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Biomedical subjects

V A Benignus

Publications and source records attributed to V A Benignus.

43 records · Page 3Linked to original sources

Compensatory tracking in humans with elevated carboxyhemoglobin.

A total of seventy-four men divided into five groups performed a compensatory tracking task for 4 hr with group mean carboxyhemoglobin (COHb) levels of 0.9, 5.6, 6.1, 11.4 or 16.6%. In all but one group, COHb was formed in approximately 5 min by having the subject breathe a high concentration of carbon monoxide (CO) from a Douglas bag. An appropriate low level of CO in the exposure/test chamber maintained the elevated COHb for the 4-hr duration of the experiment. A slow COHb formation group, not exposed to CO during bag breathing, which was only exposed to low-level CO in the exposure/testing chamber, served as a positive control. Even though mean tracking error scores increased in a nearly monotone manner as a function of COHb, the effects were not statistically significant. Even at the highest dose, the increase in tracking error was small. The increased mean error score due to rapid formation was virtually the same as that due to slow formation.

Adult↗

Dose-effects functions for carboxyhemoglobin and behavior.

Literature on dose-effects functions of carboxyhemoglobin (COHb) and human behavior is internally inconsistent. A recent study was performed to describe such a function for tracking behavior in humans (7). No significant effects were found, however, even for COHb levels up to ca. 17%. The present review and analysis of published data was undertaken to attempt to reduce uncertainty about COHb dose-effects functions. Dose-effects data from six laboratory animal operant behavior studies were reviewed. Maximum COHb levels ranged from 33 to 59%. Data were converted to a common metric and dose-effects functions were fitted. The preferred function was nonlinear, with a shallow slope, indicating small effects (if any) for COHb levels less than ca. 20%. As COHb increased further, the slope of the function became progressively steeper. Review of the human dose-effects function publications for COHb and behavior revealed that no significant findings had survived the test of direct or partial replication. Other studies found no significant effects. A dose-effects curve was fitted to the human data from one study (7) and compared to the laboratory animal curves. Extrapolation of the human curve was used to suggest that the dose-effects curves for humans and laboratory animals were of similar form and that effects of COHb on behavior in man are small or absent below ca. 20%. It is also possible that some uncontrolled variables are affecting the results so that COHb produces effects only some of the time. No conclusion can be drawn from the body of literature due to the divergence of results.

Animals↗

Carboxyhemoglobin and brain blood flow in humans.

It has been shown that with increased carboxyhemoglobin (COHb) and associated decrease in blood oxygen-carrying capacity, a compensatory increase in brain-blood flow (BBF) develops. The BBF response in humans has been shown to be quite variable. Two experiments were conducted in which humans were exposed to sufficient carbon monoxide (CO) to produce COHb levels up to 18.4%. BBF was measured by the method of impedance plethysmography. The first was a pilot study in which BBF in 14 men was studied after transient exposure to various concentrations of CO in air. BBF increased as a function of COHb but not to the same extent (or at all) in some subjects. In a confirmatory experiment with 12 men, BBF was measured once per h during a 4-h experiment. All 12 subjects received CO. The variation of the BBF response among subjects was large and statistically significant whereas the variation over time was not significant. Thus it appears that the magnitude of the BBF response is unique for a given subject and differs across subjects. These results may help predict CO-induced behavioral decrements in future studies if subjects whose BBF response to COHb is small or absent are also more susceptible to impairment by acute CO exposure.

Carbon Monoxide↗

Increasing scientific power with statistical power.

A survey of basic ideas in statistical power analysis demonstrates the advantages and ease of using power analysis throughout the design, analysis, and interpretation of research. The power of a statistical test is the probability of rejecting the null hypothesis of the test. The traditional approach to power involves computation of only a single power value. The more general power curve allows examining the range of power determinants, which are sample size, population difference, and error variance, in traditional ANOVA. Power analysis can be useful not only in study planning, but also in the evaluation of existing research. An important application is in concluding that no scientifically important treatment difference exists. Choosing an appropriate power depends on: a) opportunity costs, b) ethical trade-offs, c) the size of effect considered important, d) the uncertainty of parameter estimates, and e) the analyst's preferences. Although precise rules seem inappropriate, several guidelines are defensible. First, the sensitivity of the power curve to particular characteristics of the study, such as the error variance, should be examined in any power analysis. Second, just as a small type I error rate should be demonstrated in order to declare a difference nonzero, a small type II error should be demonstrated in order to declare a difference zero. Third, when ethical and opportunity costs do not preclude it, power should be at least .84, and preferably greater than .90.

Data Interpretation, Statistical↗

Importance of experimenter-blind procedure in neurotoxicology.

The importance of having the investigator blind to the experimental condition of a human subject was demonstrated using meta analysis of 43 reports of the effects of carbon monoxide (CO) on behavior. It was shown that 75% of single-blind studies found significant CO effects as opposed to only 26% of double-blind studies (difference was significant, p < 0.005). It was also not possible to show that the difference could have been due to different CO exposure levels, different statistical practices, or different study group sizes. The failure to follow double-blind procedure has been partly responsible for disagreement about the effects of CO reported in the literature. Investigator blinding is also important in laboratory animal research.

Carbon Monoxide↗

Neurophysiological effects of 30 day chronic exposure to toluene in rats.

Long-Evans hooded rats were exposed to 1000 ppm toluene or 0 ppm toluene 6 hr/day, 5 days/week for 30 days. Following removal from the exposure conditions (18-26 hr) flash-evoked potentials were recorded to paired light flashes and pentylenetetrazol (PTZ) seizure properties were examined. No alterations were found in the response to the first flash, but alterations in the recoverability of the nervous system were demonstrated by significant latency shifts in the response to the second of the paired flashes, using first flash latencies as covariates. No significant alterations were found in PTZ seizures. The data indicated that at these exposure levels toluene produced a small but significant alteration in brain function, even after toluene had been completely metabolized.

Animals↗

EEG as a cross species indicator of neurotoxicity.

The electroencephalogram (EEG) is a promising measure in the field of neurotoxicology. It can be well quantified by techniques which can be interpreted both physically and statistically although not necessarily physiologically. Such quantification schemes are briefly discussed in this paper. However, the quantification of EEG is not trivial in either the mathematical or computational sense. The relationship of EEG to brain function or brain pathology is not very well understood by some standards, perhaps due to poor quantitative methods or erroneous assumptions about brain-behavior relationships. EEG has a similar appearance across species. Hence the measure has great promise as a cross-species indicator of neurotoxicity. Not many quantitatively sound neurotoxicological studies using EEG have been published. It must be strongly emphasized that (a) more methods development is needed before the promise of cross species generality can be realized and (b) naive and/or half-hearted attempts to use this measure are perilous.

Animals↗