Biomedical subjects
Publications and source records attributed to J Waterhouse.
The circadian structure (i.e. rest-activity cycle) was evaluated by actometry in a group of 25 advanced NSCLC patients. A better circadian profile was observed in the 6 patients treated with corticosteroïds. However those patients had also a shortened survival.
Six Mongolian gerbils were studied for 8-10d while housed in separate cages in a 12:12h light-dark (L-D) cycle (lights on at 07:00h). Recordings of body temperature, heart rate, and spontaneous activity were made throughout. The temperature and heart rate rhythms were "purified" to take into account the effects of activity, and then the rhythm of temperature was further purified to take into account other masking influences ("non-activity masking effects" or NAME,). The methods employed in the purification processes involved linear regression analysis or analysis of covariance, the latter using functions of activity and NAME as covariates. From these methods, it was possible to obtain not only an estimate of the endogenous component of the temperature rhythm but also a measure of circadian changes in the sensitivity of temperature to masking effects. Even though all purification methods removed many of the effects of spontaneous activity from the temperature record, there remained temperature fluctuations at the L-D and D-L transitions that appeared to be independent of activity. The NAME was of only very marginal value in the purification process. Comparison of the purification methods indicated that the linear methods were inferior (both from a biological viewpoint and when the results were compared mathematically) to those that allowed the rate of rise of temperature due to increasing amounts of activity to become progressively less. The sensitivity of temperature and heart rate to the masking effects of activity showed a circadian rhythm, with sensitivities in the resting phase being greater than those in the active phase. These findings are compatible with the view that thermoregulatory reflexes are induced by spontaneous activity of sufficient amount, and that there is a circadian rhythm in the body temperature at which these reflexes are initiated and in their effectiveness.
BACKGROUND: Patients with chronic fatigue syndrome (CFS) show evidence of circadian rhythm disturbances. We aimed to determine whether CFS symptoms were alleviated by melatonin and bright-light phototherapy, which have been shown to improve circadian rhythm disorders and fatigue in jet-lag and shift workers. DESIGN: Thirty patients with unexplained fatigue for > 6 months were initially assessed using placebo and then received melatonin (5 mg in the evening) and phototherapy (2500 Lux for 1 h in the morning), each for 12 weeks in random order separated by a washout period. Principal symptoms of CFS were measured by visual analogue scales, the Shortform (SF-36) Health Survey, Mental Fatigue Inventory and Hospital Anxiety and Depression Scale. We also determined the circadian rhythm of body temperature, timing of the onset of melatonin secretion, and the relationship between these. RESULTS: Neither intervention showed any significant effect on any of the principal symptoms or on general measures of physical or mental health. Compared with placebo, neither body temperature rhythm nor onset of melatonin secretion was significantly altered by either treatment, except for a slight advance of temperature phase (0.8 h; P = 0.04) with phototherapy. CONCLUSION: Melatonin and bright-light phototherapy appear ineffective in CFS. Both treatments are being prescribed for CFS sufferers by medical and alternative practitioners. Their unregulated use should be prohibited unless, or until, clear benefits are convincingly demonstrated.
Seventeen healthy adults exercised for 30 min (70% VO2max), at different times of the day and night throughout a 24 h period. The effect on the phase of core temperature rhythm was assessed by comparing the rhythms on the day immediately before and immediately after the day of exercise with the participants living normally on these 2 days. Assessments were made upon data that had been corrected for the thermogenic effects of sleep and activity. When exercise was performed in the period between 4 h before and 1 h after the temperature minimum, there was a phase delay of 1.03 +/- 0.78 h (mean +/- s; n = 6); when performed between 3 and 8 h after the temperature minimum, there was a phase advance of 1.07 +/- 1.23 h (n = 9). Both means were significantly different from zero (Student's one-sample t-tests: P < 0.05). Performed at other times, exercise had no significant effect on the phase of the temperature rhythm. The phase changes were not significantly different from those previously observed by us in sedentary individuals exposed to domestic lighting. We conclude that the amount of physical activity has very little effect on the body clock.
Eight healthy males were studied for a total of 13 subject-days to assess if gut (from an ingested pill) and axilla (from a thermally insulated skin probe) temperatures would act as a substitute for rectal temperature in field studies of the circadian rhythm of core temperature. Subjects slept and went about their activities, indoors and outdoors, normally. Regular recordings (at 6 min intervals) were made of temperatures from the three sites. In addition, activity was measured (by a sensor on the nondominant wrist) so that the raw temperature data could be "purified," that is, corrected for the direct effects of sleep and activity. Inspection of the raw data indicated that there was a close parallelism between rectal and gut temperatures, but that the parallelism between rectal and insulated axilla temperatures was less reliable. This parallelism was supported by initial calculations of the correlations between rectal and gut temperatures (high and positive) and between rectal and insulated axilla (lower, though still positive) temperatures. Calculation of the limits of agreement between the parameters of the cosine curves fitted to the raw data confirmed that the rectal and gut temperatures were far closer with regard to acrophase and amplitude than were rectal and insulated axilla temperatures (-0.31 +/- 0.89 vs. +0.75 +/- 6.03 h and +0.002 +/- 0.116 vs. +0.083 +/- 0.625 degrees C, respectively). After purification of the temperature data, the limits of agreement for the cosine parameters acrophase and amplitude still indicated that there was a closer agreement between rectal and gut temperatures than between rectal and insulated axilla temperatures (-0.30 +/- 1.12 vs. +0.58 +/- 6.69 h, and +0.007 +/- 0.116 vs. +0.104 +/- 0.620 degrees C, respectively). Part of the explanation of this difference was the unreliable relationships between temperature changes in insulated axilla temperature and bursts of activity and going to bed. It is concluded that, whereas gut temperature is a viable alternativ to rectal temperature (from the viewpoints of both user acceptability and the reliability of data obtained), insulated axilla temperature, though acceptable to subjects, is unreliable from an experimental viewpoint.
BACKGROUND: Travelling across multiple time zones disrupts normal circadian rhythms and induces "jet lag". Possible effects of this on training and performance in athletes were concerns before the Sydney Olympic Games. OBJECTIVE: To identify some determinants of jet lag and its symptoms. METHODS: A mixture of athletes, their coaches, and academics attending a conference (n = 85) was studied during their flights from the United Kingdom to Australia (two flights with a one hour stopover in Singapore), and for the first six days in Australia. Subjects differed in age, sex, chronotype, flexibility of sleeping habits, feelings of languor, fitness, time of arrival in Australia, and whether or not they had previous experience of travel to Australia. These variables and whether the body clock adjusted to new local time by phase advance or delay were tested as predictors for jet lag and some of its symptoms by stepwise multiple regression analyses. RESULTS: The amount of sleep in the first flight was significantly greater in those who had left the United Kingdom in the evening than the morning (medians of 5.5 hours and 1.5 hours respectively; p = 0.0002, Mann-Whitney), whereas there was no significant difference on the second flight (2.5 hours v 2.8 hours; p = 0.72). Only the severity of jet lag and assessments of sleep and fatigue were commonly predicted significantly (p<0.05) by regression analysis, and then by only some of the variables. Thus increasing age and a later time of arrival in Australia were associated with less jet lag and fatigue, and previous experience of travel to Australia was associated with an earlier time of getting to sleep. Subjects who had adjusted by phase advance suffered worse jet lag during the 5th and 6th days in Australia. CONCLUSIONS: These results indicate the importance of an appropriate choice of itinerary and lifestyle for reducing the negative effects of jet lag in athletes and others who wish to perform optimally in the new time zone.
Two studies at three sites in the UK provided confirmation that systematic positive bias in NO2 diffusion tube measurement occurred because of changes to "within-tube" chemistry, rather than eddy diffusion at the mouth of the tube. In the first study in Cambridge, UK, sampler overestimation for 1 and 2 week exposures was compared to corresponding time-averaged monitor measurements (NO-NO2-NOx, O3) and weather variables. Noninearity between sampler and monitor NO2 measurements was interpreted in terms of spatial and temporal variations in relative and absolute availability of NO, NO2 and O3 at the site. A maximum overestimation occurred for an exposure mean NO2/NOx approximately 0.5. The separate contributions of reduced NO2 photolysis and eddy diffusion were compared in Study II using samplers of two materials, acrylic and quartz, and of different lengths (40, 55, 71 and 120 mm) at three sites: Norwich background, Cambridge intermediate, London kerbside. For compared sites, NO2 measured by acrylic samplers was significantly higher than for equivalent quartz samplers. For quartz samplers [NO2]mean was only just above the monitor at Norwich and London; sampler/monitor NO2 = 1.04 (P = 0.59) and 1.01(P = 0.76), respectively. For acrylic samplers the order of [NO2]mean was 40 mm > 120 mm > 71 mm > or = 55 mm. Excepting 40 mm samplers, this accords with a chemical bias where co-diffusing NO and 03 molecules in longer tubes have more time to react to form excess NO2. Bias in 40 mm samplers is discussed. Eddy diffusion is negligible for standard samplers because [NO2]mean was equivalent for 55 mm and 71 mm acrylic samplers and close to monitor NO2 for 71 mm quartz tubes. Both studies showed that sampler accuracy was dependent on location. Significantly, overestimation was greatest (approximately 3-4 ppb) where the NO2 annual mean was approximately 20 ppb, close to the UK and EU air quality standard of 21 ppb.
Athletes ingest melatonin in an attempt to improve sleep quality or alleviate symptoms of jet lag after transmeridian travel. It is not known whether there are residual effects of this hormone on physical performance in fit subjects. After a sample size estimation involving a meaningful effect on performance of 5%, five milligrams of melatonin or placebo were ingested by twelve physically-active subjects before sleep in a double-blind experiment. The following morning, subjective sleep quality (latency and maintenance) were measured together with intra-aural temperature, grip strength of the left and right hands, and time to complete a 4 km time trial on a cycle ergometer. The subjects also rated perceived exertion during the latter test. The null hypothesis of no effect of melatonin on either subjective sleep quality or physical performance measured the morning after administration could not be rejected on the basis of our observations (P > 0.30). The mean differences between treatments were less than 1% for the strength tests and time trial performance. The confidence intervals for these differences for left and right grip strength and the cycling test were - 2.1 to 2.8 kg, - 3.1 to 2.7 kg and -3.0 to 4.5 s, respectively. In conclusion, it is unlikely that 5 mg of melatonin would have any meaningful effects on physical performance in the morning after fit subjects ingest the hormone. There was also little evidence that it improves sleep quality in this population. Further research is needed concerning the effects of daytime and nighttime admistration of melatonin on performance, in both situations of normal and disturbed sleep.
There were 15 healthy female subjects, differing in their position on the "morningness-eveningness" scale, studied for 7 consecutive days, first while living a sedentary lifestyle and sleeping between midnight and 08:00 and then while undergoing a "constant routine." Rectal temperature was measured at regular intervals throughout this time, and the results were subjected to cosinor analysis both before and after "purification" for the effects of physical activity. Results showed that there was a phase difference in the circadian rhythm of core temperature that was associated with the morningness score, with calculations that "morning types" would be phased earlier than "evening types" by up to about 3 h. This difference in phase (which was also statistically significant when the group was divided by a median split into a "morning group" and an "evening group") could not be attributed to effects of waking activity and existed in spite of the subjects keeping the same sleep-wake schedule. Moreover, it persisted when the subjects' data had been purified and when the data were obtained from the constant routine. That is, there was an endogenous component to this difference in phase of the core temperature. The morning group also showed a greater fall of core temperature during sleep; this was assessed in two ways, the main one being a comparison of constant routine and nychthemeral data sets after correction for any effects of activity. Even though the morning group was sleeping at a later phase of their circadian temperature rhythm than was the evening group, neither group showed a fall of temperature due to sleep that varied with time elapsed since the temperature acrophase. It is concluded that another factor that differs between morning and evening types is responsible for this difference.
Few chronobiologists may be aware of the regression-to-the-mean (RTM) statistical artifact, even though it may have far-reaching influences on chronobiological data. With the aid of simulated measurements of the circadian rhythm phase of body temperature and a completely bogus stimulus (unicorn milk), we explain what RTM is and provide examples relevant to chronobiology. We show how RTM may lead to erroneous conclusions regarding individual differences in phase responses to rhythm disturbances and how it may appear as though unicorn milk has phase-shifting effects and can successfully treat some circadian rhythm disorders. Guidelines are provided to ensure RTM effects are minimized in chronobiological investigations.
The Great Barrier Reef (GBR) system encompasses the largest system of corals and related life forms anywhere in the world. The health of this extensive system, particularly the inshore area, is dependent on the relationship between the GBR and adjacent coastal catchments. The major impact of agricultural practices on the GBR is the degradation of water quality in receiving (rivers) waters, caused by increased inputs of nutrients, suspended sediments and other pollutants. For the past three years, the Great Barrier Reef Marine Park Authority (GBRMPA) has been involved with the co-ordination of a river-monitoring program, specifically targeting the sampling of rivers during flood events. Representative sites were set up along two North Queensland rivers, the Russell-Mulgrave and Barron Rivers. This monitoring program is run in conjunction with the Queensland Department of Natural Resources' Waterwatch program. The program involves intensive sampling of first flush, extreme flow and post flood conditions over the two rivers. Extreme flow conditions are sampled over a limited time span (48 hours) with trained volunteers at 4-hour intervals. Concentrations measured in the flood events are dependent on land use characteristic, and extent of flow. Concentrations of dissolved and particulate nutrients are higher if the extreme flow event is part of the first flush cycle. Concentrations of DIN and DIP measured before, during and after a major flood event suggest that there is a large storage of inorganic material within the Barron and Russell-Mulgrave agricultural subcatchments that move over a period of days, and perhaps weeks. This program created a forum in which GBRMPA liased with the Barron and Russell-Mulgrave community about the connectivity existing between the river and the Great Barrier Reef lagoon.
Pollution of coastal regions of the Great Barrier Reef is dominated by runoff from the adjacent catchment. Catchment land-use is dominated by beef grazing and cropping, largely sugarcane cultivation, with relatively minor urban development. Runoff of sediment, nutrients and pesticides is increasing and for nitrogen is now four times the natural amount discharged 150 years ago. Significant effects and potential threats are now evident on inshore reefs, seagrasses and marine animals. There is no effective legislation or processes in place to manage agricultural pollution. The Great Barrier Reef Marine Park Act does not provide effective jurisdiction on the catchment. Queensland legislation relies on voluntary codes and there is no assessment of the effectiveness of the codes. Integrated catchment management strategies, also voluntary, provide some positive outcomes but are of limited success. Pollutant loads are predicted to continue to increase and it is unlikely that current management regimes will prevent this. New mechanisms to prevent continued degradation of inshore ecosystems of the Great Barrier Reef World Heritage Area are urgently needed.
Factors concerning NO2 uptake by the absorbent triethanolamine (TEA) in NO2 diffusion tubes are examined. Although the nominal freezing point of TEA is 17.9-21.2 degrees C, we show that, for a range of aqueous TEA solutions (0-20%, H2O), no freezing occurs even at -10 degrees C. Therefore NO2 collection efficiency is unlikely to be impaired by low temperature exposure. The recovery of TEA from the meshes of exposed samplers is determined as approximately 98%, even after 42 days, showing that the stability in situ of TEA is unaffected by long-term exposure. A model of a diffusion tube sampling array for simultaneous exposures, with a 0.1 m sampler spacing, shows that NO2 uptake by individual samplers is not affected by the presence of neighbouring tubes in the array. This is confirmed by sampler precision at two Cambridge sites. Four sampler preparation methods are compared for differences in NO2 uptake of exposed samplers. All methods employ TEA as absorbent, transferred by either dipping meshes in a TEA-acetone solution or pipetting aliquots of a TEA-H2O solution onto the meshes. For samplers prepared by three of the methods, no difference in NO2 uptake is found, but for samplers prepared using a 50% v/v TEA-H2O solution, a mean reduction of 18% is found. Student's t-tests show that the difference is highly significant (P < or = 0.001). Reasons for the difference are discussed.
Fifteen healthy female subjects were studied for eight days while living conventionally. Subjects were free to choose the ways they spent their time within a framework of regular times of retiring and rising; in practice, much of the waking time was spent in sedentary activities. Nine of the subjects were aware of the natural light-dark cycle, this approximating to a 12:12 L:D schedule at the time of year when the study took place. Before the study, subjects were assessed for their degree of "morningness" by questionnaire; throughout the study, they wore a rectal probe, and an activity meter on their non-dominant wrist. The timing (phase) and amplitude of the circadian rectal temperature rhythm were assessed on each day by cosinor analysis as well as by a method based on visual inspection of the data. These two parameters were also assessed after the temperature data for each day had been "purified" by a number of methods. From these results it was possible to investigate the effect of purification upon the amplitude of the circadian rhythm of temperature. Also, the day-by-day variability of phase, and the relationship between morningness and phase, were compared using these methods of phase estimation, and using cross-correlation between data sets from adjacent days; in all cases, raw and purified temperature data were used. There was a significantly greater amount of daily variation in phase using purified rather than raw data sets, and this difference was present with all methods of purification as well as with all methods for estimating phase. Purification decreased the amplitude of the circadian temperature rhythm by about 30%. Finally, there was a significant correlation between the morningness score of the subjects and the phase of the circadian temperature rhythm, the phase becoming earlier with increasing morningness; when this relationship was re-examined using purified data, it became more marked. These results reflect the masking effects exerted upon raw temperature data by lifestyle. The extent to which the purification methods enable the endogenous component of a circadian rhythm - and, by implication, the output of the endogenous circadian oscillator - to be estimated in subjects living normally is addressed.
Subjective, physiological and physical performance variables are affected following travel across multiple time-zones (jet-lag). The objective of the study was to examine the effects of oral melatonin in alleviating jet-lag by investigating its effects on subjects who had flown from London to Eastern Australia, 10 time-zones to the east. Melatonin (5 mg day(-1)) or placebo capsules were administered to 14 experimental (13 males and 1 female) and 17 control subjects (15 males and 2 females), respectively, in a double-blind study; the time of administration was in accord with the current consensus for maximizing its hypnotic effect. Grip strength and intra-aural temperature were measured on alternate days after arrival at the destination, at four different times of day (between the times 07:00 - 08:00 h, 12:00 - 13:00 h, 16:00 - 17:00 h and 19:00 - 20:00 h local time). In addition, for the first 6 - 7 days after arrival in Australia, subjective ratings of jet-lag on a 0 - 10 visual analogue scale and responses to a Jet-lag Questionnaire (incorporating items for tiredness. sleep, meal satisfaction and ability to concentrate) were recorded at the above times and also on retiring (at about midnight). Subjects continued normally with their work schedules between the data collection times. Subjects with complete data (13 melatonin and 13 placebo subjects), in comparison with published data, showed partial adjustment of the diurnal rhythm in intra-aural temperature after 6 days. A time-of-day effect was evident in both right and left grip strength during adjustment to Australian time; there was no difference between the group taking melatonin and that using the placebo. Right and left grip strength profiles on day 6 were adjusted either by advancing or delaying the profiles, independent of whether subjects were taking melatonin or placebo tablets. Subjects reported disturbances with most measures in the Jet-lag Questionnaire but, whereas poorer concentration and some negative effects upon sleep had disappeared after 3 - 5 days, ratings of jet-lag and tiredness had not returned to 'zero' (or normal values), respectively, by the sixth day of the study. Subjects taking melatonin showed no significant differences from the placebo group in perceived irritability, concentration, meal satisfaction, ease in getting to sleep and staying asleep, frequency of bowel motion and consistency of the faeces. These results suggest that, in subjects who, after arrival, followed a busy schedule which resulted in frequent and erratic exposure to daylight, melatonin had no benefit in alleviating jet-lag or the components of jet-lag, and it did not influence the process of phase adjustment.
A total of 39 subjects were studied after a flight from the UK to either Sydney or Brisbane (10 time-zones to the east). Subjects varied widely in their age, their athletic ability, whether or not they were taking melatonin, and in their objectives when in Australia. For the first 6 days after arrival, subjects scored their jet-lag five times per day and other subjective variables up to five times per day, using visual analogue scales. For jet-lag, the scale was labelled 0 = no jet-lag to 10 = very bad jet-lag; the extremes of the other scales were labelled - 5 and + 5, indicating marked changes compared with normal, and the centrepoint was labelled 0 indicating 'normal'. Mean daily values for jet-lag and fatigue were initially high (+ 3.65 +/- 0.35 and + 1.55 +/- 0.22 on day 1, respectively) and fell progressively on subsequent days, but were still raised significantly (p < 0.05) on day 5 (fatigue) or day 6 (jet-lag). In addition, times of waking were earlier on all days. By contrast, falls in concentration and motivation, and rises in irritability and nocturnal wakings, had recovered by day 4 or earlier, and bowel activity was less frequent, with harder stools, on days 1 and 2 only. Also, on day 1, there was a decrease in the ease of getting to sleep (- 1.33 +/- 0.55), but this changed to an increase from day 2 onwards (for example, + 0.75 +/- 0.25 on day 6). Stepwise regression analysis was used to investigate predictors of jet-lag. The severity of jet-lag at all the times that were measured was strongly predicted by fatigue ratings made at the same time. Its severity at 08:00 h was predicted by an earlier time of waking, by feeling less alert 30 min after waking and, marginally, by the number of waking episodes. Jet-lag at 12:00 and 16:00 h was strongly predicted by a fall of concentration at these times; jet-lag at mealtimes (12:00, 16:00 and 20:00 h) was predicted by the amount of feeling bloated. Such results complicate an exact interpretation that can be placed on an assessment of a global term such as jet-lag, particularly if the assessment is made only once per day.
The examination of Air Traffic Controllers (ATCs) from the Warsaw Airport (Poland) included 24-hr ECG monitoring. The participants were 10 civil ATCs, 9 males and 1 woman. The study was carried out on a group of 19 ATCs during their duty periods, 14 of them working 12-hr shifts and 5 performing 24-hr duties. The participants collected urine every 4 hrs, and cortisol concentration was determined. Further, the survey included the quality and duration of sleep, and subjective fatigue in the 62 participants. In ATCs, shift work modifies natural rhythms of the circulatory system and decreases the ability for intensified mental work at night. In consequence ATCs experience frequent sleep disorders.
Twelve healthy male subjects each undertook two bouts of moderate exercise (70% VO2max for 30 minutes) in the morning (08:00) and late afternoon (18:00) at least 4 days apart. Measurements were made of heart rate, core (rectal) temperature, sternum skin temperature, and forearm skin blood flow during baseline conditions, during the bout of exercise, and throughout a 30-minute recovery period. Comparisons were made of the changes of heart rate, temperature, and skin blood flow produced by the exercise at the two times of day. Student t tests indicated that baseline values for core temperature (37.15 degrees C +/- 0.06 degrees C vs. 36.77 degrees C +/- 0.06 degrees C) and sternum temperature (33.60 degrees C +/- 0.29 degrees C vs. 32.70 degrees C + 0.38 degrees C) were significantly (p < .05) higher in the late afternoon than the early morning. Two-way analysis of variance (ANOVA) indicated that the increases in core and sternum temperatures during exercise were significantly less (p = .0039 and .0421, respectively) during the afternoon bout of exercise compared with the morning, even though the work loads, as determined by changes in heart rate, were not significantly different (p = .798) at the two times of testing. There were also tendencies for resting forearm skin blood flow to be higher in the afternoon than in the morning and for exercise to produce a more rapid rise in this variable in the afternoon. The possible mechanisms producing these responses to exercise are discussed in terms of those that are responsible for the normal circadian rhythm of core temperature. It is concluded that the body's ability to remove a heat load is less in the early morning, when the circadian system is in a "heat gain" mode, than in the late afternoon, when heat gain and "heat loss" modes are balanced more evenly.