Biomedical subjects

L Weibel

Publications and source records attributed to L Weibel.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of methotrexate and corticosteroids for the treatment of localized scleroderma (morphoea) in children.

BACKGROUND: Localized scleroderma (LS) or morphoea is often considered to be a benign self-limiting condition confined to the skin and subcutaneous tissue. However, the course of the disease is unpredictable and severe functional and cosmetic disability may result. Drug treatment with systemic corticosteroids in combination with methotrexate has been reported to be beneficial in LS, but data in children is limited. OBJECTIVES: To evaluate the efficacy and tolerability of systemic corticosteroids in combination with methotrexate in children with LS. METHODS: Treatment and outcome of 34 patients with LS were retrospectively analysed. Pulsed intravenous methylprednisolone was given, followed by oral prednisolone on a reducing regimen and maintenance treatment with methotrexate. We assessed treatment outcome clinically and by thermography and monitored adverse events. RESULTS: From the onset of treatment, the disease stopped progressing in 94% of the patients. All patients demonstrated significant clinical improvement within a mean time of 5.7 +/- 3.9 months. Mean duration of follow-up over the treatment period and beyond was 2.9 +/- 2.0 years. In 16 (47%) patients therapy was discontinued when the disease was considered to be inactive clinically; however, seven (44%) of the 16 developed a relapse, necessitating repeat treatment. At last follow-up (range 0.2-7.0 years), 24 (71%) of the 34 patients had completely inactive disease. Observed adverse events were moderate and transient and no patient had to stop therapy. CONCLUSIONS: These data suggest that systemic corticosteroids and methotrexate in combination are beneficial and well tolerated in the treatment of children with LS. Because of the risk of relapse after discontinuing therapy, long-term monitoring is mandatory.

Adolescent↗

PubMed2003

[Methodological guidelines for the use of salivary cortisol as biological marker of stress].

UNLABELLED: AN EASY TO DETERMINE, RELIABLE, MARKER: The measurement of cortisol in saliva provides to the basic scientist as well as to the clinician a reliable tool for investigations of the hypothalamic-pituitary-adrenal axis activity. As with plasma cortisol, the level of cortisol in the saliva is a reliable marker of stress. The major advantage of salivary cortisol is that its sampling technique is non-invasive and can be performed in non-stressful conditions and without laboratory surroundings. INDICATIONS: The use of salivary cortisol hence widens the perspectives of interesting research in "out of laboratory" scientific research and clinical research since the samples can be taken at home by the patients themselves. IN PRACTICE: However, the reliable use of salivary cortisol requires certain methodological prerequisites concerning the sampling technique (collection and storing) and the control of endogenous (individual factors, circadian variations, age, gender, hormonal status, weight) or behavioural (smoking, meals, posture) factors implied in the regulation of saliva. The respect of these prerequisites is essential in order to avoid the potential influence of artefacts during the development of a protocol for clinical research or diagnosis.

Bias↗

PubMed2002

The start of the quiescent period of cortisol remains phase locked to the melatonin onset despite circadian phase alterations in humans working the night schedule.

Using a 10-min blood sampling procedure, we established 24-h plasma melatonin and cortisol rhythms in 11 night workers and determined whether the extent in the shift of the melatonin onset, highly variable among night workers, was reflected in the shift of the markers of the cortisol rhythm, i.e. the quiescent period of secretion and the acrophase. In all day-active subjects, the melatonin onset occurred during low cortisol secretion, with a time lag between the start of the quiescent period and the melatonin onset of 1 h 28+or-27 min. In night workers, whatever the shift of the melatonin surge, the start of the quiescent period of cortisol secretion remained phase locked to the melatonin onset with a similar time lag (1 h 25+or-27 min). There was a significant correlation between the timing of the melatonin onset and the timing of the start of the quiescent period (r=0.88; P=0.0072). No preserved time lag was found between the melatonin onset and the other cortisol phase markers, either with the end of the quiescent period or with the acrophase. These results settle the start of the quiescent period of cortisol and the melatonin onset as two coordinate markers, and suggest that each of them are reliable to assess circadian phase in humans.

Adaptation, Physiological↗

PubMed2002

Circadian clock functioning is linked to acute stress reactivity in rats.

At least two major physiological systems are involved in the adaptation of the organism to environmental challenges: the circadian system and the stress reaction. This study addressed the possibility that interindividual differences in stress sensitivity and in the functioning of the circadian system are related. At 2 months of age, corticosterone secretion in response to a 20-min restraint stress was assessed in 9 Sprague-Dawley rats for which running wheel activity was recorded as a rhythmic behavioral marker of the circadian clock. Two weeks later, the adaptive response of the circadian system to an abrupt shift in the light:dark (LD) cycle was assessed in those rats using a jet-lag paradigm. Finally, after resynchronization to the new LD cycle, rats were transferred to constant darkness to assess the free-running period of their circadian rhythm of running-wheel activity. Results indicate that stress-induced corticosterone secretion was (1) positively correlated with the number of days to resynchronize the circadian activity rhythm to the new LD cycle, and with the value of its free-running period, and (2) negatively correlated with the intensity of daily locomotor activity. Those data, emphasizing the interactions between the stress response of an organism and the functioning of its circadian system, could explain interindividual differences in humans' susceptibility to shift work or other circadian-related disorders.

Acute Disease↗

PubMed2001

Melatonin or a melatonin agonist corrects age-related changes in circadian response to environmental stimulus.

The effects of a melatonin agonist, S-20098, included in the diet were tested on a specific effect of aging in hamsters: the marked decline in the phase shifting effects of a 6-h pulse of darkness on a background of constant light. In contrast to young hamsters, old hamsters fed with the control diet showed little or no phase shifts in response to a dark pulse presented in the middle of their inactive or active period. Old hamsters fed with S-20098 showed phase shifts that were ~70% of the ones in young animals and significantly greater than those in old controls. The phase advancing response to a dark pulse presented during the inactive period was dose dependent and reversed after S-20098 discontinuation. Melatonin included in the diet showed comparable restorative effects on the phase shifting response to a dark pulse in old hamsters. Replacement therapy with melatonin or melatonin-related compounds could prove useful in treating, preventing, or delaying disturbances of circadian rhythmicity and/or sleep in older people.

Acetamides↗

PubMed2000

A melatonin agonist facilitates circadian resynchronization in old hamsters after abrupt shifts in the light-dark cycle.

Age-related changes in the mammalian circadian system may be associated with a decline in circulating melatonin levels. Using 'jet lag' paradigms involving abrupt shifts in the light-dark cycle, we showed that a melatonin agonist, S-20098, accelerated by approximately 25% resynchronization of the circadian activity rhythm in old hamsters to the new light-dark cycle. It suggests the usefulness of melatonin-related compounds to treat circadian disorders associated with aging.

Acetamides↗

PubMed2000

Twenty-four-hour rhythms of plasma glucose and insulin secretion rate in regular night workers.

To determine whether the ultradian and circadian rhythms of glucose and insulin secretion rate (ISR) are adapted to their permanent nocturnal schedule, eight night workers were studied during their usual 24-h cycle with continuous enteral nutrition and a 10-min blood sampling procedure and were compared with 8 day-active subjects studied once with nocturnal sleep and once with an acute 8-h-shifted sleep. The mean 24-h glucose and ISR levels were similar in the three experiments. The duration and the number of the ultradian oscillations were influenced neither by the time of day nor by the sleep condition or its shift, but their mean amplitude increased during sleep whenever it occurred. In day-active subjects, glucose and ISR levels were high during nighttime sleep and then decreased to a minimum in the afternoon. After the acute sleep shift, the glucose and ISR rhythms were split in a biphasic pattern with a slight increase during the night of deprivation and another during daytime sleep. In night workers, the glucose and ISR peak levels exhibited an 8-h shift in accordance with the sleep shift, but the onset of the glucose rise underwent a shift of only 6 h and the sleep-related amplification of the glucose and ISR oscillations did not occur simultaneously. These results demonstrate that despite a predominant influence of sleep, the 24-h glucose and ISR rhythms are only partially adapted in permanent night workers.

Activity Cycles↗

PubMed1999

High corticosterone levels in prenatally stressed rats predict persistent paradoxical sleep alterations.

Prenatal stress predisposes rats to long-lasting disturbances that persist throughout adulthood (e.g., high anxiety, dysfunction of the hypothalamo-pituitary-adrenal axis, and abnormal circadian timing). These disturbances parallel to a large extent those found in depressed patients, in which hypercortisolemia and sleep alterations may be related to stress-inducing events. We studied sleep-wake parameters in control and prenatally stressed adult rats (3-4 months old) and examined possible relationships with their corticosterone levels (determined at 2 months of age). Under baseline conditions, prenatally stressed rats showed increased amounts of paradoxical sleep, positively correlated to plasma corticosterone levels. Other changes include increased sleep fragmentation, total light slow-wave sleep time, and a slight decrease in the percentage of deep slow-wave sleep relative to total sleep time. During recovery sleep from acute restraint stress, all sleep changes persisted and were correlated with stress-induced corticosterone secretion. High corticosterone levels under baseline conditions as well as an acute stress challenge may thus predict long-term sleep-wake alterations in rats. Taken together with other behavioral and hormonal abnormalities in prenatally stressed animals, the pronounced changes in sleep-wake parameters that are similar to those found in depressed patients suggest that prenatal stress may be a useful animal model of depression.

Analysis of Variance↗

PubMed1999

A single oral dose of S 22153, a melatonin antagonist, blocks the phase advancing effects of melatonin in C3H mice.

Disorders of the circadian system have been associated with adverse mental and physical conditions, raising the possibility that pharmacological agents acting on the circadian system could have therapeutic benefit. Compounds acting as agonists or antagonists of melatonin, an endogenous hormone able to feed back on the circadian clock, are currently under development for possible use in modulating circadian rhythmicity. In the present study, we examined the ability of an oral dose of S 22153, a synthetic melatonin antagonist, to block the phase advancing effect of a melatonin injection at circadian time 10 in free running C3H mice. Our results show that S 22153 had no effect per se on the phase or the period of the locomotor activity rhythm but was able to block the phase advancing effect of melatonin, suggesting potent antagonist effects at melatonin receptors. Availability of a melatonin antagonist may yield new insight into the role of melatonin in physiological processes and such compounds may find widespread clinical applications.

Administration, Oral↗

PubMed1999

[Biologic rhythms: their changes in night-shift workers].

ENVIRONMENTAL STRESS: Environmental cycles, such as the light-dark cycle, provide information used by the biological clock in the hypothalamus to synchronize the biological systems and maintain the organism's internal cohesion. In persons whose work schedules include night hours (approximately 20% of the working population in France) the sleep-wake cycles are not in phase with these environmental cycles. BIOLOGICAL RHYTHMS: What effect does the conflicting information perceived by night-shift workers have on their biological rhythms? Indices of the processes going on in the cerebral clock, these biological rhythms are the only tool available in man to determine possible dysfunction of the clock. Several studies have identified these rhythms in night-shift workers but results have been contradictory. PARTIAL ADAPTATION: Recently we made repeated measurements every 10 min over a 24 hour period in night-shift workers to determine the precise melatonin, cortisol, and thyrotropin (TSH) patterns, which reflect the endogenous clock, and prolactin (PRL) and growth hormone (GH) patterns which are influenced by sleep but also have a circadian component. This study demonstrated that there is some, but partial, adaptation of the biological rhythms in these persons. The shift in the melatonin pattern is quite variable from one individual to another. Night work causes a distortion in the cortisol and TSH rhythms. This partial adaptation is also seen in the GH and PRL curves, mainly related to sleep, but whose endogenous component previously described in other experimental situations is found in night workers with a distribution incompletely adapted to the secretory episodes. RESEARCH PERSPECTIVES: Both daytime sleep and night-time work are associated with perturbed endocrine functions which could explain certain health problems and sleep disorders observed (or avowed) after several years of night-shift work. These problems require further research into factors susceptible of resynchronizing the biological clock.

Adaptation, Physiological↗

PubMed1998

Pulsatile cortisol secretion and EEG delta waves are controlled by two independent but synchronized generators.

We have previously described a temporal relationship between plasma cortisol pulses and slow-wave sleep and, more recently, an inverse significant cross-correlation between cortisol secretory rates and delta wave activity of the sleep electroencephalogram (EEG). The aim of this study was to observe ACTH, cortisol, and sleep delta wave activity variations throughout 24 h to get a better insight into their initiating mechanisms. Two groups of 10 subjects participated in a 24-h study, one group with a night sleep (2300-0700) and the other with a day sleep (0700-1500). Cortisol secretory rates were calculated by a deconvolution procedure from plasma levels measured at 10-min intervals. Delta wave activity was computed during sleep by spectral analysis of the sleep EEG. When delta waves and cortisol were present at the same time at the end of the night sleep as well as during the daytime sleep, they were negatively correlated, cortisol changes preceding variations in delta wave activity by approximately 10 min. Increases in delta wave activity occurred in the absence of cortisol pulses, as observed at the beginning of the night. Cortisol pulses occurred without any concomitant variations of sleep delta wave activity, as observed during wakefulness and intrasleep awakenings. In no case did delta wave activity increase together with an increase in cortisol secretory rates. In conclusion, cortisol secretion and delta wave activity have independent generators. They can oscillate independently from each other, but when they are present at the same time, they are oscillating in phase opposition.

Activity Cycles↗

PubMed1998

Effect of the shift of the sleep-wake cycle on three robust endocrine markers of the circadian clock.

To determine the effect of a phase shift in sleep on the circadian clock, thyroid-stimulating hormone (TSH), cortisol, and melatonin, three robust markers of the circadian clock, were analyzed using a 10-min blood sampling procedure. In an initial experiment eight subjects were studied during two experimental sessions: once under baseline conditions with normal nighttime sleep from 2300 to 0700 (baseline) and once after a night of sleep deprivation followed by daytime sleep from 0700 to 1500 (day 1). In a second experiment, carried out on seven subjects, the 24-h hormone profiles of the first day (day 1) were compared with those of the second day (day 2) of the sleep shift. During the night of sleep deprivation (day 1) the TSH surge was higher than during baseline conditions, whereas melatonin and cortisol rhythms remained unaffected. On day 2 the amplitude of the nocturnal TSH surge was reduced in comparison to day 1, whereas the amplitudes of melatonin and cortisol rhythms were unchanged. There was a clear phase shift in the three endocrine rhythms. Triiodothyronine levels were slightly higher in the morning after the first night of sleep deprivation. These results demonstrate that 2 consecutive days of sleep shift are sufficient to affect the timing of the commonly accepted circadian markers, suggesting the existence of a rapid resetting effect on the circadian clock. TSH reacts in a distinctive manner to the sleep-wake cycle manipulation by modulating the amplitude of the nocturnal surge. This amplitude modulation is probably an integral part of the phase-shifting mechanisms controlled by the circadian clock.

Adult↗

PubMed1998

Disturbances in hormonal profiles of night workers during their usual sleep and work times.

In a previous study, the authors reported that the 24-h rhythms of pituitary and adrenal hormones--that is, thyrotropin (TSH), prolactin (PRL), growth hormone, and cortisol--adapted only partially in a group of permanent night workers. However, the real impact of circadian rhythm alterations on the health and well-being of subjects is still unclear. In this study, the authors focus on an ergonomic field and address questions of adaptation of these hormones during the usual day sleep time (0700-1500 h) and during the usual night work time (2200-0600 h) in permanent night workers. Eleven night workers, working a night schedule for at least 2 years, submitted to a high-frequency blood sampling procedure (10 min) and to electroencephalographic recordings during sleep. The endocrine profiles of night workers were compared to those of day-active subjects studied during their usual sleep-wake schedule. During usual day sleep, despite an adapted sleep structure, cortisol levels among night workers were abnormally enhanced, whereas the TSH decreased in comparison to the plateau observed among day-active subjects. During usual work time, some hormonal disturbances persisted, in particular concerning cortisol and PRL (two hormones known to reflect the level of activation). Among night workers, the work time was associated with the quiescent period of cortisol secretion normally occurring during the first hours of sleep, and with a transient PRL increase. These results revealed altered hormonal profiles during the sleep time of night workers that do not result in an altered sleep pattern. The nocturnal work time, which requires a high level physical and mental performance, is associated with some endocrine alterations reflecting an eventual phase of hypovigilance.

Adult↗

PubMed1997

Twenty-four-hour melatonin and core body temperature rhythms: their adaptation in night workers.

To determine whether the melatonin (MT) rhythm is adapted to a permanent nocturnal schedule, 11 night workers were studied during their usual 24-h cycle, and 8 day-active subjects during two 24-h cycles, once with night sleep and once after an acute shift of their sleep period to daytime. Rectal temperature (Tre) was continuously recorded. In day-active subjects, the MT rhythm was not affected by the acute shift in the sleep period, whereas the Tre rhythm was split in a biphasic pattern with the circadian descending phase during the night of sleep deprivation and a second descending trend during day sleep. Night workers showed a great variability in their MT profiles, with the onset of the MT release varying between 2145 and 0505. In contrast, the Tre rhythm was homogeneously entrained to their usual sleep-wake cycle, with the onset of the descending trend initiated before sleep onset so that the large decrease was found, in some subjects, to be uncoupled with their MT increase. The night-active schedule did not induce any amplitude modification of the Tre and the rhythms compared with day-active subjects sleeping at night. No relationship between work-dependent factors and the extent of the MT shift could be found. These results show the great variability in the timing of MT secretion among night workers, in contrast to the homogeneity of their Tre rhythm. The exact mechanisms by which night workers adapt their circadian systems have not yet been identified.

Activity Cycles↗

PubMed1997

Growth hormone secretion in night workers.

We previously reported that, in night workers, cortisol and TSH rhythms, known to have a high endogenous component, adapted only partially to the nocturnal schedule. The aim of the present study was to investigate the degree of adaptation of the growth hormone (GH) rhythm, considered to be mainly sleep-dependent, but for which a weak circadian drive has also been suggested. Eleven night workers were studied during their usual sleep-wake cycle, and two groups of 11 normally day-active subjects, sleeping once during the night and once after an 8-h sleep delay, were used as control groups. GH secretory rates were calculated by deconvolution of the plasma concentrations analyzed at 10-min intervals. The total amount of GH secreted during the 24 h did not differ between the three groups and the main secretory episode occurred, in most cases, during the first half of the sleep period. In night sleepers and night workers the enhanced amount of GH secreted at that time was followed by a significantly lower amount secreted during the second part of the sleep period (p < 0.001 and p < 0.05, respectively). For night sleepers, an enhanced GH pulse frequency was found at the beginning of sleep, whereas for night workers and day sleepers the pulses were distributed more randomly throughout the nychthemeron. After an abrupt sleep shift, all the subjects displayed a GH pulse at the usual time of early sleep, but such a pulse was present in only 8 of 11 night workers. Thus the amount of GH secreted between 23:00 h and 03:00 h in day sleepers did not differ significantly from that observed in night sleepers, whereas it differed for night workers. These results confirm the considerable influence of sleep in driving the GH rhythm and the existence of a circadian influence revealed by an acute shift in the sleep period. They also provide evidence of an incomplete adjustment of GH rhythms in night workers.

Adult↗

PubMed1996

Internal dissociation of the circadian markers of the cortisol rhythm in night workers.

To determine whether the circadian system of night workers is adapted to a night-active schedule, we submitted 11 night workers and 11 day-active subjects to a 10-min blood sampling procedure during their usual sleep-wake cycle, permitting a precise determination of circadian and ultradian cortisol variations. In night works, the usual shift of 8 h in the sleep period was associated with a distortion of the normal 24-h cortisol rhythm. The acrophase exhibited a shift of approximately 6.5 h, whereas the quiescent period, abruptly interrupted by a large peak, underwent a shift of only 3 h and lasted for approximately 5 h, as in day-active subjects. Slow-wave sleep and sleep onset occurred during periods of low or decreasing cortisol secretory rates, whereas awakenings were associated with an increase in cortisol secretory rates. These results revealed that the circadian system of night workers only partially adapts to night work and that adaptation processes rely on an internal dissociation of the markers of the cortisol pattern, without disturbing the processes that couple cortisol release and specific sleep stages.

Activity Cycles↗

PubMed1996

Twenty-four-hour prolactin profiles in night workers.

In addition to sleep processes, it has been suggested that an intrinsic circadian rhythmicity is involved in the temporal organization of prolactin (PRL) secretion. Eight night workers were studied to determine whether the PRL rhythm is adapted to their rest-activity schedule and whether this provides evidence in favor of an endogenous clock-driven component. Ten day-active subjects, sleeping once during the night and once after an 8-h delay in their sleep period, were used as a control group. Plasma PRL, body temperature, and plasma melatonin were measured at 10-min intervals. Twenty-four-hour PRL profiles did not differ between night workers sleeping as usual during the daytime and day-active subjects submitted to an abrupt sleep shift to daytime. For the two groups of subjects a transient PRL peak, similar in size and time of occurrence, was observed during the night. Melatonin, a strong marker of the primary circadian oscillator, displayed a phase shift that differed widely among night workers. Body temperature, on the other hand, was found to be more regularly adapted despite the persistence of a small decrease or leveling off during the night. Although no relationship was found between the melatonin increase and the nocturnal PRL peak, a concomitance with this transient temperature decrease could be demonstrated. The persistence of this PRL peak in night workers raises the question of its significance.

Acclimatization↗

PubMed1995

The circadian thyrotropin rhythm is delayed in regular night workers.

In order to determine whether the circadian thyrotropin (TSH) rhythm is adapted to a night-active schedule, plasma TSH and body temperature were measured for 28 h every 10-min in 8 regular night workers and in 8 day-active subjects. In night workers, the shift of 8-h in the sleep period induced a mean shift of 6 h 30 min of the TSH acrophase which remained located, as in day-active subjects, at about the time of sleep onset. The nadir of the body temperature rhythm was shifted by an equivalent amount and occurred systematically during the sleep period, so that both parameters maintained a fixed phase relationship. TSH and temperature rhythms had similar amplitudes in the two groups. However, mean TSH values in night workers returned more rapidly to basal values. These results demonstrate that, together with body temperature, TSH acrophase is adapted to regular night work, suggesting that TSH may be a good index for evaluating the orientation of the endogenous clock.

Adult↗