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Biomedical subjects

R H Luecke

Publications and source records attributed to R H Luecke.

8 recordsLinked to original sources

A mathematical analysis of human embryonic and fetal growth data.

There is no set of growth data from a single source for the human embryo/fetus which spans the full range of pregnancy. For mathematical and statistical analysis of the full gestational period, it was necessary to pool data from several sources. Three growth equations, which have been reported in the literature for various purposes, were tested and compared for possible use as a tool to describe the growth of the human embryo/fetus. Parameters were estimated using statistical procedures on the pooled data for the Verhulst logistic equation, a polynomial equation, and the Gompertz equation. The polynomial and Gompertz equations provided the best fit for the growth of the normal human embryo/fetus over the broadest range of 25 to 300 days, and especially in the critical period of development (gestational days 40 to 70). The relative rate of growth of the embryo/fetus was about 15% per day on the 25th day and declined progressively thereafter; the absolute rate of growth was the greatest at about the 240th day.

Embryonic and Fetal Development

Multifactorial modeling, drug interactions, liver damage and aging.

A well designed physiological flow model can be used not only to describe and analyze the basic elimination of a drug but also it can form the basis for multifactorial analysis in situations of multiple organ dysfunction and drug therapy. Physiological flow models use existent knowledge of anatomical structure and physiological processes along with the biochemical basis of drug elimination to calculate concentration-vs-time profiles of drugs in various organs and tissue regions. A tissue region or organ must be included in the model if it is an important site of storage, toxicity, elimination, or other significant pharmacological action. Such models can be a powerful tool in medicine providing a rational basis for multiple drug therapy in high risk patients with altered organ function--especially for drugs with a narrow margin of safety. For some specific types of drug systems, physiological flow model models exist which can accurately describe drug concentration profiles in tissues for a variety of situations. A definitive general model is theoretically possible; but, in practice, has not yet been developed. Future research could provide the necessary information to make multifactorial analysis a clinically useful tool in rational drug therapy.

Aging

Estimation of drug binding parameters.

Many methods have been suggested and tested to estimate the association constants and binding capabilities of ligand-macromolecule interactions from experimental data. This problem is a subset of the general problem of parameter estimation for nonlinear algebraic models where both the independent and dependent variables are subject to measurement error. It is often difficult to anticipate the effect on the parameter estimates that is caused by error in the primary measurements. In this work, a computer algorithm is described which finds the maximum likelihood estimate for the true values of the parameters and also estimates for the values of the measurements. It is applied to experimental binding data in two examples for fitting the association constants and binding capacities.

Dicumarol

A mathematical model and computer program for adriamycin distribution and elimination.

A mathematical physiological flow model is described for the distribution and elimination of adriamycin in the rat. The model includes the volume or mass of, and blood flow to the following tissues: heart, plasma, muscle, skin, kidney, bone marrow, gut, liver and bile. A compartment is also included for tight or almost irreversible binding which occurs with this drug. The program was written in FORTRAN to compute the concentration of drug in each tissue as a function of time after bolus injection or short term infusion. The computed data is printed on a line printer and recorded on disk for use in a SAS program GPLOT to obtain precision plots.

Animals

Drug elimination interactions: analysis using a mathematical model.

A mathematical model was developed to analyze the elimination kinetics of drug interactions in the rat. The model is based on physiological blood flow rates and organ weights and includes Michaelis-Menten equations for enzymatic processes which are involved in the elimination of the drug; competitive inhibition interactions are computed for shared pathways. Using data from the single drugs, the model can simulate the results of experiments of the acute warfarin-BSP interactions in rats.

Animals

Responses to preoptic temperature manipulation in the awake and hibernating marmot.

Responses of normothermic and hibernating marmots to manipulations of the preoptic-hypothalamic temperature (TPO) were studied. Independent variables included alteration of TPO and, during normothermia, room temperature. Hibernation occurred at an ambient of 6 degrees C. Dependent variables include brain, subdermal, and surface temperatures, heart rate, and behavioral, electromyographic cortical, and hippocampal responses. Although normothermic autumn marmots displayed most of the usual mammalian responses to alterations of the TPO, evidence of effective dermal vasomotion was not obtained. Single episodes of water drinking accompanied prolonged raising of the TPO; sleep was not elicited. During hibernation, effective central thermoregulation was not apparent until 3 or 4 days had elapsed. After this, thermoregulation was readily demonstrable in response to both raising and lowering the TPO. The apparent open-loop gains (OLG) for rise in body temperature after lowering of the TPO showed an exponential increase in value at lower prestimulus body temperatures. It was postulated that this could be explained on the basis of the recruitment of cold-sensitive neurones, which in turn would provide an explanation for the hypothesized "alarm temperature."

Animals

Microcomputer program for interactions in drug elimination in the rat.

In modern medicine patients often require multiple drug therapy. Such therapy can be modeled by a physiological flow model using interlinked differential equations to represent the differential rates of delivery and uptake of a drug by organs. Included in the model are the sites of action, toxicity, elimination and drug binding. A menu-driven computer program for this model was developed in FORTRAN 77 for execution on a microcomputer. The program computes the rate of uptake and concentration of drug in key tissues as a function of time. Drug administration can be modeled for bolus injection with up to 10 repeats and/or for continuous infusion of the drug. The drugs warfarin and adriamycin are used as illustrative examples. The program can handle multifactorial problems such as acute and chronic competitive elimination interactions, liver damage, and features of aging such as reduced drug binding and organ function. The computed results can be printed numerically or displayed graphically, either on a screen terminal or as hard copy. The results of several simulations may be cross-plotted for studies involving parametric changes such as would occur in multiple pathology and aging.

Animals