Regulation of the mitochondrial oxidation-reduction state in intact hepatocytes by calcium ions.
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Acetoacetates↗
Biomedical subjects
D A Otto
Publications and source records attributed to D A Otto.
Stationary pattern adaptation and the early components in human visual evoked potentials.
Pattern-onset visual evoked potentials were elicited from humans by sinusoidal gratings of 0.5, 1, 2 and 4 cpd (cycles/degree) following adaptation to a blank field or one of the gratings. The wave forms recorded after blank field adaptation showed an early positive component, P0, which decreased in amplitude with spatial frequency, whereas the immediately succeeding negative component, N1, increased in amplitude with spatial frequency. P0 and N1 components of comparable size were recorded at 1 cpd. Stationary pattern adaptation to a grating of the same spatial frequency as the test grating significantly reduced N1 amplitude at 4, 2 and 1 cpd. The N1 component elicited at 4 cpd was attenuated in log-linear fashion as the spatial frequency of the adaptation grating increased. P0, on the other hand, was unaffected by stationary pattern adaptation at all combinations of test and adapting spatial frequencies, although P0 amplitude is known to be attenuated by adaptation to a drifting grating. Since N1, but not P0, was significantly attenuated following adaptation and testing at 1 cpd, it was concluded that the neurons generating these components are functionally distinct. The use of a common adaptation grating discounted the possibility that N1, but not P0, was affected due to a difference in the rates of retinal image modulation caused by eye movements made while viewing adaptation gratings of different spatial frequencies. The neurons generating N1 were adapted at a lower rate of retinal image modulation than that apparently required for adaptation of the neurons generating P0, which suggests a difference between these neurons in the rate of stimulus modulation necessary for activation.
Adaptation, Ocular↗
Rat and human visual-evoked potentials recorded under comparable conditions: a preliminary analysis to address the issue of predicting human neurotoxic effects from rat data.
Pattern-onset visual-evoked potentials (VEPs) were recorded from rats and humans in order to perform cross-species comparison of neuronal functional properties reflected by the early VEP components. The spatial frequency of a sinusoidal test grating was varied in Experiment 1. For both species, amplitude of the first positive VEP component was larger at low spatial frequency and decreased as spatial frequency increased. The immediately succeeding negative component was small at low spatial frequency and was of maximal amplitude at moderate spatial frequency. The effects of stationary pattern adaptation on these components were investigated in Experiment 2. Subjects viewed either a blank field or the test grating prior to recording VEPs. For both species, adaptation had no effect on the positive component but strongly attenuated the negative component. Experiment 3, in which only humans were tested, indicated that the negative component was of cortical origin. Only cortical neurons are known to be orientation selective, and the effect of adaptation diminished as the orientation difference between the adaptation and test gratings increased. These results suggest that the early positive and negative components arise from parallel visual pathways, and that the rat components may reflect visual processes qualitatively similar to those of humans.
Adaptation, Physiological↗
The comparative developmental neurotoxicity of lead in humans and animals.
The effects of lead on neurobehavioral development have been extensively investigated in humans as well as animals. This valuable lode of research findings offers a basis for comparing the developmental neurobehavioral toxicity of lead across species and for assessing the validity of animal models of developmental neurotoxicity. Comparisons of human and animal findings suggest that the greatest qualitative similarities involve relatively complex behavioral processes such as cognition and learning. Quantitative comparisons based on dose-response relationships for these endpoints are difficult to make because the relationships are sometimes nonmonotonic (U-shaped) and because blood lead levels may not be directly comparable between species. However, the lowest levels of exposure at which developmental neurobehavioral effects have been observed are similar: 10-15 micrograms/dl in children, less than 15 micrograms/dl in primates, and less than 20 micrograms/dl in rodents. Although the convergence between animal and human findings for other neurobehavioral endpoints is not as striking, sensory-evoked potentials and communicative processes offer two promising areas for continued investigation and cross-species comparison.
Animals↗
Reliability of selected tests from the neurobehavioral evaluation system.
NES is a widely used battery of tests designed for use in occupational health studies. Despite its widespread use, information on the reliability of the tests is limited. This article reviews the importance of test reliability and presents the results of analyses which were undertaken to examine the reliability of 11 tests and a mood rating scale contained in the NES. The NES tests were administered to 66 subjects on two testing days separated by a minimum of seven days. Seven tests were administered twice on each test day with a 3-hour interval between testing, and four of the tests were presented only once each test day. Test reliabilities were estimated for various summary measures for each test. Suggestions are made on the appropriate selection of tests and use of these.
Adult↗
Neurobehavioral test strategies for environmental exposures in pediatric populations.
The Agency for Toxic Substances and Disease Registry convened a workshop in Atlanta, GA, that evaluated approaches and methods to ascertain whether there are neurobehavioral sequelae to children and adults exposed to hazardous substances in the environment. This article, developed from that workshop, addresses the feasibility of employing extant neurobehavioral tests to screen pediatric populations. A matrix lists basic functions to be assessed during eight developmental periods ranging from birth to high school. The best of these neurobehavioral tests for pediatric populations and the types of assessment tools that are still needed are discussed. We make 10 specific recommendations to establish a hazardous substances neurobehavioral screen for pediatric populations, including appointing a review panel, developing a structured questionnaire, convening a conference on design and analysis, addressing minority and socially disadvantaged populations, coordinating adult and child assessment methods, information sharing among Federal agencies, baseline data, methodology research, research associated with hazardous worksites, and establishment of a pediatric databank.
Adolescent↗
Feasibility and validity of three computer-assisted neurobehavioral tests in 7-year-old children.
Three tests from the computerized Neurobehavioral Examination System (NES) were administered to a group of 917 Faroese children at approximately 7 years of age. The NES Continuous Performance Test (CPT) was modified to use animal silhouettes as stimuli instead of letters. Almost all children completed Finger Tapping (FT), the modified CPT, and Hand-Eye Coordination (HE). However, 18% of the children missed at least 25% of the stimuli on the CPT (full test period), and 37% of the children did not improve their HE performance by at least 10%, as compared to the first trial. Boys obtained better results than girls, and older children performed better than younger ones. However, both factors were confounded by acquaintance with computer games. Children who used glasses, who had strabismus, or who had decreased contrast sensitivity obtained less satisfactory scores, especially on CPT and HE. The NES performance was significantly associated with functional neurological performance, including catching a ball, diadochokinesia, and finger agnosia. Slight, though statistically significant, decrements were seen with increased levels of prenatal exposure to neurotoxicants, as indicated by the mercury concentrations in cord blood obtained at the time of birth. In conclusion, the tests were feasible in this age group after slight modifications, and the test results showed meaningful associations with major predictors, thus supporting the validity of the data.
Adolescent↗
Neurobehavioral Evaluation System (NES): comparative performance of 2nd-, 4th-, and 8th-grade Czech children.
The Neurobehavioral Evaluation System was designed for field studies of workers, but many NES tests can be performed satisfactorily by children as young as 7 or 8 years old and a few tests, such as simple reaction time, can be performed by preschool children. However, little comparative data from children of different ages or grade levels are available. Studies of school children in the Czech Republic indicate that 2nd-grade children could perform the following NES tests satisfactorily: Finger Tapping, Visual Digit Span. Continuous Performance, Symbol-Digit Substitution, Pattern Comparison, and simpler conditions of Switching Attention. Comparative scores of boys and girls from the 2nd, 4th, and 8th grades and power analyses to estimate appropriate sample size were presented. Performance varied systematically with grade level and gender. Larger samples were needed with younger children to achieve comparable levels of statistical power. Gender comparisons indicated that boys responded faster, but made more errors than girls.
Adolescent↗
The influence of vision on computerized neurobehavioral test scores: a proposal for improving test protocols.
Computerized tests of neurobehavioral function are frequently administered in neurotoxicological studies with little attention given to the optical properties of test stimuli or to the vision of subjects. Yet many test stimuli are small or briefly presented, and test endpoints often involve short reaction times. Stimulus detection and reaction time are known to be strongly dependent upon stimulus luminance, contrast, and size, as well as on the subject's visual abilities. The current study assessed the influence of visual contrast sensitivity on Neurobehavioral Evaluation System 2 (NES2) test results in three data sets. Analyses indicated that vision was associated with up to 24% of the variance (Hand Eye Coordination test) in NES2 scores, even when visual acuity was normal, and that vision often influenced the significance of group differences. It is suggested that researchers measure the luminance, contrast, and size of test stimuli, the distance from the subject's eyes to the monitor, and the subject's visual contrast sensitivity. The measurement and control of stimulus parameters and the inclusion of visual function scores in analysis models could reduce the variability among computerized test scores both within and between studies. Models that assess the influence of vision on computerized test results may help to identify the CNS domains and specialized functions adversely affected by neurotoxicant exposures.
Adolescent↗
Symposium on computerized behavioral testing of humans in neurotoxicology research: overview of the proceedings.
The Symposium on Computerized Behavioral Testing of Humans in Neurotoxicology Research, held in Portland, OR (USA), on June 21-23, 1995, is the subject of the 23 articles in this issue of Neurotoxicology and Teratology. It is the first open forum to focus exclusively on computer-implemented behavioral test methods for neurotoxicology. Both the Symposium and this proceedings have been organized around the topics: new technologies and new batteries, confounders and methodologic factors, special populations (children), sensory and motor testing, clinical applications, and neurotoxicology research. The Symposium emphasized common approaches to computerized testing, highlighted fundamental differences in strategies for the selection of tests, and produced tangible evidence that the NES2 test battery has become a pervasively used instrument for presenting valid tests in human neurotoxicology research. However, the dominant impression drawn from the Symposium is that there is a methodologic vigor in the field of computerized behavioral testing. This is revealed by the appearance of new test batteries, criticism of existing procedures, challenges to the existing order of test selection, and the identification of analytic covariates for commonly used tests.
Behavior↗
Impact of contrast sensitivity performance on visually presented neurobehavioral tests in mercury-exposed children.
Presentation of neuropsychological tests on a computer screen may involve a visual challenge to the examinee. The possible need for adjustment for visual contrast sensitivity on test performance was therefore determined from data on 917 mercury-exposed children who were examined at age 7 years. Contrast sensitivity was found to be associated with performance on the computer-assisted Continuous Performance Test. However, it showed similar associations with performance on traditional pencil-and-paper tests, especially Bender Visual Motor Gestalt Test and Wechsler Intelligence Scale for Children-Revised (WISC-R) Block Designs. Contrast sensitivity was not associated with prenatal mercury exposure, and adjustment for visual function had only a negligible effect on the regression coefficients for mercury as predictor of neuropsychological deficits. The mercury-associated neurobehavioral deficits are therefore unlikely to be due to mercury-induced visual system dysfunction causing secondary deficits in cognitive domain testing. Visuospatial processing appears to be a determinant in contrast sensitivity performance, and careful consideration of whether to control for contrast sensitivity in future studies of neurotoxicant effects is therefore recommended.
Bender-Gestalt Test↗
Neurobehavioral test performance in the third National Health and Nutrition Examination Survey.
The third National Health and Nutrition Examination Survey (NHANES III) contained three computerized neurobehavioral tests from the Neurobehavioral Evaluation System (NES): simple reaction time, symbol-digit substitution and serial digit learning. The neurobehavioral data that were collected came from a nationally representative sample of adults 20-59 years old. Performance on the tests was related to sex, age, education level, family income and race-ethnicity. Performance decreased as age increased, and increased as education level and family income increased. Differences in performance between sexes, levels of education and racial-ethnic groups tended to decrease as family income increased. The relationship between age and performance on the symbol-digit substitution test varied by education level and by racial-ethnic group. The relationship between age and performance on the serial digit learning test varied by racial-ethnic group. Questionnaire variables that were related to performance on one or more of the tests included the reported amount of last night's sleep, energy level, computer or video game familiarity, alcoholic beverages within the last 3 h and effort. Persons who took the tests in English or Spanish performed differently on the symbol-digit substitution and serial digit learning tests. Performance on all the tests decreased as test room temperature increased.
Adult↗
Lead absorption and psychological function in Zagreb (Croatia) school children.
A cross-sectional study was performed on 275 pupils from the third and fourth grade of three elementary schools (three urban areas with different traffic conditions) in Zagreb. Lead exposure was environmental, mostly through leaded gasoline. The difference in traffic density around the schools was consistent with biological indicators of lead absorption. The aim of the study was to clarify the relationship between characteristic biological indicators of lead absorption including indicators of hematological status with some psychological functions. Lead absorption in pupils was relatively low (mean blood lead: 70.8 +/- 17.88 microgram/L). Pupils' socio-economic status was evaluated by parents' education. The results obtained indicate that gender and school were associated with both biological and psychological variables. After adjusting for age, parental education, and gender, lead appears to have no association with cognitive or psycho-motor measures. The nonstandardized regression coefficients for blood lead-as a measure of the size of lead effect on VIQ, NIQ, and IQ-were -0.016, -0.031, and -0.025, respectively, all nonsignificant.
Child↗
Exposure of humans to a volatile organic mixture. I. Behavioral assessment.
Exposure to a low-level mixture of volatile organic compounds, typical of those found in new buildings, has been reported to impair neurobehavioral function in persons who have experienced sick building syndrome (SBS). Sixty-six healthy young males who had no history of chemical sensitivity were exposed for 2.75 h to a complex mixture of volatile organic compounds at 0 and 25 mg/m3. Even though subjects reported more fatigue and more mental confusion following exposure to volatile organic compounds than to clean air, performance on 13 neurobehavioral tests was not affected. Practice or learning effects were observed if administration of many behavioral tests were repeated. Further studies are needed to clarify the relationship of exposure to volatile organic chemicals, neurobehavioral performance, and subject characteristics, e.g., age, gender, and chemical sensitivity.
Adolescent↗
Exposure of humans to a volatile organic mixture. II. Sensory.
Time-course functions for symptoms of the sick building syndrome were derived from 66 healthy males who, during separate sessions, were exposed to clean air and to a volatile organic compound (VOC) mixture. The mixture contained 22 VOCs (25 mg/m3 total concentration) commonly found airborne in new or recently renovated buildings. Subjects rated the intensity of perceived irritation, odor, and other variables before, and twice during, 2.75-h exposure periods. Eye and throat irritation, headache, and drowsiness increased or showed no evidence of adaptation during exposure, whereas odor intensity decreased by 30%. These results indicate that irritation intensity and other symptoms are not related in any simple way to odor intensity, which suggests that the symptoms may not be a psychosomatic response to the detection of an aversive odor. Instead, subthreshold levels of VOCs may interact additively or hyperadditively and stimulate trigeminal nerve receptors. Also, air quality ratings improved by 18% during exposure, which suggests that both odor and irritation intensity may influence assessments of air quality.
Adolescent↗
Comparison of three methods for the estimation of total nitrogen losses in hospitalized patients.
Since the measurement of total nitrogen output (TNO) is not routinely determined in the clinical setting, its level is frequently estimated using formulas based on the urinary urea nitrogen excretion (UUN). We measured TNO in 124 surgical patients over 990 days (TNO, 19.22 +/- 8.72 g N/day; total urinary nitrogen (TUN) 18.17 +/- 8.70 g N/day; UUN, 15.17 +/- 7.70 g N/day; mean gastrointestinal nitrogen (MGIN) 0.68 +/- 0.49 g N/day; integumental nitrogen (ITGN), 0.34 +/- 0.08 g N/day) and compared the results with the daily estimations using three different formulas: formula A, UUN + 4; formula B, UUN x 1.20 + 1.05, where 1.20 is the reciprocal of the mean ratio UUN/TUN and 1.05 the mean extraurinary nitrogen losses; and formula C, UUN x 1.0986 + 2.55, derived from the regression analysis of UUN vs TNO. TNO estimated by these formulas were 19.17 +/- 7.70, 19.26 +/- 9.24, and 19.22 +/- 8.70 g N/day, respectively. The regression analyses of the estimated TNO from the three formulas versus the measured TNO indicated that formulas A, B and C were equally accurate in estimating TNO over the entire range of UUN. However, when only values of UUN greater than or equal to 30 g N were considered, a modified formula A (UUN + 6) was the best predictor of TNO. Daily audits of the differences between the estimated and measured TNO showed comparable results for the three formulas. In 28.4 to 31.1% of the observed days the differences were higher than +/- 2 g N/day, an error which is not acceptable when estimating the protein requirements in many clinical conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Neurotoxic chemical exposure scenarios and suggested solutions.
This manuscript reports the results of a problem-solving exercise presented to participants at a Workshop on Neurotoxicology Testing in Human Populations held in Rougemont, North Carolina in October, 1983. Response recommendations are the consensus of workshop participants. These are not comprehensive or definitive solutions and should be interpreted with caution. Each exposure scenario represents a "real world" situation previously encountered by neurologists and epidemiologists. Ideally, a toxin affects a single, easily tested modality early in the illness before producing a complex neurological syndrome. Unfortunately this rarely happens; difficult choices and compromises about testing are usually necessary. At the end of each scenario likely areas of early subtle dysfunction were discussed and possible testing methods were outlined. Working participants were instructed to comment on the approach to the scenarios and to add to or dispute the proposed tests. It is clear that there are no right or wrong answers; however, the participants were urged to try to reach some sort of consensus. In each instance participants assumed that they were being notified by the company and not by a state or federal agency, and were to determine what would be the most reasonable and effective way to offer help or obtain outside assistance in these situations.
Adult↗
Auditory and visual dysfunction following lead exposure.
The effects of lead exposure on cognitive function have been intensively studied during the past decade, but relatively little effort has been made to understand the impact on sensory function. Subtle impairments of visual and/or auditory processing, however, could have profound effects on learning. The objectives of this paper are to review what is known about the effects of lead exposure on visual and auditory function and to identify related research needs. In particular, the effects of lead exposure on sensory function in children, which have not been studied adequately, will be discussed. Evidence from human and animal studies reveal that lead exposure impairs auditory function. The cochlear nerve and more central structures appear to be preferentially sensitive in both developing and mature humans and experimental animals. Elevations in hearing thresholds and increased latencies of brainstem auditory evoked potential have been reported at low-moderate levels of lead exposure. Higher doses of lead increase the threshold of the auditory nerve action potential, produce segmental demyelination and axonal degeneration of the cochlear nerve, but appear to have no effect on cochlear microphonics or structure. Lead exposure affects both the retina and visual cortex of the developing and mature visual system. Low to moderate level developmental lead exposure produces selective rod deficits which can be detected with electrophysiological and behavioral techniques. At slightly higher levels of lead exposure the visual cortex is affected. A wide range of functional and neurochemical effects on retinal function occurring at blood lead levels below 20 micrograms/dl, the current level of concern, have been observed in rats. Structural, biophysical and photochemical similarities of rods in rats, monkeys and humans argue the relevance of this data for pediatric lead screening. To date, however, rod-mediated visual functions have not been examined in lead-exposed children. Undetected sensory deficits of these kinds may have profound impact on the motor and mental development of children as well as on the quality of life of affected adults. There is clearly a need for more extensive sensory testing in children and workers to screen for lead-induced health effects and in animal models to clarify the mechanisms of lead neurotoxicity.
Auditory Perceptual Disorders↗