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Results for “Sleep Disorders, Intrinsic”

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PubMed2005

Sleep tendency during extended wakefulness: insights into adolescent sleep regulation and behavior.

Sleep tendency (latency to sleep onset) was examined during extended waking in prepubertal and mature adolescents to determine whether sleep pressure is lower near bedtime in the latter group. Participants were nine prepubertal (pubertal stage Tanner 1, mean age 11.1 years, SD+/-1.3 years, five males) and 11 pubertally mature adolescents (Tanner 5, 13.9+/-1.2 years, three males). They spent 10 nights at home on an identical fixed 10-h sleep schedule followed by a 36-h constant routine with sleep latency tests at 2-h intervals using standard polysomnography. Saliva was collected to assess dim-light melatonin onset (DLMO) phase. DLMO was earlier in the Tanner 1 (mean clock time=20:33 hours, SD=49 min) than Tanner 5 group (21:29 hours+/-42 min). Sleep latency compared at a 'critical period' spanning 12.5 (20:30 hours clock time) to 18.5 h (02:30 hours) after waking did not differ at 20:30 hours, but was shorter for the Tanner 1 group at 22:30 hours (Tanner 1=9.2+/-6.3 min; Tanner 5=15.7+/-5.8 min), 00:30 hours (Tanner 1=3.6+/-1.7 min; Tanner 5=9.0+/-6.4 min), and 02:30 hours (Tanner 1=2.0+/-1.7 min; Tanner 5=4.3+/-3.2 min; trend). These differences were apparent controlling for circadian phase by partial correlation. Sleep tendency after 14.5, 16.5, and 18.5 h awake was lower in mature versus prepubertal adolescents, supporting our hypothesis that a developmental change of intrinsic sleep-wake regulation may provide physiologically mediated 'permission' for later bedtimes in older adolescents.

Adolescent↗

PubMed2000

Cryptochrome: the second photoactive pigment in the eye and its role in circadian photoreception.

Circadian rhythms are oscillations in the biochemical, physiological, and behavioral functions of organisms that occur with a periodicity of approximately 24 h. They are generated by a molecular clock that is synchronized with the solar day by environmental photic input. The cryptochromes are the mammalian circadian photoreceptors. They absorb light and transmit the electromagnetic signal to the molecular clock using a pterin and flavin adenine dinucleotide (FAD) as chromophore/cofactors, and are evolutionarily conserved and structurally related to the DNA repair enzyme photolyase. Humans and mice have two cryptochrome genes, CRY1 and CRY2, that are differentially expressed in the retina relative to the opsin-based visual photoreceptors. CRY1 is highly expressed with circadian periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Mutant mice lacking either Cry1 or Cry2 have impaired light induction of the clock gene mPer1 and have abnormally short or long intrinsic periods, respectively. The double mutant has normal vision but is defective in mPer1 induction by light and lacks molecular and behavioral rhythmicity in constant darkness. Thus, cryptochromes are photoreceptors and central components of the molecular clock. Genetic evidence also shows that cryptochromes are circadian photoreceptors in Drosophila and Arabidopsis, raising the possibility that they may be universal circadian photoreceptors. Research on cryptochromes may provide new understanding of human diseases such as seasonal affective disorder and delayed sleep phase syndrome.

Animals↗

PubMed1985

Sleep and circadian rhythms in affective patients isolated from external time cues.

Sleep electroencephalographic activity, circadian rhythms in motor activity and rectal temperature, and clinical state were monitored longitudinally in four affectively ill patients (two depressed, one manic, and one rapidly cycling between depression and mania) who lived in isolation from external time cues (zeitgebers) for 3 to 4 weeks. In these conditions it was possible to observe the intrinsic or free-running behavior of circadian pacemakers and thereby to test several hypotheses about the role of sleep and circadian rhythms in the pathogenesis of depression. No hypothesis was consistently supported by the results. We found that the intrinsic rhythm of a circadian pacemaker appeared to free-run with an abnormally fast frequency in one patient. No patient remained stably depressed during temporal isolation. Our experience suggests that this type of study can be carried out safely with appropriate precautions. Temporal isolation is a means to test decisively predictions of several chronobiological hypotheses about affective illness and should be applied to additional patients.

Adult↗

PubMed2004

Arousal mechanisms related to posture and locomotion: 2. Ascending modulation.

An intrinsic function of the reticular activating system (RAS) is its participation in fight vs. flight responses such that alerting stimuli simultaneously activate thalamocortical systems, as well as postural and locomotor systems, in order to enable an appropriate response. The P50 midlatency auditory-evoked potential appears to be an ascending manifestation of the cholinergic arm of the RAS in eliciting changes in arousal state. Abnormalities in the manifestation of the P50 potential are present in disorders which include: (1) dysregulation of sleep-wake cycles; (2) abnormalities in reflex/postural, especially, startle, responses; and (3) malfunctions in flight vs. flight responses. In general, the P50 potential appears to be upregulated (increased amplitude and/or decreased sensory gating) in disorders which are marked by upregulation of RAS outputs (hypervigilance), and downregulated in disorders characterized by decreased RAS outputs (hypovigilance). Many of the disorders discussed have a developmental etiology and a postpubertal age of onset.

Afferent Pathways↗

PubMedDate not supplied

[Psychiatric manifestations of vitamin B12 deficiency: a case report].

Psychiatric manifestations are frequently associated with pernicious anemia including depression, mania, psychosis, dementia. We report a case of a patient with vitamin B12 deficiency, who has presented severe depression with delusion and Capgras' syndrome, delusion with lability of mood and hypomania successively, during a period of two Months. Case report - Mme V., a 64-Year-old woman, was admitted to the hospital because of confusion. She had no history of psychiatric problems. She had history of diabetes, hypertension and femoral prosthesis. The red blood count revealed a normocytosis with anemia (hemoglobin=11,4 g/dl). At admission she was uncooperative, disoriented in time and presented memory and attention impairment and sleep disorders. She seemed sad and older than her real age. Facial expression and spontaneous movements were reduced, her speech and movements were very slow. She had depressed mood, guilt complex, incurability and devaluation impressions. She had a Capgras' syndrome and delusion of persecution. Her neurologic examination, cerebral scanner and EEG were postponed because of uncooperation. Further investigations confirmed anemia (hemoglobin=11,4 g/dl) and revealed vitamin B12 deficiency (52 pmol/l) and normal folate level. Antibodies to parietal cells were positive in the serum and antibodies to intrinsic factor were negative. An iron deficiency was associated (serum iron=7 micromol/l; serum ferritin concentration=24 mg/l; serum transferrin concentration=3,16 g/l). This association explained normocytocis anemia. Thyroid function, hepatic and renal tests, glycemia, TP, TCA, VS, VDRL-TPHA were normal. Vitamin B12 replacement therapy was started with hydroxycobalamin 1 000 ng/day im for 10 days and iron replacement therapy. Her mental state improved dramatically within a few days. After one week of treatment the only remaining symptoms were lability of mood, delusion of persecution, Capgras' syndrome but disappeared totally 9 days after the beginning of the treatment. A neurologic examination was possible because of cooperation. All the tendon reflexes of inferior members were absent. The plantars were in flexion and there was a left inferior member hypoesthesia. The cerebral scan and EEG were normal. Fundic biopsy, realized by fibroscopy, revealed fundic atrophia and intestinal metaplasia compatible with Biermers' disease. The iron deficiency exploration concluded diet deficiency. Mme V. appeared euphoric, her speech was very rapid with play on words and overactivity. This hypomania state totally disappeared 3 days after. Six Months after her hospitalisation, she presented an hypothyroidism (TSH=3,780; T3=1,35; T4=1,08). A thyroid hormones replacement was started and she continued to receive Monthly B12 replacement. Discussion - This case report illustrates psychiatric manifestations of Biermers' disease. The clinical arguments in favour are: white woman, more than 60 Years old, no history of psychiatric problems, atypical symptoms (confusional state with psychiatric symptoms), fluctuation of symptoms (severe depression with confusional state, delusion of persecution and Capgras' syndrome; delusion with lability of mood and hypomania), dramatic improvement after 9 days of vitamin B12 replacement therapy. The biological arguments are: anemia, vitamin B12 deficiency, normal folate level, atrophia and fundic metaplasia, positive antibodies to parietal cells in the serum, association between Biermers' disease and autoimmune disease (Haschimoto thyroidite). Psychiatric manifestations can occur in the presence of low serum B12 levels but in the absence of the other well recognized neurological and haematological abnormalities of pernicious anemia. Mental or psychological changes may precede haematological signs by Months or Years. They can be the initial symptoms or the only ones. Verbank et al. described the case of a patient with vitamin B12 deficiency in whom hypomania, paranoia and depression had been successively presented during a period of 5 Years before anemia have been developed. The case of Mme V. is similar in the succession of severe depression with delusion of persecution and Capgras' syndrome, delusion with lability of mood and hypomania, during a period of two Months. This report seems to be the first one of a sequence of several psychiatric states with pernicious anemia during a period of two Months with normocytosis anemia. To illustrate this illness we reviewed the literature regarding psychopathology associated with B12 deficiency. The most common psychiatric symptoms were depression, mania, psychotic symptoms, cognitive impairment and obsessive compulsive disorder. The neuropsychiatric severity by vitamin B12 deficiency and the therapeutic efficacy depends on the duration of signs and symptoms. Conclusion - We recommend consideration of B12 deficiency and serum B12 determinations in all the patients with organic mental disorders, atypical psychiatric symptoms and fluctuation of symptomatology. B12 levels should be evaluated with treatment resistant depressive disorders, dementia, psychosis or risk factors for malnutrition such as alcoholism or advancing age associated with neurological symptoms, anemia, malabsorption, gastrointestinal surgery, parasite infestation or strict vegetarian diet. In first intention, B12 deficiency should be researched by serum B12 determination (normal 200-950 pg/ml). Studies of methylmalonic acid and homocysteine showed that they are very sensitive functional indicators of cobalamin status especially when other evidence of cobalamin (B12) deficiency was equivocal. Measurement of methylmalonic acid (normal 73-271 nmol/l) and homocysteine (normal 5,4-13,9 micromol/l) should not replace the measurement of serum cobalamin.

Depression↗

PubMed2002

A review of functional and structural components of the respiratory center involved in the arousal response.

State-dependent changes influencing both the central chemoreceptor and vagal inputs to respiratory neurons may provide useful markers to assess some intrinsic factors of the respiratory center. In this paper we discuss the following topics from our recent experiences, and their relevance to the assessment of sleep-related phenomena. (1) 'Post-sigh' apnea appears predominantly during non-REM sleep in control subjects, and is a potential marker of respiratory dysfunction during this stage of sleep. (2) The disarranged configuration of the arcuate nucleus in Fukuyama-type congenital muscular dystrophy may represent a disturbance in the tangential migration pathway in the brainstem, and may be related to the sudden death that is common in this disorder. The maldevelopment of the arcuate nucleus in the victims of sudden infant death syndrome (SIDS) may also be related to some abnormality in the differentiation and migration of this neuronal population. (3) The onset of hypoglossal nerve activity precedes inspiratory activity of the phrenic nerve, possibly representing a latent drive from the respiratory rhythm generator. These issues are not only related to respiratory rhythmogenesis itself, but are also important in understanding the pathological conditions of arousal responses.

Journal Article↗

PubMedDate not supplied

Familial symptomatic sinus bradycardia: autosomal dominant inheritance.

Symptomatic sinus bradycardia, due to either sick sinus syndrome or vagotonia, can be familial, affecting several members of a family. We report an 18-year-old male patient with palpitations and limited exercise capacity who was noted to have severe sinus bradycardia. His resting heart rate was 40/min, with normal PR and corrected QT intervals, and sinus pauses up to 6 seconds during sleep. Exercise treadmill test and pharmacologic autonomic blockade during electrophysiologic studies abolished the bradycardia, suggestive of vagotonia rather than intrinsic sinus node dysfunction. This patient's father and a female cousin had a similar clinical history but associated with syncope and severe sinus bradycardia. The mode of transmission appeared to be autosomal dominant. All three have permanent demand pacemakers implanted and are asymptomatic.

Adolescent↗

PubMed1990

Optimizing REM latency as a diagnostic test for depression using receiver operating characteristic analysis and information theory.

New diagnostic techniques must be evaluated for their intrinsic accuracy and for their applicability to particular patient groups in specific clinical settings. Using receiver operating characteristic (ROC) analysis and concepts from information theory, we have developed a new mathematical and graphical method that can evaluate, compare, and optimize the performance of diagnostic tests for any value of disorder prevalence. Our analytic method is appropriate to any test that sorts disordered from nondisordered subjects using a continuous or nonbinary diagnostic variable; its characterization of the fundamental properties of such tests thus has important implications for the evaluation and optimization of diagnostic modalities used by clinicians in all medical specialties. We demonstrate our method using published data from five studies that used sleep architecture as a "biological marker" for depression. Our analysis confirms that REM latency is comparable to the dexamethasone suppression test in its ability to discriminate depressed from control subjects. For each of the five studies, we show how optimal REM latency cut-off times may be selected so that diagnostic information yield is maximized, and we compare the ability of each study to detect depressed subjects in populations where the prevalence of affective disorder can be specified.

Adult↗

PubMed2003

Childhood pneumonia: clinical aspects associated with hospitalization or death.

OBJECTIVE: To determine which available information at an Emergency Room (ER) consultation is associated with hospitalization or death among children with pneumonia. DESIGN: Prospective cohort study. SETTING: The ER of one university and one private hospital. MEASUREMENT: Using stepwise logistic regression we analyzed factors that showed a univariate association. MAIN RESULTS: Of 2,970 cases, the median age was 1.83 years (range 2 days to 14.5 yrs, mean 2.76 +/- 2.72 yrs); 25.8% were hospitalized and 0.8% died. Age (2-11 mos, OR 0.4 [0.2-0.6]; 12-59 mos, OR 0.2 [0.1-0.4]; > or = 5 yrs, OR 0.1 [0.08-0.3]), malnutrition (OR 2.0 [1.4-2.7]), underlying chronic illness (OR 1.4 [1.1-1.8]), tachypnea (OR 1.8 [1.4-2.4]), chest indrawing (OR 1.7 [1.4-2.2]), and somnolence (OR 1.8 [1.4-2.4]) were associated with hospitalization and age (2-11 mos, OR 0.3 [0.08-0.8]; > or = 12 mos, OR 0.06 [0.02-0.2]), malnutrition (OR 3.1 [1.2-7.7]) and underlying chronic illness (OR 4.3 [1.6-11.0]) were associated with death in the multivariate analysis. CONCLUSIONS: Several clinical aspects may be used in assessing need for hospitalization (i.e. young age, malnutrition, underlying chronic illness, tachypnea, chest indrawing and somnolence) for children with pneumonia seen at the ER. Individual intrinsic factors such as age, malnutrition and underlying chronic illness were independently associated with death. Pneumonia should be considered a treatable disease and complete recovery can be achieved in the majority of the cases.

Adolescent↗

PubMed1978

The clinical activity of oxazepam.

Over the years, oxazepam has distinguished itself clinically from other benzodiazepines by virtue of its excellent tolerance. Recent research suggests that this is due to metabolic and pharmacokinetic differences rather than an intrinsically more favourable toxic-to-therapeutic dosage ratio. Because of its excellent tolerance, dosage is very flexible, and it is, therefore, possible to utilize oxazepam in a wide spectrum of anxiety-related disorders including the psychoses. The use of oxazepam in anxiety neurosis, depressive neurosis, psychotic disorders, alcoholism, and insomnia is discussed.

Alcoholism↗

PubMedDate not supplied

[The basal forebrain. Neuroanato-physiology and neurologic applications].

The Basal Forebrain region comprises the heterogeneous set of telencephalic structures on the medial and ventral aspects of the cerebral hemisphere. Basal Forebrain structures include the septal areas, olfactory tubercule, substantia innominata, and parts of the amygdala. The basal forebrain region is the site of a system of cholinergic neurons projecting to the entire cortical surface. The Basal Forebrain is a site of convergence of sleep and thermoregulatory functions. Portions of the basal forebrain play prominent roles in the control of the body temperature. The medial preoptic/anterior hypothalamic areas have both thermosensiting and thermointegrating functions. Cholinergic neurons intrinsic to the Basal Forebrain play a fundamental role in sleep onset and maintenance. Neurons of the nucleus basalis of Meynert undergo a profound degeneration in patients with Alzheimer's disease and provide a pathological substrate of the cholinergic deficiency in their brain. Behavior changes and amnesic syndrome may complicate surgery for ruptured anterior communicating artery aneurysms. Disruption of the blood supply through the perforating branches of the anterior communicating artery may probably cause the amnesic syndrome.

Acetylcholine↗

PubMed2001

Effect of REM sleep on retroglossal cross-sectional area and compliance in normal subjects.

It has been proposed that the upper airway compliance should be highest during rapid eye movement (REM) sleep. Evidence suggests that the increased compliance is secondary to an increased retroglossal compliance. To test this hypothesis, we examined the effect of sleep stage on the relationship of retroglossal cross-sectional area (CSA; visualized with a fiber-optic scope) to pharyngeal pressure measured at the level of the oropharynx during eupneic breathing in subjects without significant sleep-disordered breathing. Breaths during REM sleep were divided into phasic (associated with eye movement, PREM) and tonic (not associated with eye movements, TREM). Retroglossal CSA decreased with non-REM (NREM) sleep and decreased further in PREM [wake 156.8 +/- 48.6 mm(2), NREM 104.6 +/- 65.0 mm(2) (P < 0.05 wake vs. NREM), TREM 83.1 +/- 46.4 mm(2) (P = not significant NREM vs. TREM), PREM 73.9 + 39.2 mm(2) (P < 0.05 TREM vs. PREM)]. Retroglossal compliance, defined as the slope of the regression CSA vs. pharyngeal pressure, was the same between all four conditions (wake -0.7 + 2.1 mm(2)/cmH(2)O, NREM 0.6 +/- 3.0 mm(2)/cmH(2)O, TREM -0.2 +/- 3.3 mm(2)/cmH(2)O, PREM -0.6 +/- 5.1 mm(2)/cmH(2)O, P = not significant). We conclude that the intrinsic properties of the airway wall determine retroglossal compliance independent of changes in the neuromuscular activity associated with changes in sleep state.

Adult↗

PubMed2001

Expiratory flow limitation and orthopnea in massively obese subjects.

BACKGROUND: Morbidly obese subjects, who often complain about breathlessness when lying down, breathe at low lung volume with a reduced expiratory reserve volume (ERV). Therefore, during tidal breathing the expiratory flow reserve is decreased, promoting expiratory flow limitation (EFL), which is more likely to occur in the supine position, when the relaxation volume of the respiratory system, and hence the functional residual capacity (FRC), decrease because of the gravitational effect of the abdominal contents. PURPOSE: The aim of the study was to assess EFL and orthopnea in massively obese subjects and to evaluate whether orthopnea was associated with the development of supine EFL. METHODS: In 46 healthy obese subjects (18 men) with a mean (+/- SD) age of 44 +/- 11 years and a mean body mass index (BMI) of 51 +/- 9 kg/m(2), we assessed EFL in both the seated and the supine positions by the negative expiratory pressure method and assessed postural changes in FRC by measuring the variations in the inspiratory capacity (IC) with recumbency. Simultaneously, dyspnea was evaluated in either position using the Borg scale dyspnea index (BSDI) to determine the presence of orthopnea, which was defined as any increase of the BSDI in the supine position. RESULTS: Partial EFL was detected in 22% and 59%, respectively, of the overall population in seated and supine position. The mean increase in the supine IC amounted to 120 +/- 200 mL (4.1 +/- 6.4%), indicating a limited decrease in FRC with recumbency in these subjects. Orthopnea, although mild (mean BSDI, 1.7 +/- 1.3), was claimed by 20 subjects, and in 15 of them EFL occurred or worsened in the supine position. Orthopnea was associated with lower values of seated ERV (p < 0.05) and was marginally related to supine EFL values (p = 0.07). No significant effect of age, BMI, obstructive sleep apnea-hypopnea syndrome, FEV(1), and forced expiratory flow at 75% of vital capacity was found on either orthopnea or EFL. CONCLUSION: In morbidly obese subjects, EFL and dyspnea frequently occur with the subject in the supine position, and both supine EFL and low-seated ERV values are related to orthopnea, suggesting that dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure may be partly responsible for orthopnea in massively obese subjects.

Adult↗

PubMed2005

Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans.

The internal circadian clock and sleep-wake homeostasis regulate the timing of human brain function, physiology, and behavior so that wakefulness and its associated functions are optimal during the solar day and that sleep and its related functions are optimal at night. The maintenance of a normal phase relationship between the internal circadian clock, sleep-wake homeostasis, and the light-dark cycle is crucial for optimal neurobehavioral and physiological function. Here, the authors show that the phase relationship between these factors-the phase angle of entrainment (psi)-is strongly determined by the intrinsic period (tau) of the master circadian clock and the strength of the circadian synchronizer. Melatonin was used as a marker of internal biological time, and circadian period was estimated during a forced desynchrony protocol. The authors observed relationships between the phase angle of entrainment and intrinsic period after exposure to scheduled habitual wakefulness-sleep light-dark cycle conditions inside and outside of the laboratory. Individuals with shorter circadian periods initiated sleep and awakened at a later biological time than did individuals with longer circadian periods. The authors also observed that light exposure history influenced the phase angle of entrainment such that phase angle was shorter following exposure to a moderate bright light (approximately 450 lux)-dark/wakefulness-sleep schedule for 5 days than exposure to the equivalent of an indoor daytime light (approximately 150 lux)-dark/wakefulness-sleep schedule for 2 days. These findings demonstrate that neurobiological and environmental factors interact to regulate the phase angle of entrainment in humans. This finding has important implications for understanding physiological organization by the brain's master circadian clock and may have implications for understanding mechanisms underlying circadian sleep disorders.

Adult↗

PubMed2000

Development of the control of breathing: implications for sleep-related breathing disorders in infants.

Abnormal development of the control of breathing has implications for the occurrence and severity of SDB during infancy. Prevention of prenatal insults such as nicotine exposure should be included in public health programs. Infants at risk for SDB or with symptoms of SDB should be investigated for peripheral and central chemoreceptor dysfunction. Peripheral chemoreceptor function can be assessed using either the hyperoxic test or the alternating breath test, and central chemoreceptor function using the rebreathing test. Optimal treatment of SDB in the developing infant is of central importance for preserving normal behavior and neurocognitive development. Oxygen supplementation and/or ventilatory support during sleep prevent uncontrolled episodes of hypoxemia, sleep fragmentation, and REM sleep reduction. Finally, alterations in homeostatic responses during development may have long-term effects on breathing during sleep in childhood and adulthood. In genetically-predisposed subjects, environmental conditions during the period of development of respiratory control mechanisms may add to the intrinsic vulnerability to SDB.

Arcuate Nucleus of Hypothalamus↗

PubMed2006

Sleep and wakefulness out of phase with internal biological time impairs learning in humans.

Sleep-wake homeostatic and internal circadian timedependent brain processes interact to regulate human brain function so that alert wakefulness is promoted during the daytime and consolidated sleep is promoted at nighttime. The consequence of chronically altering the normal relationship between these processes for human brain function is largely unknown. We tested cognitive and vigilance performance while subjects lived in the laboratory for over a month. The subjects lived on either 24.0- or 24.6-hr day lengths. Half of the subjects tested maintained a normal relationship between sleep-wakefulness and internal circadian time (synchronized group), whereas the other half did not (nonsynchronized group). Levels of the sleep-promoting hormone melatonin were high during scheduled sleep in the synchronized group, whereas melatonin levels were high during scheduled wakefulness in the nonsynchronized group. Failure to adapt to the scheduled day length was dependent upon individual differences in intrinsic circadian period. Total sleep time was reduced, sleep latency and Rapid Eye Movement (REM) latency were shortened, and wakefulness after sleep onset was increased in the nonsynchronized group. Cognitive performance improved (i.e., learning) in the synchronized group, whereas learning was significantly impaired in the nonsynchronized group. Attention progressively declined in both groups, suggesting that 8 hr of scheduled sleep per night is insufficient to maintain brain vigilance even when sleep occurs at an appropriate biological time. Our results establish that proper alignment between sleep-wakefulness and internal circadian time is crucial for enhancement of cognitive performance. In addition, our results demonstrate that exposure to dim light (approximately 25 lx) is sufficient to expand the range of entrainment in humans.

Adult↗

PubMed2006

Fatigue in military aviation shift workers: survey results for selected occupational groups.

BACKGROUND: Shift workers are particularly vulnerable to increased sleepiness, chronic fatigue, and decreased performance, which can adversely impact productivity and safety in military flight operations. This study examined the association of specific risk factors including work context and shift system details (squadron: remotely piloted aircraft [RPAI vs. manned aircraft [MA]), work/rest guidelines (career field: crewmember vs. maintainer), and participation in deployed operations (environment: home base vs. deployed) on subjective fatigue using standardized and validated fatigue questionnaires. METHODS: A cross-sectional survey of 172 U.S. Air Force (USAF) personnel was conducted from October 2004 to May 2005. The study sample was recruited from four different USAF occupational groups involved in some form of shift work to include irregular, rotational, or fixed shifts. RESULTS: Participants reported a mean (SD) of 6.6 (1.8) hours of sleep per day with no differences by squadron, career field, or environment. Mean daily sleep did not correlate with scores on the fatigue questionnaires. Mean scores on the fatigue questionnaires were associated with squadron (mean fatigue score: RPA > MA), but not with career field or environment. There were no significant interaction effects, nor were there significant effects based on the covariates age, gender, and rank. CONCLUSION: Work context, shift system details, or both appeared to best explain the observed differences in fatigue between USAF shift worker populations. Crewmember work/rest guidelines did not appear to be useful for mitigating fatigue associated with shift work. Shift work is intrinsically fatiguing, regardless of whether the shift worker is at home base or deployed.

Adult↗

PubMed2006

BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.

Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.

Acetylcholine↗