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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 451 records · Page 25Linked to original sources
PubMed1992

Cocaine in pregnancy: analysis of fetal risk.

During the last decades there has been a substantial increase in the recreational use of cocaine in young adults and parallelly there has been an increase of its use by pregnant women. We analyzed all published papers on cocaine use in pregnancy and found that for most endpoints studied (eg, prematurity, head circumference) there were many studies showing effects and many showing no effects. Upon meta-analysis, most of these effects could not be shown significant when compared to control groups. In a prospective study in Toronto, babies exposed to cocaine during the first trimester only had Bayley scores at 18-mo of life that were identical to unexposed babies or to those exposed to canabinoids. Motherisk presently counsels women who discontinue cocaine use in the first trimester of pregnancy that there is no increased developmental risk for the baby.

Cocaine↗
PubMed1991

Voltage-sensing residues in the S4 region of a mammalian K+ channel.

The ability of ion-channel proteins to respond to a change of the transmembrane voltage is one of the basic mechanisms underlying electrical excitability of nerve and muscle membranes. The voltage sensor has been postulated to be the fourth putative transmembrane segment (S4) of voltage-activated Na+, Ca2+ and K+ channels. Mutations of positively charged residues within S4 alter gating of Na and Shaker-type K+ channels, but quantitative correlations between the charge or a residue in S4 and the gating valence of the channel have not yet been established. Here, with improved resolution of the voltage dependence of steady-state activation, we present estimates of the equivalent gating valence with sufficient precision to allow quantitative examination of the contribution of individual charged residues to the gating valence of a mammalian non-inactivating K+ channel. We conclude that at least part of the gating charge associated with channel activation is indeed contributed by charged residues within the S4 segment.

Animals↗
PubMed1991

Bias against negative studies in newspaper reports of medical research.

OBJECTIVE: --To assess if the reporting of controversial medical journal articles by newspapers reflects the existence of a bias against negative studies (those showing no effect), we compared the rates of newspaper reporting of two studies, one negative and one positive, published back-to-back in the March 20, 1991, issue of JAMA. Both studies analyzed an area of public health concern, radiation as a risk for cancer. DESIGN: --Seven computerized on-line databases were screened for daily newspapers published in North America during the week following JAMA's publication of the two studies. These databases had full-text access to 168 daily newspapers. Newspapers identified with reports of the two studies were analyzed for length and quality of the reports. RESULTS: --Seventeen newspapers, publishing 19 reports on the two studies, were identified. Nine reports were dedicated solely to the positive study and 10 reports covered both studies. None of the reports were dedicated to the negative study only. In reports covering both studies, the mean length of the positive reports was significantly longer than the mean length of the negative reports (354 +/- 181 words vs 192 +/- 178 words; P = .04). The mean quality score of the positive reports was significantly higher than that of the negative reports (10.1 +/- 3.4 vs 5.9 +/- 4.9; P = .02). CONCLUSIONS: --The number, length, and quality of newspaper reports on the positive study were greater than news reports on the negative study, which suggests a bias against news reports of studies showing no effects or no adverse effects.

American Medical Association↗
PubMed1991

Pretranslational mechanisms determine the type of potassium channels expressed in the rat skeletal and cardiac muscles.

We have cloned a cDNA (RMK2) coding for a Shaker type delayed rectifier K+ channel from a rat skeletal muscle cDNA library. The clone encodes a putative protein of 602 amino acids, identical with a rat brain K+ channel Kv1 (Swanson, R., Marshall, R., Smith, J. S., Williams, J. B., Boyle, M. B., Folander, K., Luneau, C. J., Antanavage, J., Oliva, C., Burhow, S. A., Bennet, C., Stein, R. B., and Kaczmarek, L. K. (1990) Neuron 4, 929-939). Northern blot analysis showed that RMK2 is expressed in skeletal and cardiac muscle. RNase protection analysis showed that the 3'-noncoding regions of the brain, cardiac, and skeletal muscle RMK2 transcripts are identical. Cloning of the gene confirmed that the protein is encoded by a single exon (Swanson et al. (1990) Neuron 4, 929-939). We expressed RMK2 in Xenopus oocytes and showed that it encodes noninactivating delayed rectifier K+ channels, resistant to block by external tetraethylammonium, with a small unitary conductance of 8.0 picosiemens. Coinjection of RMK2 and RCK1 (RMK1) (Baumann, A., Grupe, A., Ackermann, A., and Pongs, O. (1988) EMBO J. 7, 2457-2463; Koren, G., Liman, E. R., Logothetis, D. E., Nadal-Ginard, B., and Hess, P. (1990) Neuron 4, 39-51) into Xenopus oocytes resulted in the expression of currents that have tetraethylammonium inhibition curves that differ from the linear combination of inhibition curves of the two types expressed individually. Thus, RMK2 and RCK1 (RMK1) can form heteromultimers. RNA blot hybridization analysis revealed that the RMK2 transcript is developmentally regulated in a different manner in the rat skeletal muscle, ventricle, and atrium.

Aging↗
PubMed1991

Characteristics of pregnant women exposed to cocaine in Toronto between 1985 and 1990.

OBJECTIVE: To determine the characteristics of pregnant women exposed to cocaine. DESIGN: Case-control study. SETTING: Women attending the Motherisk Program, Hospital for Sick Children, Toronto, from September 1985 to March 1990. PATIENTS: All women who had admitted using cocaine before or during pregnancy. Of the two control groups the first comprised women who had admitted using cannabinoids but not cocaine before or during pregnancy and the second those who attended the clinic just before the cocaine case but who had not used illicit drugs. OUTCOME MEASURES: Age, marital status, ethnic background, number of pregnancies, children and elective or spontaneous abortions, socioeconomic status of woman and male partner, alcohol use, cigarette use, frequency of cocaine use and total amount taken. MAIN RESULTS: Of the 1625 women 91 (5.6%) admitted to using cocaine: 86 during the current pregnancy, 3 before the current pregnancy, 1 before planning a pregnancy and 1 during a previous pregnancy. None of the cocaine users were considered to be addicts; only 20% had used the drug more than 10 times. A total of 74 women used cannabinoids only. The mean age of the cocaine users was 27.1 (standard deviation [SD] 5.3) years; this was significantly lower than that of the control subjects (30.5 [SD 5.2] years) (p less than 0.001). More of the cocaine users than of the women in either of the two control groups were single (60% v. 38% and 14%, p less than 0.001). The cannabinoid users had significantly higher parity and the nonusers a significantly lower incidence of elective abortions than the cocaine users. The cocaine users had a significantly lower socioeconomic status than the control subjects (p less than 0.001); similarly, the male partners of the cocaine users had a significantly lower socioeconomic status than the partners of the control subjects (p = 0.001). CONCLUSIONS: Pregnant cocaine users who seek drug counselling represent a unique risk group, with clustering of factors such as alcohol and cigarette use and low socioeconomic status that compound the risk to the fetus. New strategies should be explored to identify such women, especially addicts, in their communities and to urge them to seek counselling and treatment.

Adult↗
PubMed1991

Exposure to ionizing radiation during pregnancy: perception of teratogenic risk and outcome.

We quantified the perception of teratogenic risk in women attending the Motherisk program for counseling about diagnostic radiation in pregnancy (n = 50) and compared it with a control group of women exposed to nonteratogenic drugs and chemicals (n = 48). Before receiving known information about the specific exposure, women exposed to radiation assigned themselves a significantly higher teratogenic risk compared with the control group (25.5 +/- 4.3% versus 15.7 +/- 3.0% for major malformations, P less than 0.01). The post-consultation perception of teratogenic risk did not differ between the two groups. Special consideration and attention should be given when counseling pregnant women exposed to low-dose ionizing radiation, as their misperception of teratogenic risk may lead them to unnecessary termination of their pregnancy.

Abnormalities, Radiation-Induced↗
PubMed1991

Relationship between gestational cocaine use and pregnancy outcome: a meta-analysis.

Despite a growing number of studies that have investigated the reproductive effects of maternal cocaine use, a homogeneous pattern of fetal effects has not been established and there is little consensus on the adverse effects of the drug. We used meta-analysis to evaluate the reproductive risks of cocaine. We reviewed the 45 scientific papers published in the English language dealing with effects of cocaine used during pregnancy on pregnancy outcome in humans, and identified 20 papers eligible for meta-analysis (cocaine use in pregnancy, pregnancy/fetal outcome studies, human studies, original work, cohort or case control studies, control group present, English language). Our analysis revealed that very few adverse reproductive effects could be shown to be significantly associated with cocaine use by polydrug users when compared to control groups of polydrug users not using cocaine [genitourinary malformations; odds ratio of 6.08 (95% CI 1.18-31.3); gestation age: Cohen's d 0.37 (CI 0.2-0.55)]. When the control groups consisted of no drug users, the polydrug users abusing cocaine had a higher risk for spontaneous abortions [odds ration 10.50 (CI 11.74-64.1)]. Similarly, comparison of users of cocaine alone or no drug users revealed a higher risk for in utero death, in addition to genitourinary tract malformations. Analysis of continuous variables (head circumference, gestational age, birth weight and length) revealed that the effect size was dependent upon the nature of the comparison. Comparison of cocaine users to no drug users consistently yielded a medium effect size (Cohen's d) between 0.50 and 0.58, while comparison of polydrug/cocaine users to polydrug/no cocaine users provided effect sizes small to non existent (0.06-0.37). These discrepancies suggest that a variety of adverse reproductive effects commonly quoted to be associated with maternal use of cocaine may be caused by confounding factors clustering in cocaine users.

Abortion, Spontaneous↗
PubMed1991

Diurnal variation of methotrexate disposition in children with acute leukaemia.

There is recent evidence that survival is improved when maintenance therapy for acute lymphocytic leukaemia in children is given at night. We have examined the possibility that diurnal variation in methotrexate pharmacokinetics may contribute to this improvement. In 6 children with leukaemia there was a significant fall in methotrexate plasma clearance at night (from 5.6 to 4.7 ml.kg-1.min-1). Renal clearance of methotrexate tended to fall at night and unbound renal clearance fell significantly (from 17.5 to 8.5 ml.min-1.kg-1 P less than 0.05). Creatinine clearance did not exhibit diurnal variation, whereas there was a significant fall in the non-glomerular clearance of methotrexate (from 14.8 to 6 ml.min-1.kg-1). Since methotrexate is a weak organic acid, its tubular secretion depends on urinary pH. At night urinary pH is more acidic, and this may result in more reabsorption and hence reduced renal clearance.

Acute Disease↗
PubMed1991

The three most common occupational exposures reported by pregnant women: an update.

Many uncertainties exist in regard to counseling women with occupational exposures during pregnancy. This is due to limited knowledge of the reproductive toxicologic effects of industrial agents, lack of safety standards aimed at protecting the fetus, and limitations in assessing the extent of exposure. The approach to this subject taken by the Motherisk Program and a review of the three most common occupational exposures are presented. Epidemiologic studies and measurements of radiation do not suggest a reproductive hazard for video display terminals. Exposure to organic solvents is hard to quantitate, and information is sparse and sometimes contradictory, and therapeutic decisions are difficult to reach. To date there is no convincing evidence that working with organic solvents within safety regulations would harm a fetus, in contradistinction to detrimental fetal effects of solvent abuse. The reproductive risks of lead are well documented, fetal exposure can be assessed, and effective treatment exists, but its effects on the pregnancy have not been fully established. However, new evidence suggests that maternal levels that are much lower than the accepted adult limits may be damaging to the fetus.

Computer Terminals↗
PubMed1991

The bentiromide test using plasma p-aminobenzoic acid for diagnosing pancreatic insufficiency in young children. The effect of two different doses and a liquid meal.

The bentiromide test was evaluated using plasma p-aminobenzoic acid as an indirect test of pancreatic insufficiency in young children between 2 months and 4 years of age. To determine the optimal test method, the following were examined: (a) the best dose of bentiromide (15 mg/kg or 30 mg/kg); (b) the optimal sampling time for plasma p-aminobenzoic acid; and (c) the effect of coadministration of a liquid meal. Sixty-nine children 91.6 +/- 1.0 years) were studied, including 34 controls with normal fat absorption and 35 patients (34 with cystic fibrosis) with fat maldigestion due to pancreatic insufficiency. Control and pancreatic insufficient subjects were studied in three age-matched groups: (a) low-dose bentiromide (15 mg/kg) with clear fluids; (b) high-dose bentiromide (30 mg/kg) with clear fluids; and (c) high-dose bentiromide with a liquid meal. Plasma p-aminobenzoic acid was determined at 0, 30, 60, and 90 minutes then hourly for 6 hours. The dose effect of bentiromide with clear liquids was evaluated. High-dose bentiromide best discriminated control and pancreatic insufficient subjects, due to a higher peak plasma p-aminobenzoic acid level in controls, but poor sensitivity and specificity remained. High-dose bentiromide with a liquid meal produced a delayed increase in plasma p-aminobenzoic acid in the control subjects probably caused by retarded gastric emptying. However, in the pancreatic insufficient subjects, use of a liquid meal resulted in significantly lower plasma p-aminobenzoic acid levels at all time points; plasma p-aminobenzoic acid at 2 and 3 hours completely discriminated between control and pancreatic insufficient patients. Evaluation of the data by area under the time-concentration curve failed to improve test results. In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended.

4-Aminobenzoic Acid↗
PubMed1991

A multicenter, prospective study of fetal outcome following accidental carbon monoxide poisoning in pregnancy.

We report the results of the first prospective, multicenter study of acute carbon monoxide (CO) poisoning in pregnancy. We collected and followed cases of CO poisoning occurring during pregnancy between December 1985 and March 1989. The sources of CO were malfunctioning furnaces (n = 16), hot water heaters (n = 7), car fumes (n = 6), and methylene chloride inhalation (n = 3). Pregnancy outcome was adversely affected in 3 of 5 pregnancies with severe toxicity; two stillbirths, and one cerebral palsy with tomographic findings consistent with ischemic damage. All adverse outcome occurred in cases treated with high flow oxygen, whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy. All 31 babies exposed in utero to mild or moderate CO poisoning exhibited normal physical and neurobehavioral development. Severe maternal CO toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity (P less than 0.001). It is concluded that while severe CO poisoning poses serious short- and long-term fetal risk, mild accidental exposure is likely to result in normal fetal outcome. Because fetal accumulation of CO is higher and its elimination slower than in the maternal circulation, hyperbaric oxygen may decrease fetal hypoxia and improve outcome.

Abnormalities, Drug-Induced↗