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P Wilding

Publications and source records attributed to P Wilding.

At least 37 records · Page 2Linked to original sources
PubMed1995

Association of Glu 27 beta 2-adrenoceptor polymorphism with lower airway reactivity in asthmatic subjects.

Cells expressing the Glu 27 beta 2-adrenoceptor polymorphism show attenuated down-regulation of the receptor after long-term exposure to agonist. We studied beta 2-adrenoceptor genotype for the Gln/Glu 27 polymorphism and airway reactivity in 65 patients with mild to moderate asthma. Glu 27 homozygotes had a four-fold higher geometric mean methacholine PD20 (provocative dose) than individuals who were homozygous for the wild-type (Gln 27) form of the receptor; heterozygotes had an intermediate value (3.23, 0.86, 1.96 mumol, respectively). These data suggest that beta 2-adrenoceptor genotype is important in the establishment of the asthmatic phenotype.

Adult↗
PubMed1995

A comparison of the effects of inhaled furosemide and ethacrynic acid on sodium-metabisulfite-induced bronchoconstriction in subjects with asthma.

Inhaled furosemide prevents bronchoconstriction induced by a number of challenges in asthma. One approach to determine the mechanism underlying this protection has been to examine the effects of diuretics with different or overlapping pharmacologic effects. We have compared the effects of furosemide on sodium metabisulfite-induced bronchoconstriction with those of equivalent diuretic doses of ethacrynic acid, a loop diuretic that, unlike furosemide, does not interact directly with the membrane Na/K/Cl cotransporter protein or inhibit carbonic anhydrase. Eight subjects with mild asthma were studied on five occasions, receiving nebulized furosemide (20 and 40 mg), ethacrynic acid (25 and 50 mg), or placebo (normal saline) in random order and double-blind 10 min before a cumulative dose challenge with inhaled sodium metabisulfite. After placebo the geometric mean sodium metabisulfite PD20 was 7.9 mumol. Furosemide 20 mg and 40 mg increased the PD20 by a mean 1.1 (95% confidence interval, -0.2-2.4; p > 0.05) and 1.6 (0.4-2.9; p < 0.02) doubling doses to 17.1 and 24.7 mumol, respectively. After inhaled ethacrynic acid 25 mg and 50 mg, the geometric mean PD20 was increased by 0.9 (-0.4-2.2; p > 0.05) and 1.5 (0.2-2.8; p < 0.05) doubling doses to 14.5 and 22.4 mumol, respectively. Thus, equivalent diuretic doses of furosemide and ethacrynic acid have a similar inhibitory effect on sodium metabisulfite-induced bronchoconstriction in asthma. This suggests that interaction with the Na/K/Cl cotransporter protein, or carbonic anhydrase inhibition, is not relevant to the effects of furosemide in asthma.

Administration, Inhalation↗
PubMed1995

The changing role of the clinical laboratory scientist: coming out of the basement.

The position of clinical chemistry within the discipline of laboratory medicine is firmly established. As a result, pathologists, chemists, and scientists have been attracted to an emerging field full of promise and expectations. For most, the expectations of a rewarding career and growth of the discipline have been met. However, in a climate where factors such as "capitation" and "managed care" influence every facet of healthcare, many are reviewing their expectations and wondering whether the 21st century will bring the same promise enjoyed by the pioneers in the 20th century. In the future, laboratory scientists must align their expectations to the demands for new technologies, medical practices, and healthcare systems that will require justification for all activities, expense, and personnel. To succeed in this new environment, the clinical chemist will need excellent managerial skills, an understanding of how to articulate the benefits of technologies and laboratory tests, and a willingness to embark on a career of unceasing education.

Career Choice↗
PubMed1994

Application of backpropagation neural networks to diagnosis of breast and ovarian cancer.

Neural network programs have been developed in an attempt to improve the diagnosis of breast and ovarian cancer using a group of laboratory tests and the age of the patient. The laboratory tests employed in this study include albumin, cholesterol, HDL-cholesterol, triglyceride, apolipoproteins A1 and B, NMR linewidth (the Fossel Index) and a tumor marker (i.e., CA 15-3 or CA 125). The breast cancer study involved 104 patients (45 malignant and 59 benign subjects). The ovarian cancer study involved 98 individuals (35 malignant, 36 benign and 27 control subjects). Methods are outlined for identification of the most influential input parameters and optimization of network structure and training. Network characteristics were contrasted with the test results of the appropriate serum tumor marker assay. For the breast cancer study, the best neural network program, using six input parameters, had a sensitivity of only 55.6% and a specificity of 72.9%. The tumor marker CA 15-3 alone gave results of 61.3% and 64.4%, respectively. For the ovarian cancer study, the best neural network program, using six input parameters, had a sensitivity of 80.6% and a specificity of 85.5%. The tumor marker CA 125 alone gave results of 77.8% and 82.3%, respectively. These methods provide an objective approach to neural network optimization and parameter selection applicable to other data bases of clinical and laboratory data.

Biomarkers, Tumor↗
PubMed1994

Circulating levels of IgG1 and IgG4 anti-IgE antibodies and asthma severity.

In this paper, we have determined the levels of IgG1 and IgG4 anti-IgE in the sera of 66 asthma patients suffering from mild (n = 24), moderate (n = 23), or severe (n = 19) symptoms, and 20 nonatopic, healthy subjects. The study has revealed that although asthma patients have significantly elevated levels of IgG1 and IgG4 anti-IgE antibodies, the concentration of these autoantibodies is not related to the severity of asthma. This conclusion may be related to the known heterogeneity of autoanti-IgE antibodies in terms of their ability to trigger basophil histamine release.

Adolescent↗
PubMed1994

PCR in a silicon microstructure.

Devices for performing polymerase chain reactions (PCR) have been developed for use with photolithographed silicon. Microchambers capable of holding between 5.0 and 10 microL of PCR reagents were constructed by etching specific areas of rectangular silicon chips (17 x 15 mm), which were then capped with Pyrex glass. These silicon devices (PCRChips), which were etched to depths of 40-80 microns, permitted free flow of fluids in the microchannels and microchambers. Access to the microchambers was through holes in the silicon. Thermal cycling of the PCR reagents was achieved by placing the disposable PCRChip in a small holder containing a computer-controlled Peltier heater-cooler. Successful amplification was demonstrated by electrophoresis of products in agarose gel containing ethidium bromide, and the migration of the product was compared with that obtained in a commercially available thermal cycler. The thermal characteristics of the silicon, coupled with the high surface area to volume ratio in the new devices, are particularly advantageous features for amplification by PCR.

Bacteriophage lambda↗
PubMed1994

Manipulation and flow of biological fluids in straight channels micromachined in silicon.

Analysis of minute sample volumes is a major analytical challenge that requires an understanding of fluid flow in microstructures. Accordingly, flow dynamics of biological fluids and cell suspensions in straight glass-capped silicon microchannels (40 to 150 microns wide, 20 and 40 microns deep) were studied. We demonstrated that these microstructures are appropriate components for microfluidic analytical devices. Different fluids were easily manipulated in the microchannels, and measurements of flow rate as a function of pressure for whole human blood, serum, plasma, and cell suspensions revealed non-Newtonian behavior. By means of micromachined filters (5 microns) located in channels, blood cells and microparticles were effectively separated from nanoliter-sized samples, clearly indicating the future role of microstructures for a variety of analytical purposes.

Albumins↗
PubMed1993

Applications of a microfabricated device for evaluating sperm function.

Mesoscale structures (microns dimensions, nL-pL volumes) have been designed and fabricated in silicon for use in various analytical tasks. We studied sperm motility and performed sperm selection in channels (80 microns wide x 20 microns deep), branching structures (40 microns wide x 20 microns deep, eight bifurcations), and channels containing barriers (7 microns feature size). Sperm-cervical mucus and sperm-hyaluronic acid interactions were assessed by using appropriate microchannel-chamber structures filled with either cervical mucus or hyaluronic acid. Simultaneous assessment of the potency of different spermicides (e.g., nonoxynol-9, C13G) and spermicide concentrations was achieved with structures comprising chambers containing spermicide connected via channels to a central chamber into which semen was introduced. Semen was also tested for the presence of sperm-specific antibodies by using microchannels filled with human anti-IgG antibody-coated microbeads.

Humans↗
PubMed1993

Evaluation of a novel point-of-care system, the i-STAT portable clinical analyzer.

We evaluated a novel system designed for rapid, point-of-care measurement of sodium, potassium, chloride, urea nitrogen, glucose, and hematocrit. The i-STAT Portable Clinical Analyzer (PCA) system is composed of a hand-held analyzer and disposable cartridges. Sample analysis takes place in the cartridge, which contains a series of thin-film electrodes microfabricated on silicon chips. The PCA was evaluated for precision, accuracy, and utility in emergency department and stat laboratory settings. Precision did not differ significantly between these two locations, the CVs being as follows: sodium, 0.46-0.89%; potassium, 1.06-1.45%; chloride, 0.69-2.76%; urea nitrogen, 2.54-6.12%; and glucose, 4.39-5.19%. The assessment of accuracy was based on comparison of patients' sample values analyzed by the PCA and the Kodak Ektachem 700 (or the Coulter ST for hematocrit). Regression statistics were acceptable for all analytes except chloride, for which the regression data were influenced by the limited range of results. A difference plot of the chloride comparison showed that the bias rarely exceeded 5 mmol/L. Mean hematocrit values significantly differed between the PCA and the Coulter ST, apparently because of different calibration procedures.

Blood Chemical Analysis↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗