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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 397 records · Page 22Linked to original sources
PubMed1993

Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication.

OBJECTIVE: Our objective was to characterize the short-term effects of maternal medications on breast-fed infants. STUDY DESIGN: A cohort of 838 infants breast-fed by women who were taking medications was prospectively studied, and the incidence of adverse reactions in the infants during maternal therapy was recorded by telephone interviews. RESULTS: No major adverse reactions necessitating medical attention were observed in 838 breast-fed infants. However, 94 women (11.2%) reported infants' minor adverse reactions that did not require medical attention to the following maternal medications: (1) Antibiotics 19.3% (32/166); (2) analgesics or narcotics 11.2% (22/196); (3) antihistamines 9.4% (8/85); (4) sedatives, antidepressants, or antiepileptics 7.1% (3/42); and (5) others 9.9% (43/435). The most common minor adverse effects varies among drug categories, as follows: Antibiotics caused diarrhea (21/32); (2) analgesics or narcotics caused drowsiness (11/22); (3) antihistamines caused irritability (6/8); and (4) sedatives, antidepressants, or antiepileptics caused drowsiness (2/3). By identifying the 31 most frequently used drugs in our cohort, we have provided the first information on safety of breast-feeding during maternal therapy with such drugs as terfenadine, diphenhydramine, astemizole, dimenhydrinate, chlorpheniramine, 5-aminosalicylic acid, and alprazolam. CONCLUSIONS: The short-term effects, if any, of most maternal medications on breast-fed infants are mild and pose little risk to the infants.

Adolescent↗
PubMed1993

Pregnancy outcome following fetal exposure to tiaprofenic acid in the first trimester.

Fetal exposure to nonsteroidal inflammatory drugs beyond the 34th week of gestation is theoretically associated with premature closure of the fetal ductus arteriosus due to the inhibition of cyclooxygenase. Inadvertent exposure to tiaprofenic exposure in the first trimester is of concern due to the paucity of prospective human data. Experiential data are limited to retrospective reports submitted to the manufacturer and animal data, the extrapolation of which to humans is very inaccurate. We report pregnancy outcome in 12 women who voluntarily contacted the Motherisk Program in Toronto about first trimester exposure to tiaprofenic acid. These women were older than women who generally contact Motherisk (30.6 years +/- 3.9 years versus 29.9 years +/- 3 years). Three pregnancies ended in first trimester miscarriages and one woman elected to terminate her pregnancy. Of the eight live births, the mean gestational age at delivery was 39.2 weeks +/- 2 weeks, the mean birthweight was 3359 +/- 503 gm, no malformations were detected, and age of attainment of developmental milestones was normal. Although 25% of exposed cases ended in miscarriages, this may not be statistically meaningful. However, a similar trend is documented in animal studies and should be borne in mind when counseling the pregnant patient.

Adult↗
PubMed1993

Preliminary studies of the effects of extracorporeal membrane oxygenator on the disposition of common pediatric drugs.

There is an increased use of extracorporeal membrane oxygenation (ECMO) in the last 15 years for critically ill neonates. While receiving ECMO therapy, the critically ill infant needs various medications. We performed an in vitro study to evaluate the potential effect of the membrane oxygenator on drug extraction. Two closed ECMO circuits were set up at rates of 320 ml/min. One circuit was new and the other was used clinically for 5 days. Morphine at 8 ng/ml, gentamicin 10 micrograms/ml, vancomycin 40 micrograms/ml, phenobarbital 20 micrograms/ml, and phenytoin 20 micrograms/ml were injected into the circuit at 1-h intervals. Blood samples were drawn from the circuit at 10, 30, 60, and 240 minutes after injection. In the new circuit, drugs were eliminated as follows: vancomycin 36%, gentamicin 10%, phenobarbital 17%, phenytoin 43%, morphine 36%. In the used system, levels fell to a much smaller extent: vancomycin 11%, phenobarbital 6%, gentamicin 0%, phenytoin 0%, and morphine 16%. In a child receiving 20 micrograms/kg/h infusion of morphine, steady-state concentrations of 68.2 ng/ml fell to 11.6 ng/ml after changing the membrane. Our data indicate that the ECMO is associated with lowering of the concentrations of commonly used medications and that this process may depend partially on how new the membrane is. Before these changes may lead to new dosing guidelines for small children receiving ECMO, more experiments with new and used systems are warranted, as well as with different types of ECMO.

Anti-Bacterial Agents↗
PubMed1993

Maturity of children to consent to medical research: the babysitter test.

The age of maturity of children to consent for medical research is under debate, as different authorities regard the capacity of young teenagers as either satisfactory or not to grant consent without parental participation in the process. The present paper contrasts the generally accepted guideline for ethics in paediatric research in Canada with what the same children are allowed and expected to be able to do as babysitters. This comparison reveals deep incongruences in the way the maturity of the same children is appreciated for two different tasks.

Adolescent↗
PubMed1993

Energy-dependent transport of digoxin across renal tubular cell monolayers (LLC-PK1).

Digoxin secretory transport across renal tubular cell monolayers (LLC-PK1) grown on permeable filters was characterized. Metabolic inhibitors reduced total and specific basolateral to apical (B-A) flux of digoxin and conversely increased the apical to basolateral (A-B) flux. The specific transport of digoxin from the basolateral to the apical compartment was saturable, with a maximum velocity of transport of 184.5 +/- 38.0 pmol.cm-2.h-1 and a Michaelis-Menten constant (Km) of 14.1 +/- 1.6 microM. In addition, B-A flux of digoxin resulted in accumulation of digoxin in the apical compartment against the concentration gradient. P-Glycoprotein inhibitors such as quinidine, verapamil, vincristine, and cyclosporine increased the net A-B flux and inhibited the total B-A flux without affecting the nonspecific flux significantly. Tetraethylammonium, a prototype substrate for an organic cation transport system, had no such effect. Our results suggest that digoxin undergoes transepithelial secretion by an energy-dependent, carrier-mediated process in renal tubules, a process that seems to be distinct from the tetraethylammonium transport system.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Prostaglandin-induced antral hyperplasia in neonates: clinical experience and dose-response characteristics.

Antral hyperplasia (AH) induced by prostaglandins (PG) has been described by us recently in 5 infants with cyanotic heart disease receiving the drug. The purpose of the present study was to analyze 14 infants diagnosed as having AH either sonographically or pathologically in an attempt to characterize the dose-response characteristics of this adverse drug reaction, its clinical course and its optimal management. Infants with AH exhibiting large gastric aspirates have received a significantly lower cumulative dose (1,633 +/- 1,266 micrograms/kg) than those presented also with a palpable mass (3,458 +/- 1,703 micrograms/kg), (p < 0.01). While in general there is a dose-related clinical toxicity, variability in the location of the hyperplasia can explain cases of no apparent obstruction despite large cumulative doses of PG. In asymptomatic cases the antral hyperplasia, although visualized, it did not result in gastric outlet obstruction. In all cases followed by us to date, discontinuation of the PG has resulted in resolution of the clinical and sonographic findings. Nasojejunal tube was successfully attempted in several cases, preventing surgery in these very-high-risk infants.

Dose-Response Relationship, Drug↗
PubMed1993

Comparison of acceptance of clinical versus basic studies on drugs and therapeutics in infants and children.

Many clinicians and clinician-scientists have serious concerns that clinical studies (i.e. studies with patients) are less favorably accepted than basic ('bench') projects by funding agencies and by promotion committees of university departments. However, this commonly held view has not been previously verified. To test whether bias exists against clinical studies, we compared the acceptance rate of clinical vs. basic studies dealing with drugs and therapeutics in children, which were submitted to a large scientific meeting. Of 197 abstracts reporting on drug/therapeutic studies, submitted to the Society for Pediatric Research in 1993, there were 133 clinical and 64 basic studies. Fifty-nine (44.3%) of the clinical studies were accepted, significantly less than the basic projects (n = 47 or 73.4%, p < 0.0001). A basic paper was 66% more likely to be accepted (95% CI 50.7-82.6%). This trend was consistent for different groups of drugs/therapeutics, including analgesics, surfactants, corticosteroids, vaccines, hormones, and antiasthmatics. To examine whether the lower rate of acceptance of clinical papers is the result of lower scientific standard, all papers were scored for their quality by raters who were blinded to their acceptance or rejection status. In general, rejected clinical papers scored significantly higher than rejected basic papers (16 +/- 1.8 vs. 14.8 +/- 1.0, p < 0.05). Our study supports the commonly held but previously unproven view that there is a bias against clinical research, in the context of patient-based studies, when compared to basic (bench) research.

Congresses as Topic↗
PubMed1993

Maternal noncompliance with antibiotics during breastfeeding.

OBJECTIVE: To determine the incidence of antibiotic prescription failure in breastfeeding women, and to characterize breastfeeding patterns during antibiotic therapy. DESIGN: Prospective cohort study by telephone follow-up of 203 breastfeeding women who were prescribed antibiotics as monotherapy. SETTING: A teratogen/drug information service (the Motherisk Program) in a tertiary care, pediatric hospital in Toronto, Canada. MAIN OUTCOME MEASURES: Number of breastfeeding women who did not initiate the antimicrobial therapy, and breastfeeding patterns during therapy in women who started it. RESULTS: Of 203 breastfeeding women who consulted the Motherisk Program for information about the safety of antimicrobials during breastfeeding, 125 (62 percent) were followed within 32 weeks (median 11). Nineteen of the 125 (15 percent) did not initiate the antimicrobial therapy. Of the remaining 106 women, 7 (7 percent) stopped breastfeeding during therapy. Despite reassuring advice, 1 in 5 women either did not initiate therapy or did not continue breastfeeding. CONCLUSIONS: Physicians should be aware of the substantial rate of noncompliance with drug regimens among nursing women and the potential negative impact of drug therapy on breastfeeding.

Anti-Bacterial Agents↗
PubMed1993

Principles of drug prescribing in infants and children. A practical guide.

Paediatric prescribing is much more complicated than prescribing for adults. The specific and general aspects of paediatric patients, the limitations of commercially available dosage formulations, the vagaries of administering medicines, the general inadequacy of clinical pharmacology training, and the dearth of information about drug use in children all add to the difficulties facing the practitioner who treats infants and children. For these reasons practitioners should prescribe judiciously, select carefully the safest dosage regimen available, and educate their patients, caregivers and staff about their choices and expected positive and negative effects. Practitioners should also have available and use written, electronic, as well as human sources of expert advice. They should write all prescriptions legibly and carefully, document their therapeutic decisions and plans, and carefully monitor their patients' responses to therapy. Careful attention to the principles of clinical pharmacology can do much to improve the efficacy of paediatric prescribing and decrease its costs and risks.

Child, Preschool↗
PubMed1993

Are current pediatric dose recommendations for intravenous theophylline appropriate?

Theophylline, a first-line antiasthma drug, is often associated with severe toxicity even when taken in the recommended schedule. Theophylline toxicity has been associated with upper respiratory tract infections (URTI) due to reduced total-body clearance of theophylline. Some researchers believe this inhibition stems from a direct effect of viruses, but others postulate it is a result of the fever. We examined whether current theophylline dose recommendations are appropriate for children with acute asthma with a concurrent URTI. We also wished to elucidate whether the viral infection or the fever inhibits theophylline clearance. A total of 2254 medical records of asthmatic children admitted to The Hospital for Sick Children in Toronto were reviewed between 1987 and 1990. Clearance rate was calculated as the ratio between the infused dose rate and measured steady-state concentrations. Subsequently, these clearance rates were used to calculate steady-state concentrations that would be achieved by the recommended dose rates of theophylline. Reduced theophylline clearance was associated with the presence of URTI (p = 0.029) but not fever. Age correlated significantly with theophylline clearance (p = 0.027). If these children were to receive the recommended intravenous dose rate of theophylline, two-thirds of them would achieve steady-state serum concentrations above 15 mg/L, and one-third would achieve concentrations above 20 mg/L. Reevaluation of the present recommended theophylline dose rate is needed, as the majority of children requiring intravenous theophylline have a concurrent URTI with compromised total-body clearance. A correction factor of 60% is recommended to adjust the dose rate during an URTI. If utilized by prescribing physicians, it may reduce theophylline toxicity during an URTI episode.

Adolescent↗
PubMed1993

Changing trends in the treatment of asthma in a tertiary Canadian pediatric hospital.

During the last few years there has been a major change in the perception of childhood asthma management, with more focus on the anti-inflammatory aspects of therapy, the use of inhaled ipratroprium bromide, and decreased home usage of theophylline. Our clinical impression that the management of asthma at our institution has altered in response to these trends prompted us to review our experience with childhood asthma. A random sample of approximately 70 cases was reviewed from admissions to The Hospital for Sick Children during the first 6 months of 1987 and 1990. There was a major reduction in theophylline usage in 1990 accompanied by increased use of ipratroprium and oral corticosteroids. Significantly fewer cases of potentially toxic theophylline serum levels were observed in 1990, suggesting increased awareness of the this drug's narrow therapeutic margin of safety. In 1990, patients tended to be pyrexial and were treated with antibiotics more often. They were also younger, which may explain the higher pulse and respiratory rates observed. Despite these trends toward younger, sicker patients being admitted to the hospital, the length of stay did not increase, and similar numbers needed intensive care. This suggests that the shift in therapeutic modality did not affect hospitalized asthmatic children adversely.

Asthma↗
PubMed1993

Medications which can kill a toddler with one tablet or teaspoonful.

To identify medicinal preparations which can be fatal to a toddler upon ingestion of one standard dose unit, four major texts in medical toxicology were reviewed for reported cases of fatal poisoning in small children as well as for fatal doses in adults when no fatalities were reported in children. Using the Physicians Desk Reference, the largest dose unit commercially available for various drugs was identified. Subsequently, the number of dose units that have to be ingested by a toddler to cause fatality was calculated. To compare these data to the clinical reality, the annual reports by the American Association of Poison Control Centers National Collection System were reviewed between 1983-1989. Very few drugs are fatal for a 10 kg toddler upon ingestion of one commercially available dose unit. These include camphor, chloroquine, tricyclics, phenothiazines, quinine, methyl salicylate and theophylline. This short list of drugs was responsible for almost half (42%) of fatal cases following acute ingestion in young children (< 2 yrs) in the US between 1983-1989. Labelling of these drugs in a unique way may help decrease the number of serious and potentially fatal toxicities in small children.

Administration, Oral↗
PubMed1993

Safety of vancomycin with or without gentamicin in neonates.

Short- and long-term side effects of vancomycin, or the combination of vancomycin and gentamicin, were retrospectively evaluated for 65 treatment courses in 47 premature infants who were exposed to high vancomycin serum concentrations. Thirty-five treatment courses involved treatment with the combination; 30 courses involved treatment with vancomycin alone. No immediate side effects were noted. Nephrotoxicity, defined as an increase in serum creatinine 0.5 mg/dl or more above baseline, was found in only 1 patient receiving vancomycin as the only antibiotic; that patient had pre-existing renal dysfunction. Three treatment courses involving the vancomycin-gentamicin combination resulted in nephrotoxicity; renal function returned to normal by 14 days after treatment. Thrombocytopenia was noted in 5 patients, but none exhibited clinical bleeding. Low platelet counts persisted throughout treatment, but by two weeks after treatment, this was resolved. In conclusion, the use of vancomycin or the combination of vancomycin and gentamicin in seriously ill premature infants is usually safe. The adverse effects noted were reversible, and monitoring creatinine and platelet counts during treatment is recommended.

Drug Monitoring↗