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Biomedical subjects

J M Waterhouse

Publications and source records attributed to J M Waterhouse.

At least 19 recordsLinked to original sources

Sleep on a shortening day/night schedule.

In 2 experiments subjects were exposed for 3.5 weeks to a gradually (0.2 h/day initially) shortening day/night cycle, ending at 22.8 h and 22.0 h, respectively. Shortening of the cycle led to an initial but temporary increase of sleep latency. When the reduction ceased at 22.8 h and this length was maintained, sleep parameters were not further affected and the temperature rhythm in most subjects remained entrained to the 22.8 h period, although some instability occurred towards the end. In the 22.0 h experiment the continued reduction beyond 22.8 h led to disturbed sleep on day 15, at a day length of 22.4 h. Total sleep time, stage 2 and sleep efficiency were then markedly reduced. At this point sleep coincided with the peak of the body temperature rhythm and the amplitude of the latter was extremely small. This was also the point when the body temperature rhythm 'broke out' from the sleep/wake rhythm and showed a large 6 h phase jump (delay). Towards the end of the experiment, when sleep was initiated in the circadian temperature trough, REM propensity was increased. It was concluded that several sleep parameters were affected by the reduction of the day/night cycle although the specific effects depended on the amount of phase advance and on whether desynchronization occurred. Within the range of entrainment, however, most sleep parameters were remarkably unperturbed by the considerable changes of circadian parameters.

Adult

Investigating the endogenous component of human circadian rhythms: a review of some simple alternatives to constant routines.

Several types of constant routine are accepted as an important means by which the endogenous component of circadian rhythms can be studied. Nevertheless, they are impracticable to perform and unsuitable for routine use in many individuals. We describe a group of simple methods with which rhythms measured in normal circumstances can be dissociated into the components due to masking and the internal clock. Each method is best suited to a particular type of experimental condition. Results from a variety of protocols are analysed by these and conventional methods to assess the validity of the new methods.

Body Temperature

A human phase-response curve to light.

Using 'classical' experimental protocols, a human phase-response curve (PRC) to a single 3-h bright light pulse has been established. When the light pulse was centred slightly before the time of body temperature minimum, the circadian system delayed, whilst a pulse slightly after the minimum advanced it. Maximum phase shifts were about 2 h. When light pulses over 3 successive cycles were used, larger shifts (4-7 h) were produced. It is concluded that the human PRC does not differ in principle from that found in other species, except with respect to the light intensity required.

Adolescent

Circadian rhythms: principles and measurement.

The physiological basis of rhythmic processes is explained, and the influence of rhythmicity on pathological processes and pharmacological responses is outlined. Methods of data collection and analysis are described, and the importance of taking account of, and even exploiting, rhythmicity in experimental design is discussed.

Animals

"Demasking" the temperature rhythm after simulated time zone transitions.

Simulated time zone transitions were performed in an isolation unit upon groups of one to four human subjects. In the first series of experiments, the adjustment of the circadian rhythm of body temperature, measured in the presence of sleep and other masking factors, was assessed by cosinor analysis and by cross-correlation methods. These methods modeled the circadian timing system either as a single component or as the sum of two components, those due to exogenous and endogenous influences. The one-component models described a more rapid adjustment of the temperature rhythm to the time zone transition than did the two-component models; we attribute this difference to the masking effects of the exogenous component. In a second series of experiments, we showed that the shift of the endogenous component, as assessed by the two-component models, was not significantly different from that measured during constant routines. The results also showed that, if the zeitgebers were phased in advance of the endogenous component, then advances of the endogenous component were produced only if this mismatch was less than about 10 hr. Mismatches greater than this, and cases where the zeitgebers were delayed with respect to the endogenous component, both produced delays of the endogenous component. We conclude that the two-component cross-correlation methods can be used to estimate shifts of the endogenous component of a circadian rhythm in the presence of masking factors. They are therefore an alternative to constant routines when these latter are impracticable to carry out.

Adaptation, Physiological

The circadian system and affective disorders: clocks or rhythms?

There have been a number of proposals that a pathology of the circadian system involving clock functioning underlies the affective disorders. It is argued that neither current findings from research into the neurophysiological substrates of the affective disorders, recent clinical findings regarding these illnesses or their phenomenology support such a contention. This does not mean however that there is not a primary pathological disturbance of the circadian system at the heart of the affective disorders. The same neurophysiological, phenomenological and clinical evidence can be offered in favour of a disturbance of circadian rhythms in the presence of grossly normal clock functioning. The research and remedial implications of this alternative are outlined briefly.

Biological Clocks

Removing masking factors from urinary rhythm data in humans.

We have previously developed simple models that enable the exogenous and endogenous components of the circadian rhythm of body temperature to be separated. The present paper extends the method to urinary data. First, we have shown that the basic superiority of the two-component model over the one-component model persists when temperature data are converted into a format that is appropriate for urine sampling (that is, a single overnight sample and two-hourly samples during waking). Second, we provide normative endogenous data for urinary sodium, potassium and urate, data obtained from about 80 constant routines. These data are required for the two-component model. Third, we have compared the rate of adjustment to a simulated eastward time-zone transition of 8 hr in 8 subjects. This showed that the rate of adjustment assessed by the two-component model was significantly less than that assessed by the one-component model and much closer to that assessed in separate experiments (n = 15 subjects) using constant routines. We conclude that the two-component model can be used upon urinary data to give a closer approximation to the shift of the endogenous component, as assessed by constant routines, than can estimates that do not take into account the problem of masking caused by exogenous factors.

Adolescent

Retrospective study of temperature rhythms of intensive care patients.

The hourly rectal temperature record of 15 patients who spent greater than or equal to 8 days in the ICU were analyzed for circadian rhythmicity. Using cosinor analysis, a statistically significant rhythm in a period of 24 h was present on 80% of the patient days studied. The position of the acrophase, or peak, of the rhythm varied markedly both between patients and within patients, with changes of several hours from day to day. There was a tendency for the amplitude of the rhythm to be greater when the patients were unconscious than when they were conscious and in those patients who died compared with those who survived.

Adult

Masking in humans: the problem and some attempts to solve it.

Different types of masking are discussed together with an account of the masking effect that the sleep-wake cycle exerts upon the circadian rhythms of body temperature and urinary excretion. The relative importance to masking of the several components of differences between sleeping and wakefulness are then assessed. Means to deal with the problem of masking fall into two major categories. These attempt to minimise masking effects by protocols such as constant routines or control days, and mathematical models which separate results obtained in the presence of masking influences into endogenous and exogenous components. (The problem of the extent to which masking influences can render the endogenous component of a rhythm an impure reflection of the internal oscillator is considered also.) These different techniques are compared with respect to their usefulness and assumptions. Finally, a brief speculation is given of the usefulness of masking.

Body Temperature

Variation in meals and sleep-activity patterns in aged subjects; its relevance to circadian rhythm studies.

The study was performed upon a sample of aged and non-institutionalized subjects. Information was obtained by questionnaires and diaries on personal factors during a typical week. A random subset was subjected to a more detailed analysis of the composition of their meals. Results showed that increasing age was correlated with: a decreased day-by-day variability in an individual's time of retiring, rising and eating meals; earlier sleep times; increased frequency of daytime naps and nocturnal awakenings; and decreased physical activity. These results occurred both in subjects living alone and in those living with company. Day-by-day differences in the composition of meals tended to decrease with age. When differences between individuals were considered then these tended to increase with age. Some implications of these findings for studies of circadian rhythmicity in aged subjects--in whom the timing of circadian rhythms becomes more erratic and amplitude falls--are discussed.

Aged

Mathematical and statistical analysis of circadian rhythms.

The mathematical and statistical analysis of biological time series is complex and often involves specialised techniques. In this article we review several of these techniques, placing particular emphasis on the usefulness, assumptions and kind of data that they require. Because classical methods of time series analysis often require long spans of data that are not frequently available in biological studies, particularly in clinical circumstances, several alternative techniques are described. Where possible, emphasis is placed upon simple rather than esoteric mathematical descriptions of data. Also covered are problems of interpretation that might arise as a result of the mathematical analysis.

Circadian Rhythm

Effects upon circadian rhythmicity of an alteration to the sleep-wake cycle: problems of assessment resulting from measurement in the presence of sleep and analysis in terms of a single shifted component.

Experiments were performed upon groups of three or four human subjects in an isolation chamber (total n = 14). Subjects lived initially on a conventional lifestyle and then delayed their hours of sleep by 8 hr (so mimicking some aspects of nightwork) for 2 or 5 days. They also performed two constant routines--protocols designed to minimize any effects due to the environment, mealtimes, and activity. Regular samples of urine were taken when subjects were awake, and were analyzed for sodium, potassium, and chloride; rectal temperature was measured and logged at 6-min intervals throughout. Shifts in circadian rhythms produced by the change in sleep time were assessed by cosinor and cross-correlation techniques. The protocol enabled these assessments to be made on days when sleep was allowed and under constant-routine conditions, so that masking and behavioral effects could be investigated also. The results confirmed that adjustment to the change in sleep time was slow and only partial, and that assessments made on days when sleep was allowed overestimated this adjustment. Furthermore, it was concluded that, whereas cosinor and cross-correlation techniques using only one shifting component were equally useful in describing the observed changes, both were inferior to a cross-correlation technique that made use of two shifting components. Some practical and theoretical implications of these results are discussed.

Adolescent

Circadian rhythms and their mechanisms.

Recent work concerning the number, site(s) and means of adjustment to the 24-h day of internal clocks is reviewed. Work on humans is considered wherever possible though much of the work involving ablation and in vitro techniques necessarily involves other species, particularly rodents. It is concluded that, though recent advances have been impressive and present techniques appear likely to continue to produce results and stimulate discussion, more attention should be directed to considering the circadian system as a whole rather than as an assemblage of individual components.

Animals