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Biomedical subjects

Franz Halberg

Publications and source records attributed to Franz Halberg.

At least 73 records · Page 4Linked to original sources

Seven-day (24-h) ambulatory blood pressure monitoring, self-reported depression and quality of life scores.

OBJECTIVE: Effects of environmental conditions on blood pressure (BP) and heart rate (HR) variations as putative factors underlying the onset of vascular events. METHODS: BP and HR were monitored around the clock for 7 days on 54 residents from Urausu, Hokkaido, Japan. Daytime, night-time, and 24-h means served to identify dippers and non-dippers. Questionnaire-assessed depression and subjective quality of life were related to BP and HR by analyses of variance and linear regression. Statistical significance was at 5%. RESULTS: A circaseptan (about 7-day) component characterizes the 24-h mean and standard deviation (SD) of HR, and the daytime and day-night ratio of systolic BP. The SD of HR is higher on weekends and lower on Mondays and Thursdays. When awake, systolic BP is lowest on Sundays and the day-night ratio is optimal on weekends (Saturdays: 15.7 +/- 9.4%; Sundays: 14.0 +/- 13.2%). Depression was detected in 15 subjects, who had higher mean systolic and diastolic BP values (systolic BP: P = 0.028 Fridays, P = 0.021 Tuesdays; diastolic BP: P = 0.022 Mondays, P = 0.006 daytime Mondays) and a lower day-night ratio of diastolic BP (P = 0.012 Tuesdays, P = 0.005 Wednesdays, and P = 0.038 Thursdays). A depressive mood correlated positively with 24-h averages of systolic (P = 0.037) and diastolic (P = 0.030) BP. CONCLUSIONS: Depression (and subjective quality of life) can affect BP and HR variability. The results indicate the role that psychological factors may play in the pathogenesis of cardiovascular disease. Therapeutic implications are suggested for primary and secondary prevention.

Adult↗

Selected contribution: circadian rhythm of tumor necrosis factor-alpha uptake into mouse spinal cord.

Circadian variations in the actions of tumor necrosis factor-alpha (TNF-alpha) have been observed. Because a saturable transport system at the blood-brain barrier mediates most of the influx of TNF-alpha from blood to the central nervous system (CNS), the circadian variation of the CNS effects of TNF-alpha could be related to changes in this transport system. Accordingly, we measured the uptake of intravenously injected TNF-alpha into various CNS regions at different times and compared these measurements with the uptake into a peripheral control (muscle). We found that the spinal cord, but not the brain, showed a circadian rhythm in the uptake of TNF-alpha. This pattern is similar to that of leptin but different from that of interleukin-1. The circadian rhythm of the influx of TNF-alpha into this region of the CNS suggests a functional role for the spinal cord in the physiological actions of TNF-alpha.

Animals↗

Circaseptan aspects of self-assessed sleep protocols covering 70 nights on 33 clinically healthy persons.

This study aimed to describe quantitatively some changes in sleep behavior. During 70 consecutive nights, 28 women and 3 men, 30 to 40 years of age and presumably clinically healthy, recorded the time of each awakening. Time of falling asleep were estimated from markings at 10-min. intervals from the times of lying down to sleep as an indication that the subject had not yet fallen asleep. Sleep duration and an index of effective sleep derived therefrom were analyzed by rhythmometric methods. On a group basis, anticipated components with periods of 1 and 0.5 wk., synchronized with the social schedule, were detected with statistical significance. Until long-term polysomnographic monitoring can readily cover the week automatically rather than only one or a few daily sleep spans, the self-monitoring of sleep behavior, yielding the circaseptan endpoints derived herein, may serve as a cost-effective tool in sleep research. By virtue of their relative simplicity, they could be part of a protocol designed to assess pharmacologic or nonpharmacologic interventions of sleep disturbance aimed at restoring undisturbed sleep.

Adult↗

Biological rhythms and behavior--then and now.

BACKGROUND: Living matter has its own 'biological time': a set of rhythmic oscillations, paced by genes whose expression varies over regular cycles. The resulting chronomes, or time structures, are usually studied in living matter. A human chronome is preserved long after death in the structure of tooth enamel. This fossil record can be compared with contemporary enamel thus providing insight into an ancient biological rhythm, and consequently into behavior in pre-historic civilizations. MATERIAL/METHODS: Eight adult 3rd molar teeth from human burials in Atacama oases of Northern Chile, dating from AD 400 to 900 and belonging to the pre-Hispanic San Pedro culture, were compared to 20 discarded contemporaneous teeth from Albuquerque, N. M. USA. Two adjacent, 100 mm thick ground sections from each tooth were examined using a stereoscopic dissecting microscope and polarized light. The intervals between consecutive brown striae of Retzius (TBS) and the width of the enamel were measured. We recorded the number of TBS and the number of Wilson's bands and calculated a ratio of enamel width/number of TBS for each section. We used ANOVA for statistical analysis and cosinor methodology for chronomics, time structure (chronome) mapping. RESULTS: The 'biological week' in the chronome (time structure) of ancient enamel, gauged by TBS, varied according to a multiseptan (multiple of seven) component faster than did the multiseptan of contemporaneous teeth (1/2.7 versus 1/4.6 biological weeks). CONCLUSIONS: Until now no human chronome has been isolated from fossilized structures. Our discovery indicates that behavior of ancient populations, such as rest and work spans, can be deduced to some extent after millennia.

Behavior↗

Hurdles to asepsis, universal literacy, and chronobiology-all to be overcome.

A joining of chronobiology and endocrinology was achieved in 1974 at a symposium focusing on the critical role of the hypothalamic-pituitary-adrenal network on the basic side and on the first drug to carry timing in its name. The next step is a section on chronobiology in this neuroendocrinology journal. An account of the problems encountered before both asepsis and universal literacy became the law of the profession and of the land serves here as background to endeavors in behalf of chronobiologic literacy. A step toward the latter goal is the use of systematically collected measurements of heart rate and blood pressure evaluated by computer against reference standards from peers of corresponding age, gender and ethnicity. Thereby, an illustrative, clinically relevant aspect of everyday physiology is resolved within the otherwise neglected normal range, and disease risk syndromes are detected so that preventive treatment can be instituted before catastrophic disease occurs. The scope of this chronobiology section of the Neuroendocrinology Letters is to map the time-qualified feedsideward interactions within the neuroendocrines, in the rest of an organism and in the environment. Thereby, we replace time-unqualified feedbacks and feedforwards, along imaginary axes, by neuroendocrine and cellular networks operating predictably insofar as rhythmically within the range of everyday physiology. Subtle effects are thus found that are otherwise covered by the curtain of ignorance drawn over the normal range. More important, feedsidewards account for opposite effects that recur rhythmically, and thus help clarify mechanisms that may underlie the difference between stimulating or inhibiting a malignancy and thus shortening or lengthening the lifespan.

Journal Article↗

Cross-spectrally coherent ~10.5- and 21-year biological and physical cycles, magnetic storms and myocardial infarctions*

Magnetic storms trigger myocardial infarctions with mechanisms relating to heart rate variability. Solar cycle-to-solar cycle differences and solar cycle stage dependence shown herein may resolve prior controversy and serve to advocate coordinated worldwide systematically aligned biological and physical monitoring. * This paper was originally invited by the historian-geophysicist Wilfried SCHRöDER of Bremen, Germany, for his biographical "Encounters," and is to serve as an update on the project on the BIOsphere and the Cosmos (BIOCOS) and its offspring ICEHRV (Dr. Kuniaki Otsuka's International Chronome Ecologic Study of Heart Rate Variability). It is intended for distribution at a NATO conference on space weather hazards, organized by Dr. Ioannis Daglis, June 18-29, 2000.

Journal Article↗

General and unspecific damping by malignancy of the circadian amplitude of circulating human melatonin?

The circadian rhythm of serum melatonin of 39 cancer patients is compared with that of 28 healthy subjects matched by gender and age. Each subject provided 6 blood samples at 4-hour intervals for determination of melatonin by RIA. After log10-transformation, data series were analyzed by single and population-mean cosinor and compared between the two groups and among patients subgrouped by cancer site, stage and treatment. A circadian rhythm (P<0.001) is demonstrated for both groups, with a contributing 12-hour harmonic (P<0.001). In the absence of a difference in MESOR, the circadian amplitude of the cancer patients is smaller than that of the healthy subjects (P=0.003). Numerically, nocturnal (00:00 and 04:00) melatonin concentrations are lower and daytime (08:00-20:00) melatonin concentrations are higher in the cancer patients than in the healthy subjects (P=0.032 at 12:00 and P=0.058 at 16:00). In the age ranges examined, no differences are found with age in either group or by gender in health. No differences are found among cancer patients subgrouped either by site, stage (localized vs. metastasized) or treatment. If these results are validated, other Janus-like (two-faced: stimulation or inhibition, depending on chronome stage) effects of malignancy should be taken into consideration for screening and for timing treatment.

Journal Article↗

A half-yearly aspect of circulating melatonin in pregnancies complicated by intrauterine growth retardation.

In investigating mechanisms underlying intrauterine growth retardation (IUGR), circulating melatonin and cortisol were radioimmunoassayed. Blood samples were collected every 4 hours during 24 hours on a strict 24-hour standardized routine in hospital from two groups of women in their third trimester of pregnancy. One group consisted of 14 healthy, uncomplicated pregnancies (HAGA); the other group consisted of 11 pregnancies complicated by intrauterine growth retardation (IUGR) confirmed at birth. The circadian characteristics of melatonin and cortisol were assessed for each woman and compared between the two groups by analyses of variance for repeated measures and by parameter tests based on the cosinor. Since a circasemiannual (about half-yearly) component prominently characterizes body weight and length at birth of children with birth characteristics below usual norms, the circadian characteristics of melatonin and cortisol were also analyzed transversely (across women within each group). The 24-hour average and the 24-hour and 12-hour amplitudes of melatonin of women in the IUGR, but not in the HAGA group, were indeed found to be modulated by an about half-yearly component. This study confirms the circadian rhythmicity of melatonin in healthy pregnant women and extends the finding to pregnancies complicated by IUGR, uncovering about half-yearly changes in melatonin in women with IUGR, thereby extending results obtained in healthy non-pregnant women and men. These variations may reflect influences from geomagnetic disturbances also characterized by a prominent half-yearly pattern, to which the pineal has been shown to be sensitive.

Journal Article↗

The Story Behind: Pineal mythology and chronorisk. The Swan Song of Brunetto TARQUINI.

Brunetto Tarquini became professor of medical semeiotics and cardiology in 1981, and chief of an internal medicine department in 1990, a position he held until his untimely death. As director of the Inter-University Center for Clinical Chronobiology and as coordinator of a post-doctoral school in chronobiology, Brunetto influenced many young Italian physicians. He became the leader of a budding specialty of chronomedicine, coordinating an international group. His focus included temporal aspects of vascular diseases from womb-to-tomb as well as oncological risk factors. His research thus ranged from neonatology over neuroendocrinology to geriatrics, by studies on the pineal in particular, documenting the signature of heliogeomagnetic master switches for circulating human melatonin.

Journal Article↗

Chronobiologically explored effects of Telmisartan.

Effects of Micardis (Telmisartan), alone or with low-dose aspirin, on blood pressure and other cardiovascular endpoints are examined in 20 patients with MESOR-hypertension in a crossover, double-blind, randomized study consisting of three stages, each lasting 7 days: I-placebo, II-Micardis, and III-Micardis with low-dose aspirin. Treatment was administered each day at a different circadian stage, upon awakening, and 3, 6, 9, 12, 15 and 18 hr after awakening. During each stage, the following variables were measured at 3-hr intervals during waking: systolic and diastolic blood pressure, heart rate, ejection fraction, intrarenal resistive index, acceleration time, and serum creatinine. Each data series was analyzed by single cosinor. Results were summarized by population-mean least squares spectra. At matched treatment times, the MESOR and circadian amplitude of each variable were compared among the three treatments by paired t-tests. A prominent circadian rhythm characterizes all variables. Micardis was associated not only with a lowering of blood pressure, but also with a reduction of the circadian blood pressure amplitude. The ejection fraction was increased, and the resistive index and acceleration time were decreased, the effect being more pronounced when low-dose aspirin was added to Micardis. Any circadian-stage dependent effect of Micardis, with or without low-dose aspirin, will require monitoring over spans longer than a single day for a given treatment administration time.

Administration, Oral↗

Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond.

We suggest a putative benefit from timing nutriceuticals (substances that are both nutrients and pharmaceuticals) such as antioxidants for preventive or curative health care, based on the proven merits of timing nutrients, drugs, and other treatments, as documented, i.a., in India. The necessity of timing melatonin, a major antioxidant, is noted. A protocol to extend the scope of chronoradiotherapy awaits testing. Imaging in time by mapping rhythms and broader time structures, chronomes, for earliest diagnoses, for example detection of vascular disease risk, is recommended. The study of rhythms and broader chronomes leads to a dynamic functional genomics, guided by imaging in time of free radicals and antioxidants, amongst many other variables.

Animals↗

Engineering and governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate screening: Part I.

This review provides evidence that the bioengineering community needs to develop cost-effective, fully unobtrusive, truly ambulatory instrumentation for the surveillance of blood pressure and heart rate. With available instrumentation, we document a disease risk syndrome, circadian blood pressure overswinging (CHAT, short for circadian hyper-amplitude-tension). Circadian hyper-amplitude-tension is defined as a week-long overall increase in the circadian amplitude or otherwise-measured circadian variability of blood pressure above a mapped threshold, corresponding to the upper 95% prediction limit of clinically healthy peers of the corresponding gender and age. A consistently reduced heart rate variability, gauged by a circadian standard deviation below the lower 5% prediction limit of peers of the corresponding gender and age, is an index of a separate yet additive major risk, a deficient heart rate variability (DHRV). The circadian amplitude, a measure of the extent of reproducible variability within a day, is obtained by linear curve-fitting, which yields added parameters: a midline-estimating statistic of rhythm, the MESOR (a time structure or chronome-adjusted mean), the circadian acrophase, a measure of timing of overall high values recurring in each cycle, and the amplitudes and acrophases of the 12-hour (and higher order) harmonic(s) of the circadian variation that, with the characteristics of the fundamental 24-hour component, describe the circadian waveform. The MESOR is a more precise and more accurate estimate of location than the arithmetic mean. The major risks associated with CHAT and/or DHRV have been documented by measurements of blood pressure and heart rate at 1-hour or shorter intervals for 48 hours on populations of several hundred people, but these risks are to be assessed in a 7-day/24-hour record in individuals before a physical examination, for the following reasons. (1) The average derived from an around-the-clock series of blood pressure measurements, computed as its MESOR, the proven etiopathogenetic factor of catastrophic vascular disease, can be above chronobiologic as well as World Health Organization limits for 5 days or longer and can be satisfactory for months thereafter, as validated by continued automatic monitoring. The MESOR can be interpreted in light of clock-hour-, gender-, and age-specified reference limits and thus can be more reliably estimated with a systematic account of major sources of variability than by casual time-unspecified spot checks (that conventionally are interpreted by a fixed and, thus, rhythm, gender-, and age-ignoring limit). With spot checks, in a diagnostically critical range of "borderline" blood pressures, an inference can depend on the clock-hour of the measurement, usually providing a diagnosis of normotension in the morning and of hypertension in the afternoon (for the same diurnally active, nocturnally resting patient!). Long-term treatment must not be based upon the possibility of an afternoon vs a morning appointment. Moreover, the conventional approach will necessarily miss cases of CHAT that are not accompanied by MESOR hypertension. (2) Circadian hyper-amplitude-tension indicates a greater risk for stroke than does an increase in the around-the-clock average blood pressure (above 130/80 mm Hg) or old age, whereas (3) CHAT can be asymptomatic, as can MESOR hyptertension. (4) Deficient heart rate variability, the fall below a threshold of the circadian standard deviation of heart rate, an entity in its own right, is also a chronome alteration of heart rate variability (CAHRV). Deficient heart rate variability can be present together with CHAT, doubling the relative risk of morbid events. In each case--either combined with CHAT or as an isolated CAHRV--a DHRV constitutes an independent diagnostic assessment provided as a dividend by current blood pressure monitors that should be kept in future instrumentation designs. CHAT and DHRV can be screened by systematic focus on variability, preferably by the use of automatic instrumentation and analyses, which are both available (affordably) for research in actual practice, in conjunction with the Halberg Chronobiology Center at the University of Minnesota.

Adult↗