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Biomedical subjects

Franz Halberg

Publications and source records attributed to Franz Halberg.

At least 37 records · Page 2Linked to original sources

100 or 30 years after Janeway or Bartter, Healthwatch helps avoid 'flying blind'.

Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with 'non-dipping'). A non-parametric approach consisting of a computer comparison of the subject's profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention).

Chronotherapy↗

Circadian hypo- and hyper-amplitude-tension (CHAT) associated with putative pheochromocytoma and 12-hourly phenoxybenzamine treatment.

A 26-year-old white woman had an ablated sino-atrial node and ventricular pacemaker as an unusual feature of a pheochromocytoma-compatible history. Her status quo included, on three occasions, elevated 24-hour urinary epinephrine and metanephrine excretion. She monitored her blood pressure (BP) and heart rate (HR) at 15- to 60-minute intervals over several days, with interruptions, before and after the institution of 10 mg phenoxybenzamine per os every 12 hours (between 7:30 and 8:00 and between 19:30 and 20:00), with continued monitoring over several months. Her data were summarized for consecutive 3-day intervals by sphygmochron. Circadian parameters and original data are compared with gender- and age-specified reference values, yielding also non-parametric endpoints, such as the percentage time elevation, the extent of excess, and the timing of excess, that all can be acceptable for some days but unacceptable for other days. In her broader time structure, or chronome, cosinor analyses revealed a prominent and statistically significant circadian rhythm in BP and HR before and during the 12-hourly therapy. The 12-hour component of BP was more prominent during therapy than prior to it. A statistically significant decreasing trend occurred before therapy, and recurred during treatment. Chronomically interpreted monitoring revealed: 1) the persistence of a statistically significant circadian rhythm during 12-hourly phenoxybenzamine treatment; 2) days-long changes in BP MESOR, the duration of which could not be previously determined based on spotchecks; 3) changes in the circadian amplitude of BP, which can be either very small or very large, compatible with the diagnosis of intermittent circadian hyper-amplitude-tension (CHAT); and 4) a very wide range of BP and HR values, so that occasional (casual) measurements fail to convey the dynamics that may underlie this infrequently found clinical condition of an elevated catecholamine excretion compatible with a pheochromocytoma. All findings support the need for long-term monitoring of BP and HR that may account for controversy in earlier publications.

Adult↗

No baseline for blood pressure in ordinary life: another case of transient chronome alterations.

Half-hourly systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) monitoring with gaps demonstrates transient elevations of unknown origin of the chronome (time structure)-adjusted mean, the MESOR, M, of BP, and of the circadian double amplitude of BP of TS, a clinically healthy-appearing engineering student who was 27 years of age at the start of the study. An assessment of large and small arterial vessel elasticity was in keeping with no detection of functional or structural alteration in her vasculature. The recovery of normality in BP endpoints at the time of this report is speculatively associated with a weight loss of 40 pounds and the formation of a friendship by correspondence. Whatever the underlying mechanisms of a long series of abnormal records may be, a 'baseline' can include weeklong spans of abnormality and is best replaced by comparisons with chronomic reference values.

Activities of Daily Living↗

Time structures, chronomes, of soldiers' stature mimicking Hale cycle in neonatal body length.

The systematic patterns in human adult physical stature are explored in connection with Wolf's relative sunspot numbers. This topic should be of interest to economists, physicians as well as physicists. There is a need for more than a check of any similarity of curves in variables approximating the economy and human stature and for more than the application of mathematical models, as done herein. Ours is at best a halting step at one frequency, presented only to document the challenge of a transdisciplinary approach to multifrequency intermodulations of hosts of variables, yet to be untangled. The circumstance that at birth some decisions concerning adult stature are already made is challenging. The signature of the environment in terms of the about 21-year Hale bipolarity cycle of Wolf's relative sunspot numbers found in adult soldiers shows that the association at birth is not a transient one, even if other evidence beyond our scope herein points to the possibility that observations on presumably healthy soldiers can be extrapolated to abnormal growth. Nonetheless, the task for those concerned with short stature could become preventive if the sensitive stages when growth may be inhibited by the environment could be found, as well as means to shield from or counter the undesirable effects.

Adolescent↗

About-weekly variations in nocturia.

The aim of this study was to assess components of variation in nocturia and to determine any putative geomagnetic influence. A 54-year old man with benign prostatic hyperplasia had recorded for about 4 years the number of times he awoke each night to urinate. The data have been reanalyzed for chronomics, the mapping of time structures (chronomes), involving the computation of least squares spectra of the urinary record and of environmental variables recorded during the same 4-year span. In addition to the previously reported monthly variation, other periodicities have been documented, including two separate components with periods of one week and of a near-week. The precise 7-day period may be a mainly exogenous resonance with external influences such as a weekly social schedule, whereas the near-week may be a partial resonance with natural changes in geomagnetics, reflecting in part changes in other non-photic natural environmental factors.

Biological Clocks↗

Chronoastrobiology: proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and ontogenetic memories.

"Chronoastrobiology: are we at the threshold of a new science? Is there a critical mass for scientific research?" A simple photograph of the planet earth from outer space was one of the greatest contributions of space exploration. It drove home in a glance that human survival depends upon the wobbly dynamics in a thin and fragile skin of water and gas that covers a small globe in a mostly cold and vast universe. This image raised the stakes in understanding our place in that universe, in finding out where we came from and in choosing a path for survival. Since that landmark photograph was taken, new astronomical and biomedical information and growing computer power have been revealing that organic life, including human life, is and has been connected to invisible (non-photic) forces, in that vast universe in some surprising ways. Every cell in our body is bathed in an external and internal environment of fluctuating magnetism. It is becoming clear that the fluctuations are primarily caused by an intimate and systematic interplay between forces within the bowels of the earth--which the great physician and father of magnetism William Gilbert called a 'small magnet'--and the thermonuclear turbulence within the sun, an enormously larger magnet than the earth, acting upon organisms, which are minuscule magnets. It follows and is also increasingly apparent that these external fluctuations in magnetic fields can affect virtually every circuit in the biological machinery to a lesser or greater degree, depending both on the particular biological system and on the particular properties of the magnetic fluctuations. The development of high technology instruments and computer power, already used to visualize the human heart and brain, is furthermore making it obvious that there is a statistically predictable time structure to the fluctuations in the sun's thermonuclear turbulence and thus to its magnetic interactions with the earth's own magnetic field and hence a time structure to the magnetic fields in organisms. Likewise in humans, and in at least those other species that have been studied, computer power has enabled us to discover statistically defined endogenous physiological rhythms and further direct effects that are associated with these invisible geo- and heliomagnetic cycles. Thus, what once might have been dismissed as noise in both magnetic and physiological data does in fact have structure. And we may be at the threshold of understanding the biological and medical meaning and consequences of these patterns and biological-astronomical linkages as well. Structures in time are called chronomes; their mapping in us and around us is called chronomics. The scientific study of chronomes is chronobiology. And the scientific study of all aspects of biology related to the cosmos has been called astrobiology. Hence we may dub the new study of time structures in biology with regard to influences from cosmo- helio- and geomagnetic rhythms chronoastrobiology. It has, of course, been understood for centuries that the movements of the earth in relation to the sun produce seasonal and daily cycles in light energy and that these have had profound effects on the evolution of life. It is now emerging that rhythmic events generated from within the sun itself, as a large turbulent magnet in its own right, can have direct effects upon life on earth. Moreover, comparative studies of diverse species indicate that there have also been ancient evolutionary effects shaping the endogenous chronomic physiological characteristics of life. Thus the rhythms of the sun can affect us not only directly, but also indirectly through the chronomic patterns that solar magnetic rhythms have created within our physiology in the remote past. For example, we can document the direct exogenous effects of given specific solar wind events upon human blood pressure and heart rate. We also have evidence of endogenous internal rhythms in blood pressure and heart rate that are close to but not identical to the period length of rhythms in the solar wind. These were installed genetically by natural selection at some time in the distant geological past. This interpretive model of the data makes the prediction that the internal and external influences on heart rate and blood pressure can reinforce or cancel each other out at different times. A study of extensive clinical and physiological data shows that the interpretive model is robust and that internal and external effects are indeed augmentative at a statistically significant level. Chronoastrobiological studies are contributing to basic science--that is, our understanding is being expanded as we recognize heretofore unelaborated linkages of life to the complex dynamics of the sun, and even to heretofore unelaborated evolutionary phenomena. Once, one might have thought of solar storms as mere transient 'perturbations' to biology, with no lasting importance. Now we are on the brink of understanding that solar turbulences have played a role in shaping endogenous physiological chronomes. There is even documentation for correlations between solar magnetic cycles and psychological swings, eras of belligerence and of certain expressions of sacred or religious feelings. Chronoastrobiology can surely contribute to practical applications as well as to basic science. It can help develop refinements in our ability to live safely in outer space, where for example at the distance of the moon the magnetic influences of the sun will have an effect upon humans unshielded by the earth's native magnetic field. We should be better able to understand these influences as physiological and mechanical challenges, and to improve our estimations of the effects of exposure. Chronoastrobiology moreover holds great promise in broadening our perspectives and powers in medicine and public health right here upon the surface of the earth. Even the potential relevance of chronoastrobiology for practical environmental and agricultural challenges cannot be ruled out at this early stage in our understanding of the apparently ubiquitous effects of magnetism and hence perhaps of solar magnetism on life. The evidence already mentioned that fluctuations in solar magnetism can influence gross clinical phenomena such as rates of strokes and heart attacks, and related cardiovascular variables such as blood pressure and heart rate, should illustrate the point that the door is open to broad studies of clinical implications. The medical value of better understanding magnetic fluctuations as sources of variability in human physiology falls into several categories: 1) The design of improved analytical and experimental controls in medical research. Epidemiological analyses require that the multiple sources causing variability in physiological functions and clinical phenomena be identified and understood as thoroughly as possible, in order to estimate systematic alterations of any one variable. 2) Preventive medicine and the individual patients'care. There are no flat 'baselines', only reference chronomes. Magnetic fluctuations can be shown statistically to exacerbate health problems in some cases. The next step should be to determine whether vulnerable individuals can be identified by individual monitoring. Such vulnerable patients may then discover that they have the option to avoid circumstances associated with anxiety during solar storms, and/or pay special attention to their medication or other treatments. Prehabilitation by self-help can hopefully complement and eventually replace much costly rehabilitation. 3) Basic understanding of human physiological mechanisms. The chronomic organization of physiology implies a much more subtle dynamic integration of functions than is generally appreciated. All three categories of medical value in turn pertain to the challenges for space science of exploring and colonizing the solar system. The earth's native magnetic field acts like an enormous umbrella that offers considerable protection on the surface from harsh solar winds of charged particles and magnetic fluxes. The umbrella becomes weaker with distance from the earth and will offer little protection for humans, other animals, and plants in colonies on the surface of the moon or beyond. Thus it is important before more distant colonization is planned or implemented to better understand those magnetism-related biological- solar interactions that now can be studied conveniently on earth. (ABSTRACT TRUNCATED)

Chronobiology Phenomena↗

Transdisciplinary unifying implications of circadian findings in the 1950s.

Afew puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-one-goes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal.

Journal Article↗

Chronomics of tree rings for chronoastrobiology and beyond.

Gliding spectral windows illustrate the changes as a function of time in the relative prominence of signals in a given frequency range, viewed in 3D or as surface charts. As an example, the method is applied to a 2,189-year series of averages of ring measurements on 11 sequoia trees published by Douglass. Analyses of the original data and after filtering reveal, among others, components with periods of about 10.5 and 21 years similar to the Schwabe and Hale solar activity cycles. An alignment of gliding spectra with a global spectrum serves to define, by minima, the ranges of variability around the anticipated Schwabe and Hale cycles. This procedure may have more general applicability when dealing with ranges of only transiently synchronized, wobbly, and perhaps sometimes free-running periodicities. Solar activity is known to affect climate and changes in climate are reflected to some extent in tree growth. The spectral structure in tree rings could serve not only to check any relations of climate with sunspots, auroras and more modern measures of solar activity, but also to check any purely mathematical extrapolations from the much shorter available actual data on solar activity. With such extrapolated series and the data analyzed herein, the task remains to align physical and physiological variables to further study the influence of natural environmental factors near and far on biota, including international battles, which cover an even longer span of 2,556 years.

Chronobiology Phenomena↗

Point and interval estimations of circadian melatonin ecphasia in Smith-Magenis syndrome.

An inferential statistical quantification of chronomes (time structures) in the range of everyday physiology has earlier revealed changes affecting the circadian amplitude of melatonin in the absence of changes in the chronome-adjusted mean value (MESOR) or in the acrophase. A chrono-meta-analysis of published data on patients with the Smith-Magenis syndrome herein quantifies the average extent of shift in the acrophase of the circadian melatonin rhythm, reported earlier by others time-macroscopically as an antiphase. Time-microscopically, the phase shift averages 9.6 +/- 0.9 h. Circadian melatonin ecphasia complements blood pressure ecphasia in non-insulin-dependent diabetes mellitus, associated with autonomic dysfunction. The shift in phase of the peak melatonin secretion from the night into the day, associated with specific genetic findings, raises basic questions concerning the designation of melatonin as a hormone associated with darkness. Whether a resetting of the circadian acrophase beyond providing melatonin for sleep improvement can provide benefit remains to be investigated.

Adolescent↗

About 7-day (circaseptan) and circadian changes in cold pressor test (CPT).

We assess circadian (CD) and circaseptan (CS) changes in the blood pressure (BP) response to a 1-min immersion of the hand into ice water, the cold pressor test (CPT). An about 8 mmHg BP increase in the CPT reported by others for health and an elevation >25 mmHg for patients with "hypertension" have been viewed as predisease, but variables related to the vascular system exhibit prominent CD, CS and circannuals, among other components of their genetically anchored time structure or chronome, and may also have to be considered. Hence, a 16-year-old adolescent (ML) immersed her hand into ice water every 2-4 h for 2 days and once daily in the morning thereafter for 1 week (N = 25), as did, only for <2 days (> or =24 h), four adults 20-66 years of age. BP and heart rate (HR) were monitored automatically around the clock at 15-min intervals and at 1-min intervals before and immediately after the CPT. Data were analyzed by cosinor. The difference between the first post-CPT BP value and the mean of the last seven values prior to the CPT was a measure of CPT response (at 1-min). Overall, ML's systolic (S) BP increased by 8.2 +/- 1.4 mmHg and her diastolic (D) BP by 6.2 +/- 0.9 mmHg (P < 0.001). Increases were found in 96% of the tests for SBP, 92% for DBP and 20% for HR. There was only one tie for HR (4%), resulting in a HR decrease in 76% of CPTs. The BP response to CPT at 1 min was CS-dependent. The CS double amplitudes are 12.5 +/- 4.1 for SBP (P = 0.019) and 7.8 +/- 2.8 mmHg for DBP (P = 0.030), with acrophases occurring on late Sunday, early Monday (at -50 degrees and -67 degrees from 00:00 h from Saturday to Sunday for SBP and DBP, respectively, with 360 degrees identical with 1 week). The response of HR did not allow the detection of a CS rhythm (P = 0.969). The CD response peaked in the early morning hours; with 24 h identical with 360 degrees and 0 degrees = local midnight, the acrophase (phi) for SBP is at -80 degrees and for DBP at -113 degrees, in keeping with earlier results from four adult subjects (SBP: -37 degrees; DBP: -42 degrees ), individual differences notwithstanding. The average timing of the largest overall response of BP to CPT coincides with the timing of the response to other stimuli. The CS acrophases coincide with the times of increased morbidity/mortality from vascular diseases. Chronomes, time structures broader than circadian, notably their about-weekly components, should be considered, not only at the extremes of life when the CS and about-half-weekly rhythms are particularly prominent in BP and HR but also in interpreting BP responses as a gauge of vascular disease status in adolescents.

Adolescent↗

Circasemiannual chronomics: half-yearly biospheric changes in their own right and as a circannual waveform.

Geomagnetic activity has a strong half-yearly but no precise yearly component in its spectrum, as Armin Grafe suggested nearly half a century ago. We have postulated elsewhere that non-photic cycles such as those in geomagnetics may have signatures in the biosphere and vice versa that biological rhythms have likely counterparts in the physical environment. Accordingly, we document phenomena characterized by a prominent about half-yearly variation, re-analyzed to constitute the start of a transdisciplinary chronomic (time structural) map, aligning these conditions with a half-yearly cycle in the geomagnetic index Kp. At least some biospheric phenomena fitted concomitantly with 1- and 0.5-year cosine curves exhibit an amplitude (A) ratio of A(0.5-year)/A(1-year) larger than unity. Methodologically, it is pertinent that even if data were read off published graphs, the resulting analyses were practically the same as those in the original data received subsequently. The main point is a circasemiannual pattern in status epilepticus, in several morbid oral conditions, in the cell density of vasopressin-containing neurons in the human suprachiasmatic nuclei (SCN), in circulating melatonin at middle latitudes at night during years of minimal solar activity or around noon at high latitudes, and in an unusual circasemiannual aspect of a birth-month-dependence of human longevity. Others have asked whether annual rhythms in human reproduction are biological, sociological or both. We show some other possibilities herein, involving the physical environment, hardly to be neglected in the case of open systems. As to almost certainly multifactorial circasemiannual rhythms, geomagnetics may also be a signal, a proxy or a putative, at least partial mechanism. Geomagnetic activity is related in its turn to solar and galactic activity, and may be a marker for other cyclic events that affect the biosphere. The similarity of cycle lengths in itself can only be a hint prompting the search for causal relations.

Atmosphere↗

Non-photic, non-thermic circadecadal solar cycle interaction with cardiovascular circannual and circasemiannual variation in heated air-conditioned habitat.

In order to re-examine the extent to which secular circulatory variation can be resolved into possibly accountable, if not yet predictable behavior, the 15-year record of blood pressure and heart rate of an adult male cardiologist (Y.W.) is reanalyzed. Gliding spectral windows with an interval of 4 years progressively displaced throughout the data series examine monthly means from August 1987 to August 2002. A circannual variation is only intermittent and appears to drift for years. A circasemiannual variation is consistent and prominent, yet only for a fraction of the record examined. By contrast to the circadian rhythm in blood pressure and heart rate, which is reliably detectable in most subjects in clinical health, the circannual variation in the human circulation is inconsistent and hence should be monitored, as in this case for its assessment as one goes, a conclusion that also applies to the circasemiannual variation, prominent for years but not detected thereafter. The results prompt the search for interactions between the photic, thermic and societal effects of the seasons that, if solely pertinent, should yield a consistent 1-year spectral component. That non-photic effects may also play an important role may point to modulation by solar cycle stage and solar cycle number, perhaps mediated by the solar wind. This conclusion is extended in proof to the role played by the most recently discovered transannual component in human blood pressure and heart rate, which is a probable further signature of the solar wind. The beating of the transannual and circannual components documented on another data series may contribute to the lack of a consistent 1-year synchronized circannual variation in this case and many others.

Adult↗