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Biomedical subjects

S A Burns

Publications and source records attributed to S A Burns.

At least 19 recordsLinked to original sources

Induction of interleukin-8 messenger RNA in heart and skeletal muscle during pediatric cardiopulmonary bypass.

BACKGROUND: Interleukin-8 (IL-8), the major neutrophil chemoattractant factor, contributes to inflammatory tissue injury by activating neutrophils and promoting their migration into tissue. IL-8 levels increase in serum of patients undergoing cardiopulmonary bypass (CPB). The purpose of this study was to determine if IL-8 gene expression is activated in tissues subjected to CPB with or without hypothermic arrest. METHODS AND RESULTS: IL-8 transcript levels were measured by ribonuclease protection in samples of human atrium and skeletal muscle from children before and after CPB for repair of congenital heart defects. Results were quantified by PhosphorImager. Atrial IL-8 mRNA levels increased during CPB in 14 of 16 patients tested (median increase, 2.9-fold; P = .0029). In skeletal muscle, IL-8 mRNA increased in 11 of 12 patients (median, 12-fold; P = .012). Degree of IL-8 induction in atrium and muscle was not directly associated with total support time or cross-clamp time. Transcript increase in skeletal muscle occurred with or without a period of circulatory arrest, suggesting that the stimulus of CPB alone was sufficient to induce message production. Baseline values for IL-8 mRNA varied widely among patients in atrium and skeletal muscle. In situ hybridization analysis revealed diffuse increase in IL-8 mRNA throughout the tissue after CPB, with striking increase in some small veins. CONCLUSIONS: We conclude that production of IL-8 mRNA occurs in most patients during CPB in both myocardium and skeletal muscle. This may result in high local IL-8 concentrations, contributing to the tissue injury after CPB.

Cardiopulmonary Bypass

P-selectin expression in myocardium of children undergoing cardiopulmonary bypass.

Cardiopulmonary bypass is a planned support technique that results in a period of myocardial ischemia and reperfusion. In addition, it is associated with an inflammatory response likely involving endothelial cell activation. In previous studies, we showed that E-selectin and intercellular adhesion molecule-1 (ICAM-1) messenger ribonucleic acid (mRNA) are increased in human myocardium after cardiopulmonary bypass. We have now examined the expression of P-selectin mRNA by ribonuclease protection in paired atrial biopsy specimens from 12 patients before and after cardiopulmonary bypass. By means of immunocytochemistry, we have also examined the endothelial cell surface expression of P-selectin protein, as well as that of E-selectin and ICAM-1 in three additional patients. Patient ages ranged from 1 day to 8.5 years (median 12 months), and cardiopulmonary bypass times ranged from 46 to 196 minutes (median 144 minutes). By ribonuclease protection, there was marked variability in the expression of P-selectin in biopsy specimens before bypass. However, when compared with prebypass levels, P-selectin mRNA decreased modestly in 10 of 12 patients after bypass (median decrease 1.5-fold, p = 0.016). As seen with immunocytochemistry, P-selectin protein was distributed diffusely through the vascular bed on large vessels and small vessels before bypass but was virtually absent on capillaries in specimens taken after bypass. E-selectin, which was absent in prebypass biopsy specimens, was induced in one of the three specimens after bypass, but no change in ICAM-1 protein expression above baseline was noted. We also find that cultured human endothelial cells treated with tumor necrosis factor-alpha in doses which induce ICAM-1 mRNA simultaneously decrease their expression of P-selectin mRNA as compared with untreated cells. These observations suggest that endothelial P-selectin is transcriptionally downregulated after cardiopulmonary bypass at times when E-selectin and ICAM-1 are induced. Furthermore, we find that E-selectin and ICAM-1 are expressed at times and at sites where P-selectin is absent. Although it is possible that P-selectin may have been induced and lost at early times before reperfusion, these data suggest that endothelial P-selectin plays a limited role in the inflammatory response that ensues after cardiopulmonary bypass.

Adolescent

Gender differences in schizotypic features in a large sample of young adults.

Research with self-report measures of schizotypic or psychosis-prone features in nonclinical populations suggests that, similarly to schizophrenic populations, males score higher on more "negative" schizotypic features and females score higher on more "positive" schizotypic features. We administered the Schizotypal Personality Questionnaire and the Chapman Scales of Psychosis Proneness--impulsivity/nonconformity, magical ideation, perceptual aberration, physical anhedonia, and social anhedonia--to a large, nonclinical, young adult sample (N = 1179: 453 males and 726 females). Results indicated increased negative symptomatology in males compared with females, but not increased positive symptomatology in females compared with males. Findings on Schizotypal Personality Questionnaire factors suggested that interpersonal deficits differed by gender as well. Finally, a measure of impulsive behavior and nonconformity not typically associated with negative symptomatology indicated gender differences not predicted by a negative/positive dichotomy.

Adolescent

Direct measurement of human-cone-photoreceptor alignment.

We have developed an imaging reflectometer to measure cone-photoreceptor alignment. One makes measurements by bleaching the cone photopigment and imaging the distribution of light returning from the retina, which is illuminated from a small source imaged in the plane of the eye's pupil. If the source is near the optimal entry pupil position as determined psychophysically, the distribution of light returning from the retina is peaked, and the magnitude of the peak depends on the location of the source in the pupil of the eye. If the source is far from the optimal entry pupil position, then there is no measurable peak. The location of the peak varies across individuals and coincides with the reported location of best visibility of the measuring light and with previous psychophysical and reflectometric measurements of the Stiles-Crawford peak. The source of this directionality must arise either from the photoreceptors or from behind the photoreceptors because the peak is not present if measurements are made when the cone photopigments have high optical density.

Adult

Analysis of nonlinearities in the flicker ERG.

The electroretinogram (ERG) response to steadily flickering fields shows significant nonlinear components. These nonlinear components have been used to investigate the ERG. We find the following. (1) The fundamental retinal response can be recorded at frequencies greater than 100 Hz and the second and higher harmonic responses have measurable response frequencies as high as 200 Hz. Both the fundamental response component and the second harmonic response component have multiple local maxima as a function of frequency. (2) Measurement of the response of the retina to the sum of two sine waves indicates that there is an early low-pass temporal filter in the retina. This early filter has a cutoff frequency between 40 and 50 Hz. (3) The high frequency nonlinearity is not a compressive nonlinearity.

Electroretinography

Aging and human cone photopigments.

We used a noninvasive technique to investigate changes in photoreceptor function with aging in observers 13-69 years of age. This technique, steady-state color matching, provides estimates of the optical density of cone photopigments, the illuminance that bleaches half of the photopigment, and the ratio of the primaries required at moderate light levels. In normal human retinas, we found that the optical density for a 4-deg field is affected minimally by aging from the second through the seventh decades. The average optical density is 0.27 +/- 0.054. The optical densities of older observers varied more than those of younger observers. The change in optical density with age is nonmonotonic, with slightly lower values for the youngest and oldest observers in our study. The retinal illuminance that bleaches half of the cone photopigment varied little across observers, averaging 4.37 log Td +/- 0.119. The change with age, which averages 0.00018 log Td per year over all observers, also is nonmonotonic. Moderate illuminance color matches did change with age, as expected, with a monotonic decrease with age in the ratio of the long-wavelength primary to the short-wavelength primary required for the color match.

Adolescent

A psychophysical technique for measuring cone photopigment bleaching.

A new, clinically applicable test has been developed to measure the bleaching of the foveal cone photopigments. This noninvasive test is called steady-state color matching. Steady-state color matching is based on the dependence of a color match on the optical density of the cone photopigments. By measuring the color match as a function of retinal illuminance, it is possible to compute the optical density of the cone photopigments at each illuminance. Thus, abnormalities of photopigment bleaching can be detected. This study demonstrates that the technique is readily performed by a clinical population. Patients with central serous retinopathy and retinitis pigmentosa are shown to have low effective optical densities.

Adolescent

Cone photopigment bleaching abnormalities in diabetes.

We have used a color-matching technique to obtain estimates of the optical density of cone photopigments as a function of retinal illuminance in patients with insulin-dependent diabetes mellitus (IDDM). We found that the half-bleach illuminance of some patients is abnormally high. That is, it takes more light to bleach an equivalent amount of photopigment in these patients. Since low illuminance color matches for these patients are normal, this implies that these patients have normal amounts of photopigment, but the photopigment is not bleaching normally. This result clearly points to abnormalities in the outer retina of these diabetic patients. The most likely causes of this abnormality are either decreases in the ability of the cones to absorb light, or an increased rate of regeneration of the cone photopigments.

Adolescent

Retinal toxicity of amphotericin B in vitrectomised versus non-vitrectomised eyes.

The retinal toxicity of intravitreally administered amphotericin B was compared in non-vitrectomised versus vitrectomised rabbit eyes. Doses of 5 and 10 micrograms in both groups resulted in transient vitritis but had no effect on electroretinograms. Histopathological examination four weeks after injection showed vitreous cells and minimal areas of retinal necrosis in both groups at 5 or 10 micrograms doses. At these doses vitrectomy did not modify the retinotoxic effects of intravitreally administered amphotericin B. At higher doses marked toxicity was found in both vitrectomised and non-vitrectomised groups.

Amphotericin B

Chromaticity discrimination: effects of luminance contrast and spatial frequency.

We examined the effects of luminance contrast and spatial frequency on chromaticity discrimination of grating bars. Alternate bars of gratings were filled with light of a standard wavelength and light that could be varied in wavelength. The observer set the variable bars to match the standard bars in hue. Discrimination, as measured by the standard deviation of the matches, decreased as spatial frequency increased. Luminance contrast did not improve chromaticity discrimination but did lead to Bezold-Brücke hue shifts that were spatial-frequency dependent.

Color Perception

Color matching at high illuminances: the color-match-area effect and photopigment bleaching.

We evaluated whether a self-screening hypothesis can account for changes in red-green color matches with changes in retinal illuminance and changes in the size of the matching field. The dependence of the color match on field size measured at moderate illuminances was not present at high illuminances. For color matches made with normal pupil entry, there was no need to postulate any factors other than self-screening to account for the changes with either illuminance or field size. The self-screening model allowed us to estimate the optical density of the foveal cones and the retinal illuminance that caused half of the photopigment to be bleached at equilibrium. These estimates were in quantitative agreement with previous estimates made using other techniques. We also found that the change in a color match with increasing illuminance was inconsistent with first-order kinetics.

Adult

The Abney effect: chromaticity coordinates of unique and other constant hues.

We compared unique and other constant hue loci measured at a fixed retinal illuminance for the same observers. When expressed in Judd chromaticity coordinates, unique hue and constant hue data agreed. Unique blue loci were curved, and unique red and green loci were noncollinear. These data imply that unique hues are not a linear transformation of color matching functions. Linear models are only an approximation, even at a single luminance level.

Color Perception

The inverse electro-oculogram.

An electro-oculogram ratio of less than one was found to be caused by limited ocular excursions under photopic conditions in a patient with a rod-cone dystrophy. Because this inverse electro-oculogram ratio was not caused by a decrease in standing potential under photopic conditions, it should be considered an artefact.

Adult

Brightness of equal-luminance lights.

The brightness of lights defined by heterochromatic flicker photometry as being of equal luminance was determined by direct comparison with a white standard. Stimuli included mixtures of white and colored lights. Eight different colorimetric purities were tested for each of eleven primaries. Adaptation to a known white was maintained. Resulting brightnesses were expressed in terms of the ratio of the amount of light required for a brightness match to the amount required for a flicker photometric match (B:F). B:F ratios varied with the primary, being largest for red and blue primaries. The variation of B:F ratio with colorimetric purity differed depending on the primary, although for any given dominant wavelength the highest-purity stimulus always had the largest B:F ratio. The data qualitatively exclude a number of simple models of brightness generation.

Color

Detection threshold for lights of varying purity.

Duration thresholds for hue substitution stimuli of various wavelenghts and colorimetric purity were determined. Results indicated an inverse relationship between duration thresholds and colorimetric purity. It was also found that short-wavelength sensitive (SWS) cones can contribute to the detection of low purity, short duration (less than 5 ms) stimuli.

Color