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Biomedical subjects

D W Quinn

Publications and source records attributed to D W Quinn.

6 recordsLinked to original sources
PubMed2000

Pericardial mesothelioma: the diagnostic dilemma of misleading images.

A young man with a short history of increasing dyspnea, cough, and ascites was initially diagnosed as having idiopathic constrictive pericarditis and referred for an operation. The procedure revealed an atypical invasive encapsulating disease. Complete resection was impossible, and only partial relief of constriction was achieved. The patient died shortly after. Histology revealed primary mesothelioma of the pericardium. The case illustrates the difficulty in establishing this diagnosis by echocardiography and computed tomography.

Adult↗
PubMed1997

Parallel dermal subcompartments for modeling chemical absorption.

Understanding the absorption of chemicals through the skin is of importance to many fields of study. Biologically-based models can be used to simulate the absorption process and predict the rate of absorption and the amount of the chemical in various parts of the body and skin. When these models consist of physiological and biochemical parameters that can be measured, they can be extremely useful. When a model is appropriately validated, the results can be extrapolated across species to predict the effect of human exposure. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) models which predict the concentration of Dibromomethane in the blood of rats after dermal vapor exposure. These two new models expand a previously developed homogeneous skin model by adding parallel skin subcompartments to represent skin appendages and layered subcompartments to represent the distinct layers of the skin. The predictions of these new models match the experimental data better than the original homogeneous model, as well as being more physiologically descriptive. Sensitivity analysis showed us which parameters were the most sensitive to change and thus revealing the parameters we should be most concerned with measuring. After being properly validated, these models could be a great improvement over previous models in the ability to extrapolate results for different species, doses, and durations.

Animals↗
PubMed1996

Multilayered dermal subcompartments for modeling chemical absorption.

Dermal penetration of chemicals and drugs is of concern to both toxicologists and pharmacologists. Environmental professionals try to limit exposure to chemicals using protective clothing and gloves or barrier creams to trap chemicals. Drug developers try to enhance penetration of chemicals through the skin for medical purposes. Both can use predictive biologically-based mathematical models to assist in understanding the processes involved. These models are especially useful when they are based on physiological and biochemical parameters which can be measured in the laboratory. Appropriately validated models based on conservation of mass, diffusion and chemical transport by flow can be predictive of human exposures. In this paper we develop two new physiologically-based pharmacokinetic (PBPK) skin models to predict blood concentrations of dibromomethane in rats after skin-only vapor exposures. These new models improve the predictions of the blood concentrations especially at the beginning of the exposures. Sensitivity analysis shows that the permeability constants followed by partition coefficients have the most impact on blood concentration predictions. With proper validation the new models could be used to improve species, dose, and duration extrapolations of chemical or drug penetration. They could also be used to investigate and predict concentrations of drugs or chemicals in the skin.

Animals↗
PubMed1995

An improved approximation to the exact solution of the two-stage clonal growth model of cancer.

Multistage clonal growth models are of interest for cancer risk assessment because they can explicitly incorporate data on cell replication. Both approximate and exact formulations of the two stage growth model have been described. The exact solution considers the conditional probability of tumors arising in previously tumor-free animals; the approximate solution estimates total probability of tumor formation. The exact solution is much more computationally intensive when time-dependent cell growth parameters are included. The approximate solution deviates from the exact solution at high incidences and probabilities of tumor. This report describes a computationally tractable, 'improved approximation' to the exact solution. Our improved approximation includes a correction term to adjust the unconditional expectation of intermediate cells based on the time history of formation of intermediate cells by mutation of normal cells (recruitment) or by cell division in the intermediate cell population (expansion). The improved approximation provided a much better match to the exact solution than the approximate solution for a wide range of parameter values. The correction term also appears to provide insight into the biological factors that contribute to the variance of the expectation for the number of intermediate cells over time.

Algorithms↗