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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 685 records · Page 38Linked to original sources
PubMedDate not supplied

Pregnancy outcome following gestational exposure to organic solvents: a prospective controlled study.

CONTEXT: Numerous women of childbearing age are exposed occupationally to organic solvents. Previous retrospective studies have reported conflicting results regarding teratogenic risk. OBJECTIVE: To evaluate pregnancy and fetal outcome following maternal occupational exposure to organic solvents. DESIGN: A prospective, observational, controlled study. SETTING: An antenatal counseling service in Toronto, Ontario. PATIENTS: One hundred twenty-five pregnant-women who were exposed occupationally to organic solvents and seen during the first trimester between 1987 and 1996. Each pregnant woman who was exposed to organic solvents was matched to a pregnant woman who was exposed to a nonteratogenic agent on age (+/-4 years), gravidity (+/-1), and smoking and drinking status. MAIN OUTCOME MEASURE: Occurrence of major congenital malformations. RESULTS: Significantly more major malformations occurred among fetuses of women exposed to organic solvents than controls (13 vs 1; relative risk, 13.0; 95% confidence interval, 1.8-99.5). Twelve malformations occurred among the 75 women who had symptoms temporally associated with their exposure, while none occurred among 43 asymptomatic exposed women (P<.001). (One malformation occurred in a woman for whom such information was missing.) More of these exposed women had previous miscarriage while working with organic solvents than controls (54/117 [46.2%] vs 24/125 [19.2%]; P<.001). However, exposed women who had a previous miscarriage had rates of major malformation that were similar to exposed women who had no previous miscarriage. CONCLUSIONS: Occupational exposure to organic solvents during pregnancy is associated with an increased risk of major fetal malformations. This risk appears to be increased among women who report symptoms associated with organic solvent exposure. Women's exposure to organic solvents should be minimized during pregnancy. Symptomatic exposure appears to predict higher fetal risk for malformations.

Abortion, Spontaneous↗
PubMedDate not supplied

Bioavailability of nifedipine: a comparison between two preparations.

In a random cross-over study, eight healthy volunteers received single 10 mg doses of either nifedipine capsule (Adalat, Bayer) or nifedipine tablets (Taro) after an overnight fast. The areas under the serum concentration time curves were not significantly different (AUC0----infinity 319.8 +/- 28.0 (SEM) ng ml-1 h-1 for capsules, 260.8 +/- 15.3 ng ml-1 h-1 for tablets). The peak serum levels and the time of their occurrence were 162.4 +/- 23.4 ng ml-1 at 30 min for capsules and 43.0 +/- 3.0 ng ml-1 at 1-2 h for tablets, indicating that the absorption of nifedipine from the capsule is faster than from the tablet form. Clinical symptoms of vasodilation corresponded with the nifedipine peak levels. We conclude that although the bioavailability in general of the two preparations is similar, the therapeutic equivalence may differ. Depending on the therapeutic indication each preparation may have its merits.

Adult↗
PubMedDate not supplied

The nephrotoxic potential of drugs and chemicals. Pharmacological basis and clinical relevance.

Scores of drugs in common clinical use are capable of inflicting various degrees of damage to the kidney. Similarly, a large number of widely employed chemicals may adversely affect renal tissue as part of their toxic potential. A xenobiotic may damage the kidney by more than one mechanism. For example, NSAIDs may cause decreased renal perfusion, interstitial nephritis, primary glomerulopathy and/or altered potassium homeostasis. A large number of drugs and chemicals inflict their damage on the renal tubular cell secondary to intracellular accumulation to concentrations substantially higher than in the plasma or in other tissues. These include aminoglycosides, mercury and carbon tetrachloride and cephaloridine. Drug-induced interstitial nephritis is characterised by inflammatory lesions of the renal interstitium developed after at least 7 to 10 days of therapy. The immunological nature of this reaction is suggested by the associated fever, maculopapular rash and arthralgia observed in some of the patients. Although eosinophilia, eosinophiluria, and raised blood IgE levels are characteristic, immunoglobulins are not deposited in renal tissue, and the basic mechanism has not been elucidated. Renal biopsy demonstrates oedema and interstitial inflammatory reaction, mainly with lymphocytes, monocytes, eosinophils and plasma cells. Less frequent, vasculitis of small vessels or granulomatous reaction may develop, leading to necrotising glomerulonephritis. The drugs most commonly causing acute interstitial nephritis are methicillin, ampicillin, cephalosporins, rifampicin (rifampin), sulphonamides, phenindione and allopurinol. Other penicillins, NSAIDs, phenytoin, thiazides and frusemide (furosemide) are less frequently associated with this syndrome. Drugs and chemicals may affect renal function by pharmacologically decreasing glomerular filtration rate and/or renal blood flow. These include the NSAIDs, radiological contrast media and cyclosporin. Normal renal function depends upon an intact glomerular apparatus. Many drugs and chemicals are capable of damaging the glomerulus, causing its increased permeability to large molecules such as proteins. Several drugs including d-penicillamine, thiopronine, captopril, pyrithioxine and methimazole, are believed to exert their damage through their sulfhydryl group which bind with high affinity to glomerular structures. A variety of xenobiotics or their metabolites may be deposited in the renal tubule causing obstruction of urine flow and a secondary damage to tubular epithelium. Sulphonamides, methotrexate and ethylene glycol are good examples.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglycosides↗
PubMedDate not supplied

Prenatal adverse effects of various drugs and chemicals. A review of substances of frequent concern to mothers in the community.

Using the number of calls to the Canadian Motherisk Program as an indicator of the drugs and chemicals frequently of concern to mothers during pregnancy, the risks to the fetus of exposure to these compounds have been reviewed. The drugs which were of concern, and have been proven to be teratogenic, included alcohol, alkylating and antimetabolite agents, stilboestrol, disulfiram, heparin, lithium carbonate, phenytoin, tretinoin (retinoic acid), troxidone and valproic acid. For other compounds studied, there was either no data in the literature or no clear evidence of teratogenicity. The combination of doxylamine and pyridoxine, for example, has been associated with limb reduction defects in isolated case reports: cohort and case-control studies have failed to show a higher-than-baseline risk of malformations. In some cases of exposure to compounds with no known teratogenic potential, other adverse effects to the fetus are possible, and these effects are discussed in detail. In conclusion, when advising a pregnant woman about the potential teratogenic effect of a particular drug or chemical exposure, the health professional should also discuss other factors such as age, obstetric and medical history and the history of other exposures (including alcohol and smoking). In every pregnancy there is a 1 to 5% risk of mayor malformations, and even if the exposure does not appear to increase the teratogenic risk, such a risk still exists.

Adult↗
PubMedDate not supplied

Steady state pharmacokinetics of mefloquine in long-term travellers.

Mefloquine is an antimalarial drug with a 3-week elimination half-life, which has led to concerns that toxic accumulation may occur during weekly administration for long-term malaria chemoprophylaxis. Despite the endorsement of weekly mefloquine by the World Health Organization and the United States Centers for Disease Control, mefloquine pharmacokinetics have been incompletely studied in subjects taking the drug once weekly for more than 4 weeks. Our objective was to study plasma mefloquine concentrations in travelers taking mefloquine 250 mg once weekly for 3 months. Multiple mefloquine concentrations were measured by high pressure liquid chromatography following the 1st, 2nd and 10th to 13th of 13 weekly doses of 250 mg mefloquine taken by 15 Canadian travellers (median age 23 years; 6 male, 14 white). Steady state was achieved in all subjects by or before the 10th dose. Mefloquine pharmacokinetic values were comparable to those previously reported by other investigators. In 7 subjects, 2 peaks of mefloquine and metabolite concentration followed ingestion, suggesting redistribution of mefloquine. Mefloquine concentration 14 d after the last dose was 74% of the level 7 d after the last dose. In conclusion, pharmacokinetic values determined by this study support mefloquine weekly dosing for long-term malaria chemoprophylaxis; toxic accumulation does not occur and weekly dosing is associated with significantly higher trough levels than 14 d dosing.

Adult↗
PubMedDate not supplied

Topical skin anesthesia.

Explore the source record for details and available documents.

Administration, Cutaneous↗
PubMedDate not supplied

Maternal and neonatal characteristics following exposure to cocaine in Toronto.

We prospectively ascertained gestational cocaine use by neonatal urine and hair tests in 600 mother infant pairs in 3 nurseries in Toronto. The 37 (6.25%) babies who tested positive for cocaine and their mothers were compared to the 563 nonexposed with regard to pregnancy outcome and neonatal complications. Mothers using cocaine were not different in their ages, racial distribution, and obstetric history from those nonexposed. Cocaine-using women had significantly higher risk for vaginal bleeding (16% vs 6%, P < 0.05), hepatitis B carrier state (8% vs 0.8%, P < 0.005), and perhaps more urinary tract infections (8% vs 2.5%, P = 0.08). Cocaine-using mothers were significantly more likely to smoke cigarettes (29% vs 10%, P < 0.001). Infants exposed to cocaine in utero were of lower birth weight (3162 +/- 645 [SD] g vs 3391 +/- 573, P < 0.05) and birth length (49.9 +/- 2.9 cm vs 51.1 +/- 3.1 cm, P < 0.05). Further stratification of babies exposed to cocaine by maternal cigarette smoking suggests that cigarette smoking accounted for most of this variability [birth weight of babies exposed to cocaine and cigarettes 2899 +/- 7.50 g (and 50% of them weighed less than 2500 g), vs 3423 +/- 612 (and only 8% less than 2500 g) in those exposed to cocaine only (P < 0.05)]. Babies exposed to cocaine in utero were significantly more likely to need initial medical support or resuscitation (52% vs 30%, P < 0.05). We conclude that gestational exposure to cocaine, ascertained by a sensitive biologic marker, is associated with substantial perinatal risks.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Effect of counseling on maternal reporting of adverse effects in nursing infants exposed to antibiotics through breast milk.

In a recent trial, we found that nursing women reported diarrhea in their nursing infants after maternal use of antibiotics. However, because they were told that this could occur during a medication counseling session, the observed effect could have been due to a reporting bias. The objectives of this study were to determine if counseling nursing women about side effects of antibiotic they used could (a) influence the adverse event reporting rate or (b) influence maternal nursing and medication compliance behavior. In a randomized, controlled trial, nursing women calling a teratogen information service for advice about selected antibiotics received one of two possible counseling formats (A and B). Both groups were informed that the antibiotics were safe to use. Mothers in group B were also informed about a theoretical risk of diarrhea in the infant. Mothers later reported clinical events they noted in the infants and judged whether they were due to the antibiotic. Eighty-seven percent (54/62) of group A subjects compared to 68% (52/76) of group B subjects reported clinical events in their infants during their antibiotic therapy (P = 0.017). The incidence of reported diarrhea was 26% in group A compared to 17% in group B (P = 0.3); 34% of subjects in both groups attributed clinical events to antibiotic therapy (P = 1.0). Diarrhea was attributed to antibiotic therapy in 13% of group A and 12% of group B subjects (P = 1.0). No differences were observed between groups in breastfeeding pattern and antibiotic compliance. Breastfeeding women counseled about adverse effects were not more likely to report side effects in their infants or to change nursing behavior and medication compliance.

Adverse Drug Reaction Reporting Systems↗
PubMedDate not supplied

Use of the Retinoid Pregnancy Prevention Program in Canada: patterns of contraception use in women treated with isotretinoin and etretinate.

We sought to describe demographic characteristics of and pattern of contraception use by Canadian women prescribed synthetic retinoids who voluntarily contacted the Motherisk Program in Toronto and to describe the degree of use of the Pregnancy Prevention Program (PPP) for retinoids. Prospectively gathered intake data from isotretinoin-exposed women was statistically compared to that from matched controls selected from our database. Intake data is qualitatively reported for etretinate-exposed women. We included women who voluntarily contacted the Motherisk Program from November 1, 1988, to January 30, 1991, for counseling about reproductive risks of isotretinoin or etretinate. Primary outcome parameters were maternal age, race, marital status, socioeconomic status; gravity, parity, previous miscarriages and elective abortions, maternal tobacco and ethanol exposure, contraception use, and use of PPP (educational components used, patient recollection of warnings). The 26 isotretinoin-exposed women were younger than controls (25.2 [SD 6.7] years vs 28.9 [SD 5.1] years, P = 0.03), tended to be adolescent (30.8% vs. 3.8%, P = 0.014) and sought counselling later in gestation (10.1 [SD 8] weeks vs. 6 [SD 4.2] weeks, P = 0.01). Twenty (77%) knew the drug was teratogenic, yet 10 (38.5%) used no contraception, 6 (23.1%) experienced method failure, and 2 (8%) stopped contraception during isotretinoin therapy. In conclusion, although cognizant of the teratogenicity of isotretinoin, more than one-third of the women in this study used no birth control or experienced contraception failure. In this same group, however, compliance with contraception use appeared to increase in those who saw more of the PPP.

Adult↗
PubMedDate not supplied

Tibial hemimelia and tetralogy of Fallot associated with first trimester exposure to amantadine.

Although amantadine hydrochloride has been extensively used for the prevention of influenza A2, few data exist regarding its safety in pregnancy. We report the outcome of a pregnancy during which the mother was treated with amantadine in the first trimester. The infant, born at 29 weeks gestation, has tetralogy of Fallot and tibial hemimelia. Follow-up of the four prospective cases known to date to the Motherisk Program in Toronto did not identify any abnormalities.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

The use of teratogen information services for research: assessment of reliability of data entry.

Teratogen information services (TIS) have been able to prospectively follow large cohorts of women with specific exposures during pregnancy. TIS researchers have increasingly relied on computerized databases to retrieve information, although little attention has been focused on the quality of the actual data. We examined the reliability of data entry at Motherisk, one such TIS. Data abstracted from 37 semi-standardized clinic forms were entered into the database by three counselors experienced in data entry. Inter- and intracoder reliability were assessed by intraclass correlation coefficient (ICC) for continuous variables and kappa (K) or weighted kappa (Kw) for categorical variables. An ICC, K, or Kw value of > or = 0.60 with a P < 0.05 was considered adequate. Demographics, obstetric history, smoking, and caffeine intake were all reliably entered. The number of primary exposures and alcohol were not. The former stemmed from the unreliable data entry of one coder, whereas the latter resulted from misuse of the alcohol nomogram by all coders. As a result, data entry has now been assigned to one person (who will be assessed for intrarater reliability), and our quality assurance program stresses staff retraining in all aspects of data collection.

Abnormalities, Drug-Induced↗