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Biomedical subjects

J H Fischer

Publications and source records attributed to J H Fischer.

At least 73 records · Page 4Linked to original sources

Flush solution 2, a new concept for one-to-three-day hypothermic renal storage preservation. Functional recovery after preservation in Euro-Collins, Collins' C2, hypertonic citrate, and F.2 solution.

Experiments were performed on the quality of renal functional recovery after 24, 48, or 72-hr hypothermic storage preservation of canine kidneys in Euro-Collins solution (EC), Collins' solution C2, hypertonic citrate solutions (HC, HC-D2O), or our new flush solution 2 (F.2). Clearance tests (inulin, paraaminohippuric acid, and creatinine) and resorption rates for sodium, potassium, and glucose indicated a high superiority in the early functional recovery of F.2-preserved kidneys after all preservation periods tested. The excellent function after preservation in F.2 contrasted especially with the poor or even absent function after 72-hr preservation in HC and HC-D2O or EC. Thus F.2--a hyperosmolar solution containing sucrose with a balanced Na-K relation on the basis of "heavy water" (D2O)--is especially suitable for preservation up to 72 hr if cyclosporine is used for immunosuppression in the recipient. The recipient can be supplied with an organ with immediate good functional recovery because cyclosporine banishes the higher risk for rejection of these well-functioning organs; simultaneously, the possibility for continuous functional supervision allows avoidance of nephrotoxic side effects from the immunosuppressant.

Animals↗

Investigations on the effects of heavy water (D2O) on the functional activity of human platelets.

Heavy water (D2O) is able to activate or to inhibit biological systems and thus influences metabolism and functions of tissues and organs. On the basis of results obtained in preservation experiments performed on various organs, the effects of D2O on the functions of human platelets (retraction, spreading, aggregation induced by adrenaline, ADP and collagen) have been investigated. The effects of D2O, involving changes of membrane receptor conformation, binding strength of substances to their specific receptors, pH-values or enzyme activities, resulted in a significant decrease of ADP- and collagen-induced aggregation, while adrenaline-induced aggregation was significantly increased at the same D2O concentration. Retraction in the presence of D2O was significantly inhibited in a dose-related manner, while spreading was diminished, but not fully inhibited even by highest concentrations of D2O (95%).

Adenosine Diphosphate↗

Valproic acid pharmacokinetics in children. II. Discontinuation of concomitant antiepileptic drug therapy.

We studied the pharmacokinetics of valproic acid (VPA) in 11 children before and after discontinuance of enzyme-inducing antiepileptic drugs (AEDs). Valproic acid elimination half-life increased from 7.1 to 11.8 hours. Total and intrinsic VPA clearance decreased by approximately 40%. Valproic acid serum protein binding varied among patients from 7 to 23.8%, but was not altered by AEDs. Seizure control was maintained and mental status improved once all other AEDs were withdrawn. After discontinuation of enzyme-inducing AEDs, serum VPA concentrations can be maintained with a lower VPA dosage given less frequently.

Adolescent↗

Volume of distribution of theophylline in acute exacerbations of reversible airway disease. Effect of body weight.

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.

Adolescent↗

[High-dosage aprotinin (Trasylol) therapy--is it safe for the kidney?].

In canine experiments the infusion of 50000 KIE/kg body weight aprotinin (Trasylol) resulted in a transient significant reduction of sodium resorption and a lower potassium excretion. This functional impairment coincides with the accumulation of 90% of the infused aprotinin in the proximal tubular cells of the kidney, which has been reported in the literature. Glomerular filtration as well as kidney perfusion and PAH secretion (measured by clearances of inulin or creatinine and PAH) did not change significantly during 24 h following the application of aprotinin. Thus in normothermia in normal kidneys the functional changes following a single infusion of a high dosage of aprotinin are small and transient. The severe damage seen in aprotinin loaded kidneys preserved hypothermically thus seems to be confined to the hypothermic situation.

Animals↗

Pharmacokinetics of valproic acid in children: I. Multiple antiepileptic drug therapy.

We studied the pharmacokinetics of valproic acid (VPA) in 37 children who were taking other antiepileptic drugs. Thirteen children were studied both after initial and while on maintenance valproic acid therapy. Significant differences occurred between initial and maintenance therapy in the mean apparent volume of distribution and in apparent VPA clearance, whereas VPA half-life remained relatively constant. Analysis of data in the 13 children studied on two occasions demonstrated wide intrapatient variability of VPA pharmacokinetics. Children taking VPA together with other antiepileptic medications generally require higher doses of VPA given more frequently.

Adolescent↗

The upper urinary tract following a ureteroneocystostomy (UNC) in animal experiments: I. Functional findings.

A ureteroneocystostomy (UNC) was carried out on 32 dogs. A standardised measurement of flow across the ureterovesical anastomosis revealed a significant obstruction on the day of the operation itself and on the first 5 days after the operation. On the 1st, 7th and 28th day after the operation there was no significant reduction in either tubulo-secretory or glomerular function on the operated and non-operated kidneys.

Animals↗

The upper urinary tract following a ureteroneocystostomy (UNC) in an animal experiment: II. Morphological findings.

This report deals with the macroscopic and microscopic histopathological findings of the upper urinary tract following a unilateral ureteroneocystostomy (UNC) in dogs. Both sides, operated and unoperated, were examined. The area of antireflux surgery was of particular significance. The decrease of flow which was always present on the operated side was caused by submucosal oedema of the bladder and not by the fatty tissue deposited intramurally or by the bladder muscle itself. The morphological findings were less pronounced than was to be expected following the significant obstruction on the operated side caused by anti-reflux surgery (ARS) and shown by the flow measurement and the sequential findings on scintigraphy.

Animals↗

Renin release after furosemide and ethacrynic acid in man. Evidence for neural reflex control mechanisms.

The mechanisms of renin release after furosemide (F) and ethacrynic acid (EA) in man were examined. We evaluated whether acute volume shifts within the low pressure system after F induce renin release via neural pathways. Immersion in a water-bath or beta-blockade reduced the increase of plasma renin concentration after F but not after EA. It is concluded that acute renin release after F but not after EA in man is partially due to neurally mediated reflexes originating from volume receptors in the cardiopulmonary area.

Adult↗

Adenine nucleotide levels of canine kidneys during hypothermic aerobic or anaerobic storage in Collins solution.

The influence of retrograde oxygen persufflation (ROP) on renal adenine nucleotide, glucose and lactate contents was examined in canine kidneys during up to 5 days of hypothermic preservation. Organs with or without predamage in 30-min normothermic ischemia were preserved and the results compared to kidneys after hypothermic ischemic storage (HIS): ROP preservation resulted in a significantly higher maintenance of cellular energy-rich substances than in HIS with even normal adenine nucleotide contents and energy charge potentials for the first 24 h. As in HIS preservation of normal kidneys, where the total adenine nucleotide content (SAN) paralleled the loss of viability for the first 1-2 days, in ROP were SAN and even the lactate content also correlated to renal viability for 2-3 days. But in contrast to this correlation, which would favor adenine nucleotide determinations for viability testing, in predamaged kidneys no correlation of SAN or lactate with renal viability was found during HIS or ROP. Thus the determination of cellular energy-rich adenine nucleotides and lactate accumulation confirms the superiority of ROP over HIS preservation. But the SAN or lactate tests lose their prognostic value for posttransplant renal viability if normothermic ischemia precedes the preservation period.

Adenine Nucleotides↗

Phenobarbital maintenance dose requirements in treating neonatal seizures.

We studied the pharmacokinetics of phenobarbital in 15 neonates after a single intramuscular dose. The mean apparent distribution volume, half-life, and apparent total body clearance were 0.81 liter per kilogram, 103.4 hours, and 6.4 ml per hour per kilogram, respectively. Substantial interpatient variation was observed in the half-life and apparent total body clearance. Maintenance doses of 3.1 and 3.8 mg per kilogram per day were projected from the mean apparent total body clearance to produce plasma concentrations of 20 and 25 micrograms per milliliter, respectively. These recommendations provide initial maintenance dosage guidelines, which should be adjusted according to plasma concentrations and clinical effects.

Humans↗

A simple method for orthotopic liver transplantation in the rat. Cuff technique for three vascular anastomoses.

A simple method for orthotopic liver transplantation in the rat is described in detail. A cuff technique was applied to all anastomoses of the supra- and infrahepatic venae cavae and the portal vein. It simplified and shortened the implantation of the graft as well as eliminating the need for microvascular suture technique. In the last series of 20 transplants, the survival rate was 85% after 1 week and 55% after 2 months with normal hepatocellular function.

Animals↗

[Dosage related effect of fenoterol on fetal hemoglobin oxygen affinity (author's transl)].

Fenoterol induced displacements of the fetal oxygen dissociation curve were investigated in animal experiments by determining the oxygen halfsaturation pressure (P 50). At term pregnant rabbits were infused intravenously over 3 hours with an increasing Fenoterol dosis (10 to 30 microgram/kg/min) up to a dosis level which produced complete labour inhibition. By cesarean section fetal aortic blood was collected and the oxygen halfsaturation pressure (P 50) was determined as described by Lichtman et al. (14). All P 50 values were corrected to so-called standard conditions (pH: 7.4; PCO2: 40 mmHg; t: 37 degrees C). Likewise, in a second series P 50 values were measured in newborn rabbits which received Fenoterol subcutaneously as a single shot injection. In the first series standardized P 50 significantly fell from 20.9 to 15.0 mmHg and in the second series it fell from 20.9 to 14.4 mmHg. This raised oxygen hemoglobin affinity, i.e. leftward shift of the fetal oxygen dissociation curve, is probably due to a Fenoterol induced diminution of the red cell 2.3-DPG concentration. In all cases of severe fetal hypoxia a beneficial effect on O2-transport is discussed whereas at normoxia or mild hypoxia a rightward shift of the oxygen dissociation curve would be more favourable.

Animals↗

[Deuterium oxide (D2O)--a protective factor for cellular stabilization in hypothermic preservation of the liver? (author's transl)].

Rat livers were preserved by ischemic hypothermic storage in extra- or intracellular type solutions for 24 h. A substitution of 85% of the tissue water by deuterium oxide (D2O) resulted in increased glycolytic energy production, better maintenance of the energy potential of the cells but a higher AMP loss, and a reduction of edema formation. Preservation using "retrograde oxygen persufflation" (ROP) resulted in optimal maintenance of the metabolic state which could be further influenced positively by D2O in the total nucleotide content.

Animals↗