Search PubMed⌕ Search

Biomedical subjects

Gideon Koren

Publications and source records attributed to Gideon Koren.

At least 145 records · Page 8Linked to original sources
PubMed2004

Active and passive tobacco smoke exposure: a comparison of maternal and child hair cotinine levels.

The objective of this study was to compare tobacco smoke exposure in mothers and their healthy children less than 3 years old using hair cotinine (HC) levels as an objective long-term measure of exposure. Hair samples were obtained from mother/child pairs recruited from the Columbus Children's Hospital Primary Care Center, and were analyzed by radioimmunoassay to compare HC levels. Mothers were both self-reported smokers and nonsmokers. Contributing and confounding variables were assessed based on questionnaires completed by participants. Exclusion criteria for children were prematurity and presence of chronic cardiopulmonary disease. Hair samples and questionnaires were obtained from 104 mother/child pairs. Child and maternal HC levels were correlated for both self-reported maternal smokers (R2 = .13, p < .013) and self-reported maternal nonsmokers (R2 = .54, p < 001). Child HC levels were higher than maternal HC levels (1.18 ng/mg vs. .78 ng/mg, p < .001). Children of nonsmokers had higher HC levels than their mothers (.77 ng/mg vs. .35 ng/mg, p < .001), while HC levels of smokers and their children were no different (1.91 ng/mg vs. 1.92 ng/mg, p = .978). The relationship between child and maternal HC did not differ by child age, gender, or race. In conclusion, environmental tobacco smoke exposure in young children as reflected by HC is higher than expected based on prior studies of biomarkers and passive tobacco smoke exposure in adult nonsmokers.

Adult↗
PubMed2004

Electrical remodeling and arrhythmias in long-QT syndrome: lessons from genetic models in mice.

Mutations in cardiac voltage-gated K+ channels cause long-QT syndrome (LQTS) and sudden death. We have created a mouse with a long-QT phenotype by overexpression of truncated K+ channels in the heart and have investigated the phenotype of these mice. These mice have long-QT phenotype, and spontaneous and inducible arrhythmias. Optical mapping of Kv1DN mice revealed spatial and temporal dispersion of repolarization that underlies the arrhythmias. Here I review our attempts to abolish arrhythmias in this model by crossbreeding with Kv4DN and Kv2DN mice or direct injection of adenoviral or adeno-associated viral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. Our published work suggests that the viral vectors rescue the phenotype at the cellular level, while crossbreeding with Kv4DN mice attenuates the spontaneous and inducible arrhythmias.

Action Potentials↗
PubMed2004

N-acetylcysteine for the treatment of clove oil-induced fulminant hepatic failure.

We present a 3-month-old female who developed fulminant hepatic failure after ingesting less than 8 mL of clove oil. Initial treatment involved gastrointestinal decontamination, supportive measures, and admission to hospital. She subsequently developed fulminant hepatic failure and was treated with intravenous N-acetylcysteine (N-AC) according to a protocol used for acetaminophen poisoning. Over the next 72 h her liver synthetic function and clinical status improved, and she made a complete recovery. Previous reported cases of clove oil toxicity and the potential role of N-AC therapy are reviewed.

Acetylcysteine↗
PubMed2004

Effects of perioperative oral amantadine on postoperative pain and morphine consumption in patients after radical prostatectomy: results of a preliminary study.

BACKGROUND: Amantadine is known to be a noncompetitive N-methyl-D-aspartate receptor antagonist and may be useful in preventing postoperative central sensitization, acute opioid tolerance, and opioid-induced hyperalgesia, thereby decreasing pain and analgesic requirements. The aim of this pilot study was to evaluate the effects of perioperative oral amantadine on postoperative pain and analgesic consumption. METHODS: Twenty-four patients scheduled to undergo radical prostatectomy were given oral amantadine before and after surgery in a randomized, double-blind, placebo-controlled manner. After surgery, patients received intravenous patient-controlled analgesia with morphine for 48 h. Wound pain intensity, sensitivity to mechanical pressure around the surgical wound, and incidence of bladder spasm pain were assessed. Blood samples were drawn for analysis of amantadine, morphine, and the morphine metabolites. Adverse effects and patient satisfaction were assessed. RESULTS: The cumulative morphine consumption was significantly lower in the amantadine group at all time points (except at 48 h), amounting to a 32% reduction over the 48-h period. Forty-eight hours after surgery, visual analog pain scores to pressure applied near the wound were significantly lower in the amantadine group than in the placebo group. In addition, the number of patients reporting bladder spasm pain was significantly lower in the amantadine group. Plasma concentration of morphine-3-glucuronide was significantly lower at the end of surgery in the amantadine group. Pharmacokinetic analyses showed that the plasma clearance of morphine at 22-24 h after surgery was also significantly lower in the amantadine group. CONCLUSION: The results suggest that perioperative oral amantadine reduces postoperative opioid consumption by pharmacokinetic mechanisms, although additional pharmacodynamic interactions may also be involved.

Adolescent↗
PubMed2004

Fetal exposure to alcohol as evidenced by fatty acid ethyl esters in meconium in the absence of maternal drinking history in pregnancy.

The detection of fatty acid ethyl esters (FAEE) in neonatal meconium has been proposed as a novel screening method for intrauterine exposure to alcohol. We investigated the potential use of meconium FAEE screening in a high-risk neonatal population in the absence of maternal drinking history. One hundred forty-two meconium samples of neonates suspected of intrauterine illicit substance exposure and referred to the Motherisk Laboratory were analyzed for the existence of drugs by enzyme-linked immunosorbent assay (ELISA) and FAEE by gas chromatography-flame ionization detection (GC-FID). A positive FAEE test was previously defined as a cumulative measurement of 7 individual FAEE > or = 2 nmol/g. Seventy-one percent of the samples tested positive for at least 1 illicit drug, with cannabis being the most prevalent (52.3%). Fourteen percent of all samples tested positive for prenatal alcohol exposure, as evidenced by cumulative meconium FAEE > or = 2 nmol/g. Ethyl oleate, linoleate, palmitate, and arachidonate were detected most often and at the highest levels. At least 3 individual FAEE were detected in 95% of all positive samples, and none could be identified by the use of 1 selected FAEE. Significantly elevated levels of FAEE above the baseline and the presence of multiple FAEE species in meconium are exclusive to neonates who have likely been exposed to excessive amounts of alcohol in utero. Babies born to mothers who are suspected to use illicit drugs in pregnancy are at elevated risk for exposure also to alcohol in utero. Meconium FAEE are emerging biologic markers that can potentially facilitate earlier diagnosis and intervention for less apparent forms of alcohol-related disabilities that cannot be confirmed in the absence of maternal drinking history.

Alcohol Drinking↗
PubMed2004

Amphotericin B nephrotoxicity in children.

Amphotericin B is the treatment of choice for severe systemic fungal infections. Nephrotoxicity is the most clinically significant adverse effect, but studies examining nephrotoxicity in children are scarce. Nephrotoxicity includes decreased glomerular filtration rate and distal tubulopathy with urinary loss of potassium and magnesium, renal tubular acidosis, loss of urine concentrating ability, and sometimes Fanconi's syndrome. The mechanisms involved in nephrotoxicity include the use of deoxycholate, the vehicle for amphotericin, reduction in renal blood flow and glomerular filtration rate, increased salt concentrations at the macula densa, interaction of amphotericin with ergosterol in the cell membrane, and apoptosis in proximal tubular cells and medullary interstitial cells. Some risk factors for amphotericin nephrotoxicity have been determined over the years. Cumulative dosage, treatment duration, and dosing schedule as well as the combination of amphotericin with other nephrotoxic drugs, such as diuretics and cyclosporine, are important risk factors. Mechanisms to prevent nephrotoxicity include the use of lipid formulations such as amphotericin B lipid complex, amphotericin B colloidal dispersion, and liposomal amphotericin B and the concurrent use of volume repletion. Amiloride can be considered in serious potassium loss.

Adult↗
PubMed2004

Prevalence of depression during pregnancy: systematic review.

OBJECTIVE: Current estimates of the prevalence of depression during pregnancy vary widely. A more precise estimate is required to identify the level of disease burden and develop strategies for managing depressive disorders. The objective of this study was to estimate the prevalence of depression during pregnancy by trimester, as detected by validated screening instruments (ie, Beck Depression Inventory, Edinburgh Postnatal Depression Score) and structured interviews, and to compare the rates among instruments. DATA SOURCES: Observational studies and surveys were searched in MEDLINE from 1966, CINAHL from 1982, EMBASE from 1980, and HealthSTAR from 1975. METHODS OF STUDY SELECTION: A validated study selection/data extraction form detailed acceptance criteria. Numbers and percentages of depressed patients, by weeks of gestation or trimester, were reported. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted data; a third party resolved disagreement. Two raters assessed quality by using a 12-point checklist. A random effects meta-analytic model produced point estimates and 95% confidence intervals (CIs). Heterogeneity was examined with the chi(2) test (no systematic bias detected). Funnel plots and Begg-Mazumdar test were used to assess publication bias (none found). Of 714 articles identified, 21 (19,284 patients) met the study criteria. Quality scores averaged 62%. Prevalence rates (95% CIs) were 7.4% (2.2, 12.6), 12.8% (10.7, 14.8), and 12.0% (7.4, 16.7) for the first, second, and third trimesters, respectively. Structured interviews found lower rates than the Beck Depression Inventory but not the Edinburgh Postnatal Depression Scale. CONCLUSION: Rates of depression, especially during the second and third trimesters of pregnancy, are substantial. Clinical and economic studies to estimate maternal and fetal consequences are needed.

Depressive Disorder↗
PubMed2004

Intratympanic gentamicin for Menière's disease: a meta-analysis.

OBJECTIVES: To systematically review the published experience on intratympanic gentamicin treatment for intractable Menière's disease. STUDY DESIGN: Meta-analysis using a random effect model. METHODS: A comprehensive literature search was performed for articles using intratympanic gentamicin as a sole treatment modality with reporting of results according to the American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) guidelines for Menière's disease. Two reviewers independently assessed trial quality and extracted data. RESULTS: Fifteen trials with 627 patients met the inclusion criteria. All trials reported "before-after" outcome measures, using patients as their own controls. No double-blind or blinded prospective control trials were identified. Complete (class A) vertigo control was achieved in 74.7% (confidence interval [CI]95% 67.8-81.5%) of patients, and complete or substantial (class B) control was achieved in 92.7% (CI95% 89.5-96.0%). The success rate was not affected by gentamicin treatment regimen (fixed vs. titration). Hearing level and word recognition were not adversely affected, regardless of gentamicin treatment regimen. Analysis of functional level was not performed because of lack of data in the selected articles. CONCLUSIONS: Intratympanic gentamicin treatment for intractable Menière's disease appears to be effective in the relief of vertigo. Cochleotoxicity and ototoxicity is unlikely to be a major side effect. However, the level of evidence reflected from the eligible articles is insufficient, especially because of relatively poor study design. Therefore, it is prudent that patients eligible for this type of treatment should be selected carefully and titrated with low-dose gentamicin. Further investigation with this treatment modality with control subjects is warranted.

Audiometry↗
PubMed2004

The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study.

OBJECTIVE: Ondansetron (Zofran) is a drug used for the treatment of nausea and vomiting caused by cancer chemotherapy. Despite the fact that it is not indicated, women are being prescribed this drug for the treatment of nausea and vomiting of pregnancy (NVP). There is a paucity of information on fetal safety for this indication. The objective of this study is to determine whether this drug increases the baseline rate of major malformations. DESIGN: A prospective comparative observational study. SETTING: Teratogen Information Services (TIS). POPULATION: Pregnant women. METHODS: Our three groups included women who were exposed to ondansetron and women exposed to (1) other anti-emetics and (2) non-teratogen exposures. All of the women called either our NVP Helpline or TIS at The Motherisk Program in Toronto, Canada, or The Mothersafe Program in Sydney, Australia. MAIN OUTCOME MEASURE: Rates of major malformation. RESULTS: We have completed 176 pregnancy outcomes in each group. In the ondansetron cohort, there were 169 live births, 5 miscarriages, 2 therapeutic abortions, 6 (3.6%) major malformations and the mean birthweight was 3362 g [SD 525]. There were no statistical differences in any of the study endpoints between the ondansetron and the comparison groups. CONCLUSIONS: This drug does not appear (although the sample size is limited) to be associated with an increased risk for major malformations above baseline.

Adult↗
PubMed2004

Caveolin-3 and SAP97 form a scaffolding protein complex that regulates the voltage-gated potassium channel Kv1.5.

The targeting of ion channels to particular membrane microdomains and their organization in macromolecular complexes allow excitable cells to respond efficiently to extracellular signals. In this study, we describe the formation of a complex that contains two scaffolding proteins: caveolin-3 (Cav-3) and a membrane-associated guanylate kinase (MAGUK), SAP97. Complex formation involves the association of Cav-3 with a segment of SAP97 localized between its PDZ2 and PDZ3 domains. In heterologous expression systems, this scaffolding complex can recruit Kv1.5 to form a tripartite complex in which each of the three components interacts with the other two. These interactions regulate the expression of currents encoded by a glycosylation-deficient mutant of Kv1.5. We conclude that the association of Cav-3 with SAP97 may constitute the nucleation site for the assembly of macromolecular complexes containing potassium channels.

Animals↗
PubMed2004

Attenuation of I(K,slow1) and I(K,slow2) in Kv1/Kv2DN mice prolongs APD and QT intervals but does not suppress spontaneous or inducible arrhythmias.

Overexpression of a truncated Kv1.1 or Kv2.1 channel polypeptide in the heart (Kv1DN or Kv2DN) resulted in mice with a prolonged action potential duration (APD) due to marked attenuation of rapidly activating, slowly inactivating K+ current (I(K,slow1)) or slowly inactivating outward K(+) current (I(K,slow2)) in ventricular myocytes. ECG monitoring, optical mapping, and programmed electrical stimulation of Kv1DN mice revealed spontaneous and inducible reentrant ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Recently, we demonstrated upregulation of I(K,slow2) in apical cardiomyocytes derived from Kv1DN mice. We therefore hypothesized that the selective upregulation of Kv2.1-encoded currents underlies the apex-to-base dispersion of repolarization and the reentrant arrhythmias. To test this hypothesis, the Kv1DN line was crossbred with the Kv2DN line to produce Kv1/Kv2DN lines. Whole cell voltage-clamp recordings from left ventricular cells of Kv1/Kv2DN confirmed that the 4-aminopyridine- and tetraethylammonium-sensitive components of IK,slow were eliminated, resulting in marked APD prolongation compared with wild-type, Kv1DN, and Kv2DN cells. Telemetric ECG recordings revealed prolongation of the corrected QT in Kv1/Kv2DN compared with Kv1DN and Kv2DN mice. However, attenuation of Kv2.1-encoded currents in Kv1DN mice did not suppress the arrhythmias. Thus, the elimination of I(K,slow2) prolongs APD and the QT intervals, but does not have an antiarrhythmic effect.

Action Potentials↗
PubMed2004

Perinatal risks of untreated depression during pregnancy.

OBJECTIVE: To review the literature on the perinatal risks involved in untreated depression during pregnancy. METHOD: We searched Medline and medical texts for all studies pertaining to this area up to the end of April 2003. Key phrases entered were depression and pregnancy, depression and pregnancy outcome, and depression and untreated pregnancy. We did not include bipolar depression. RESULTS: While there is wide variability in reported effects, untreated depression during pregnancy appears to carry substantial perinatal risks. These may be direct risks to the fetus and infant or risks secondary to unhealthy maternal behaviours arising from the depression. Recent human data suggest that untreated postpartum depression, not treatment with antidepressants in pregnancy, results in adverse perinatal outcome. CONCLUSION: The biological dysregulation caused by gestational depression has not received appropriate attention: most studies focus on the potential but unproven risks of psychotropic medication. No in-depth discussion of the role of psychotherapy is available. Because they are not aware of the potentially catastrophic outcome of untreated maternal depression, this imbalance may lead women suffering from depression to fear teratogenic effects and refuse treatment.

Abortion, Spontaneous↗
PubMed2004

Neonatal genital herpes simplex virus type 1 infection after Jewish ritual circumcision: modern medicine and religious tradition.

OBJECTIVE: Genital neonatal herpes simplex virus type 1 (HSV-1) infection was observed in a series of neonates after traditional Jewish ritual circumcision. The objective of this study was to describe neonate genital HSV-1 infection after ritual circumcision and investigate the association between genital HSV-1 after circumcision and the practice of the traditional circumcision. METHODS: Eight neonates with genital HSV-1 infection after ritual circumcision were identified. RESULTS: The average interval from circumcision to clinical manifestations was 7.25 +/- 2.5 days. In all cases, the traditional circumciser (the mohel) had performed the ancient custom of orally suctioning the blood after cutting the foreskin (oral metzitzah), which is currently practiced by only a minority of mohels. Six infants received intravenous acyclovir therapy. Four infants had recurrent episodes of genital HSV infection, and 1 developed HSV encephalitis with neurologic sequelae. All four mohels tested for HSV antibodies were seropositive. CONCLUSION: Ritual Jewish circumcision that includes metzitzah with direct oral-genital contact carries a serious risk for transmission of HSV from mohels to neonates, which can be complicated by protracted or severe infection. Oral metzitzah after ritual circumcision may be hazardous to the neonate.

Circumcision, Male↗
PubMed2004

Topical 4% amethocaine gel reduces the pain of subcutaneous measles-mumps-rubella vaccination.

OBJECTIVES: Ametop gel (4% amethocaine) is a relatively new topical anesthetic that produces anesthesia within 30 to 45 minutes and therefore may be appropriate for use in busy outpatient settings. The objective of this study was to assess the efficacy and safety of 4% amethocaine in reducing the pain of subcutaneous measles-mumps-rubella vaccination in 1-year-old infants. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in pediatric outpatient clinics. RESULTS: A total of 120 infants participated in the study; 60 were followed up for assessment of antibody titers after 1 month. Either 1 g of amethocaine or placebo was applied for 30 minutes before vaccination. The Modified Behavioral Pain Scale was used to assess pain; the mean (standard deviation) pain scores for the amethocaine group (n = 61) was 1.5 (1.6) versus 2.3 (2.2) for the placebo group (n = 59). The rate of vaccination success (88% and 87%) was not different between treatment groups. CONCLUSIONS: 4% Amethocaine significantly reduces the pain of measles-mumps-rubella vaccination in infants when compared with placebo and does not seem to interfere with subsequent development of protective antibody levels. Because of its relatively short application time (30 minutes), 4% amethocaine may be suitable for busy clinics and emergency departments.

Anesthetics, Local↗
PubMed2004

Malformation rates in children of women with untreated epilepsy: a meta-analysis.

BACKGROUND: It is widely quoted that women with epilepsy have a higher than baseline risk for giving birth to a child with malformations, independent of the effects of antiepileptic drugs. OBJECTIVE: To determine, based on available evidence, if epilepsy per se represents a teratogenic risk. To systematically review all studies investigating the occurrence of major malformation rates among children of treated or untreated women with epilepsy and non-exposed controls who do not have epilepsy. METHODS: A meta-analysis, using a random effects model, was conducted of all cohort and case-control studies reporting malformation rates in children of women with epilepsy exposed or unexposed to antiepileptic drugs compared with that of children of nonepileptic women. Medline (1966-2001), EMBASE, the Cochrane database as well as REPROTOX (an information system on environmental hazards to human reproduction and development) databases were accessed. RESULTS: We found ten studies reporting results of untreated epilepsy (n = 400) and their non-epileptic healthy controls (n = 2492). Nine out of ten studies also reported results on 1443 patients exposed to antiepileptic drugs and their 2526 unexposed healthy controls. The risk for congenital malformations in the offspring of women with untreated epilepsy was not higher than among nonepileptic controls (odds ratio [OR] = 1.92; 95% CI 0.92-4.00). There was evidence of publication bias, thus with bias removed the OR was 0.99 (95% CI 0.49-2.01). In contrast, the offspring of epileptic women who received antiepileptic drugs had higher incidences of malformation than controls (OR 3.26; 95% CI 2.15-4.93). CONCLUSION: Our study does not support the commonly held view that epilepsy per se represents a teratogenic risk. Our study suggests that this view is the result of a publication bias, with several small (< 100 participants) positive studies leading to a premature conclusion.

Abnormalities, Drug-Induced↗
PubMed2004

Medications that can be fatal for a toddler with one tablet or teaspoonful: a 2004 update.

OBJECTIVE: To provide an updated list of the highly toxic medications in North America that can kill a 10 kg toddler upon ingestion of 1-2 dose units. METHODS: All drugs available in North America were reviewed and their reported lethal doses in children or adults (where no pediatric data existed) were identified. The dose units of drugs available in North America were subsequently identified, followed by those dose units that could kill a toddler upon ingestion of 1-2 dose units or teaspoonfuls. RESULTS: Tricyclic antidepressants, antipsychotics, quinine derivatives, calcium channel blockers, opioids, and oral hypoglycemics can kill a toddler with 1-2 dose units. This list of drugs was responsible for 40% of toddler fatalities reported to the American Association of Poison Control Center Toxic Exposure Surveillance System between 1990-2000. CONCLUSION: Drugs that can kill a toddler with 1-2 dose units should be known to clinicians as such exposures warrant immediate and intensive management. A new system of special labeling of these drugs should be considered.

Administration, Oral↗
PubMed2004

Physicians' perceptions of teratogenic risk associated with radiography and CT during early pregnancy.

OBJECTIVE: The objective of our study was to determine family physicians' and obstetricians' perceptions of the risk of major fetal malformations associated with exposure to radiation from radiography and CT during early pregnancy. MATERIALS AND METHODS: Structured questionnaires were sent to 400 family physicians and 100 obstetricians selected randomly across Ontario, Canada. The physicians were informed about the 1-3% baseline risk for major malformations and were asked about their perceptions of the risk to the fetus associated with an abdominal radiograph and an abdominal CT scan during early pregnancy and whether they would recommend a therapeutic abortion after such exposure. RESULTS: Fifty-five percent (218/400) of the family physicians and 69% (69/100) of the obstetricians responded to our questionnaire. Forty-four percent of family physicians estimated the risk associated with an abdominal radiograph to be 5% or greater, and 61% estimated the risk associated with an abdominal CT scan to be 5% or greater. Eleven percent of obstetricians estimated the risk associated with radiographs to be 5% or greater (p < 0.001), and 34% estimated the risk associated with CT scans to be 5% or greater (p < 0.001). Among family physicians, 1% recommended an abortion if the fetus was exposed to radiation from radiography and 6% after exposure to radiation from CT. None of the obstetricians recommended an abortion after exposure to radiation from an abdominal radiograph, but 5% recommended an abortion after exposure to radiation from an abdominal CT scan in early pregnancy. CONCLUSION: Our survey shows that physicians who care for pregnant women perceive the teratogenic risk associated with an abdominal radiograph and an abdominal CT scan to be unrealistically high during early pregnancy. This misperception could lead to increased anxiety among pregnant women seeking counseling and to unnecessary terminations of otherwise wanted pregnancies. This perception of high teratogenic risk associated with radiation could also lead to a delay in needed care of pregnant women.

Abnormalities, Radiation-Induced↗