Do plasma melatonin concentrations decline with age?
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Adult↗
Biomedical subjects
F Halberg
Publications and source records attributed to F Halberg.
Circadian periodicity of urinary volume, creatinine and 5-hydroxyindole acetic acid excretion in healthy Indians.
The circadian periodicity of urinary output, creatinine (Cr) and 5-hydroxyindole acetic acid (5-HIAA) excretion was studied under near-tropical conditions in 130 healthy volunteers (65 men and 65 women, 16-75 years of age) with a diurnal activity from about 06:30 to about 22:00 and nocturnal rest. These volunteers were divided into 4 groups, 16-30, 31-45, 46-60 and 61-75 years of age, comprising 20, 20, 15 and 10 participants of each gender, respectively. A marked circadian rhythm was recorded for urine volume, Cr and 5-HIAA excretion in healthy Indians of different ages. The acrophase tended to be delayed in the older age group. The relative amplitude decreased with advancing age, notably in women. Overall, men produced a larger urine volume as compared to women. Excretions of Cr and 5-HIAA in healthy Indian volunteers of different ages may be influenced by diet, societal relations, climate and/or geographic location. The contribution of such factors in metabolism and degradation warrants further study.
Adolescent↗
Report of the 1997 SCAROP survey on resident training. Society of Chairmen of Academic Radiation Oncology Programs.
RATIONALE AND OBJECTIVES: Members of the Society of Chairmen of Academic Radiation Oncology Programs (SCAROP) were surveyed in November 1997 to evaluate the current status of radiation oncology training in the United States and to help determine how it should be carried out in the coming decade. MATERIALS AND METHODS: A detailed questionnaire was sent to all members of SCAROP; 68 of 82 questionnaires were returned, for a response rate of 83%. RESULTS: The responses to the survey show a serious shortage of radiation oncologists in university settings, despite an apparent surplus in private practice. Although recent changes in health care have added additional clinical responsibilities for radiation oncologists in university practices, approximately 75% of the chairpersons answering the survey continue to give their faculty protected time for research. Even with additional research and teaching responsibilities, the average radiation oncologist in university practice saw 206 patients per year in 1997, a number similar to that reported by the Patterns of Care Study for radiation oncologists overall. Approximately two-thirds of respondents believe that academic chairs should strive to have all clinical faculty members participating in research. Nevertheless, most think that basic research is better performed by dedicated researchers with PhD degrees rather than radiologists with MD degrees. Most respondents believe that the training programs adequately prepare radiation oncologists for a career in academic medicine but do not provide good training in research. Eighty-four percent agreed that resident performance on the American Board of Radiology examination should be considered in the accreditation of residency programs in radiation oncology but should not be the major criterion. CONCLUSION: There is a shortage of academic radiation oncologists in the United States despite the large number of radiation oncologists completing training. This probably is due to a variety of factors, including a relatively small pool of candidates for academic positions, increasing demands for performance from academic physicians (to see more patients, perform research, publish, write grants, and teach), and competition from the private sector for recruitment of these individuals.
Data Collection↗
Meta-analysis of sequential luteal-cycle-associated changes in human breast tissue.
We chronobiologically estimate the time relations of physiological and morphological changes in breast tissue during the luteal phase of the menstrual cycle, as a cascade led by the progesterone peak. The timing and uncertainties of maxima in epithelial mitotic frequency, breast and epithelial volume, breast surface temperature, water content, blood flow and apoptosis are given as parts of a rhythmic element in a broader time structure or chronome.
Apoptosis↗
Feedsidewards: intermodulation (strictly) among time structures, chronomes, in and around us, and cosmo-vasculo-neuroimmunity. About ten-yearly changes: what Galileo missed and Schwabe found.
The spectrum of biological rhythms is extended far beyond circadians, circannuals, and ultradians, such as 1.5-hourly melatonin and 8-hourly endothelin-1 (ET-1) rhythms by statistics of natality, growth, morbidity, and mortality, some covering decades or centuries on millions of individuals. These reveal infradian cycles to be aligned with half-weekly rhythms in ET-1, weekly and half-yearly ones in melatonin, and even longer--about 50-, about 20-, and about 10-year cycles found in birth statistics. About daily, weekly, yearly, and ten-yearly patterns are also found in mortality from myocardial infarctions; the 10-yearly ones are also in heart rate and its variability; in steroid excretion, an aspect of resistance, for example, to bacteria; and in the genetic changes of the bacteria themselves. Automatic physiological measurements cover years and, in one case, cover a decade; the latter reveal an about 10-year (circadecennial) cycle. ECGs, covering months beat-to-beat, reveal circaseptans, gaining prominence in response to magnetic storms or after coronary artery bypass grafting. A spectrum including cycles from fractions of 1 Hz to circasemicentennians is just one element in biological time structures, chronomes. Chaos, trends, and any unresolved variability are the second to fourth elements of chronomes. Intermodulations, feedsidewards, account for rhythmically and thus predictably recurring quantitive differences and even for opposite treatment effects of the same total dose(s) of (1) immunomodulators inhibiting or stimulating DNA labeling of bone in health or speeding up versus slowing down a malignant growth and thus shortening or lengthening survival time, or (2) raising or lowering blood pressure or heart rate in the vascular aspect of the body's defense. Latitude-dependent competing photic and nonphotic solar effects upon the pineal are gauged by alternating yearly (by daylight) and half-yearly (by night) signatures of circulating melatonin at middle latitudes and by half-yearly signatures at noon near the pole. These many (including novel near 10-yearly) changes, for example, in 17-ketosteroid excretion, heart rate, heart rate variability, and myocardial infarction in us and those galactic, solar, and geophysical ones around us have their own special signatures and contribute to a cosmo-vasculo-immunity and, if that fails, to a cosmo(immuno?) pathology.
Animals↗
Nocturnal melatonin patterns in children.
Time patterns in nocturnal concentrations of circulating melatonin of children are quantified in 8 girls and 8 boys, 8.7-16.8 yr of age, classified by Tanner pubertal stage. Between 1900 and 0700 h, each provided blood samples at 30-min intervals for melatonin RIA. Associations with gender, body mass index, and chronological and pubertal age determined by multiple linear regression and ANOVA reveal that the area under the curve of 12-h melatonin concentrations was affected by pubertal rather than chronological age, an effect to which data collected during darkness contributed the most. Each data series was also analyzed by a least squares spectrum at frequencies of 1-20 cycles/day. Ultradian changes with periods of 3.4 and 1.5 h, putatively associated with rapid eye movement sleep cycles, characterize nocturnal melatonin in boys and girls.
Activity Cycles↗
The biological week and broader time structures (chronomes): in memory of Gunther Hildebrandt.
Data illustrating the biological week and chronomes are presented in recognition of extensive work of G. Hildebrandt.
Balneology↗
The cosmos and CHAT, prompting blood pressure and heart rate monitoring for Dérer's week.
BACKGROUND: The effects of natural environmental factors upon health, documented in Minnesota, support the proposition of Bratislava's champions of the cosmos and of the biological week, gauged via circaseptan rhythms by the late Ladislav Dérer, whose "macro-rhythm" lasted "most frequently about 6 days". MAIN PURPOSE: To introduce 7-day monitoring of blood pressure and heart rate into routine practice. STARTING POINTS AND METHODS: Cosinor analysis on 7-day series determines (conventionally ignored) consistent blood pressure overswinging, i.e., circadian hyper-amplitude-tension (CHAT), a disease risk syndrome, whether it is associated with a normal average blood pressure or a high blood pressure. RESULTS: Summary of information understandable by the general population on the dynamics of blood pressure. CONCLUSIONS AND MEANING FOR PRACTICE AND THEORY: Space weather reports may prompt preventive measures. Caution dictates in any event monitoring blood pressure and heart rate for 7 days to attempt to prevent strokes, rather than to ignore the greatest yet detectable risk of catastrophic vascular disease, CHAT, a risk greater than old age or high blood pressure. (Tab. 1, Fig. 3, Ref. 31.)
Blood Pressure Monitoring, Ambulatory↗
Blood pressure and heart rate rhythmicity: differential effects of late pregnancy.
Arterial blood pressure (BP) and heart rate (HR) of 31 hospitalized pregnant women at low risk of hypertension were automatically monitored for 48 h at 15-min intervals. Each of the recorded 56 data series for systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and HR was chronobiologically assessed by linear-nonlinear rhythmometry. The rhythm-adjusted mean (MESOR), circadian amplitude, circadian acrophase, and best-fitting period were grouped by pregnancy trimester and further subjected to analysis of variance. BP MESOR remained unaltered, whereas HR MESOR increased significantly in middle and late pregnancy. Ultradian rhythms, with an amplitude higher than that of the circadian rhythm, were found in 25% of the SAP records in the second and third trimester. Such ultradian rhythms were not detected in the simultaneously recorded HR. Finally, the group BP and HR circadian acrophases coincided in the first trimester, but were significantly apart in mid and late pregnancy. These observations support the notion that the coordination of BP and HR rhythmicity involves different physiological mechanisms. Analysis of the individual variability in the chronobiological end points (based on the records of nine women monitored in each pregnancy trimester) revealed that only the BP MESOR was well reproducible in the course of pregnancy and may be useful in early diagnosis of gestational hypertension.
Activity Cycles↗
Commentary: Chronomes: time structures within the physiological range identify early disease risk aiming at primary prevention.
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Aged↗
Genetic and environmental influences on human cord blood leptin concentration.
OBJECTIVE: To examine in a population sample of cord blood the time structure (chronome) of leptin, an adipocyte-derived hormone, and to assess any effect of a familial history of noninsulin-dependent diabetes mellitus and obesity, separately, on both the maternal and the paternal side. SUBJECTS AND METHODS: Leptin concentration was determined in cord blood from 93 infants. Effects of gender, gestational age, birth weight, maternal weight, familial antecedents of obesity and noninsulin-dependent diabetes mellitus, and circadian and about-yearly stage were assessed by linear regression and ANOVA. RESULTS: Cord blood leptin concentration is elevated in the presence of a family history of obesity on the paternal side, but not on the maternal side. Leptin concentrations are higher in spring and summer than in fall and are higher in infants born before noon. In keeping with earlier work, leptin concentration in cord blood correlates positively with birth weight and height and is higher in infants who are appropriate for or large for gestational age than in infants who are small for gestational age or born prematurely. DISCUSSION: Changes along the scales of the day and the seasons point to synchronizing environmental as well as genetic influence. An association of cord blood leptin concentration with obesity on the paternal side may help clarify the role of leptin in parental contributions to human obesity and may prompt focus on cholesterol metabolism.
Circadian Rhythm↗
Circadian rhythm of gene expression of myocardial contractile protein, left ventricular pressure and contractility.
Objective. A number of cardiovascular variables exhibit a circadian rhythm. Whether myocardial contractile response and gene expression of the contractile protein also show changes with a similar period was here investigated. Method. Circadian variabilities in the left ventricular developed pressure (LVP) and contractility (LV dp/dt max) were measured in 24 Sprague-Dawley rats by directly left ventricular catheterizing and compared with changes in the gene expression of alpha-myosin heavy chain (alpha-MHC) in myocytes obtained from the same animals by dot blotting analysis. Results. A circadian rhythm was seen in the variability of LVP (P<0.001), LV dp/dt max (P<0.001) and the biochemically measured expression of the alpha-MHC gene (P<0.01). As compared to the amplitude of the rhythm in alpha-MHC gene expression, the amplitude of the contractility rhythm was large (P<0.01) and the circadian amplitude of the LVP (P<0.001) was the largest, representing perhaps a composite of intracardiac plus any extracardiac contributions. Conclusion. One of factors determining the circadian rhythm of myocardial contractile function is alpha-MHC gene expression level.
Animals↗
About 8-hour variation of circulating human endothelin-1.
Plasma endothelin-1 (ET-1) and cortisol were measured around the clock at hourly intervals on 7 clinically healthy, diurnally active, nocturnally resting subjects 22-27 years of age. The circadian rhythm in cortisol is demonstrated for each subject (p < or = 0.020) as well as on a group basis (p = 0.002), peaking in the morning. By contrast, the circadian variation of ET-1 is statistically significant in only one of the subjects, and it is not detected for the group as a whole (p > 0.20). Instead, ET-1 is characterized by an about 8-h component (p < 0.001) that is not found for cortisol.
Adult↗
Interpreting vital sign profiles for maximizing patient safety during dental visits.
Concerns about local anesthetics and dental treatment stress are still prevalent in today's medical and dental communities. The authors conducted 24-hour monitoring of heart rate and blood pressure for 23 patients undergoing two root planing procedures and a single periodontal surgical procedure. Chronobiologic analysis of circadian blood pressure and heart rate rhythms revealed that neither epinephrine vasoconstrictor in anesthetics nor increased invasiveness of the procedure resulted in statistically significant deviations from regular, individualized blood pressure rhythms. For surgical appointments, time of day had the greatest effect on cardiovascular variables, with the greatest elevations in blood pressure seen for surgery at 8 a.m. and the largest blood pressure decreases seen for surgery at 2 p.m.
Adult↗
7-year (circaseptennian) patterns in psychology and biology? Comment on Verhulst and Onghena.
Nonlinear rhythmometry confirms a pattern of about 7 years, describing the number of births by birth year of quantum fathers reported by Verhulst and Onghena in 1996 and estimates the period to be 6.53 years with a 95% confidence interval overlapping 7 years. Other patterns of about 7 years are found in biology, as shown herein for the mean gonadal weight of an echinoderm (the purple sea urchin) and a mollusk (the black chiton). A number of periodic components with different frequencies, some shown to be genetically anchored, await applications in psychology as well as in other fields of medicine and biology.
Animals↗
Circadian and ultradian variation in pancreatic secretion of meal-fed pigs after weaning.
We studied the time structure of pancreatic secretion in two experiments involving seven 6- to 7-wk-old intact male pigs, surgically fitted with a jugular vein catheter for blood sampling, pancreatic catheter, and a duodenal T-cannula for chronic pancreatic juice sampling for 72 h at 30- to 60-min intervals. Pigs were kept in metabolic cages in a regimen of 12 h of light alternating with 12 h of darkness and were fed at 0800, 1500, and 2200 daily a standard diet based on barley, soybean meal, and fish meal. Beginning 4 d after surgical recovery, three 24-h collections of pancreatic juice and blood sampling were begun either at 0700 or 0800 every 2nd d for 5 d. Pancreatic secretion exhibited a pattern characterized by distinct meal-related secretions of the first phase (postprandial), containing large amounts of protein and enzymes (trypsin and chymotrypsin), and by non-food-stimulated secretions of the second phase with less protein and enzymes. During the dark span, the first phase was practically absent; the response of the pancreatic secretion to the 2200 meal was not very pronounced. Apart from the anticipated circadian rhythm demonstrable by single cosinor analysis on a group basis, a prominent 8-h component was almost invariably statistically significant. Moreover, an approximately 3.43-h component was also prominent. These data indicate that pancreatic secretions are circadian periodic and that their response to a standard meal is also circadian-stage dependent. The circadian components may have been free-running because the pigs were adjusting themselves to the changing phase and that resulted in the period being different from exactly 24 h.
Activity Cycles↗
Circadian rhythmic fractal scaling of heart rate variability in health and coronary artery disease.
BACKGROUND: In clinical cardiology, heart rate variability is a putative index of autonomic cardiovascular function. Signs of reduced vagal activity are not only associated with an enhanced risk of sudden cardiac death, but such impaired heart rate variability became a new predictor of sudden cardiac death and other mortality in patients with a variety of diseased states. HYPOTHESIS: It is postulated (1) that the time structure (chronome) of heart rate variability in clinical health includes a circadian rhythm and deterministic chaos, the latter gauged by the correlation dimensions of RR intervals; and (2) that this chronome is altered in patients with coronary artery disease (CAD). METHODS: From 24-h Holter records of 11 healthy controls and 10 patients with CAD, 500-s sections around 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours were analyzed for smoothed RR intervals sampled at 4 Hz. Correlation integrals were estimated for embedding dimensions from 1 to 20 with a 1.0-s time lag, using an algorithm modified from Grassberger and Procaccia. The Wilcoxon signed-rank test compares circadian end points assessed by cosinor between the CAD patients and age-matched controls. RESULTS: A circadian rhythm characterizes the correlation dimension of healthy subjects peaking during the night (p < 0.005). Patients with CAD have a lowered correlation dimension (p < 0.05) and an altered circadian variation which requires the consideration of an approximately 12-h (circasemidian) component. CONCLUSION: The results demonstrate the sensitivity of circadian rhythms for the detection of disease. A partial 24- to 12-h (circadian-to-circasemidian) frequency multiplication (or partial variance transposition) in CAD of the correlation dimension, apart from being a potential clue to the etiology of the disease, adds a new feature to a chronocardiology combining, with the fractal scaling, an assessment of circadian and circasemidian components as measures of predictable variability to be tested for use in diagnosis, prognosis, and as putative guides to treatment timing.
Adult↗
Endothelin-1's chronome indicates diabetic and vascular disease chronorisk.
Plasma endothelin-1 was measured around the clock in 72 subjects. Cosinor methods were used to assess circadian and other recurrent variation and trends, that is, the time structure (chronome) of this peptide. Multifactorial analyses of variance and linear regressions assessed chronome alterations associated with different risk factors: diabetes, obesity, high cholesterol, high blood pressure, vascular disease, smoking, and age. The rhythm-adjusted mean (MESOR) of endothelin-1 is elevated in diabetes and vascular disease. Diabetes is also associated with a larger circadian amplitude. A circadian variation in a subgroup of low-risk subjects is modulated by components with both lower and higher frequency.
Adult↗