenic risk, there have been case reports of neonatal withdrawal. Symptoms were described soon after birth and lasted up to 1 month. OBJECTIVE: To investigate whether there is a clinically important discontinuation syndrome in neonates exposed to paroxetine in utero. METHODS: Prospective, controlled cohort study. PATIENTS: Fifty-five pregnant women counseled prospectively by the Motherisk program in Toronto, Ontario, regarding third-trimester exposure to paroxetine and their infants were included in the study group. Pregnant women who discontinued paroxetine before the third trimester or those receiving other drugs known to cause withdrawal-type symptoms, such as opioids or benzodiazepines, were excluded. A comparison group of 27 women using paroxetine during the first or second trimester and 27 women using nonteratogenic drugs were matched for maternal age, gravity, parity, social drug use, and nonteratogenic drug use. RESULTS: Of the 55 neonates exposed to paroxetine in late gestation, 12 had complications necessitating intensive treatment and prolonged hospitalization. The most prevalent clinical picture was respiratory distress (n = 9), followed by hypoglycemia (n = 2), and jaundice (n = 1). The symptoms disappeared within 1 to 2 weeks. In the comparison group, only 3 infants experienced complications (P =.03). In logistic regression, only third-trimester exposure to paroxetine was associated with neonatal distress (odds ratio, 9.53; 95% confidence interval, 1.14-79.3). CONCLUSION: When used near term, paroxetine is associated with a high rate of neonatal complications, possibly caused by its common discontinuation syndrome.

Adult↗
PubMed2002

Ethical framework for observational studies of medicinal drug exposure in pregnancy.

BACKGROUND: The conduct of human research in the teratogenicity of drugs, chemicals, radiation and infections is needed in order to close critical gaps in knowledge. METHODS: We reviewed the various aspects of the ethics of conducting prospective human research in teratogenicity. RESULTS: Such research should respect the confidentiality of pregnant women and their families. Because this research is observational, interpretation of results is difficult, and the study design should strive to meet the highest possible scientific standards attainable in the particular research conditions. It should also be acknowledged that confidentiality cannot be always adhered to (e.g., if the interview reveals risks to minors). CONCLUSIONS: In general, the benefit risk ratio in this type of research is very favorable, although in specific cases the research follow-up may induce fears (e.g., drugs of abuse) in the woman being interviewed.

Abnormalities, Drug-Induced↗
PubMed2002

Pregnancy outcome post renal transplantation.

BACKGROUND: The success in performing organ transplantations and prevention of rejection has resulted not only in a substantial increase in life expectancy, but also improvement in the patients' quality of life. Thus, women who underwent organ transplantation are now reaching puberty and the age of reproduction. This has presented new challenges regarding the teratogenicity and the long-term effect of immunosuppressive medications used by these patients. Previous studies have shown that pregnancies after renal transplantation are associated with an increased risk for both the mother and the fetus. There is, however, very little information available on neonatal and long-term pediatric follow-up of babies born to mothers who have undergone renal transplantation and have been exposed to immunosuppressive medications, compared to controls. We report the experience of our center, the largest in Canada, regarding the prenatal and long-term postnatal outcome of pregnancies after renal transplantation. METHODS: This is a retrospective case series reporting the outcome of 44 consecutive pregnancies followed by the Toronto Renal Transplant Program. Follow-up data were gathered on the 32 live born children by either a return visit to the clinic or by telephone interview. Medical, as well as developmental information, was gathered on all children and the study group was compared to controls, matched for maternal age (+/-2 years) and smoking status, obtained through the Motherisk Program. RESULTS: Of the 44 pregnancies followed by us, there were 32 live-born children delivered by 26 mothers and 12 stillborn/abortuses. Twenty-six pregnancies were treated with cyclosporine, azathioprine and prednisone, 13 with azathioprine and prednisone and five with cyclosporine and prednisone. The mean gestational age at delivery in the study group was 36.5 +/- 2.7 weeks compared to 40.2 +/- 1.6 weeks in the control group (P < 0.001). The mean birthweight in the study group was 2.54 +/- 0.67 kg, compared to 3.59 +/- 0.53 kg in the control group (P < 0.0001). In the study group there was one child with multiple anomalies and four stillbirths compared to zero in the control group. There were also six spontaneous abortions and two therapeutic abortions in the study group. On follow-up (from 3 months to 11 years of age) there was one child with insulin-dependent diabetes mellitus, two children with asthma and one child with recurrent otitis media. Developmental follow-up revealed one child with moderate to severe sensorineural hearing loss, one child with a learning disability and one child with pervasive developmental disorder. In none of these cases were there signs of perinatal asphyxia. CONCLUSION: There are significantly more stillbirths, preterm deliveries and increased incidence of low birth weight in the transplant group. Most pregnancies in the study group went well, however, and their offspring had normal postnatal growth and development. Further studies with long-term pediatric follow-up are needed to delineate their outcome and rule out possible long term effects of the immunosuppressive medication on their growth, development, reproduction and general health.

Abortion, Spontaneous↗
PubMed2002

Biologic markers of pain in the vulnerable infant.

Detecting and quantifying pain in infants and young children is a complex task because young children cannot communicate this subjective phenomenon. In the 1950s, it was postulated that there might be "wound hormones" produced in injured tissues that activated the pituitary-adrenal axis. Research in adults demonstrated that plasma levels of different hormones, including corticosteroids, cathecholamines, growth hormone, and insulin, changed in response to emotionally and physically stressful stimuli. Stress response is the term given to those hormonal and metabolic changes that follow injury or trauma, but the debate as to whether increased stress response is a sign of pain or whether decreased stress response is a sign of diminished pain has not been resolved yet. Following the study of systemic response to surgery, the ability of anesthetic agents to substantially attenuate intraoperative and postoperative stress response has been reported. In newborns, a strong correlation between preoperative stress and postoperative complication rate was found. The full extent of the vulnerable infant's pain is still poorly understood, but further research of known biologic markers and newly discovered ones could promote our understanding of the pain response and increase our ability to prevent undesirable outcome.

Catecholamines↗
PubMed2002

Use of proton pump inhibitors during pregnancy and rates of major malformations: a meta-analysis.

Proton pump inhibitors are used to treat gastroesophageal reflux, a symptom common in pregnancy. The aim of this study was to systematically analyze the available data on the risk for malformations following use of these agents in the first trimester of pregnancy. Medline, EMBASE, published abstracts, and reference lists were searched for articles reporting on proton pump inhibitor use in pregnancy. Summary relative risks and 95% confidence intervals (95% CI) were calculated using the Mantel-Haenszel method. Five cohort studies met the inclusion criteria for this meta-analysis. With almost 600 exposed pregnancies, the overall relative risk was 1.18 with a 95%CI of 0.72-1.94. In conclusion, proton pump inhibitors do not present a major teratogenic risk when used in recommend doses. These data are reassuring for the countless patients who have used these agents in the early part of their pregnancies.

Abnormalities, Drug-Induced↗