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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 325 records · Page 18Linked to original sources

67Gallium kinetics in the blood of patients with malignant tumors.

67Gallium was injected into 60 patients with malignant tumors and into 42 patients in whom malignant tumors had been excluded by clinical investigation. 67Ga kinetics in blood were evaluated by non-linear least square regression computer analysis according to an open 2-compartment model where elimination proceeds from the peripheral compartment. Parameters of 67Ga kinetics in tumor patients showed a bimodal distribution, as was also the case in patients without tumors. No difference could be demonstrated between kinetic parameters of tumor patients and patients without tumors. In 4 patients, 67Ga kinetics could be evaluated before and after treatment of their malignant tumors, but a decrease in the volume of distribution was the single alteration of kinetic parameters occurring after treatment. This decrease may be explained by a smaller peripheral compartment resulting from the loss of tumor mass after treatment. Nevertheless, we conclude that the evaluation of 67Ga kinetics in blood will provide only limited information about the presence, size and growth rate of malignant tumors in man.

Female↗

Criticism of pharmacokinetic clearance concepts.

The value of pharmacokinetic parameters is confirmed by clinical impacts. Drug dosage recommendations are usually derived from the one-compartment model and linear first-order kinetics. These are described by the parameters bioavailability, volume of distribution, and elimination half-life. Thus, elimination half-life and volume of distribution are the most important clinical pharmacokinetic parameters and the one-compartment model is the most universal pharmacokinetic concept. Drug clearance provides no further information. To evaluate drug clearance, the AUC must be extrapolated. This requires the assumption of a compartment model. The intrinsic hepatic clearance cannot be equated with hepatic metabolism capacity. Therefore, drug clearance does not appear to be a superior pharmacokinetic parameter.

Biological Availability↗

Effect of plasma protein binding, volume of distribution and molecular weight on the fraction of drugs eliminated by hemodialysis.

The correlation between plasma protein binding, the volume of distribution, molecular weight, and percentage removed by hemodialysis was investigated in 89 drugs using information available in the literature. The correlation was significantly linear between dialyzability and plasma protein binding, as well as with the reciprocal volume of distribution. This is in agreement with the theoretical deduction of dialyzability from diffusion and convection kinetics. Multiple linear regression analysis revealed that only 27% of the variance in dialyzability could be explained by plasma protein binding (17%), the volume of distribution (6%), and the molecular weight (4%) of the drugs. Therefore, the dialyzability of drugs can not be predicted reliably.

Blood Proteins↗

Localization of trehalase in vacuoles and of trehalose in the cytosol of yeast (Saccharomyces cerevisiae).

Protoplasts of Saccharomyces cerevisiae synthesized and degraded trehalose when they were incubated in a medium containing traces of glucose and acetate. Such protoplasts were gently lyzed by the polybase method and a particulate and soluble fraction was prepared. Trehalose was found in the soluble fraction and the trehalase activity mostly in the particulate fraction which also contained the vacuoles besides other cell organelles. Upon purification of the vacuoles, by density gradient centrifugation, the specific activity of trehalase increased parallel to the specific content of vacuolar markers. This indicates that trehalose is located in the cytosol and trehalase in the vacuole. It is suggested that trehalose, in addition to its role as a reserve may also function as a protective agent to maintain the cytosolic structure under conditions of stress.

Cell Compartmentation↗

Quantification in macroscopic autoradiography with carbon-14--an evaluation of the method.

Macroscopic autoradiograms can generally be quantified by exposing previously calibrated standard sources together with the labeled sections and measuring the silver grain density by photometric methods. Variation in section thickness is a real problem with isotopes like 14C, with beta-particles of higher energy than those of 3H. Differences in self-absorption between tissues may be neglected at low section thickness. A simple fitting procedure for non-linear relationship between radiation dose and optical density is described. The combined effect of the examined errors for the practical evaluation of autoradiograms is discussed.

Animals↗

Supplementary dose after hemodialysis.

It is the aim of this paper to review in tabulated form the supplementary dose of drugs required after hemodialysis and to discuss the basic pharmacokinetics of these drugs in the presence of reduced renal function. This review is intended to point out practical aspects of clinical nephrology, It refers to data available from the literature. The descriptions of pharmacokinetics focus on the amount of drug in the body. The fraction of this amount removed by dialysis is replaced by the supplementary dose to maintain effective drug action. The rebound phenomenon affecting plasma drug levels after dialysis renders the calculation of the supplementary dose difficult. Linear extrapolation from plasma drug concentrations measured 6-12 h or more after dialysis may offer a solution to this problem.

Drug Administration Schedule↗

Methoxyethylmercury chloride poisoning: clinical findings and in vitro experiments.

A patient attempting suicide ingested 5682 mg methoxyethylmercury chloride, which corresponds to 4375 mg mercury. The bulk of the dose was eliminated by vomiting and gastric rinsing. About 706 to 977 mg mercury were absorbed in the gastrointestinal tract. Only 11.2 mg mercury could be removed by two activated charcoal hemoperfusions. Chelating agents were given for 12 weeks. The terminal elimination half-life calculated from blood and urine mercury levels was 23 and 25 d, respectively. No toxic effects on the kidneys and central nervous system were seen. The identification of methoxyethylmercury chloride in the gastric rinsing fluid was done by gas chromatography/mass spectrometry. The protein binding of methoxyethylmercury chloride was determined by ultrafiltration (93%). In the presence of dimercaprol sulfonate and penicillamine, protein binding was 83 and 88%, respectively. Activated charcoal and amberlite hemoperfusion revealed equal in vitro clearances for methoxyethylmercury chloride (62 mL/min at a flow rate of 80 mL/min).

Dimercaprol↗

Hemoperfusion for organic mercury detoxication?

A case is reported with suicidal ingestion of 125 g Ceresan, a fungicide containing 3.5% Hg2=s methoxyethylmercury-chloride. Final absorption of mercury was approximately 706 to 977 mg, as extrapolated from mercury eliminated in urine. Activated charcoal hemoperfusion removed only 1% to 2% of the amount absorbed. During treatment with D-penicillamine and dimercaprol, which were alternated fortnightly, the mercury elimination half life was 25 days, as calculated from blood concentrations and 23 days as calculated from urine data. Except for local cauterization of the mouth and throat, no signs of liver, kidney or central nervous system intoxication were seen within a 3-month follow-up period.

Female↗

Diagnostic haemoperfusion for rapid detection of bacteremia. First clinical results of a comparison with the conventional blood culture technique.

The new method of diagnostic haemoperfusion was compared with the conventional blood culture technique in 25 patients with suspected septicaemia. The chance of obtaining a positive result proved to be clearly greater than that by conventional techniques (16:9). Furthermore, in the case of a positive result with the haemoperfusion technique both the bacterial identification and antibiotic sensitivities were available earlier than was previously possible. The procedure of diagnostic haemoperfusion is safe and carries a minimal risk of complications for the patient.

Adult↗

First-pass effect: nonlinear concept comprising an explicit solution of integrated Michaelis-Menten equation.

The first-pass effect results from metabolism during the first liver passage of a drug given by mouth. The metabolism is described by the Michaelis-Menten equation, but the integrated form of the Michaelis-Menten equation has no explicit solution for concentration and its handling requires a computer. However, the presented nonlinear equation of the first-pass effect is an explicit integration of the Michaelis-Menten equation and involves only general mathematics. However, the problem of evaluating the Michaelis-Menten constants Vm and Km is not resolved. Therefore, linear equations are also derived, which correspond to previous clearance models.

Biological Availability↗