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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 19 recordsLinked to original sources
PubMed1995

GH3 cell-specific expression of Kv1.5 gene. Regulation by a silencer containing a dinucleotide repetitive element.

A silencer element (Kv1.5 repressor element; KRE) was characterized by deletion analyses in the promoter of Kv1.5, a voltage-gated potassium channel. The silencer element selectively decreases expression of Kv1.5- and thymidine kinase-chloramphenicol acetyl-transferase reporter gene constructs in cell lines that do not express Kv1.5 polypeptide. It contains a dinucleotide repetitive element (poly(GT)19(GA)1(CA)15(GA)16), and self-associates spontaneously in vitro to form complexes with slow electrophoretic mobility. Deletion of the repetitive element abolished self-association in vitro and the silencing activity in transient transfection experiments in vivo. Electromobility gel shift assays of KRE with GH3 cells nuclear extracts detected the formation of a unique DNA-protein complex, which was not detectable in Chinese hamster ovary and COS-7 cells. This complex does not react with an antibody against nonhistone high mobility group 1 protein, which binds KRE in gel retardation assays. These observations establish that a dinucleotide tandem repeat sequence, capable of self-association, forms part of a cell-specific silencer element in a mammalian gene.

Animals↗
PubMed1995

Camphorated oil: still endangering the lives of Canadian children.

Camphor is a volatile, aromatic compound familiar to many people as a principal ingredient in topical home remedies for colds. It is highly toxic when ingested. Although camphorated oil in concentrations of 11% or greater is not longer sold in the United States, preparations containing concentrations of up to 20% are still sold over the counter in Canada. The authors describe two children who suffered severe poisoning after accidental ingestion of a small amount of camphorated oil. Both children exhibited generalized tonic-clonic seizures with subsequent respiratory depression. Treatment was symptomatic, consisting of seizure control and respiratory assistance. The authors argue that because camphorated oil is of questionable benefit and poses a danger to the public it should be removed from the market.

Administration, Oral↗
PubMed1995

Iron-chelation therapy with oral deferiprone in patients with thalassemia major.

BACKGROUND: To determine whether the orally active iron chelator deferiprone (1,2-dimethyl-3-hydroxy-pyridin-4-one) is efficacious in the treatment of iron overload in patients with thalassemia major, we conducted a prospective trial of deferiprone in 21 patients unable or unwilling to use standard chelation therapy with parenteral deferoxamine. METHODS: Hepatic iron stores were determined yearly by chemical analysis of liver-biopsy specimens or magnetic-susceptibility measurements. Detailed clinical and laboratory studies were used to monitor safety and compliance. RESULTS: The patients received deferiprone therapy for a mean (+/-SE) of 3.1 +/- 0.3 years. Ten patients in whom previous chelation therapy with deferoxamine had been ineffective had initial hepatic iron concentrations of at least 80 mumol per gram of liver, wet weight -- values associated with complications of iron overload. Hepatic iron concentrations decreased in all 10 patients, from 125.3 +/- 11.5 to 60.3 +/- 9.6 mumol per gram (P < 0.005), with values that were less than 80 mumol per gram in 8 of the 10 patients (P < 0.005). In all 11 patients in whom deferoxamine therapy had previously been effective, deferiprone maintained hepatic iron concentrations below 80 mumol of iron per gram. CONCLUSIONS: Oral deferiprone induces sustained decreases in body iron to concentrations compatible with the avoidance of complications from iron overload. The risk of agranulocytosis associated with deferiprone may restrict its administration to patients who are unable or unwilling to use deferoxamine.

Administration, Oral↗
PubMed1995

Effect of neonatal circumcision on pain responses during vaccination in boys.

Using data from one of our randomised trials, we investigated post-hoc whether male neonatal circumcision is associated with a greater pain response to routine vaccination at 4 or 6 months. Pain response during routine vaccination with diphtheria-pertussis-tetanus (DPT) alone or DPT followed by Haemophilus influenzae type b conjugate (HIB) was scored blind. 42 boys received DPT and 18 also received HIB. After DPT, median visual analogue scores by an observer were higher in the circumcised group (40 vs 26 mm, p = 0.03). After HIB, circumcised infants had higher behavioural pain scores (8 vs 6, p = 0.01) and cried longer (53 vs 19 s, p = 0.02). Thus neonatal circumcision may affect pain response several months after the event.

Circumcision, Male↗
PubMed1995

Measurement of drugs in neonatal hair; a window to fetal exposure.

Because the hair neonates are born with grows during the last 3 months of pregnancy, the presence of drugs (e.g. cocaine) or environmental toxins (e.g. nicotine) reflects fetal exposure to such compounds. In the case of cocaine, hair measurement are several fold more sensitive than maternal history or urine measurements. Measurements of cotinine in neonatal hair are capable of distinguishing between fetal exposure to passive versus active smoking. Because most cocaine users also smoke cigarettes, neonatal measurements of both cocaine and cotinine will allow cumulative quantification of fetal risk.

Cocaine↗
PubMed1995

Use of a eutectic mixture of local anesthetics for prolonged subcutaneous drug administration.

The efficacy of a eutectic mixture of local anesthetics (EMLA) in alleviating the pain associated with subcutaneous needle insertion for infusion of the iron-chelating agent, deferoxamine, was examined in 12 patients with homozygous beta-thalassemia. As reported by the patient using a 100-mm visual analogue scale, the pain of insertion was rated as significantly less after application of EMLA (mean +/- SD, 1.5 +/- 2.2 mm) than the pain associated with needle insertion without EMLA (34.8 +/- 33.5 mm, P = .005). Subsequently, in a double-blind randomized trial of 10 beta-thalassemia patients, EMLA was significantly better (5.7 +/- 8.2 mm) than placebo (27.0 +/- 22.8 mm, P = .01) in reducing the pain of needle insertion for deferoxamine infusion. No adverse effects were reported with the use of EMLA cream. These results suggest that EMLA may be effective in reducing the pain associated with needle insertion for subcutaneous deferoxamine infusion in beta-thalassemia patients, which may lead to improved compliance with this irritating, prolonged therapy. The safety of EMLA use in these patients, and others receiving regular parenteral therapy, should now be examined.

Anesthetics, Local↗
PubMed1995

Radiologic features of gastric outlet obstruction in infants after long-term prostaglandin administration.

Long-term prostaglandin (PG) therapy has recently been associated with gastric mucosal hyperplasia. We reviewed the clinical and radiologic (especially sonographic) records of eight patients with complex congenital heart disease who were on PG therapy. Feeding problems, vomiting, and abdominal distension were present in six patients. Barium meal revealed antral narrowing in three patients, suggestive of hypertrophic pyloric stenosis in two. Sonography showed a variable degree of increased gastric mucosal lobulation often accompanied by a marked polypoid or lobular appearance. Cortical hyperostosis related to PG therapy was seen in three patients. PG-associated gastric mucosal hyperplasia can cause feeding problems and pronounced gastric lobulation.

Alprostadil↗
PubMed1995

Initiation and duration of breast-feeding in women receiving antiepileptics.

OBJECTIVE: Our purpose was to characterize breast-feeding initiation and the duration of breast-feeding in women receiving antiepileptics. STUDY DESIGN: A cohort study was performed on 34 pregnant epileptic women receiving antiepileptics and 34 pregnant age-matched controls. RESULTS: Fifty percent of the group receiving antiepileptics chose breast-feeding as the initial feeding method, which was significantly less than the controls (85%, p = 0.004). The decision to choose initial feeding methods was closely associated with advice from physicians and other sources. The 17 women in the antiepileptics group who chose breast-feeding initially terminated breast-feeding significantly earlier than did the control group (4.7 +/- 2.6 vs 9.3 +/- 5.7 months post partum, p < 0.005). CONCLUSIONS: Mothers receiving antiepileptics tend to choose formula feeding. Even when they choose breast-feeding initially, its duration is shorter than usual. Consensus and guidelines on this matter among experts remain to be reflected on and effectively implemented in current medical practice.

Adult↗
PubMed1995

Safety of metronidazole in pregnancy: a meta-analysis.

OBJECTIVE: Our purpose was to determine from published experience in humans whether metronidazole exposure during the first trimester of pregnancy is associated with an increased teratogenic risk. STUDY DESIGN: All published articles reporting on metronidazole use during pregnancy were screened by two independent reviewers to select those including pregnant patients exposed during the first trimester and comparing the outcomes of their pregnancies with that of patients either not exposed to metronidazole or exposed only during the third trimester. The outcome under consideration was the occurrence of birth defects in live-born infants. The overall odds ratios of first-trimester exposure versus no first-trimester exposure was calculated by combining the selected studies in a meta-analysis according to the procedure of Mantel and Haenszel. RESULTS: From 32 identified studies, 7 met the inclusion criteria for meta-analysis. Six were prospective and included 253 women exposed to the drug in the first trimester of pregnancy; one was retrospective and reported on 1083 exposed women. The overall weighted odds ratio of exposure versus no exposure during the first trimester calculated by meta-analysis of the 7 studies was 0.93 (95% confidence interval 0.73 to 1.18). The odds ratio calculated from the 6 prospective studies was 1.02 (95% confidence interval 0.48 to 2.18). CONCLUSION: Metronidazole does not appear to be associated with an increased teratogenic risk.

Abnormalities, Drug-Induced↗
PubMed1995

Disposition of maternal ketoconazole in breast milk.

Infant exposure to ketoconazole in human milk was calculated to be 0.4% on average (maximum 1.4%) of those expected from therapeutic doses given directly to infants. Potential risk of adverse reactions from this low exposure level seem to be outweighed by the benefits of breast-feeding.

Adult↗
PubMed1995

Pregnancy outcome after gestational exposure to amiodarone in Canada.

OBJECTIVE: Our purpose was to quantitate the risk of perinatal thyroid dysfunction and other amiodarone-induced adverse effects among infants exposed in utero to amiodarone. STUDY DESIGN: A historic cohort study of gestational exposure to amiodarone was conducted by contacting Canadian cardiac electrophysiologists. RESULTS: Twelve cases were identified. Of six with first-trimester exposure, one child had congenital nystagmus with synchronous head titubation. There was one case each of transient neonatal hypothyroidism (9%) and hyperthyroidism (9%). A fourth child, exposed to amiodarone from 20 weeks' gestation, had developmental delay, hypotonia, hypertelorism, and micrognathia. Four small-for-gestational-age infants were also exposed to beta-blockers, which in addition to maternal cardiac disease, have been recognized to cause growth restriction. beta-Blockers may also have contributed to bradycardia in one of the three fetuses in whom this was observed. CONCLUSIONS: Gestational exposure to amiodarone may be complicated by perinatal hypothyroidism or hyperthyroidism and possibly neurologic abnormalities, intrauterine growth retardation or fetal bradycardia. Concomitant beta-blocker therapy should probably be avoided. Full neonatal thyroid function tests and developmental follow-up are recommended.

Adrenergic beta-Antagonists↗
PubMed1995

Pemoline-associated fulminant liver failure: testing the evidence for causation.

BACKGROUND: Pemoline is a central nervous system stimulant used in treating children with attention deficit-hyperactivity disorder. Hepatotoxicity has been commonly reported in association with pemoline; however, only two reports of cases of fatal liver failure have been published. OBJECTIVES: We report on a 14-year-old boy who received concomitant pemoline and methylphenidate in whom fulminant liver failure occurred and for whom liver transplantation failed. Other causes of fulminant liver failure were ruled out, and the liver biopsy was suggestive of drug toxicity. We estimated the probability that these three cases represent an increased risk of fulminant liver failure associated with pemoline. RESULTS: Based on the three known cases of fatal liver failure associated with pemoline use, we calculated that a child receiving pemoline has a relative risk of development of fulminant liver failure of 45.3 (95% confidence interval, 4.1 to 510). This highly significant association (p < 0.001) suggests causation. CONCLUSIONS: Because pemoline has been widely used in recent years, further studies are needed to better quantify this risk in children with attention deficit-hyperactivity disorder.

Adolescent↗
PubMed1995

Fetal genital effects of first-trimester sex hormone exposure: a meta-analysis.

OBJECTIVE: To determine if first-trimester exposure to sex hormones, and oral contraceptives (OCs) specifically, is associated with an increased risk of external fetal genital malformations. DATA SOURCES: MEDLINE and Science Citation Index data bases were searched for the years 1966-1992 for relevant English-language articles on first-trimester sex-hormone exposure and fetal genital changes. METHODS OF STUDY SELECTION: One hundred eighty-six articles were identified initially. Inclusion criteria were cohort or case-control studies, first-trimester sex-hormone exposure, and live infants or full-term stillborn infants with external genital malformations. Exclusion criteria were diethylstilbestrol exposure, spontaneous abortions, and teratogen exposure. DATA EXTRACTION AND SYNTHESIS: The Methods section of each study was reviewed independently by two authors and two outside reviewers, using the above criteria. Fourteen studies, seven cohort and seven case-control, involving 65,567 women, met the criteria for meta-analysis. Extracted data were entered into 2 x 2 tables. The overall summary odds ratio (OR) was 1.09 (95% confidence interval [CI] 0.90-1.32); subanalysis of OC exposure identified an OR of 0.98 (95% CI 0.24-3.94). CONCLUSION: There was no association between first-trimester exposure to sex hormones generally (or to OCs specifically) and external genital malformations. Thus, women exposed to sex hormones after conception may be assured there is no increased risk of fetal sexual malformation.

Case-Control Studies↗
PubMed1995

A revised measure of acute pain in infants.

Acute pain in infants is not assessed or managed optimally. The objectives of the study were (a) to adapt a behavioral pain assessment measure (Children's Hospital of Eastern Ontario Pain Scale, CHEOPS) for use with infants, and (b) to establish the reliability and validity of the measure in a study of infants undergoing immunization. Ninety-six healthy 4- to 6-month-old infants were randomized to receive either the local anesthetic cream Eutectic Mixture of Local Anesthetics (EMLA) (N = 49), or a placebo (N = 47) prior to immunization. The infant's behavioral response was videotaped immediately before and following the immunization. Postprocedural pain scores were assessed from the videotape and were significantly lower in infants who received EMLA (P = 0.01). Pain scores were also significantly correlated with visual analogue scale (VAS) scores assessed during vaccination. Five independent raters also independently rated ten infants to determine interrater reliability. Agreement between raters' scores was high (intraclass correlation coefficient, 0.95). Results from this study suggest that this measure has beginning construct and concurrent validity and interrater reliability when used in a research study. Further testing of the measure in the clinical setting is required.

Acute Disease↗
PubMed1995

Evaluation of therapeutic drug monitoring of methotrexate in saliva of children with rheumatic diseases.

Pediatric patients with leukemia, other malignancies, and rheumatological disease receive methotrexate chronically. Because of the documented correlation between methotrexate levels of compliance and clinical outcome, it is conceivable to verify appropriate systemic exposure to the drug. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is ethically limited. Our study shows poor correlation between serum total/free methotrexate concentrations and saliva levels, precluding the clinical use of this test.

Adolescent↗
PubMed1995

Fetal toxicology of environmental tobacco smoke.

During the past decade, new evidence has been collected regarding the fetal risks of environmental tobacco smoke. Throughout gestation, the unborn baby is exposed to increasing concentrations of nicotine through maternal blood and gastrointestinal and skin absorption of the nicotine in the amniotic fluid. Recent research shows measurable concentrations of cotinine in the hair of infants born to passively smoking mothers. This exposure has been recently associated with effects on fetal growth.

Female↗
PubMed1995

A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension.

In a crossover design, control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension. Compliance with once daily felodipine was higher than with nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine, at 77.6 (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age) was lower for felodipine than for nifedipine: 43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though this did not reach statistical significance. These data suggest that once a day felodipine is effective in children with hypertension. This may be because of improved compliance.

Adolescent↗