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Biomedical subjects

G Koren

Publications and source records attributed to G Koren.

At least 577 records · Page 32Linked to original sources
PubMed1988

Endogenous digoxin-like substance(s) associated with uneventful and high-risk pregnancies.

We assessed the existence of endogenous digoxin-like substance(s) (EDLS) in mother-neonate pairs using a routine radioimmunoassay for digoxin. None of those studied had been treated with cardiac glycosides during or before pregnancy. In uneventful pregnancies, cord EDLS levels (0.31 +/- 0.02 ng/ml mean +/- SEM) were significantly higher (p less than 0.001) than both antepartum and postpartum maternal levels (0.14 +/- 0.02 and 0.17 +/- 0.02 mg/ml, respectively). This observation was in contrast with findings in high-risk pregnancies. In general, EDLS levels in the high-risk group were significantly higher than in normal pregnancies (cord 0.94 +/- 0.38 ng/ml; antepartum 1.63 +/- 0.54 ng/ml; postpartum 0.89 +/- 0.73 ng/ml). In the high-risk group there was a remarkably wide range of maternal and cord EDLS concentrations. The present studies suggest that following pregnancies of high risk for a variety of reasons, EDLS determination may be commonly high in the perinatal period and may affect the determination of 'true' digoxin. Consequently, digoxin dosing based on monitoring drug concentration may be futile.

Blood Proteins↗
PubMed1988

A method for meta-analysis of epidemiological studies.

This article presents a stepwise approach for conducting a meta-analysis of epidemiological studies based on proposed guidelines. This systematic method is recommended for practitioners evaluating epidemiological studies in the literature to arrive at an overall quantitative estimate of the impact of a treatment. Bendectin is used as an illustrative example. Meta-analysts should establish a priori the purpose of the analysis and a complete protocol. This protocol should be adhered to, and all steps performed should be recorded in detail. To aid in developing such a protocol, we present methods the researcher can use to perform each of 22 steps in six major areas. The illustrative meta-analysis confirmed previous traditional narrative literature reviews that Bendectin is not related to teratogenic outcomes in humans. The overall summary odds ratio was 1.01 (chi 2 = 0.05, p = 0.815) with a 95 percent confidence interval of 0.66-1.55. When the studies were separated according to study type, the summary odds ratio for cohort studies was 0.95 with a 95 percent confidence interval of 0.62-1.45. For case-control studies, the summary odds ratio was 1.27 with a 95 percent confidence interval of 0.83-1.94. The corresponding chi-square values were not statistically significant at the p = 0.05 level.

Antiemetics↗
PubMed1988

Comparison of the digitalis receptor in erythrocytes from preterm infants and adults.

We compared 86rubidium by erythrocytes of preterm infants and adults as a measurement of their Na+, K+, ATPase enzyme system. In neonates, total uptake (0.92 +/- 0.13 micrograms/10(6) cells) and specific uptake (0.64 +/- 0.076 micrograms/10(6) cells) were significantly higher than in adults (0.52 +/- 0.1 and 0.29 +/- 0.06 micrograms/10(6) cells, respectively; p less than 0.025). The percentage of specific uptake from total uptake was higher in infants (73.3 +/- 2.3%) than in adults (57.9 +/- 4.6%) (p less than 0.005). No differences were found in the affinity constant of 86Rb uptake between infants (4.35 +/- 0.48 ng/ml) and adults (4.85 +/- 0.48 ng/ml). Stratification of infants according to their serum K+ concentrations revealed that levels above 5.4 mEq/liter were associated with a higher specific uptake (0.79 +/- 0.107 micrograms/10(6) cells) than in normokalemic infants (0.54 +/- 0.09 micrograms/10(6) cells) or adults (0.304 +/- 0.061 micrograms/10(6) cells) (p less than 0.05). The difference between hyperkalemic and normokalemic infants persisted after excluding those who received adult packed cells (0.88 +/- 0.1 and 0.6 +/- 0.12 micrograms/10(6) cells, respectively) (p less than 0.05). Infants with serum K+ greater than 5.8 mEq/liter received on average significantly more K+ in previous days (2.46 +/- 0.49 versus 1.13 + 0.34 mEq/kg.day; p less than 0.025). The different K+ level could not be attributed to different creatinine clearance in the two groups.

Adult↗
PubMed1988

Enhancement of digoxin clearance by mannitol diuresis: in vivo studies and their clinical implications.

Because of its narrow margin of safety, digoxin toxicity may occur even during routinely prescribed doses. Due to its very large distribution volume (10 L/kg), only less than 1% of the body load is available for removal, making hemodialysis and hemoperfusion ineffective. Until recently it was assumed that most of the body load of digoxin is eliminated by glomerular filtration. It is now evident that substantial tubular reabsorption and secretion take place. As for the other drugs which are reabsorbed by the tubule (eg Aspirin), we wished to assess whether urine flow rate affect digoxin renal clearance. We studied anesthetized, ventilated dogs. They were preloaded with 25 micrograms/kg IV digoxin the day prior to the experiment. The dogs were infused initially with saline and after a urine collection for digoxin renal clearance 200 ml 10% mannitol were infused over 30 minutes. Digoxin renal clearance was increased 2-3 folds in all cases with a small increase in inulin clearance. Based on these results, the ability of mannitol diuresis to remove significant systemic amounts of digoxin should be tested in acute toxicity in animals. This may be an adjunct modality to FAB antibodies and activated charcoal.

Animals↗
PubMed1988

Effects of quinidine on the renal tubular and biliary transport of digoxin: in vivo and in vitro studies in the dog.

Quinidine is known to inhibit the renal clearance of digoxin without affecting glomerular filtration rate. The renal interaction between these drugs was investigated by a combination of in vivo and in vitro methods. The uptake of digoxin by brush border membrane vesicles was not affected by quinidine. Similarly, digoxin did not inhibit the uptake of the cation N-methylnicotinamide by these vesicles and did not alter the binding kinetics of digoxin to the Na+, K+-adenosine triphosphatase by the antiluminal membrane vesicles. By using the in vivo multiple indicator dilution technique transtubular transport of digoxin was documented; renal-artery infusion of quinidine did not affect the recovery of digoxin in the renal vein or urine. Clearance studies documented that the decrease in the renal clearance of digoxin is paralleled by a significant fall in renal blood flow evidenced by a decrease in p-aminohippuric acid clearance. It is concluded that quinidine inhibits the renal excretion of digoxin not by competition at the tubular cell membrane level, but rather by decreasing renal blood flow. A parallel decrease in biliary clearance of digoxin is documented and may suggest a similar mechanism.

Animals↗
PubMed1987

Prediction of atrial and ventricular fibrillation complicating myocardial infarction from admission data: a prospective study.

This study set out to examine prospectively two logistic formulae based on admission clinical data to predict ventricular or atrial fibrillation complicating acute myocardial infarction. A prospective study of 87 consecutive patients with acute transmural myocardial infarction was conducted. The formula for predicting ventricular fibrillation from the diastolic blood pressure, degree of ST-segment elevation, and QTc had a sensitivity of 93%, specificity of 83%, and a predictive value for an abnormal test of 62% (13 of 14 patients who developed ventricular fibrillation were identified). The formula for predicting atrial fibrillation from the age of the patient, a history of heart failure, systolic blood pressure, and four electrocardiographic parameters had a sensitivity of 78%, specificity of 85%, and a predictive value of 67% (14 of 18 patients identified). Our study shows that patients with myocardial infarction who are liable to develop ventricular or atrial fibrillation can be identified on admission from simple clinical data.

Atrial Fibrillation↗
PubMed1987

The influence of hypothermia on the disposition of fentanyl--human and animal studies.

The effect of hypothermia on the disposition of fentanyl was evaluated in 18 children undergoing corrective cardiac surgery. They received a bolus of fentanyl followed by a continuous infusion which was stopped when cardiopulmonary bypass was established and profound hypothermia was achieved (18 degrees C-25 degrees C). Fentanyl plasma concentration remained essentially unchanged during hypothermia (6.45 ng/ml 5 min into hypothermia and 5.26 ng/ml 100-140 min later; p greater than 0.1). In subsequent experiments, the effect of hypothermia on the pharmacokinetics of fentanyl was studied in 4 piglets serving as their own controls. Both distribution volume (Vz) and total body clearance (CL) were significantly smaller during hypothermia. Our studies indicate that being a drug with a large distribution volume and a high hepatic extraction ratio, both CL and Vz are significantly reduced by hypothermia-induced hypoperfusion. In addition, TBC is influenced by the temperature-dependent hepatic metabolism of fentanyl.

Adolescent↗
PubMed1987

Pharmacokinetics of inhaled salbutamol in patients with cystic fibrosis versus healthy young adults.

We studied the disposition of inhaled salbutamol in adolescents with cystic fibrosis (CF) and compared it with the pharmacokinetics of the drug given by the intravenous and inhaled routes in healthy adults. After inhalation of salbutamol, CF patients had a significantly larger area under the concentration-time curve derived from amounts of drug in the systemic circulation. The differences in serum concentration of salbutamol were not reflected in differences in change of heart rate. We conclude that the rate and extent of pulmonary absorption of inhaled salbutamol in patients with CF differ from those in healthy adults.

Administration, Inhalation↗
PubMed1987

Ethics of drug studies in infants: how many samples are required for accurate estimation of pharmacokinetic parameters in neonates?

Our study aimed to determine the least number of samples that are required to obtain accurate pharmacokinetic parameters in neonates. Patients treated with either netilmicin or ceftazidime had between five and eight samples drawn for drug concentration measurement after the first or the last dose of the drug. Pharmacokinetic parameters were calculated using all the available points as a reference and then recalculated with 2, 3, or 4 points. Systemic clearance and volume of distribution were significantly different from the reference value when 2 points were used for netilmicin after the first dose and ceftazidime after the last dose. Had parameters obtained from 2 points been used, mean dosage would have been underestimated by 15% for ceftazidime and 11% for netilmicin, and some patients would have received only 65% of the dose calculated from all available points. When 3 points were used, dosage would have been underestimated by a mean of only 1% for ceftazidime and 5% for netilmicin when compared with the dosage estimated from the reference parameters. We conclude that 3 concentration time points may be all that are required for estimation of pharmacokinetic parameters sufficiently accurate for practical purposes in neonates.

Bacterial Infections↗
PubMed1987

Reduction of platelet counts induced by mechanical ventilation in newborn infants.

The association between platelet counts and mechanical ventilation was assessed in 61 newborn infants with respiratory distress syndrome, 10 infants with congenital diaphragmatic hernia, and 10 infants with tracheoesophageal fistula. A significant decrease in platelet counts was observed during mechanical ventilation: (mean +/- SD) reduction of 39% +/- 5%, 42% +/- 5.6%, and 11.9% +/- 5.4% in the three groups, respectively, independent of other causes. In the group with congenital diaphragmatic hernia, there was a significant correlation between mean airway pressure and the reduction in platelet counts. In a subsequent series of experiments, platelet counts were recorded before and during ventilation in rabbits. A significant mean decrease of 37.3% in platelet counts was associated with ventilation with either air or pure oxygen. Results of these studies indicate that mechanical ventilation itself may cause a major decrease in platelet count in newborn infants.

Animals↗
PubMed1987

Comparison of oral and intravenous administration of sodium bromide for extracellular water measurements.

Extracellular water (ECW) is a component of body composition and an indicator of nutritional status. Although bromide has been used to measure ECW, no data regarding serial measurements are available. We attempted to validate giving bromide orally and to determine whether serial measurements of ECW are possible. Seven healthy adult volunteers were studied. Each received 1 cc 3% NaBr solution per kg body weight once intravenously and 3 times orally over 6 wk. Bromide concentrations were determined by neutron activation. ECW did not differ significantly at 2, 3, or 4 h after drug administration although there was a small but significant difference between modes of administration (p = less than 0.05). With repeated oral doses the estimate of ECW was unchanged; thus, oral bromide can be used for serial determination of ECW.

Administration, Oral↗
PubMed1987

The pharmacokinetics of alfentanil in children.

The pharmacokinetics of alfentanil were studied in 18 children (3 months to 14 yr of age) undergoing surgery. Alfentanil was administered as a 30-s infusion of either 50 or 120 micrograms.kg-1. Pharmacokinetic values were independent of dose. There was no correlation between Vdss (Volume of distribution at a steady state, measured as l.kg-1) and age or weight, and there was a weak correlation between clearance and age (r = 0.51, P less than 0.05). Vdss and elimination t1/2 were not different in infants less than 1 yr of age when compared to older children. The mean value of Vdss was 0.419 (SE .028) l.kg-1) for the whole group, and elimination t1/2 was 76.3 (SE 6.5) min. The clearance rate [TBC = 7.9 (SE 0.41) ml.kg-1.min-1] was within the range of values previously determined in adult studies. From these data, it would appear that, although there may be differences in the disposition kinetics between children aged 3 months to 14 yr and those measured in adults in some studies by other investigators, age-related differences within this group were not demonstrable.

Adolescent↗
PubMed1987

Corticosteroids-salicylate interaction in a case of juvenile rheumatoid arthritis.

In an 11-year-old child with juvenile rheumatoid arthritis (JRA), the addition of prednisone caused a significant decrease in salicylate serum concentrations. A pharmacokinetic assessment suggested that these changes were not the result of altered compliance or impaired absorption of salicylate but rather an increase in salicylate clearance induced by the corticosteroid.

Arthritis, Juvenile↗
PubMed1987

Vancomycin pharmacokinetics and dose recommendations for preterm infants.

The pharmacokinetics of intravenous vancomycin was studied in 20 preterm infants (gestational age, 26.5 weeks +/- 2.6 weeks [standard deviation]; birthweight, 880 +/- 340 g). At the time of the studies their postconceptional age was 36.4 +/- 4.5 weeks. The drug was infused over 30 min in a dose between 9.2 and 18 mg/kg. A highly significant correlation existed between postconceptional age or body weight and vancomycin t1/2 and clearance. Serum creatinine concentrations correlated with vancomycin t1/2 and clearance. Serum creatinine tended to decrease with increasing postconceptional age. Based on the excellent correlation between age (or weight) and vancomycin pharmacokinetics, dose and dose-interval recommendations are presented.

Drug Administration Schedule↗