Biomedical subjects

B M Stone

Publications and source records attributed to B M Stone.

At least 37 records · Page 2Linked to original sources

PubMed1986

Modulation of catecholamine transmission and sleep in man.

The effect of modulation of catecholamine transmission on sleep in man was studied using mianserin (20 and 40 mg) and nomifensine (50 and 100 mg). It is suggested that reduced wakefulness induced by mianserin during sleep is primarily related to postsynaptic antagonism of alpha adrenoceptors, though a possible synergistic effect with antagonism of histamine H1 receptors cannot be excluded, while increased wakefulness with nomifensine is related to inhibition of the uptake of catecholamines and/or direct or indirect dopaminergic activity. The reduction in rapid eye movement (REM) sleep with both drugs is believed to be a non-specific effect which arises from a disturbance of the balance between monoaminergic and cholinergic influences.

Adult↗

PubMed1986

Hypnotics and transient insomnia.

An hypnotic should be used only when there is evidence of sleep disturbance. The wide range of sleep disorders (e.g. delayed sleep onset or problems of sleep maintenance) and the added complication that the patient may be involved subsequently in skilled work demand that the pharmacokinetics of various hypnotics must be understood before the correct hypnotic can be chosen. Impaired performance is more severe and persists far longer with compounds that are slowly eliminated and with the use of higher doses. The particular situations of aircrew and mountaineers have been studied in detail. Caution must be exercised in the management of aircrew coping with irregularity of rest and work. Temazepam has been used for aircrew for over 10 years and the absence of adverse effects ensures that it remains the recommended hypnotic in this area of medical practice. The relationship of insomnia with the hypoxic environment is undetermined. To investigate this, sleep was studied in six individuals during an expedition to the Himalayas. At altitude, temazepam led to less wakefulness and to drowsy sleep--there were no prolonged sleep latencies.

Altitude↗

PubMed1986

Irregularity of rest and activity: studies on circadian rhythmicity in man.

1. Rectal temperature, electrolyte excretion and performance were studied in young adults who followed an irregular pattern of work and rest for 9 days in an isolation unit. 2. In the analysis, effects evoked by the pattern of work and rest were separated from the oscillatory component, and rhythms for individual days were examined by the cosinor method. 3. During the schedule, rhythms no longer showed a period of exactly 24 h, and this effect was confirmed by studies using a repeated cycle of irregular work and rest and by studies using constant routines. 4. Temperature and urinary constituents differed in the strength and phase of their rhythms when corrected for evoked effects, as well as in the strength of the evoked effects themselves. 5. There was evidence of deterioration in performance during work periods which exceeded 9 h, but there was no evidence of progressive deterioration in performance over the 9 day schedule.

Activity Cycles↗

PubMed1986

Nocturnal sleep and daytime alertness of aircrew after transmeridian flights.

The nocturnal sleep and daytime alertness of aircrew were studied by electroencephalography and the multiple sleep latency test. After a transmeridian flight from London to San Francisco, sleep onset was faster and, although there was increased wakefulness during the second half of the night, sleep duration and efficiency over the whole night were not changed. The progressive decrease in sleep latencies observed normally in the multiple sleep latency test during the morning continued throughout the day after arrival. Of the 13 subjects, 12 took a nap of around 1-h duration in the afternoon preceding the return flight. These naps would have been encouraged by the drowsiness at this time and facilitated by the departure of the aircraft being scheduled during the early evening. An early evening departure had the further advantage that the circadian increase in vigilance expected during the early part of the day would occur during the latter part of the return flight.

Adult↗

PubMed1985

Histaminergic systems and sleep. Studies in man with H1 and H2 antagonists.

Effects of H1 (mepyramine, mequitazine, triprolidine and brompheniramine) and H2 (cimetidine and ranitidine) antagonists on sleep were studied in healthy man. There were no effects of mepyramine (50 and 100 mg), and the only effect of mequitazine (5 and 10 mg) was a reduction in the number of awakenings. Triprolidine (10 and 20 mg) and brompheniramine (4 and 8 mg) did not alter wakefulness during sleep or the total sleep time, but rapid eye movement sleep was reduced. There were no effects of ranitidine (150 and 300 mg), but slow wave sleep was increased by cimetidine (200 and 400 mg). It is tentatively suggested that the histaminergic system is concerned with the mechanisms which favour vigilance during the wakeful state, and the balance between wakefulness and slow wave activity during sleep. Effects of some H1 antihistamines on rapid eye movement sleep are believed to be due to their monoaminergic rather than their histaminergic activity.

Adolescent↗

PubMed1985

Central effects during the continuous osmotic infusion of a benzodiazepine (triazolam).

The effects of relatively constant plasma levels of a rapidly eliminated benzodiazepine (triazolam) were studied in young healthy males to determine whether tolerance to certain effects may develop over a relatively short period of time. The drug was given over a period of 30 h (2 days and 1 night) at zero-order rate using a rectal osmotic pump. Performance was measured at 2 hourly intervals during the day and was continuously impaired during the infusion, though there was a rapid recovery when the infusion ceased. All tasks were affected, in particular mental arithmetic and letter cancellation, but there was some improvement in performance during the second day. The normal circadian improvement in performance may have contributed to this effect, but some degree of tolerance to the effect of the drug cannot be excluded. Overnight there was a marked reduction in wakefulness, suppression of slow wave sleep, and delay to the onset and reduction in the duration of rapid eye movement sleep. During the night after infusion there was less slow wave sleep and increased wakefulness. The experimental design may prove useful in the study of tolerance to drugs.

Adult↗

PubMed1985

Sustained performance with short evening and morning sleeps.

The effect which early evening sleep may have on overnight and subsequent daytime performance, and the effect which morning sleep may have on daytime performance after overnight sleep deprivation has been studied in six healthy male volunteers. It would appear that relatively short periods of natural and drug induced (brotizolam 0.125 mg) sleep have a beneficial effect on subsequent performance even in the absence of preceding sleep debt. In the event of disturbed sleep in shiftwork an hypnotic may be helpful, and in this context, one which is rapidly eliminated and sustains sleep is appropriate.

Adult↗

PubMed1985

Hypnotics and aircrew.

The management of sleep difficulties which arise during air operations must be related, at least initially, to the cause, but the aeromedical specialist is frequently faced with the possible use of hypnotics. There are no simple guidelines, but an understanding of various issues will help toward the effective use of these drugs in those who have to cope with irregularity of rest and carry out skilled work. Some knowledge of the pharmacokinetics of the drugs concerned is useful as persistence of effect and the potential for accumulation with repeated ingestion are important factors, while efficacy in relation to sleep of different durations and at unusual times must also be considered.

Adult↗

PubMed1984

Ascorbic acid and performance in man.

Effects on performance of 1, 2 and 4 g ascorbic acid were studied from 0.5-5.5 h after ingestion in six healthy females. Diazepam (5 mg) was included as an active control, and it impaired digit symbol substitution, visuomotor coordination and complex reaction time. There were no effects of any dose of ascorbic acid on performance.

Adult↗

PubMed1984

The H2-antagonists, cimetidine and ranitidine: studies on performance.

The effects of single oral doses of cimetidine (200 and 400 mg) and ranitidine (150 and 300 mg) were evaluated on visuo-motor coordination, dynamic visual acuity, digit symbol substitution, symbol copying, and critical flicker fusion, and on subjective assessments of mood and well-being in seven healthy female volunteers. The study was double blind and placebo controlled, and triprolidine (10 mg) was used as an active control. With cimetidine and ranitidine there were no adverse changes in performance, central nervous function or subjective assessment of mood. Triprolidine impaired visuo-motor coordination, reduced the number of substitutions on the digit symbol substitution test and the number of symbols copied, lowered the critical flicker fusion threshold and reduced dynamic visual acuity. Cimetidine (200-400 mg) and ranitidine (150-300 mg) are highly unlikely to impair performance, and may be used in individuals involved in skilled activity.

Adult↗

PubMed1984

Studies on the possible central effects in man of a neuropeptide (ACTH 4-9 analogue).

The central effects of a neuropeptide, ACTH 4-9 analogue (Organon 2766), were studied in man using digit symbol substitution (DSS), symbol copying, digit span, electroencephalography and auditory evoked potentials, critical flicker fusion (CFF) and pupillary response to light. Performance was measured overnight, and each of 6 subjects ingested 300 mg caffeine, 40 mg ACTH 4-9 analogue and matching placebo. With placebo there was a marked deterioration in performance overnight. The number of substitutions on DSS and the numbers of symbols copied fell, and the threshold for CFF and number of errors on the vigilance task increased. These effects were not seen after ingestion of caffeine (300 mg), though caffeine may have led to some deterioration in the ability to remember digits. The neuropeptide did not attenuate the decrements in performance overnight.

Adrenocorticotropic Hormone↗

PubMed1984

Pencil and paper tests--sensitivity to psychotropic drugs.

The literature on pencil and paper tests and the effects of psychotropic drugs is reviewed. Performance at digit symbol substitution, symbol copying, letter cancellation, arithmetic, logic and cognitive processing with a relatively constant level of triazolam was compared with placebo. Analysis of variance, covariance analysis and principal component analysis were applied to the data. Pencil and paper tests which measure various skills are useful for detecting drug effects. Letter cancellation, arithmetic and DSST appear to be most sensitive, although logic and symbol copying may be useful.

Anti-Anxiety Agents↗

PubMed1984

Sleep of shiftworkers within the arctic circle.

The sleep of shiftworkers in the Arctic has been investigated using electroencephalography. The subjects were studied four times a year over a 2-year period. There was a trend toward less restful sleep during the autumn and winter months, but otherwise sleep at various times of the day was similar to that of individuals elsewhere. This would suggest that sleep disturbance in polar shiftworkers can be managed in a similar way to that of shiftworkers in temperate regions.

Adult↗

PubMed1984

Adaptation to irregularity of rest and activity.

The adaptation to a 9-d schedule of irregular rest and activity was studied. Sleep was recorded; patterns of oral temperature, urinary excretion, and performance at a series of tasks were measured. The relationships between circadian rhythmicity, length of time on task, and cumulative sleep loss were examined.

Activity Cycles↗

PubMed1983

The H1-antagonist mequitazine: studies on performance and visual function.

The effects of single oral doses of mequitazine (5 and 10 mg), terfenadine (60 mg) and triprolidine (10 mg) as active controls, and placebo were evaluated on visuo-motor coordination, digit symbol substitution, critical flicker fusion and dynamic visual acuity, and on subjective assessments of mood and well-being in six normal female volunteers. The study was double-blind. Mequitazine (5 mg) impaired visuo-motor coordination 7.5 h after ingestion (considered to be a chance result), but there was no effect on digit symbol substitution, critical flicker fusion threshold or dynamic visual acuity. Mequitazine (10 mg) impaired visuo-motor coordination and reduced the number of substitutions on the digit symbol substitution test. Terfenadine (60 mg) had no effect on performance or on subjective feelings. Triprolidine (10 mg) impaired visuo-motor coordination, reduced the number of substitutions on the digit symbol test, lowered the critical flicker fusion threshold and reduced dynamic visual acuity. Mequitazine (5 mg) and terfenadine (60 mg) are likely to prove acceptable H1 antagonists when sedation must be avoided.

Adult↗

PubMed1983

Variability of response to hypnotics: sleep studies in man.

Effect of diazepam on sleep in man was investigated in a series of placebo controlled studies and the data on various measures from two groups (young adults and middle age) were retrospectively analysed. Variability of the measures between the two groups with placebo was not different, but the variability of their response to the drug was different, and that of the middle aged group was high. In the young adults there were drug effects, but in the middle aged group no drug effects could be established. The studies suggest that variability of data must be taken into consideration when it is used to indicate the most appropriate dose range. If the variability of response is low the data may indicate the likely effect of the drug on each individual. On the other hand if the variability is high then data obtained from analysis of the group may have limited relevance, and suggest doses which are too high for the majority of the individuals within that group.

Adolescent↗

PubMed1983

Midazolam: sleep and performance studies in middle age.

Effects of 10, 20 and 30 mg midazolam on sleep and on performance the next day were studied in six healthy adult males aged between 47 and 53 years. The study was double-blind, placebo-controlled and included another rapidly eliminated benzodiazepine (brotizolam, 0.25 mg) as an active control. With 10 mg midazolam, sleep-onset latency was quicker, and the duration and percentage of stage 2 sleep was increased over the first 6 h. Effects of 20 and 30 mg midazolam were similar to each other. Sleep onsets were earlier, total sleep times and stage 2 sleep were increased, and the sleep efficiency indices improved. During the first 6 h there was reduced duration and percentage of drowsy (stage 1) sleep. There was no consistent evidence of delay to the first period of rapid eye movement sleep, but over the dose range the duration was reduced during the first 2 h. Digit symbol substitution did not show any residual decrement 9 h after ingestion of 10, 20 or 30 mg midazolam. Midazolam may prove to be a particularly useful hypnotic for shiftworkers whose rest periods tend to be shorter than in those who have a regular nocturnal sleep pattern.

Anti-Anxiety Agents↗

PubMed1983

Zopiclone: sleep and performance studies in healthy man.

Effects of 2.5, 5.0, 7.5, and 10.0 mg zopiclone on sleep and on performance the next day were studied in 6 healthy adult males aged between 21 and 33 years. The experiment was double-blind and placebo controlled. 5.0 and 10.0 mg zopiclone decreased the amount of awake activity and drowsy (stage 1) sleep over the first 6 h of sleep, but this effect was only present for the whole sleep period with the 10.0-mg dose. The duration and percentage of stage 3 sleep were increased with 7.5 mg. The 7.5- and 10.0-mg doses increased the combined duration of stages 2, 3, and 4 sleep over the first 6 h and over the whole night. The first period of rapid eye movement sleep was delayed with 7.5 mg, and with 10.0 mg the time spent in rapid eye movement sleep was reduced during the first 6 h of sleep, but not over the whole night. The number of substitutions in the digit symbol substitution test was decreased 9 h after ingestion of 7.5 and 10.0 mg, and the number of symbols copied reduced after 10.0 mg. The clinical dose range of zopiclone is likely to be up to 7.5 mg. The latter dose provides a useful hypnotic effect with minimal residual effects the next day, whilst 5.0 mg is appropriate for those involved in skilled tasks where even the most minor changes in performance during the early part of the next day must be avoided.

Adult↗