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Biomedical subjects

J E Yingling

Publications and source records attributed to J E Yingling.

9 recordsLinked to original sources

Triazolam and zolpidem: a comparison of their psychomotor, cognitive, and subjective effects in healthy volunteers.

The psychomotor/cognitive performance, subject-rated, and observer-rated effects of single oral doses of the benzodiazepine hypnotic triazolam (0.125, 0.25, and 0.5 mg/70 kg) and the imidazopyridine hypnotic zolpidem (5, 10, and 20 mg/70 kg) were compared in 11 volunteers, in a double-blind, placebo-controlled, crossover design. Triazolam and zolpidem produced similar dose-related decrements on several performance measures, and similar dose-related increases on most observer-rated and several subject-rated measures. The drugs differed in the time course of their effects on these measures; the effects of zolpidem typically peaked 30 min earlier (1-1.5 h postdrug) than the effects of triazolam (1.5-2 h postdrug). Triazolam and zolpidem produced a different profile of effects on other performance measures which could not be attributed to time course differences. Triazolam produced significantly more impairment than zolpidem in time estimation. Triazolam, but not zolpidem, produced significant impairment on a short-term memory task. Zolpidem produced significantly more impairment than triazolam on several novel measures of performance on a computerized trail-making test. The observed differences between triazolam and zolpidem may be related to zolpidem's reported binding selectivity for the omega 1 receptor subtype.

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Effects of tetrahydrocannabinol content on marijuana smoking behavior, subjective reports, and performance.

This study investigated the smoking topography of marijuana and its effect on heart rate, subjective reports, and cognitive/psychomotor task performance. Male subjects (N = 12) with histories of moderate marijuana use smoked ad lib one cigarette containing 0, 1.3, or 2.7% delta 9-THC on separate days. Smoking topography measures revealed smaller puff and inhalation volumes and shorter puff duration for the high marijuana dose compared to the low dose. No other smoking behavior differed between the active doses. Heart rate was increased dose dependently over placebo levels. Active marijuana also increased subjective reports of drug effect over placebo, but not dose dependently. Significant memory impairment was observed on a forward and reverse digit span task, and performance was impaired on the digit symbol substitution task by the high, but not low, dose of marijuana. Performance on a divided attention task was not affected by marijuana. Thus, although subjects adjusted their smoking of cigarettes varying in THC content, dose-related effects of marijuana were obtained on several measures. The observed differences and individual variation in smoking topography measures suggest that precise control of smoking behavior would improve the accuracy of marijuana dose delivery.

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Carbon monoxide exposure from commercial brand cigarettes under controlled smoking conditions.

Carbon monoxide (CO) exposure from ultralow-, low- and high-CO delivery commercial cigarettes was examined under controlled smoking conditions. Seven chronic smokers of mid- to high-CO delivery commercial cigarettes served in the experiment. CO level increases of 2.10, 5.76 and 7.38 ppm were obtained from ultralow-yield (1.6 mg CO delivery), low-yield (5.9 mg CO delivery) and high-yield (14.3 mg CO delivery) cigarettes, respectively. Subjects achieved significantly higher increases in CO levels from both low- and high-yield cigarettes than from ultralow-yield cigarettes, but increased levels of CO from low- and high-yield cigarettes were not different from each other. The data suggest that degree of CO absorption by the lungs during a short period of time may limit increases in CO levels obtained from high-yield cigarettes.

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Human cigarette smoking: effects of puff and inhalation parameters on smoke exposure.

This study determined effects of three smoking behavior components: puff volume, inhalation volume and lung exposure duration on biological measures of smoke exposure. A microcomputer-based auditory feedback system allowed subjects (N = 9 or 10 per experiment) to control puff and inhalation parameters as they smoked usual brand cigarettes. In each of four experiments, one smoking parameter was manipulated across sessions while two other parameters were held constant. Biological samples were obtained before and after each 8-puff smoking session conducted under a given set of behavioral parameters for analysis of plasma nicotine and expired air carbon monoxide (CO) levels. In Experiment I, both nicotine and CO levels were influenced systematically as puff volume was varied from 15 to 60 ml (inhalation volume = 50% of vital capacity, lung exposure time = about 9 sec). Nicotine boost (post- minus presession levels) increased 4-fold and CO boost increased 9-fold over this range of puff volume values. In Experiment II, nicotine levels were unaffected when average lung exposure times varied from 5 to 21 sec (puff volume = 50 ml, inhalation volume = 50% of vital capacity), suggesting that all the nicotine available may be absorbed during a normal smoking inhalation cycle with no breathholding. CO levels increased systematically with longer breathholds. In Experiments III and IV, inhalation volumes from 10% and 20% to 60% of vital capacity had no effect on either nicotine or CO levels, and this was true whether lung exposure time was about 8 sec (Experiment III) or about 4 sec (Experiment IV). This series of studies has shown that puff volume is an important determinant of tobacco smoke exposure, but that inhalation components of smoking behavior, at least within the range of parameters tested, have no effect on nicotine exposure levels.

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Cigarette filter vent blocking: effects on smoking topography and carbon monoxide exposure.

Two studies were conducted using smokers of unventilated cigarettes to determine the effects of filter vent blocking on smoke exposure (Experiment 1) and smoking topography (Experiment 2). In both studies, subjects were exposed to ultra low yield cigarettes that had 0%, 50%, and 100% of their filter vents blocked with tape. In Experiment 1, carbon monoxide (CO) exposure from eight 60 ml puffs increased in an orderly fashion as a function of filter vent blocking. By blocking filter vents, smoke was no longer diluted with air as it passed through the filter, and hence, exposure to smoke constituents was increased. In Experiment 2, when puff and inhalation parameters were allowed to vary, subjects took significantly more puffs, and larger puffs from unblocked cigarettes than from completely blocked cigarettes, but CO exposure from the completely blocked cigarette was double that from the unblocked cigarette (8.96 ppm vs. 4.32 ppm). The increased number and volume of puffs taken from ultra low yield cigarettes with unblocked filter vents may be due to changes in physical characteristics of the cigarette, and not to smokers actively compensating for reduced smoke constituent yields.

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Minute-to-minute covariations in cardiovascular activity of conscious dogs.

Cardiovascular activity of chronically instrumented conscious dogs was monitored continuously during daily sessions of rest or of intermittent aversive stimulation. Data analysis of minute-to-minute averages revealed that cardiovascular variables changed in patterns, rather than as isolated independent events. Variations in cardiac output were highly positively correlated with concurrent variations in heart rate in all subjects under both conditions (mean r = +0.93). Variations in heart rate were two to five times as great as stroke volume, which was remarkably constant (coefficient of variation averaged only 4.6%). Variations in mean arterial pressure were consistently correlated with the variations in cardiac output (mean r = + 0.66) and heart rate (mean r = +0.68), but were poorly correlated with the small changes in stroke volume (mean r = -0.17) and total peripheral resistance (mean r = -0.16).

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Aversive conditioning of elevations in total peripheral resistance in dogs.

Operant conditioning experiments were performed with 12 chronically instrumented dogs to which aversive stimulation was presented whenever total peripheral resistance (mean pressure/cardiac output) decreased acutely below a criterion level. Initial experiments in which aversive stimulation occurred whenever total peripheral resistance decreased below mean base-line levels resulted in sustained decreases in total peripheral resistance, accompanied by elevations in heart rate, cardiac output, and arterial pressure. Subsequent experiments showed, however, that if aversive stimulation occurred only following large-magnitude decreases in resistance (30% below base-line levels), a progressive cardiovascular response pattern emerged during daily sessions of 5--16 h. This cardiovascular pattern included progressive elevations in resistance (10--50%), accompanied by progressive decreases or no change in heart rate and cardiac output and moderate increases in arterial (up to 20 mmHg) and pulse pressure. These within-session cardiovascular changes were accompanied by sustained inhibition of overt behavioral acitivity and progressive inhibition in respiratory activity. Implications of these observation for behavioral regulation of circulatory function are discussed.

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Cardiovascular responses to avoidance conditioning in the dog: effects of alpha adrenergic blockade.

Laboratory dogs were trained to press a response panel to postpone shocks during daily one-hour avoidance conditioning periods. Each dog was also confined in the experimental environment for 5 hours prior to the avoidance periods. Blood pressure and heart rate were monitored continuously during these experiments from chronically indwelling arterial catheters. Extended training resulted in the emergence of a cardiovascular response pattern during the pre-avoidance interval characterized by gradual increases in blood pressure together with decreases in heart rate. Elevations in both blood pressure and heart rate were sustained during the avoidance periods. During sessions in which alpha adrenergic activity was suppressed by phenoxybenzamine, absolute levels of blood pressure were found to be lower than during control (non-drug) sessions, but a progressive rise in blood pressure continued to be observed during pre-avoidance. These results suggest that sustained cardiovascular responses during avoidance periods are associated with activation of the sympathetic nervous system, but that the gradual rise in blood pressure during pre-avoidance is due to other factors.

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Total peripheral resistance changes in dogs during aversive classical conditioning.

The arterial pressure, heart rate, stroke volume, cardiac output and total peripheral resistance of laboratory dogs were monitored continuously before and during a 30 min period in which aversive classical conditioning procedures were applied. The experimental stimulation generated inhibition of behavioral activity ("freezing") together with sustained increases in arterial pressure averaging 30%, and increases in heart rate anc cardiac output of 60-70%. The calculated total peripheral resistance decreased by an average of 20%. The behavioral and cardiovascular responses were sustained during the aversive conditioning period. The results suggest that significant peripheral vasodilation occurred under these conditions which was probably not due to metabolic byproducts of behavioral activity, but probably reflected sympathetic cholinergic effects upon blood vessels in the skeletal muscles. These data document the significance of the skeletal muscle circulation in the total peripheral resistance to blood flow in unanesthetized animals.

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