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Biomedical subjects

P Wilding

Publications and source records attributed to P Wilding.

At least 19 recordsLinked to original sources

The application of backpropagation neural networks to problems in pathology and laboratory medicine.

Neural networks are a group of computer-based pattern recognition technologies that have been applied to problems in clinical diagnosis. This review focuses on one member of the group of neural networks, the backpropagation network. The steps in creating a backpropagation network are (1) collecting adequate training facts, (2) choosing the specific network structure, (3) training the network, and (4) cross-validating the trained network. The first published applications of backpropagation networks to problems in pathology and laboratory medicine have appeared recently. These applications are in the areas of image analysis and interpretation of laboratory results, and they demonstrate the feasibility of the approach.

Evaluation Studies as Topic

The impact of legislation on future technology development.

In this paper I examine some of the factors influencing technology development and attempt to explain whether CLIA '88 enhances the opportunities or exacerbates the problems for U.S.-based technology development. The viewpoint I express is concentrated on the clinical chemistry segment of the diagnostics arena.

Chemistry, Clinical

Application of neural networks to the interpretation of laboratory data in cancer diagnosis.

Neural networks are a relatively new method of multivariate analysis. The purpose of this study was to investigate the ability of neural networks to differentiate benign from malignant breast conditions on the basis of the pattern of nine variables: patient age, total cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-I, apolipoprotein B, albumin, the tumor marker CA15-3, and the Fossel index (measurement of methylene and methyl line-widths in proton NMR spectra). The laboratory analyses were made with blood plasma or serum specimens. The neural network was "trained" with 57 patients: 23 patients with breast malignancies and 34 patients with benign breast conditions. A neural network with nine input neurons, 15 hidden neurons, and two output neurons correctly classified all 57 patients. The ability of the network to predict the diagnoses of patients that it had no encountered in training was tested with a separate group (cross-validation group) of 20 patients. The network correctly predicted the diagnoses for 80% of these patients. For comparison we analyzed the same sets of 57 training patients and 20 cross-validation patients by quadratic discriminant function analysis. The quadratic discriminant function, calculated from the same 57 patients used to train the neural network, correctly classified 84% of the 57 patients, and correctly diagnosed 75% of the 20 cross-validation patients. The results suggest that neural networks are a potentially useful multivariate method for optimizing the diagnostic utility of laboratory data.

Antigens, Tumor-Associated, Carbohydrate

Effect of glycation of low-density lipoprotein on the immunological determination of apolipoprotein B.

Non-enzymatic glycation of low-density lipoprotein (LDL) may contribute to the premature atherogenesis of patients with diabetes mellitus. To assess whether glycation of apolipoprotein B, the predominant protein of LDL, interferes with the ability to immunologically quantify this protein, we prepared and purified glycated LDL by incubating normal plasma samples with high concentrations of glucose. Although both the plasma and the LDL specimens incubated with glucose contained significantly more glycated protein than control specimens, the quantitative interaction of an apolipoprotein B-specific antibody with glycated vs nonglycated LDL was not significantly different. We conclude that apolipoprotein B can be accurately quantified immunologically despite the presence of clinically excessive degrees of LDL glycation.

Apolipoproteins B

Macroenzymes: biochemical characterization, clinical significance, and laboratory detection.

"Macroenzymes" are enzymes in serum that have formed high-molecular-mass complexes, either by self-polymerization or by association with other serum components. Many enzymes in serum that are measured in clinical chemistry laboratories can occur in a macroenzyme form. Macroenzymes are interesting clinically because of their association with several diseases, including autoimmune diseases and liver disease, and are being investigated as possible diagnostic markers. Most importantly, macroenzymes frequently interfere with the interpretation of serum enzyme results, and as a result can cause diagnostic and therapeutic errors. We review the biochemical characterization, clinical significance, and laboratory detection of macroenzymes.

Autoimmune Diseases

Assessment of proton nuclear magnetic resonance spectroscopy for detection of malignancy.

Water-suppressed proton nuclear magnetic resonance spectra were generated (by using 360 and 500 MHz systems) from human plasma and serum samples taken from 35 apparently healthy individuals, 52 patients with overt malignancies, and 37 patients with hypertriglyceridemia (triglycerides greater than 200 mg/dL or 2.26 mmol/L). The line widths from the lipoprotein-lipid methylene and methyl resonances at approximately 1.3 and 0.9 ppm were averaged by the method of Fossel et al. (N Engl J Med 1986;315:1369-76), but, contrary to their findings, we were unable to distinguish normal individuals from those with malignant tumors (e.g., mean +/- SD line width at 360 MHz: normal group = 32.9 +/- 3.6 Hz, malignant group = 28.3 +/- 4.9 Hz). The average line-width measurements (y), however, varied with the triglyceride content (x, mg/dL) of the plasma or serum as follows (logarithmic transformation of the data determined at 360 MHz and regression analysis): y = 110 (x-0.27). Data from both nonmalignant and malignant specimens fit this equation, the coefficient of correlation being -0.91. These findings suggest that considerable caution should be used in interpreting water-suppressed proton NMR spectra for cancer detection.

Adult

The "intelligent workstation" for cell-surface phenotyping based on principles of pattern recognition and image analysis.

Technical advancements in computer hardware and the associated computerized architectures allow the design and fabrication of dedicated, modestly expensive computerized workstations to aid humans in complex decision-making tasks. We refer to these as "Intelligent Workstations" because they accommodate the hypothesis-driven reasoning ability of the user into the system. Concomitant with the rapid developments in computers, diagnostic and therapeutic technologies related to cell analysis have undergone growth. Combining these technologies requires careful formulation and analysis of the diagnostic model involving image cytometry. Here we present a model of the intelligent workstation for image cytometry and illustrate its advantages in cell-surface phenotyping. Combining cell morphology with cell-surface phenotyping has clear diagnostic utility that no other widely available methods can supply. Although the reported results are based on samples of peripheral blood, cell suspensions of disaggregated cells can also be analyzed.

Aged

Fc receptors for IgG on human neutrophils: analysis of structure and function by using monoclonal antibody probes.

Structural and functional characteristics of Fc receptors for IgG (Fc gamma) on human neutrophils were examined with two monoclonal antibody probes specific for the Fc gamma receptors, Leu 11b and 3G8. To determine the distribution, density, and membrane mobility of the Fc gamma receptor, we used immunogold staining techniques, flow cytometry analysis, and fluorescence microscopy. Both 3G8 and Leu 11b inhibited several cell functions, thereby depicting the regulatory role of the Fc gamma receptor in mediating neutrophil activities. Among the functions studied were release of lysosomal enzymes, release of superoxide anion (O2-), and Fc-dependent rosette formation and phagocytosis. The densities of Fc gamma determinants recognized by Leu 11b and 3G8 on cells from a patient with chronic myelogenous leukemia were less than the density of epitopes on neutrophils from a normal individual. Taken together, the detailed analysis of physical and functional aspects of the Fc gamma receptor on neutrophils described in this study serve as a model for further assessment of the use of Fc gamma phenotyping of cells as a diagnostic tool.

Antibodies, Monoclonal

Use of pattern recognition technology for determination of the human differential leukocyte count.

The imprecision, inaccuracy, and clinical sensitivity of an automated differential counter based on pattern recognition technology (HEMATRAK model 590) were evaluated using the NCCLS standard H20-T. The data show that the instrument is capable of performing assays in a manner comparable with the reference method proposed by NCCLS. In addition, data are presented from a multicenter study involving 174 HEMATRAK instruments which showed that the automated systems produce results equivalent to manual procedures (based on approximately 350 individual assays).

Evaluation Studies as Topic

Spectral analysis of urinary reactions: a preliminary study based on a novel concept.

The concept of spectral analysis of urinary reactions (a range of simple chemical tests combined with pattern analysis) is described. A preliminary study in which we used 10 nonspecific tested on untimed urine specimens from 20 controls and 20 diabetics, matched for age and sex, suggested that a combination of these tests could be used to separate diabetics from healthy subjects. This combination, however, did not prove satisfactory for a further group of 13 diabetics. Closer examination revealed that factors such as therapy and glycosuria affected the results of these tests. This approach, which should extend the usefulness of urinalysis, may prove viable when larger groups, and possibly a different set of tests, are used to establish a more robust combination of tests.

Adult

Drug interference in clinical chemistry: studies on ascorbic acid.

The expert group "Drug Interference in Clinical Chemistry" of the Bureau of Reference, Directorate General for Research, Science and Education of the Commission of the European Communities, consisting of one participant of each member of the European Communities, presents this first report on the final results of its activities. Within the framework of a first stage basic program, the paper describes interferences of therapeutic and elevated doses of ascorbic acid on commonly used clinical chemical methods. This is the result of a bipartite study that was jointly planned, carried out and evaluated. Local and personal influences have been eliminated, as have variations due to methodology, measurement equipment and reagents, in order to be able to present distinct causal effects of ascorbic acid. No definite influence of ascorbic acid on analytical values for urea, cholesterol, calcium, protein, bilirubin, aspartate aminotransferase and alkaline phosphatase could be detected. At therapeutic concentrations, ascorbic acid distinctly interferes with the analysis of glucose, uric acid, creatinine and inorganic phosphate. The extent and direction of interferences vary, depending on the type of reaction, kit and apparatus. In some cases the influence of ascorbic acid results in severe disturbance of the analytical methods leading to useless values.

Ascorbic Acid