Showing papers by "Gideon Koren published in 1987"
TL;DR: The results suggest that the MHC isozyme transition during hemodynamic overload is mainly regulated by pretranslational mechanisms, and that a complex interplay exists between hemodynamic and hormonal stimuli in MHC gene expression.
Abstract: Expression of the cardiac myosin isozymes is regulated during development, by hormonal stimuli and hemodynamic load. In this study, the levels of expression of the two isoforms (alpha and beta) of myosin heavy chain (MHC) during cardiac hypertrophy were investigated at the messenger RNA (mRNA) and protein levels. In normal control and sham-operated rats, the alpha-MHC mRNA predominated in the ventricular myocardium. In response to aortic coarctation, there was a rapid induction of the beta-MHC mRNA followed by the appearance of comparable levels of the beta-MHC protein in parallel to an increase in the left ventricular weight. Administration of thyroxine to coarctated animals caused a rapid deinduction of beta-MHC and induction of alpha-MHC, both at the mRNA and protein levels, despite progression of left ventricular hypertrophy. These results suggest that the MHC isozyme transition during hemodynamic overload is mainly regulated by pretranslational mechanisms, and that a complex interplay exists between hemodynamic and hormonal stimuli in MHC gene expression.
453 citations
TL;DR: With repeated oral doses the estimate of ECW was unchanged; thus, oral bromide can be used for serial determination ofECW.
78 citations
TL;DR: The authors' 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, and TBC is influenced by the temperature-dependent hepatic metabolism of fentanyl.
Abstract: 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 °C–25 °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>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.
67 citations
TL;DR: Dose and dose-interval recommendations are presented based on the excellent correlation between age (or weight) and vancomycin pharmacokinetics, and serum creatinine tended to decrease with increasing postconceptional age.
Abstract: 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.
56 citations
TL;DR: Tubular secretion appears to be a major route of the renal elimination of digoxin and does not appear to be associated with the anionic or cationic transport systems, nor the Na+/K+-ATPase receptor.
Abstract: Tubular secretion appears to be a major route of the renal elimination of digoxin. Secretion of the drug by the tubules is modulated by renal blood flow, by a number of commonly coadministered drugs (e.g. quinidine, spironolactone, verapamil, amiodarone), and by age. The maximal transport capacity does not appear to be achieved with clinically relevant concentrations. The tubular transport of digoxin does not appear to be associated with the anionic or cationic transport systems, nor the Na+/K+-ATPase receptor. Further studies are needed to elucidate the exact mechanisms involved in the transtubular movement of the glycoside.
31 citations
TL;DR: It is concluded that 3 concentration time points may be all that are required for estimation of pharmacokinetic parameters sufficiently accurate for practical purposes in neonates.
24 citations
TL;DR: It is concluded that the rate and extent of pulmonary absorption of inhaled salbutamol in patients with CF differ from those in healthy adults.
23 citations
21 citations
TL;DR: A guide presented in this article provides the sonographer with a list of fetal malformations that have been described in association with specific drugs or chemicals and that can be visualized by current ultrasonographic techniques.
17 citations
16 citations
TL;DR: It is suggested that mechanical ventilation itself may cause a major decrease in platelet count in newborn infants, and this decrease was associated with ventilation with either air or pure oxygen.
TL;DR: It is indicated that early thrombolytic therapy of acute myocardial infarction preserves myocardium, and since the infarct-related artery is patent, but narrowed, the jeopardized area is responsible for a high-risk syndrome with an increased likelihood of ischemic symptoms.
Abstract: • Fifty-one successive patients treated with intravenous streptokinase 1.7 ±0.8 (mean ± SD) hours after onset of symptoms of acute myocardial infarction were evaluated during a three-month posthospital follow-up period. Coronary angiography was performed four to nine days after the initial hospital admission. Twenty-eight patients had a second late angiogram. Forty-one patients had successful reperfusion but only 25% of all patients were without significant clinical cardiovascular manifestations during this period. Postmyocardial infarction angina pectoris occurred in 21 patients, an abnormal stress test result was present in 28 patients, eight patients developed congestive heart failure, and five patients had reinfarction. An intervention with percutaneous transluminal coronary angioplasty or coronary artery bypass graft was performed in 15 (37%) of 41 reperfused patients. A significantly higher intervention rate was present in patients treated with streptokinase within one hour following the onset of symptoms. Early reocclusion (within three months of the infarct) was noted in patients with 60% or more residual stenosis in their infarct-related coronary artery. These patients also had a significantly greater incidence of angina pectoris. Our findings indicate that early thrombolytic therapy of acute myocardial infarction preserves myocardium, and since the infarct-related artery is patent, but narrowed, the jeopardized area is responsible for a high-risk syndrome with an increased likelihood of ischemic symptoms. An early aggressive approach may be indicated, especially for patients with greater than 60% residual stenosis in their infarct-related coronary artery. ( Arch Intern Med 1987;147:237-240)
Journal Article•
Journal Article•
TL;DR: In vitro studies verify that this new species is produced by the brush border membrane of the renal tubular cell, and is identified by thin layer chromatography by performing single pass experiments in the dog.
Abstract: By performing single pass experiments in the dog, we could identify by thin layer chromatography a digoxin metabolite produced by the kidney. In vitro studies verify that this new species is produced by the brush border membrane of the renal tubular cell.
TL;DR: It is indicated that there does not exist a consensus of ethicists on this important issue of limitation of the number of blood samples obtained from infants and that most participants indicated the need for a knowledgable decision on how many samples should be allowed, based on scientific evidence.
Abstract: ETHICS OF DRUG STUDIES IN NEONATES: HOW MANY SAMPLES SHOULD BE PERMUTED FOR PHARMACO-KINETIC ANALYSIS