[Organ metabolism in normothermic ischemia as related to the age-dependant metabolic status].
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Adenine Nucleotides↗
Biomedical subjects
J H Fischer
Publications and source records attributed to J H Fischer.
[Anaerobic organ metabolism of newborn and adult animals].
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Adenine Nucleotides↗
[Kidney function following hypothermic aerobic ischemia in situ].
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Aerobiosis↗
Guidelines for nonemergency use of parenteral phenytoin products: proceedings of an expert panel consensus process. Panel on Nonemergency Use of Parenteral Phenytoin Products.
This document summarizes the proceedings of an expert panel consensus process addressing the nonemergency use of parenteral phenytoin products for management of seizures in pediatric and adult patients. The algorithm and consensus statements developed by the expert panel emphasize strategies for lowering the probability of adverse events associated with the use of parenteral phenytoin products. Specific patient characteristics are defined to guide administration and monitoring of parenteral phenytoin therapy. The algorithm provides a decision pathway for the selection of the product and the route of administration of phenytoin sodium or fosphenytoin sodium after it has been determined that a parenteral phenytoin product is appropriate. Key factors covered in the algorithm include a list of patient characteristics and considerations necessary to prevent parenteral phenytoin adverse effects during selection of administration route and recommendations for monitoring of parenteral phenytoin therapy once it has been initiated. Situations requiring rapid attainment of high phenytoin concentrations, such as in the management of acute seizures, are not addressed in these guidelines.
Adolescent↗
Valproic acid pharmacokinetics in children: III. Very high dosage requirements.
Nine children were studied who required very high doses of valproic acid (VPA) (63.6-105 mg/kg/day) in order to achieve VPA serum concentrations between 50-100 micrograms/ml. These nine children had poorly controlled seizures and were receiving other antiepileptic drugs at the time of this study. The children with very high dose requirements were significantly lighter, shorter, and had less body surface area than the control group. Of the pharmacokinetic parameters studied, total and intrinsic clearance, distribution volume, and valproic acid free fraction were significantly increased in the very high dose group. In three patients who were investigated after co-medications were eliminated, clearances and dosage requirements decreased by more than 50%. We concluded that very high VPA dosages are sometimes required to achieve therapeutic serum drug concentrations and that this therapy occasionally improves seizure control. There were no adverse effects of very high dose therapy that required dosage reduction.
Adolescent↗
[Cryosurgical ablation of bone tissue with a newly developed miniature cryoprobe--adaptation of the method for use in bones in vitro and in vivo].
AIM: Up to now, modern miniature cryoprobes have been used successfully for local destruction of soft tissue tumors without damaging adjacent healthy tissue. In this study, the methodology of cryoablation was applied to bone and the freezing effect as well as the cooling capacity of the probe was examined in vivo and in vitro. METHODS: Freezing was performed by cooling one or two probes, with a diameter of 3.2 mm to -180 degrees C with liquid nitrogen. The cooling capacity of the probes was determined under thermic control by an in vitro measurement on human bone, followed by an in vivo measurement on femoral and tibia bones of a sheep. RESULTS: The in vitro freezings achieved a sufficient tissue cooling using one or two cryoprobes. The simultaneous use of 2 probes resulted in a synergistic effect between the probes. According to the body heat, the registered temperature curves, during the in vivo freezings, showed a more flat trend. Nevertheless, temperatures below -50 degrees C were achieved at a distance of 1 cm from the probe due to the synergistic effect. Local or systematical intraoperative complications have not been observed. CONCLUSION: An adequate tissue cooling of bone matrix can be achieved within in vivo freezings through the use of one or more miniature cryoprobes so that the use of this probe could possibly become an alternative or supplement to the surgical resection of pathologic bone processes.
Animals↗
The influence of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries.
Ten patients with burn injuries (mean total body surface area burn = 29% +/- 16) were studied at various points in the course of their burn therapy. Alpha 1-Acid glycoprotein, albumin, and vancomycin concentrations were determined with either a trough or peak vancomycin quantitative determination. Alpha 1-Acid glycoprotein concentrations ranged from 125 to 333 mg/dl and albumin concentrations ranged from 1.7 to 4.2 gm/dl. Vancomycin protein binding, as determined by ultrafiltration, averaged 29% +/- 6%. There was a strong (r = 0.92) relationship between percent protein-bound vancomycin and albumin. There was a poor statistical relationship between percent protein-bound vancomycin and alpha 1-acid glycoprotein (r = 0.28). Alpha 1-Acid glycoprotein appeared to have virtually no effect on the protein-binding characteristics of vancomycin over the range of concentrations studied.
Adult↗
Microcirculatory changes associated with gastric tube formation in the pig.
The standard reconstruction after esophagectomy is the formation of a gastric tube with partial devascularization of the lesser curvature. The purpose of this experimental study was to establish an animal model in order to analyze microcirculation associated with the formation of a gastric tube. In 17 pigs tissue perfusion was measured with a laser Doppler imager (LDI) and partial tissue oxygen pressure (ptO(2)) with a Clark-type polarographic oxygen electrode before and after formation of a gastric tube in well-defined regions of the stomach. The operative procedure included the dissection of the left gastric and short gastric arteries; the left gastroepiploic artery along the greater curvature was preserved. LDI and ptO(2) baseline measurement were significantly lower in the fundus compared to the antrum and corpus. After formation of a gastric tube LDI and ptO(2) baseline values calculated from the mean measurements of the antrum, corpus and fundus decreased significantly (LDI: 1,099 PU +/- 228 SD to 601 PU +/- 125 SD, p < 0.0001; ptO(2): 50.8 mm Hg +/- 5.9 SD to 40.7 mm Hg +/- 9.3 SD, p = 0.0003). Microcirculatory changes did not correlate with changes of cardiac output and systemic vascular resistance. This study suggests that the pig is an appropriate model to investigate microcirculation associated with gastric tube formation. Its use for esophageal reconstruction by pull-up of the gastric interponate is limited.
Animals↗
Pharmacokinetics and antibacterial activity of two gentamicin products given intramuscularly.
The pharmacokinetics and antibacterial activity of two injectable gentamicin products given i.m. were compared. Ten healthy men randomly received either Schering or Invenex gentamicin 1 mg/kg (as the sulfate salt) by intramuscular injection into the deltoid muscle. Four to six weeks later, subjects received the alternate preparation at the same dose in the opposite arm. Blood samples for gentamicin concentrations were obtained before drug administration and at various times for up to four hours after drug administration; urine from each subject was also collected before and after drug administration. Values for area under the curve, elimination rate constant, peak serum gentamicin concentration and time to peak concentration, clearance, half-life, and percentage of drug excreted in the urine over four hours were compared for each preparation in each subject. The serum inhibitory and bactericidal activities of each gentamicin preparation against Escherichia coli and Klebsiella pneumoniae were also evaluated. None of the pharmacokinetic values for the two preparations was significantly different. The inhibitory and bactericidal activities resulting from each product were also comparable and adequate. No clinically important differences in pharmacokinetic behavior or inhibitory or bactericidal activity were found between gentamicin products of Schering and Invenex.
Adult↗
Absorption characteristics of three phenytoin sodium products after administration of oral loading doses.
The absorption characteristics of three phenytoin sodium products given orally as loading doses in five healthy men were studied. Extended phenytoin sodium capsules, prompt phenytoin sodium capsules, and phenytoin sodium injection were administered in a randomized, crossover trial as single 18-mg/kg doses and as divided doses of 6 mg/kg every three hours for three doses. Each dose was given with 200 ml of water, and a two-week washout period followed each treatment. The maximum plasma concentration (Cmax), time to reach maximum plasma concentration, time to reach the lower end (10 mg/liter) of the therapeutic range, time to reach a plasma concentration greater than 15 mg/liter, and time within the therapeutic range were determined for each loading-dose regimen. Prompt phenytoin sodium capsules (prompt PHT) given in divided doses produced a mean Cmax of 22.0 mg/liter, which was significantly higher than that observed with any of the other loading-dose regimens. In addition, all subjects receiving prompt PHT in divided doses had plasma phenytoin concentrations of 10 mg/liter within six hours; only this treatment produced plasma concentrations greater than 15 mg/liter at nine hours in all subjects. Plasma concentrations remained within the therapeutic range (10-20 mg/liter) for 81 and 78% of the first 24-hour period for prompt PHT in divided and single doses, respectively. Adverse effects were minimal in all regimens. The prompt-release phenytoin sodium capsules used in this study may provide an alternative means for rapidly achieving therapeutic phenytoin concentrations in situations where i.v. administration is not indicated or practical.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral↗
Reversal of the electrocardiographic effects of cocaine by lidocaine. Part 2. Concentration-effect relationships.
Ventricular arrhythmias due to cocaine may be related to its ability to slow ventricular conduction or prolong repolarization. We previously showed that lidocaine reversed QRS prolongation due to cocaine. The purposes of these experiments were to characterize cocaine's concentration-effect relationship on both ventricular conduction and repolarization, and to determine the effects of lidocaine on these relationships. The effects of lidocaine on cocaine-induced electrocardiographic changes were studied in 20 isolated, Tyrode-perfused guinea pig hearts. Variables at cocaine concentrations ranging from 3-195 microM were measured and repeated in the presence of a fixed concentration of lidocaine 30 microM. Using nonlinear regression analysis, the sigmoid Emax and simple Emax models were fit to cocaine concentration versus percentage change in QRS plots. Measures of best fit indicated that this relationship was best described by the sigmoid Emax model. Compared with cocaine alone, the curve for cocaine with lidocaine showed a greater EC50 (concentration at 50% of maximum effect) (59 vs 100 microM) but similar Emax (371 vs 367%), consistent with competition. Similar values were obtained from the linear transformation of the data. Cocaine concentration versus percentage change in the JTc interval showed a biphasic effect: concentrations below 65 microM prolonged JTc, but those above 65 microM had no effect or decreased JTc. In contrast to changes in QRS, addition of lidocaine increased the effects of cocaine on JTc: area under the concentration-effect curve for cocaine alone was 720 versus 859 microM% for cocaine with lidocaine. Lidocaine reverses cocaine-induced slowed ventricular conduction through competition for binding, but it appeared to increase cocaine-induced prolongation of repolarization.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Evaluation of transdermal theophylline pharmacokinetics in neonates.
Theophylline may be administered by several routes, but problems are associated with neonatal dosing. The transdermal route may provide a safer and noninvasive method of administration, yet produce therapeutic concentrations in a consistent and reliable manner. To study the feasibility of this in the apnea of prematurity, stable neonates were administered a subtherapeutic transdermal dose for 24 hours in order to assess pharmacokinetics and bioavailability. This was followed with routine intravenous theophylline therapy according to institutional policy. Six of nine neonates had detectable serum theophylline concentrations that increased slowly after patch application. Mean (+/- SD) maximum serum concentration was 2.4 +/- 1.3 micrograms/ml, mean time to maximum serum concentration was 22 +/- 8.2 hours, and mean latency period was 8.0 +/- 4.9 hours. Mean total amount of theophylline delivered to the skin was 18.6 +/- 4.1 mg. Mean fractional absorption at 30 hours was 0.25 +/- 0.12. These data demonstrate that it is possible to produce systemic theophylline concentrations with a transdermal patch in preterm infants sufficient to study pharmacokinetics and bioavailability, and that transdermal delivery of therapeutic doses is technologically feasible.
Administration, Cutaneous↗