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Biomedical subjects

W J Dunn

Publications and source records attributed to W J Dunn.

At least 19 recordsLinked to original sources

A critical view of the rationale for routine, initial and periodic radiographic surveys.

Most dentists and dental faculties use an initial radiographic survey for the comprehensive-care patient rather than selective radiography, as recommended by professional organizations and radiation protection agencies. Survey or screening radiography has been justified in the belief that it is an essential health service designed to disclose serious occult disease and that failure to use such films might expose the dentist to successful malpractice litigation. However, incidence data indicate the chance of disclosing tumors, non-inflammatory cysts or other serious bone disease in the asymptomatic patient by screening jaw films is infinitesimal. On this basis, the practice is not justifiable as a public health measure, nor is the dentist who follows published national guidelines for prescription radiography vulnerable to successful litigation.

Canada

QSAR approaches to predicting toxicity.

Due to the demands of time and the high cost of testing compounds for toxicity in test animals, it would be an advantage to be able to estimate the toxic response of chemical agents using theoretical approaches. Predicting whether a compound will be toxic or nontoxic is a classification problem and the methods of studying quantitative structure activity relationships (QSAR) can be used for this purpose [Hansch, C. (1969) Accounts Chem. Res., 2, 232]. It should be recognized, however, that formulating the QSAR problem as one of active vs. inactive makes it different from classical QSAR problems. This requires that methods be applied that can predict the category of a compound to be used, i.e., so-called methods of pattern recognition (Varmuza, K. (1983) J. Chem. Info. Comp. Sci. 23, 6) being required. There are several methods of pattern recognition that can be used with some being more suitable than others. The nature of this unique QSAR problem, the appropriate methods to apply, and some of the pitfalls of applying QSAR techniques to predicting toxicity are discussed.

Computer Simulation

Choroidal malignant melanoma with early vitreous seeding.

Primary choroidal malignant melanoma with extension through the overlying retina is a rarely reported entity, and to our knowledge actual seeding of the vitreous has never been reported. The pathologic findings in a 41-year-old woman who presented with a large amelanotic subretinal mass near the optic disc of the right eye are discussed. Fundus examination preoperatively revealed a concentration of discrete, fleshy, oval to round, vitreous bodies of varying size, limited to the area overlying the mass. Histopathology of this tumor revealed a spindle cell posterior choroidal melanoma with marked atrophy of the overlying retina. At the apex, the retina was discontinuous and melanoma cells extended into the overlying vitreous. Some of the cells surrounded asteroid bodies overlying the tumor, altering their clinical appearance. This behavior, while only involving a small fraction of the tumor cells, may imply a more aggressive tumor.

Adult

The role of solvent-accessible surface area in determining partition coefficients.

The logarithm of the partition coefficient (log P) of low-molecular-weight organic compounds is a physicochemical parameter used extensively in structure-biological activity studies to model interactions of the compounds with nonpolar phases in vitro and in vivo. The partition coefficient can be determined between water and a number of nonpolar solvents. The most common nonpolar solvent is 1-octanol, but solvents such as benzene, carbon tetrachloride, and chloroform are frequently used as models for the nonpolar phases. The functional relationship between chemical structure and partitioning is not well-understood. In this paper, partition coefficient data for 50 solutes in six nonpolar solvent systems are analyzed by using principal components analysis. The objective of the work is to explore the relationship between solute structure and partitioning behavior for simple organic compounds. Two structural factors are found to be important, with the isotropic surface area being the most important. The isotropic surface area can be used to estimate log P in some solvents and as an independent variable in quantitative structure-activity relationships (QSAR). This is illustrated by estimating the rate of epidermal diffusion of steroids.

Diffusion

Botulinum toxin for the treatment of dysthyroid ocular myopathy.

Eight consecutive patients with acquired deviations due to dysthyroid ocular myopathy were injected with botulinum A toxin for relief of their diplopia. Seven patients were acute in the onset of symptoms and one was chronic. All showed improvement in motility and experienced a reduction if not total relief of their symptoms. Six patients required reinjection. Complications were limited to transient ptosis, transient involvement of adjacent muscles and transient but prolonged paralysis that eventually resolved. No systemic complications were noted. We conclude that chemodenervation with botulinum A toxin may have a role in the management of dysthyroid ocular myopathy not amenable to prism treatment and may act as an adjunct to or eliminate the need for surgical correction in some patients.

Adult

Toxicity modeling and prediction with pattern recognition.

Empirical models can be constructed relating the change in toxicity to the change in chemical structure for series of similar compounds or mixtures. The first step is to translate the variation in structure to quantitative numbers. This gives a data table, a data matrix denoted by X, which then is analyzed. The same type of the models can be used to relate the variation of in vivo data to the variation of a battery of in vitro tests. A single data analytical model cannot be applied to a set of compounds of diverse chemical structure. For such data sets, separate models must be developed for each subgroup of compounds. The data analytical problem then partly is one of classification, pattern recognition (PARC). The assumption of structural and biological similarity within each subset of modeled compounds is then essential for empirical models to apply. PARC is often used to classify compounds as active (toxic) or inactive. The data structure is then often asymmetric which puts special demands on the data analysis, making the traditional PARC methods inapplicable. Depending on the desired information from the data analysis and on the type of available data, four levels of PARC can be distinguished: (I) the data X are used to develop rules for classifying future compounds into one of the classes represented in X; (II) same as I, but the possibility of future compounds belonging to "unknown" classes not represented in X is taken into account; (III) same as II, plus the quantitative prediction of one activity variable (here toxicity) in some classes; (IV) same as III, but several quantitative activity (toxicity) variables are predicted.

Mathematics