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Biomedical subjects

R I Herning

Publications and source records attributed to R I Herning.

54 records · Page 3Linked to original sources

Blood cotinine levels as indicators of smoking treatment outcome.

Pretreatment blood cotinine levels, expired carbon monoxide levels, and self-reported cigarette consumption were evaluated as predictors of smoking treatment outcome in 114 patients. Of these indices of nicotine intake, blood cotinine level was the most useful predictor. High blood cotinine level was the best predictor of dropping out before completion of treatment and of smoking at the end of treatment and at follow-ups. The usefulness of cotinine as a marker of tobacco dependence is discussed.

Adult↗

Smokers of low-yield cigarettes do not consume less nicotine.

Advertisements suggest that smokers of cigarettes low in nicotine are exposed to less nicotine and tar. Nicotine yields are measured with smoking machines, but machines do not smoke cigarettes as people do. We therefore measured the actual nicotine content of commercial cigarettes with different nicotine and tar yields as determined with smoking machines, and also measured actual nicotine intake as indicated by blood concentrations of its metabolite, cotinine, in 272 subjects smoking various brands of cigarettes. We found that low-yield cigarette tobacco did not contain less nicotine; in fact, the nicotine concentration in tobacco inversely correlated (r = -0.53, P less than 0.05) with the concentration measured by smoking machines. Blood cotinine concentrations correlated with the number of cigarettes smoked per day but not with the nicotine yield measured by smoking machines. Only 3.8 to 5.0 per cent of total variance in blood cotinine was contributed by nicotine yield. We conclude that smokers of low-nicotine cigarettes do not consume less nicotine.

Adult↗

A comparison of methods for measuring event-related potentials.

Visual event-related potentials (ERPs) were recorded from 21 hyperactive children under 2 attention conditions and 4 doses of stimulant drug (methylphenidate). This data base was used to evaluate several methods of EP component measurement. These methods were (1) conventional visual peak and trough selection; (2) automatic feature extraction based on peaks; (3) automatic features extraction based on segments; (4) gross amplitude measures; (5) principal components analysis on normalized data and latency-adjusted data. No one method emerged as the best overall. Rather it is the case that different methods are best suited to different purposes, and criteria for choosing methods are outlined.

Brain↗

How a cigarette is smoked determines blood nicotine levels.

Indirect evidence suggests that smoking low-tar and nicotine cigarettes does not necessarily reduce exposure to these substances. Puff volume, duration and number, interpuff interval, and volume and duration of inhalation were measured while 11 subjects smoked two or four tobacco cigarettes. Nicotine blood levels and breath CO were measured before and after smoking. The machine-determined nicotine yields of the cigarettes correlated (r = 0.52) with the increase in nicotine blood levels after smoking but, when individual differences in smoking behavior were taken into account along with the nicotine yield, there was a stronger correlation with nicotine blood levels (r = 0.84 to 0.93).

Breath Tests↗

Puff volume increases when low-nicotine cigarettes are smoked.

Variables of smoking were measured when subjects smoked the first cigarette of the day after an eight- to 10-hour period of abstinence. The cigarettes smoked had high, medium, or low nicotine yields but the tar and carbon monoxide yields, taste, and draw characteristics remained constant. The number of puffs and interval between puffs did not differ between nicotine doses. The smokers took larger puffs, however, when smoking cigarettes delivering lower nicotine yields than their normal brands. This change in the size of puff must be attributed to the change in nicotine yield since all other characteristics of the cigarettes remained constant. Thus encouraging the smoking of low-nicotine cigarettes may increase exposure to combustion products and not appreciably decrease exposure to nicotine, since the smokers increased the size of their puffs in response to the decreased nicotine yield.

Adult↗

Evidence that cannabidiol does not significantly alter the pharmacokinetics of tetrahydrocannabinol in man.

The pharmacokinetics of delta 9-tetrahydrocannabinol (THC) administered intravenously was evaluated in four subjects after oral administration of placebo and 1500 mg of cannabidiol (CBD) according to a crossover design. The cannabidiol pretreatment had no apparent effect on THC pharmacokinetics, yet there may have been minimal effect on the formation and excretion of metabolites. The total (metabolic) blood clearance of THC averaged 17.4 ml/min/kg without CBD and 20.9 ml/min/kg with CBD, and was probably hepatic blood flow limited. The apparent steady-state volume of distribution averaged 9.86 (with CBD, 10.54) liters/kg. Irrespective of CBD pretreatment, the renal clearance of THC metabolites ranged from 17 ml/min after approximately 1 hr to 1.13 ml/min 3.5 days after dosing with THC. The apparent terminal halflife for metabolites averaged 8.2 days.

Adult↗

Metabolic and psychophysiologic studies of cannabidiol-hexobarbital interaction.

Cannabidiol (CBD), 600 mg/day orally for 5 to 12 days, inhibited hexobarbital metabolism in ten subjects. Hexobarbital oral clearance was 36% lower and apparent volume of distribution was 35% smaller, with no change in half-life during CBD. In four subjects who received intravenous and oral hexobarbital, systemic clearance was 36% lower while bioavailability was 10% greater during CBD. Hexobarbital increased fatigue and tremor, impaired eye-tracking performance, and altered the electroencephalogram. Hexobarbital effects were not affected by CBD. Inhibition of metabolism of other drugs should be considered when large amounts of CBD are taken or when CBD is used for therapy.

Absorption↗

Dissociation of autonomic and cognitive effects of THC in man.

Intravenous THC, 30--44.8 microgram/kg, was administered to four subjects. Each received THC on four occasions preceded by either i.v. saline, 0.04 mg/kg atropine sulfate, 0.2 mg/kg propranolol, or both drugs together. Heart rates, subjective intoxication and symptom ratings, time productions, and EEG activity were measured. In the absence of autonomic blocking drugs, THC produced characteristic tachycardia, subjective intoxication, and EEG effects. After combined autonomic blockade, THC had no effect on heart rate, while subjective and EEG changes remained as intense. These findings argue against the hypothesis that the subjective and EEG effects of THC are mediated by autonomic receptors or by interoception of peripheral autonomic actions of THC.

Adult↗

Changes in human event related potentials with prolonged delta-9-tetrahydrocannabinol (THC) use.

Auditory event related potentials and contingent negative variation (CNV) were recorded in a series of behavioral tasks from 27 hospitalized human volunteers before, early during (1--3 days), late during (10--14 days) and after chronic THC intoxication at two dose levels (70--90 mg/day or 180--210 mg/day in divided doses). Twelve additional hospitalized volunteers served as a control group. The N1 component of the auditory event related potential in all tasks was depressed when tested early during 180--210 mg/day THC administration. No N1 changes were seen for the subjects receiving 70--90 mg/day or the control subjects. Ten to 14 days during the chronic THC perioe CNV was depressed in all tasks except the control task for both doses at the early THC testing. Only at the most difficult task at the higher of the doses was the CNV depressed at the test late in the THC period. The changes seen in the N1 and the CNV may be indicative of different aspects of a common attentional alteration during stimulus processing. The results on our more difficult tasks suggest the alteration may continue in complex stimulus processing tasks in heavy marijuana users.

Attention↗

On the influence of task relevance and stimulus probability on event-related-potential components.

Fifteen subjects were presented with series of tones. Any one tone was either loud or soft, and in any one series the probability of one tone intensity was either 0.9 or 0.1. Subjects were instructed to count the frequent tones or to count the rare tones. The stimuli were also presented while the subjects were solving a word-puzzle. Event-related potentials (ERPs) were recorded from 9 scalp locations (F3, C3, P3, FZ, CZ, PZ, F4, C4, P4) referred to linked mastoids. ERP components were measured with a Principal Components analysis and the relations between these measures and the independent variables were evaluated with the ANOVA procedure. This paradigm allowed an evaluation of the effect of stimulus probability, stimulus relevance, and task relevance on the waveform of the ERPs. We conclude that the P350 component is enhanced whenever the eliciting stimulus is both rare and in some sense relevant to the subject's task and the degree of enhancement is greatest when the rare--relevant tone is loud. A "slow wave" component which follows P350 is related to the same variables but has a scalp distribution quite different from that of P350. The slow wave shows a progressive shift in polarity from negative to positive from the frontal to the parietal sites, while the P350 is of nearly equal amplitude (and positive) at the central and parietal sites and has a smaller (positive) and amplitude at FZ. A third prominent component, negative in polarity, peaking at about 210 msec, is most pronounced following rare stimuli, whether or not they were task relevant. The amplitude of N210 tended to be largest at the frontal electrode. This study then demonstrates that when suitable measurement techniques are used, multiple endogenous ERP components can be observed, each related to distinct aspects of cognitive behavior.

Acoustic Stimulation↗

A simulation study of the efficacy of stepwise discriminant analysis in the detection and comparison of event related potentials.

Cortical average evoked potentials were simulated by summing five damped sinusoids. The characteristics of these "evoked" responses could be manipulated by changing parameters of the sinusoids. The synthesized signals were mixed with noise processes whose power and band-width were manipulated. Thus data were generated to stimulate a variety of conditions which could conceivably occur in an experiment on evoked potentials. Stepwise discriminant analysis (BMD07M) has been applied to these simulated data in an attempt to determine the degree to which the program identifies, in a sensible manner, the differences we introduced into the synthesized evoked responses. The simulation results indicate that stepwise discriminant analysis can indeed be an efficacious tool in research on evoked potentials. The program does detect differences in evoked potentials. It can be used, with some reservations, to identify the components of an evoked potential which the experimental variables have affected. In a special set of simulations we have attempted to determine the degree to which stepwise discriminant analysis could serve to detect the presence or absence of an evoked potential. These simulations show that the score of an average evoked potential in the data. The implications of this finding to the use of evoked potentials in sensory sensitivity testing were evaluated in studies for the effect on them of stimulus intensity.

Electroencephalography↗

Clinical relevance of cannabis tolerance and dependence.

Psychoactive drugs are often widely used before tolerance and dependence is fully appreciated. Tolerance to cannabis-induced cardiovascular and autonomic changes, decreased intraocular pressure, sleep and sleep EEG, mood and behavioral changes is acquired and, to a great degree, lost rapidly with optimal conditions. Mechanisms appear more functional than metabolic. Acquisition rate depends on dose and dose schedule. Dependence, manifested by withdrawal symptoms after as little as 7 days of THC administration, is characterized by irritability, restlessness, insomnia, anorexia, nausea, sweating, salivation, increased body temperature, altered sleep and waking EEG, tremor, and weight loss. Mild and transient in the 120 subjects studied, the syndrome was similar to sedative drug withdrawal. Tolerance to drug side effects can be useful. Tolerance to therapeutic effects or target symptoms poses problems. Clinical significance of dependence is difficult to assess since drug-seeking behavior has many determinants. Cannabis-induced super sensitivity should be considered wherever chronic drug administration is anticipated in conditions like epilepsy, glaucoma or chronic pain. Cannabis pharmacology suggests ways of minimizing tolerance and dependence problems.

Cannabinoids↗

Cognitive brain potential alterations in boys exposed to opiates: in utero and lifestyle comparisons.

Several studies have observed that intrauterine exposure to opiates results in emotional and cognitive complications for the child, but genetic and postnatal social-environmental factors may also affect the CNS development of these children. To assess the relative contribution of the in utero and social-environmental (lifestyle) effects of opiate exposure, event-related potentials (ERPs) and performance were studied in three groups of 7- to 12-year-old boys: (1) the in utero/lifestyle group (IU/LS) contained 16 boys who were exposed to opiates (in utero and lived with opiate-abusing mothers, (2) the lifestyle group (LS) included 14 boys who lived with opiate-abusing mothers, and (3) the control group (CON) composed of 13 boys. The cognitive ERP components and task performance were recorded in the Auditory Rare Event Monitoring (AREM) task and the Sternberg Memory task (Sternberg, 1975). On the AREM and Sternberg Memory tasks, P200 component was significantly decreased for the IU/LS and LS groups. On the Sternberg Memory task, percent correct was also significantly impaired in IU/LS and LS groups. The ERP alterations in the boys living with opiate-abusing mothers with and without intrauterine opiate exposure were similar. A dysfunctional social environment may contribute to the cognitive deficits seen in the sons of opiate-abusing mothers.

Arousal↗