Circadian rhythms during gradually delaying and advancing sleep and light schedules

The circadian rhythms of the night shift worker show very little phase shift in response to the daytime sleep and night work schedule. One strategy for producing circadian adaptation may be to use appropriately timed exposure to high-intensity light. We attempted to shift the circadian temperature rhythms of seven normal subjects while they followed a sleep schedule that gradually delayed (2 h per day) until sleep occurred during the daytime, as is customary for workers during the night shift. After 5 days, the sleep schedule was gradually advanced back to baseline. High illuminance light (2 h per day) and the attenuation or avoidance of sunlight were timed to facilitate temperature rhythm phase shifts. In general, the temperature rhythm did not shift along with the sleep-wake schedule, but appeared either to free run or remain entrained to the natural 24-h zeitgebers. This study showed how difficult it can be to shift human circadian rhythms in the field, when subjects are exposed to competing 24-hr zeitgebers.     

Rhythms in the central nervous system and 1/f fluctuations of the heart rate

We have developed a system to analyze heart rate variability (HRV) (power spectral array of the HRV) during 24 h ambulatory electrocardiographic monitoring. Several rhythms (circadian and several ultradian rhythms) were observed in the power spectral array of the heart rates and 1/f-like fluctuations in the log-log scaled heart rate power spectrum. The circadian change of the heart rate is closely related to the body temperature rhythm. The 90 min rhythm of HRV during sleep was suspected to be produced by the sleep cycle (REM/NREM) and the lower frequency peak of the HRV was coherent with oscillation in amplitude modulated respiration. These circadian and ultradian rhythm as assessed by heart rate variability exist both in normal subjects and in patients with autonomic failure. The power of the high frequency band decreases in subjects with autonomic failure. The power of low frequency components increases during periodic breathing or Cheyne-Stokes respiration. Log-log scaled analysis of the power spectrum of HRV disclosed that the slope of the HRV is markedly modulated by the range of the frequency applied for the least square regression line analysis. The increased power that might be produced by periodic breathing and decreased power in patients with autonomic failure might strongly modulate the slope of the log-log scaled HRV. It is concluded that the power spectral array of the HRV during 24 h period is useful in the detection of circadian and ultradian rhythm, and log-log scaled power spectra might be useful in the overall integration of the heart rate dynamics produced by the central nervous system. The several rhythm factors that might be produced by the central nervous system might modulate 1/f fluctuations of the HRV.     

Circadian and ultradian rhythms of drinking behavior of albino rats maintained in constant darkness

The objective of the present study was to investigate the circadian and the ultradian rhythms of drinking behavior in Wistar rats maintained under conditions of constant darkness. Six mature male rats (weighing 270-350 g) were exposed to light-dark 12:12-h cycles (LD 12:12, light on at 12:00 h) for 35 days and then switched to constant darkness (DD) conditions for at least 2 weeks. Drinking behavior was monitored continuously with a standard drinkometer circuit and the data was stored in 5-min bins. A modification of Enright's periodogram technique was used to evaluate the free-running drinking behavior circadian rhythm. Ultradian rhythms in drinking behavior were estimated by the Fast Fourier Transform (FFT) technique. Two of the animals (rats 4 and 6) showed no statistically significant circadian or ultradian rhythms and the other four showed free-running drinking circadian rhythm behavior shorter than 24 h (ranging from 23.333 to 23.967 h). Ultradian rhythms of drinking behavior of 12- and 8-h periods were detected in 4 (rats 1, 2, 3 and 5) and 2 (rats 1 and 5) animals, respectively. The relation of the compound structure of the circadian and ultradian rhythms is discussed demonstrating that drinking behavior is a good marker for studies of physiology of temporal organization.     

Perceptual grouping due to pitch and amplitude in hallucinating schizophrenics

Acquired deficiencies of fibrinogen, antithrombin III and plasminogen are reported in liver disease, and it is known that their plasma levels fluctuate during the day. The aim of this study was to investigate the circadian rhythms of these three factors in chronic liver disease. Five groups of subjects were considered: (A) 15 healthy controls: (B) 15 patients with hepatic alcoholic steatosis; (C) 15 patients with chronic active hepatitis; (D) 15 patients with compensated cirrhosis of the liver, and (E) 15 patients with decompensated cirrhosis with ascites. The levels of fibrinogen, antithrombin III and plasminogen were determined in blood samples drawn in each subject during the span of a day every 3 h starting from midnight. The time-related values were analyzed using the 'population-mean cosinor' method. Groups A and B presented a significant (p < 0.05) circadian rhythm for each variable, group C a significant (p < 0.05) circadian rhythm for fibrinogen and antithrombin III and groups D and E no significant (p > 0.05) circadian rhythms. Statistically significant differences (p < 0.05) were demonstrated among the groups in the mean daily levels of the three variables by ANOVA, the concentrations decreasing with disease severity. These data confirm the existence of a significant diurnal periodicity in the circulating levels of fibrinogen, antithrombin III and plasminogen in controls and suggest that liver disease is associated with progressive circadian modifications in the temporal structure of fibrinogen, antithrombin III and plasminogen, related to the stage of the liver disease. The rhythm derangements may be considered markers of evolution in liver disease.     

Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or "zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA) axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states.     

Expression of the POU transcription factor Brn-5 is an early event in the terminal differentiation of CNS neurons

OBJECTIVE: To evaluate transesophageal echocardiography (TEE) as an intraoperative monitoring modality and to assess its safety, reliability, and overall utility in real-time use during cardiac surgery. DESIGN: Prospective, observational cohort study performed from January 1993 to June 1997. SETTING: Operating room of a tertiary care hospital for cardiology and cardiovascular surgery. PARTICIPANTS: Five thousand and sixteen adult patients with acquired heart disease, who underwent 1,356 valve procedures and 3,660 coronary artery bypass graftings (CABGs). INTERVENTIONS: All patients were monitored with radial artery and pulmonary artery catheters, along with continuous TEE monitoring with a multiplane transducer. MEASUREMENTS AND MAIN RESULTS: Prebypass imaging yielded unsuspected findings that either helped or modified the surgical plan in 158 of 1,356 valve procedures (11.65%) and in 993 of 3,660 CABGs (27.13%). There were 3,217 TEE-guided hemodynamic interventions in 944 patients (25.79%) in the CABG group and 629 in 142 patients (10.47%) in the valve group. TEE was the sole guiding factor in initiating therapy in 23.53% of events, whereas it was supportive to other monitoring modalities in 76.46% of events. Postbypass TEE identified the need for graft revision in 29 patients (0.8%), intra-aortic balloon pump (IABP) requirement in 29 patients (0.8%), and inadequate valve repair in 28 patients (2.08%). For the entire series, 38.78% of patients benefited from prebypass and 39.16% from postbypass use of TEE. There were no complications attributable to the use of TEE in the entire series. There was 87% concordance between online interpretation by a trained anesthesiologist and offline analysis by a cardiologist. CONCLUSION: Intraoperative TEE is useful in formulating the surgical plan, guiding various hemodynamic interventions, and assessing the immediate results of surgery. It is safe and the results are reliable in the hands of trained anesthesiologists.     

An improved sample packing device for rapid freeze-trap electron paramagnetic resonance spectroscopy kinetic measurements

Circadian rhythms are generated by the suprachiasmatic nuclei (SCN) and synchronized (entrained) to environmental light-dark cycles by the retinohypothalamic tract (RHT), a direct pathway from the retina to the suprachiasmatic nuclei. In anophthalmic mice, the optic primordia are resorbed between embryonic days 11.5 and 13, before retinal ganglion cells emerge. Thus the retinohypothalamic tract, which is the primary "zeitgeber" for circadian rhythms in sighted animals, never forms, and there is no retinal or photic input to the circadian system. We have used wheel running activity, a highly consistent and reliable measure of circadian rhythmicity in rodents, to establish the properties of endogenous locomotor rhythms of anophthalmic mice. We have identified three subpopulations of anophthalmic mice: a) rhythmic with strong stable circadian period but significantly increased period length; b) rhythmic with unstable circadian period; and c) arrhythmic. Future correlation of locomotor rhythms with properties of the suprachiasmatic nuclei in these mice will clarify the relationship between generation and properties of circadian rhythms and the neuroanatomical, neurochemical, and molecular organization of the circadian clock.     

Melatonin entrains the restored circadian activity rhythms of syrian hamsters bearing fetal suprachiasmatic nucleus grafts

A circadian pacemaker consists of at least three essential features: the ability to generate circadian oscillations, an output signal, and the ability to be entrained by external signals. In rodents, ablation of the suprachiasmatic nucleus (SCN) results in the loss of circadian rhythms in activity. Rhythmicity can be restored by transplanting fetal SCN into the brain of the lesioned animal, demonstrating the first two of the essential pacemaker features within the grafts. External signals, such as the light/dark cycle, have not, however, been shown to entrain the restored rhythms. Melatonin injections are an effective entraining stimulus in fetal and neonatal Syrian hamsters of the same developmental ages used to provide donor tissue for transplantation. Therefore, melatonin was used to test the hypothesis that SCN grafts contain an entrainable pacemaker. Daily injections of melatonin were given to SCN-lesioned hosts beginning on the day after transplantation of fetal SCN. Two groups that received melatonin at different times of day 12 hr apart each showed significantly clustered phases but with average phases that differed by 8.67 hr. Thus melatonin was able to entrain the restored circadian activity rhythms. In contrast to these initial injections, injections given 6 weeks after transplantation were unable to entrain or phase shift the rhythms. The results demonstrate that SCN grafts contain an entrainable circadian pacemaker. In addition, the results also indicate that the fetal SCN is directly sensitive to melatonin and, as with intact hamsters, sensitivity to melatonin is lost during SCN development.     

Management of Nausea, Vomiting, and Diarrhea During Critical Illness

Symptoms are subjective patient experiences that may negatively impact the patient's hospitalization, treatment plan, and quality of life. Critically ill patients frequently experience nausea, vomiting, and diarrhea related to underlying disease, procedures, and medical interventions (eg, medication, enteral feeding, surgery). Optimally, the nurse performs a subjective assessment that explores the patient's perception and impact of these symptoms to develop a comprehensive plan of care. Unfortunately, little evidence is available to guide assessment of nausea, vomiting, and diarrhea in critically ill nonverbal patients. Understanding the disease processes, medical treatments, and pathophysioglogy of these symptoms will assist the critical care nurse in the anticipation of symptoms and development of a proactive plan to alleviate the symptom-associated discomfort.

     

The circadian periodicity of urinary 17-ketosteroids, corticosteroids, and electrolytes in congenital adrenal hyperplasia

The circadian periodicity of adrenal function in patients with congenital virilizing adrenal hyperplasia (CAH) was examined by measuring the urinary 17-ketosteroids, 17-hydroxycorticosteroids, sodium, and potassium. Patients with the salt-losing and the non-salt-losing types were studied with and without treatment. Cosine curves were fitted to the data by the least-squares method to determine the mesors, amplitudes, and acrophases of the variable for each patient. The data reveal distinct circadian rhythms for all variables measured whether or not the patient was receiving treatment. The acrophases for 17-ketosteroids and 17-hydroxycorticosteroids were between 1500 and 1800 h. These acrophases are about 6 h later than those for normal subjects. The treatment on a fixed daytime schedule for many years may have shifted the natural rhythm.     

Extent of autonomic activation following cerebral ischemia is different in hypertensive and normotensive humans

OBJECTIVES: To evaluate whether the extent of autonomic activation following brain infarction differs between hypertensive and normotensive humans, and to investigate the role of the insular cortex for this sympathetic activation. DESIGN: Prospective, hospital-based study. SETTING: Department of Neurology of a university medical center. SUBJECTS: Forty-two patients with essential hypertension and 45 patients who were normotensive. MAIN OUTCOME MEASURES: Extent of autonomic activation following stroke as indicated by circadian blood pressure patterns, serum norepinephrine levels, and cardiovascular variables. RESULTS: Normotensive patients with insular infarction showed a significantly reduced circadian blood pressure variation and a higher frequency of nocturnal blood pressure increase compared with patients suffering from essential hypertension and insular stroke. These findings were also associated with higher serum norepinephrine concentrations and more frequent electrocardiographic abnormalities. No significant changes in these variables were seen between normotensive and hypertensive patients without insular involvement. CONCLUSIONS: Our findings suggest a difference in cortical control of autonomic function between hypertensive and normotensive patients after stroke and point to a possible role of the insular cortex in the pathogenesis of essential hypertension.     

Circadian rhythm of heart rate variability is reversibly abolished in ischemic stroke

BACKGROUND AND PURPOSE: Acute brain infarction significantly decreases heart rate variability as a result of cardiovascular autonomic dysregulation. However, information regarding circadian rhythms of heart rate and heart rate variability is limited. METHODS: In this prospective study, we analyzed 24-hour circadian rhythm of heart rate and the time and frequency domain measures of heart rate variability in 24 patients with hemispheric brain infarction, 8 patients with medullary brainstem infarction, and 32 age- and sex-matched healthy control subjects. ECG data were obtained from the patients in the acute phase and at 6 months after the infarction. RESULTS: In the acute phase of stroke, all the components of heart rate variability, ie, standard deviation of RR intervals, total power, high-frequency power, low-frequency power, and very-low-frequency power, were similar at night (from midnight to 6 AM) and during the day (from 9 AM to 9 PM), indicating that the circadian oscillation of heart rate variability had been abolished. At 6 months after brain infarction, the circadian rhythm had returned and, as in the control subjects, the values at night were significantly higher than those in the daytime. The values in hemispheric and in brainstem infarction did not differ significantly from each other. CONCLUSIONS: These results suggest that circadian fluctuation of heart rate variability is reversibly abolished in the acute phase of ischemic stroke and that it returns during the subsequent 6 months. The loss of the relative vagal nocturnal dominance may contribute to the incidence of cardiac arrhythmias and other cardiovascular complications after acute stroke.     

Effect of transplantation of embryonic anterior hypothalamic tissue from spontaneously hypertensive rats to normotensive Wistar rats on circadian rhythms of systolic arterial pressure and heart rate

The anterior hypothalamus (AH) participates in the regulation of arterial pressure. The suprachiasmatic nuclei (SCN) of the AH are a major circadian oscillator necessary for the generation and/or the entrainment of circadian rhythms. Circadian rhythms of systolic arterial pressure (SAP) and heart rate (HR) were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar rats (NWI) with intact SCN, grafted with SHR embryonic AH tissue containing the SCN. Prominent circadian rhythms for SAP and HR in both NWI and SHR with acrophases during dark were found. The elevation of the MESOR (midline-estimated statistic of rhythm) of the SAP in normotensive rats grafted with AH embryonic tissue obtained from SHR was accompanied by disappearance of the circadian rhythm of SAP. This result suggests an interaction between the grafted tissue containing the SCN on the one hand, and the host SCN on the other hand. Our data ascribe a role for the SCN in the entrainment of the circadian rhythm of arterial pressure. The circadian rhythm of HR was not eliminated by the SCN graft in spite of the amplitude decrease and the phase delay observed. It seems that the entrainment of the circadian rhythm of HR is probably not crucially dependent on the SCN in rats. The circadian rhythms of SAP and HR in rats were differently affected by the grafts, thus suggesting a multioscillatory system for circadian regulation in rats.     

Clinical trial enrollers vs. nonenrollers: the Cardiac Arrhythmia Suppression Trial (CAST) Recruitment and Enrollment Assessment in Clinical Trials (REACT) project

The Recruitment and Enrollment Assessment in Clinical Trials (REACT) was a National Heart, Lung, and Blood Institute (NHLBI)-sponsored substudy to the Cardiac Arrhythmia Suppression Trial (CAST). Two-hundred-sixty (260) patients who enrolled in CAST and 140 partially or fully eligible patients who did not enroll were compared across several parameters, including demographic variables, disease severity, psychosocial functioning, health beliefs, recruitment experience, and understanding of informed consent procedures used in CAST. Significant predictors of enrollment included several demographic variables (e.g., being male, not having medical insurance), episodes of ventricular tachycardia, and health beliefs (e.g., extra beats are harmful, a higher degree of general health concern). Enrollment was higher for those who read and understood the informed consent and those who were initially recruited after hospital discharge, particularly nondepressed patients. In the multivariate model, the key variables that emerged were the patient's reading of the informed consent form and the patient's lack of medical insurance. These results suggest that (1) the clinical trial staff's interaction with the patient and the time when recruitment is initiated contribute significantly to the decision to enroll; and (2) it may be a greater challenge to motivate patients to enroll in future clinical trials if health care reform improves access to medical insurance coverage. Some of the significant variables are modifiable, suggesting interventions that may increase enrollment rates in future trials.     

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published. The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms. Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded. The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime. In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02). Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.     

Chronopharmacological effects on nicotine repeated administration on heart rate, body temperature and locomotor activity circadian rhythms in rats

The aim of this study was to compare morning and evening repeated nicotine administration on the circadian rhythms of heart rate (H), body temperature (T) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. The study was divided into three 7-day periods: a control period (P1), a treatment period (P2) and a recovery period (P3). During P2, four rats received nicotine (1mg.kg(-1)) subcutaneously at 09.00 h and four rats received nicotine in the same conditions at 21.00 h. For P1, P2 and P3, a power spectrum analysis was applied in order to determine the dominant period of rhythmicity. If H, T and A circadian rhythms were detected, the characteristics of these rhythms were determined by cosinor analysis, expressed as means+/-SEM and compared by ANOVA. Our results indicated: (1) a lack of detection of A circadian rhythm during P2 for the morning group while H and T circadian rhythms were detected for the morning and evening group whatever the period. (2) alterations of mesors, amplitudes and acrophases of H and T circadian rhythms for the morning and evening group during P2 and alterations of mesor, amplitude and acrophase of A circadian rhythm for the evening group. Furthermore these alterations were significantly different for the morning and evening group during P2. These results showed that the time of administration of nicotine differently affect H, T and A rhythms. The authors suggest that these effects can be mediated by central cholinergic and/or monoaminergic mechanisms.     

Olfactory bulbectomy impedes social but not photic reentrainment of circadian rhythms in female Octodon degus

Recent studies demonstrated that nonphotic (social) cues markedly accelerate reentrainment to large phase shifts of the light-dark (LD) cycles in female Octodon degus and that such changes are likely effected by chemosensory stimuli. This experiment investigated the effects of olfactory bulbectomies on (1) socially facilitated reentrainment rates of circadian rhythms following a 6-h phase advance of the LD cycle, (2) photic reentrainment rates of circadian rhythms following a 6-h advance of the LD cycle, (3) photic entrainment, and (4) the circadian period (tau) of activity rhythms in constant darkness (DD). olfactory bulbectomies (BX) blocked socially facilitated reentrainment rates but did not alter reentrainment rates of circadian rhythms to photic cues alone. In addition, BX lowered mean daily locomotor activity levels and decreased the amplitude of the activity rhythm in degus housed in entrained (LD 12:12) conditions but did not alter the phase of activity onset or offset, duration (alpha) of activity, or mean daily core body temperature. Bulbectomies also failed to modify tau of free-running activity rhythms. This experiment confirms that the olfactory bulbs and chemosensory cues are necessary for socially facilitated reentrainment. In contrast to their effects in nocturnal rodents, BX do not produce significant circadian photic changes in diurnal degus. This is the first experiment to determine that chemosensory stimuli modulate the circadian system in a diurnal rodent.     

Studies on new process procedures in plasma fractionation and industrial scale. III. Removal of precipitates by filtration through a horizontal leaf filter with centrifugal cleaning (Funda filter) as an alternative to tubular-bowl centrifuges

To study the eyes' role in maintaining the circadian rhythm in pituitary-adrenal function, 24-h patterns of corticosterone levels were compared in intact and blinded adult female rats. Rats were blinded by optic enucleation at approximately 80 days of age. Nonstress plasma corticosterone levels were determined fluorometrically in serial blood samples obtained from a tail vein at 4-h intervals for 44-h periods, 3 and 10 weeks after surgery. At 3 weeks after surgery, blinded and intact rats demonstrated comparable rhythms in corticosterone levels. At 10 weeks, steroid fluctuations in individual blinded rats still had an approximate 24-h periodicity. However, these fluctuations were no longer synchronized with the light-dark cycle or with those of other rats. These findings suggest that rats blinded as adults have a free-running pituitary-adrenal circadian rhythm.     

Implementing the Put Prevention into Practice program

Put Prevention into Practice (PPIP) is a national program designed to improve the delivery of preventive care to patients by all primary care clinicians. It covers the full range of clinical preventive services, including immunizations, screening tests, chemoprophylaxis, and counseling interventions. The materials that comprise this program involve patients, office/clinic systems and staff, and clinicians, including nurse practitioners. The need for preventive care, the barriers to be overcome, the PPIP program, and a strategy for its implementation are delineated. Principles for successful implementation include: high level administrative support, ownership by all the players in the implementation process, a person designated to manage implementation, and an ongoing evaluation/auditing process that provides feedback to clinicians and others participating in the program.