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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 37 records · Page 2Linked to original sources
PubMed2005

Yearly and perhaps transyearly human natality patterns near the equator and at higher latitudes.

Data on the daily numbers of births in Davao, Philippines, available from 1993 to 2003 are re-analyzed herein by linear-nonlinear rhythmometry, as are data from Italy and Japan. A transyear, characterizing the solar wind and other non-photic physical environmental factors, corresponds to a spectral peak of the near-equatorial natality series. This component with a period of about 1.3 years is found to have an amplitude larger than the calendar year, the amplitude ratio being 134%. Whereas the transyear is validated nonlinearly, the 95% confidence interval for the period extending from 1.21 to 1.38 years and the 95% confidence interval for the amplitude not overlapping zero (P < 0.05), the annual variation is only demonstrable by linear least squares analysis. The results bring added evidence for an influence of non-photic environmental effects on human physiology, in this case data collected near the equatorial region, Davao being situated at 7 degrees N, 126 degrees E. They are in keeping with some degree of generality of a rule of reciprocity among mutually supporting physical and biological periodicities. They do not detract from the fact that in other longer data sets at higher latitudes, the calendar year, presumably reflecting climatic influences, dominates the spectrum.

Adult↗
PubMed2005

An attempt to integrate Western and Chinese medicine: rationale for applying Chinese medicine as chronotherapy against cancer.

Current Western medical treatment lays its main emphasis on evidence-based medicine (EBM) and cure is assessed by quantifying the effects of treatment statistically. In contrast, in Chinese medicine, cure is generally assessed by evaluating the patient's "pattern" (Zheng) [cf. Glossary] and medicines are prescribed according to this. We believe that traditional Chinese medicine (TCM) cannot be evaluated precisely according to Western principles, in which a constant amount of the same medicine is given to a group of patients to be evaluated. When assessing cure using TCM, Zheng is more important than the determination of medical effects. This means that quantitative evaluation of TCM treatment can be very difficult. In this paper, we focused on the Yin-Yang [cf. Glossary]balance to determine Zheng, and at the same time attempted to determine the treatment effects by applying the concept of regulation of Yin-Yang according to chronotherapeutic principles. According to Zheng, advanced cancer patients generally lack both Yin and Yang. Chinese medical treatment therefore seeks to supplement both Yin and Yang. However, we divided patients into two groups and compared them with respect to survival. One group was administered a predominantly Yang (Qi) [cf. Glossary] tonic herbal treatment during the daytime, while the other group was administered Yin (Blood) [cf. Glossary] tonics during night time. A comparison of the results of treatment showed that the patients in the group receiving Yang (Qi) replenishment during the daytime lived longer than patients receiving Yin (Blood) nourishment during the night. Moreover, the patients in the daytime Yang (Qi) replenishment group also fared significantly better than patients treated solely by Western methods.

Adult↗
PubMed2005

Why continued surveillance? Intermittent blood pressure and heart rate abnormality under treatment.

Several opinion leaders have monitored their blood pressure systematically a sufficient number of times a day for chronomic (time structural) analyses, from the time of encountering chronobiology until their death; they set an example for others who also may not wish to base treatment on single spotchecks in a health care office. Such self-measurements, while extremely helpful, were not readily feasible without a noteworthy interruption of activities during waking as well as of sleep. New, relatively unobtrusive instrumentation now makes monitoring possible and cost-effective and will save lives. Illustrative results and problems encountered in an as-one-goes self-survey by GSK, a physician-scientist, are presented herein. Both MESOR-hypertension and CHAT (circadian hyper-amplitude-tension) can be intermittent conditions even under treatment, and treatment is best adjusted based on monitoring, rather than "flying blind".

Adult↗
PubMed2005

Plasma catecholamines: follow-up on 10-year study in health and cardiovascular disease.

The predictive value of blood pressure (BP), heart rate (HR), and catecholamines in terms of any subsequent development of cardiovascular disease was investigated. Systolic (S) and diastolic (D) BP, HR, epinephrine (E) and norepinephrine (NE) were measured three times a year in 1980, 1984, and 1989 on 20 clinically healthy subjects, 18 patients with 'essential hypertension', and 22 patients with angina pectoris. Of the 22 patients in the latter group, 15 died during a 2-year follow-up (1990-1991). Each individual data series was analyzed by single cosinor to assess the circannual variation. Results were summarized by population-mean cosinor for each group. Parameter tests were used to compare the circannual rhythm characteristics among the different patient groups. A circannual rhythm was invariably demonstrated on a group basis (P < 0.05). Differences in MESOR and/or circannual amplitude were found among the different groups. In particular, patients with angina pectoris who will die within the 2-year follow-up differ in terms of their E and NE from all other patient groups, a difference already detected at the beginning of the study, more than 10 years before they die. A similar separation is not achieved in terms of BP or HR.

Adult↗
PubMed2005

Prokaryotic and eukaryotic unicellular chronomics.

An impeccable time series, published in 1930, consisting of hourly observations on colony advance in a fluid culture of E. coli, was analyzed by a periodogram and power spectrum in 1961. While the original senior author had emphasized specifically periodicity with no estimate of period length, he welcomed further analyses. After consulting his technician, he knew of no environmental periodicity related to human schedules other than an hourly photography. A periodogram analysis in 1961 showed a 20.75-h period. It was emphasized that "... the circadian period disclosed is not of exactly 24-h length." Confirmations notwithstanding, a committee ruled out microbial circadian rhythms based on grounds that could have led to a different conclusion, namely first, the inability of some committee members to see (presumably by eyeballing) the rhythms in their own data, and second, what hardly follows, that there were "too many analyses" in the published papers. Our point in dealing with microbes and humans is that analyses are indispensable for quantification and for discovering a biologically novel spectrum of cyclicities, matching physical ones. The scope of circadian organization estimated in 1961 has become broader, including about 7-day, about half-yearly, about-yearly and ex-yearly and decadal periodisms, among others. Microbial circadians have become a field of their own with eyeballing, yet time-microscopy can quantify characteristics with their uncertainties and can assess broad chronomes (time structures) with features beyond circadians. As yet only suggestive differences between eukaryotes and prokaryotes further broaden the perspective and may lead to life's sites of origin and to new temporal aspects of life's development as a chronomic tree by eventual rhythm dating in ontogeny and phylogeny.

Acetabularia↗
PubMed2005

Chronomics reveal and quantify circadian rhythmic melatonin in duodenum of rats.

A circadian rhythm is documented in duodenal melatonin in rats, peaking 16.8 hours after light onset. This component is more readily detected after log10-transformation of the data. It differs between male and female rats, females having a larger circadian amplitude and an earlier acrophase. The circadian rhythm in duodenal melatonin is also found to lead that of pineal melatonin. The results are qualified by the presence at the start of mapping of the second extremum of a double magnetic storm.

Animals↗
PubMed2005

Chronomics: circadian lead of extrapineal vs. pineal melatonin rhythms with an infradian hypothalamic exploration.

A circadian rhythm is documented for plasma, pineal, and hypothalamic melatonin of male and female rats kept on staggered lighting regimens. Log[_10]-transformation of the data usually normalizes, when need be, the distribution of residuals from the 24-hour cosine curve fits. A tentative circadian acrophase chart is presented that shows a lead in circadian acrophase of duodenal over pineal melatonin. The use of antiphasic lighting regimens facilitates circadian studies that can be carried out for several days, thereby allowing the assessment of infradian components such as a circasemiseptan variation in hypothalamic melatonin documented herein. The results are qualified by the presence of a second extremum of a double magnetic storm at the start of mapping.

Animals↗
PubMed2005

Chronomics affirm extending scope of lead in phase of duodenal vs. pineal circadian melatonin rhythms.

In Göttingen, Germany, circadian variations in melatonin had been determined time-macroscopically in pineal glands, blood plasma and duodenum of chicken and rats. When these data were meta-analyzed, they agreed with the results from an independent survey on tissues from rats collected in a laboratory in Pécs, Hungary. In the latter study, tissues were analyzed chemically in Bratislava, Slovakia, and numerically in Minneapolis, MN, USA, all by single- and multiple-component cosinor and parameter tests. In rats and chickens, these inferential statistical procedures clearly demonstrated a lead in phase of the 24-h cosine curves best fitting all of the duodenal vs. those best fitting all of the pineal melatonin values in each species in 2 geographic (geomagnetic) locations. The 24-h cosine curve of circulating melatonin was found to be in an intermediate phase position. Mechanisms of the phase differences and the contribution of gastrointestinal melatonin to circulating hormone concentrations are discussed.

Animals↗
PubMed2005

Circasemidian rather than circadian variation of circulating osteoprotegerin in clinical health.

Osteoprotegerin (OPG) serves as a soluble decoy receptor for RANKL to inhibit osteoclast formation and activity. Hormones such as PTH and glucocorticoids have been reported to decrease OPG concentrations, while estrogens, transforming growth factor b, related bone morphogenic factor and thrombopoietin reportedly enhance the OPG production in the osteoblastic and bone stromal cells. Since bone turnover shows a prominent circadian rhythm in laboratory animals and humans, with bone resorption increasing at night, we investigated the time structure of circulating OPG concentrations in a group of nine healthy subjects (six women and three men; in the age range of 26-49 years). Blood samples for OPG determination were collected every 4 h for 24 h on the same day, starting at 08:00 in the morning. Data were analyzed by inferential statistical procedures, including the single and population-mean cosinor. A 12-h component was found to characterize serum OPG concentrations (P = 0.038) with peak concentrations around noon and midnight. No statistically significant circadian rhythm of OPG concentrations could be found by cosinor in our study population. The mean 24-h OPG concentration was higher in women than in men (mean +/- S.E.: 3.13 +/- 0.44 vs. 1.94 +/- 0.26 pmol/l, Student t = 2.325, P = 0.053). Since PTH concentrations also exhibit a bimodal pattern along the 24-h scale, PTH may be tested as a putative determinant of the observed changes in serum concentrations of osteoprotegerin.

Adult↗
PubMed2005

Chronomics of circulating plasma lipid peroxides and anti-oxidant enzymes and other related molecules in cirrhosis of liver. In the memory of late Shri Chetan Singh.

BACKGROUND: The chronome (from chronos, time, and nomos, rule; time structure) of lipid peroxidation and anti-oxidant defense mechanisms may relate to the efficacy and management of preventive and curative chronotherapy. PATIENTS AND METHODS: Thirty patients with liver cirrhosis, 25-45 years of age, and 60 age-matched clinically healthy volunteers were synchronized for 1 week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was around 08:30, lunch around 13:30 and dinner around 20:30. Drugs known to affect the free-radical system were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, presumably 24-h synchronized conditions. Determinations included plasma lipid peroxides, in the form of malondialdehyde (MDA), blood superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, and serum total protein, albumin, ascorbic acid, and uric acid concentrations. RESULTS: A marked circadian variation was demonstrated for each variable in each group by population-mean cosinor (P < 0.01). In addition to anticipated differences in overall mean value (MESOR), patients differed from healthy volunteers also in terms of their circadian pattern. CONCLUSION: Mapping the broader time structure (chronome) with age and multifrequency rhythm characteristics of antioxidants and pro-oxidants is needed for exploring their putative role as markers in the treatment and management of liver cirrhosis.

Adult↗
PubMed2005

Incidence of sudden cardiac death, myocardial infarction and far- and near-transyears.

We analyzed cycles with periods, tau, in the range of 0.8-2.0 years, characterizing, mostly during 1999-2003, the incidence of sudden cardiac death (SCD), according to the International Classification of Diseases, 10th revision (ICD10), code I46.1. In the tau range examined, only yearly components could be documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong Kong, in the latter two locations based on relatively short time series. By contrast, in Minnesota, USA, we found only a component with a longer than (= trans) yearly (transyearly) tau of 1.39 years; the 95% confidence interval (CI) of the tau extended from 1.17 to 1.61 years, falling into the category of transyears (defined as a tau and a 95% CI between 1.0 and 2.0 years, with the limits of the 95% CI of the spectral component's tau overlapping neither of these lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of about 1-year in length was present, and in addition, one with a tau of 1.69 year with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far-transyears being defined as having a tau with a CI between 1.20 and 2.0 year, with the CI overlapping neither of these lengths. In the Czech Republic, there was also a calendar-yearly tau and one of 1.76 years. In the latter two geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes were of similar prominence. The taus are only candidate transyears; the 95% CIs of their taus overlap the 2-year length. When a series on SCD from 1994 to 2003 from the Czech Republic was analyzed, the 95% CI of the transyear's tau no longer overlapped the 2-year length. Transyears were also found in the Czech Republic for myocardial infarctions (MI), meeting the original transyear definition in both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from the Czech Republic, a near-transyear was also found, meeting the definition of a period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along with a far-transyear, defined as a tau between 1.2 and 2.0 years, again with the 95% CI covering neither of these lengths. Herein, we discuss near- and far-transyears more generally in the light of their background in physics and the concept of reciprocal cyclicities.

Chronobiology Phenomena↗
PubMed2004

In vitro circadian ANP secretion by gene transferring cells encapsulated in polycaprolactone tubes: gene chronotherapy.

A new insofar as chronobiologic therapeutic approach by atrial natriuretic peptide (ANP) for hypertension and/or congestive heart failure (CHF) is based on the release of ANP from ANP cDNA transfected Chinese Hamster Ovary (CHO) cells encapsulated in polycaprolactone (PCL) tubes. ANP secretion was maintained for at least 6 months. The encapsulated cells remained viable during culturing. Control cells without transferred ANP cDNA were negative. ANP secretion is circadian periodic, peaking around 04:18, shifted to around 07:56 by melatonin treatment. The encapsulation technique, based on principles of chronotherapy, may provide a more efficient gene therapy, applicable for eventual human implantation of gene transferred cells.

Animals↗
PubMed2004

Positive impact of social intervention on disturbed neurobehavioral function in an elderly community-dwelling population: longitudinal investigation for longevity and aging in Hokkaido County (LILAC).

Several kinds of health consultation and rehabilitation for functional disorders aimed at stroke prevention and maintenance of cognitive function in an elderly population in Hokkaido county, Japan. Changes in cardiovascular and neurobehavioral endpoints between 2000 and 2002 were assessed in 72 of 115 subjects over 75 years of age. Direct social intervention, including lifestyle modification can have a positive impact, notably on subjects with cardiovascular disorders.

Aged↗
PubMed2004

Chronomic community screening reveals about 31% depression, elevated blood pressure and infradian vascular rhythm alteration.

Depression, which is a risk factor for cardiac morbidity and mortality, is not an unusual occurrence among individuals with coronary heart disease (CHD), but evidence concerning its role in the pathogenesis of this condition is less clear. Ambulatory blood pressure monitoring (ABPM) has become an important tool in the diagnosis and management of hypertension. Several previous studies have indicated that various kinds of target organ damage and cardiovascular morbidity are more strongly associated with a diagnosis by ABPM than through spot-checks in a clinical setting. This study investigated whether depressive mood was associated with changes in the about-weekly (circaseptan) and half-weekly (circasemiseptan) variations in blood pressure (BP) and heart rate (HR), including a BP surge on Mondays, in community-dwelling subjects monitored chronomically for the time structure (chronome) of their BP and HR variabilities. From April 2001 to April 2003, 217 subjects (85 men and 132 women; mean age: 56.8 +/- 11.3 yr) from U town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), self-monitored their BP and HR for 7 days starting around 11 a.m. on Thursday, and took readings at 30-minute intervals between 7 a.m. and 10 p.m., then at 60-minute intervals between 10 p.m. and 7 a.m. The data were retrieved and analyzed on a PC with appropriate commercial software (TM-2430-15; A&D Co., Japan). Subjects were asked about 15 items on a depression rating scale through a self-administered questionnaire. When the score amounted to 5 or higher, subjects were considered to be depressive. Student's t-test, a one-way analysis of variance (ANOVA), and cosinor methods with parametric tests were also used. A p-value below 0.05 was considered to indicate statistical significance (below 0.10: borderline statistical significance). Depression rating scales were obtained for 192 out of the 217 subjects enrolled in this study. Depression scores were (>) 5 in 72 subjects. The average values of systolic (S) and diastolic (D) BP were statistically significantly higher in depressed subjects (SBP: 129.2 vs 124.5 mmHg; p = 0.034; DBP: 79.0 vs 76.5 mmHg; p = 0.041). The 7-day average for HR did not differ between subjects with depression scores of < 5 or > 5. DBP dipping was less in the depressed subjects (16.30 vs 18.22%; p = 0.048). The dipping ratios of SBP and HR showed no statistically significant difference. In the group with depression scores of < 5, HR variability (estimated by the SD of HR and HR dip) was higher during vacations and lower on Mondays. The 24-h BP measures showed a novelty effect and a surge on Mondays. In the depressed group, a prominent circaseptan rhythm appeared to replace the novelty effect, vacation dip, and Monday surge. The results of this investigation indicate the clinical importance of the monitoring of depressed subjects. Fewer than 7 days of monitoring means a greater risk of false diagnosis, and thus a therapeutic decision including potentially unnecessary or inappropriate long-term treatment. Records shorter than 7 days would not have detected circaseptan BP dysrhythmia associated with a depressive state. Prominent circaseptans can provide new indications on the mechanisms underlying the strong relation between depression and adverse cardiac events. Future studies should aim at determining whether the treatment of depression, especially from the standpoint of a chronodiagnosis and chronotherapy, can reduce the incidence of adverse cardiac events, and whether this depends upon restoring normal BP and HR variability, i.e. anormal BP and HR chronome.

Blood Pressure Monitoring, Ambulatory↗
PubMed2004

Circadian renal rhythms influenced by implanted encapsulated hANP-producing cells in Goldblatt hypertensive rats.

Renal excretion in experimental hypertensive rats implanted with encapsulated human atrial natriuretic peptide (hANP)-producing cells is circadian periodic. Chinese hamster ovary (CHO) cells transfected with the plasmid hANP-cDNA were encapsulated in biocompatible polycaprolactone capsules for intraperitoneal implantation into two-kidney, one-clip (2K1C) hypertensive rats. During a 12:12 light-dark cycle, as compared to control CHO cells, the implantation of encapsulated hANP-producing CHO cells was associated with an increase in the net excretion of water, sodium and potassium, and with a reversal of the advanced circadian phases related to renovascular hypertension in 2K1C rats. The increase in blood pressure postimplantation was delayed, and increases in renal blood flow, glomerular filtration rate, sodium output, urinary excretion and urinary cyclic GMP concentrations were also found. Implantation of encapsulated hANP-producing cells affects circadian rhythms in kidney excretion functions of 2K1C rats, and may be useful for the treatment of cardiovascular disease.

Animals↗
PubMed2003

Chronomics for chronoastrobiology with immediate spin-offs for life quality and longevity.

Effects of geomagnetic disturbance on heart rate variability (HRV), the 1/f fractal scaling in particular, are being assessed in adults living at high latitude, where magnetic storms are more frequent and more intense than at lower latitudes. The latter may constitute a signal or a proxy, and possibly a mechanism underlying both undesirable and desirable effects, depending upon circumstances yet to be elucidated. Any circadecadal stage-dependence of morbidity and/or mortality from certain conditions such as myocardial infarctions remains to be studied in both adult and pediatric populations. Further work could thus examine whether any associations of geomagnetic disturbances may account, at least in part, through effects upon the circulation, for long-term infra-annual changes, possibly anchored in the population's gene pool, observed in a number of anthropologic measurements at birth as well as in other population statistics. In order to assess the development of several chronome components of the electrocardiogram (ECG), around-the-clock ambulatory ECG were recorded from 19 infants (25 days-3 months of age), 22 children (3-9 years of age), 18 boys and girls (10-14 years of age), pubertal boys (15-20 years of age), and 10 young men (21-29 years of age). Time- and frequency-domain measures of HRV were obtained by spectral analysis, using the maximal entropy method (MEM). The frequency of detection of the circadian, circasemidian and circaoctohoran components, with periods of about 24, 12 and 8 h, respectively, was compared among the five groups for several HRV endpoints, notably 1/f fractal scaling, total spectral power within a 5-min span, and its distribution into several frequency regions. A circadian component is already detectable in a sizeable proportion of infants and children for most of the HRV indices considered. The incidence of detection of the circadian component increases with age for the spectral power in different frequency regions, notably around 10.5 s ("LF") and around 3.6 s ("HF"); it peaks around puberty for 1/f in our data; and it did not detectably change with age for the total spectral power. Similar changes with age are not observed for the circasemidian or circaoctohoran components. The latter characterizes primarily 1/f and less so the about 3.6 s power ("HF"). Several aspects of the HRV chronome may thus develop differently as a function of age. In 2000, we began a community-based study named "Longitudinal Investigation of Longevity and Aging in Hokkaido County (LILAC study)". The ambulatory blood pressure (BP) of middle-aged subjects, aged 40-74 years, was monitored 7-day/24-h, and the cardiovascular and neurobehavioral functions of elderly people above 75 years were evaluated. Our goal was the prevention of stroke and myocardial infarction and the decline in cognitive function of the elderly in a community. Of 115 elderly people recruited in a longitudinal community-based study in 2000, 72 completed yearly follow-ups in 2002. A cardiovascular score based on BP, pulse wave velocity, and 1-h ECG-based HRV endpoints served to distinguish between normal, mildly disordered, or disordered participants. A comparison of cognitive function in 2002 vs. 2000, assessed with the MMSE, HDSR, the Up & Go and Functional Reach tests, gauged any effect of social intervention. Cognitive function was maintained or improved, especially for people suffering from hypertension, tachycardia, or a decreased HRV, suggesting that cardiovascular function is a major factor affecting cognitive function.

Cardiovascular Diseases↗
PubMed2002

Graded response of heart rate variability, associated with an alteration of geomagnetic activity in a subarctic area.

It is becoming recognized that geomagnetic activity may influence biological processes, including the incidence of various human diseases. There is evidence that heart rate variability (HRV) may serve not only as an index of autonomic coordination of the circulation, but also as a powerful predictor of risk in apparently healthy subjects. This study focuses on the effects of geomagnetic disturbance on HRV, by comparing different indices of HRV of young, healthy men living in a subarctic area on days of low (Ap; 0-7), middle (Ap; 7-20), and high (Ap; 20-45) geomagnetic activity. The effect of geomagnetic disturbance on HRV is examined on the basis of 7-day records by Holter ECG, obtained longitudinally on 5 clinically healthy men, 21-31 years of age, in Alta, Norway (70 degree N). Frequency- and time-domain measures of HRV were analyzed for each subject on separate 24-hour spans. A graded alteration of HRV endpoints was found in association with increased geomagnetic activity. As time-domain measures of HRV, SDNNIDX and the 90% length of the Lorenz plot decreased statistically significantly on days with increased geomagnetic disturbance (p = 0.0144 and p = 0.0102, respectively). A graded decrease in frequency-domain HRV measures was also validated statistically for the total spectral power (decrease of 18.1% and 31.6% on days when 7 < Ap < 20 and 20 < Ap < 45 versus days when Ap < 7; p = 0.0013). The decrease in spectral power was mainly found at frequencies below 0.04 Hz, in the "ultra-low-frequency" (0.0001-0.003 Hz; 18.1% and 27.5% decrease, respectively; p = 0.0102) and "very-low-frequency" (0.003-0.04 Hz; 12.9% and 28.6% decrease, respectively; p = 0.0209) regions of the spectrum. The decrease in spectral power was much less pronounced around 10.5 sec ("low frequency"; N.S.) and around 3.6 sec ("high frequency"; N.S.). Evidence is provided here that HRV decreases on magnetically disturbed days, and that it does so in a dose-dependent fashion, HRV being depressed more on days when 20 < Ap < 45 than on days when 7 < Ap < 20, by comparison with days when Ap < 7. This graded response of HRV to geomagnetic activity should encourage us to search for human magnetoreceptors and for a better understanding of putative mechanisms of magnetoreception.

Adult↗