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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 397 records · Page 22Linked to original sources

The chronobiology of prostate-specific antigen (PSA): case report and chrono-metaanalysis.

The circadian profiles of circulating PSA of a 72-year-old man (FH) and of 11 other clinically relatively healthy men are compared. The time course of FH's PSA was also followed longitudinally with single samples for over 3 years. A transient peak in PSA exceeding the upper time-unspecified age-corrected reference limit prompted a retrospectively premature biopsy which indicated prostatitis. Watchful waiting and additional PSA determinations may be the preferred approach before biopsy, notably in the elderly, for reasons of cost and invasiveness of the procedure. The load associated with a biopsy is also evaluated by a cardiovascular response.

Aged↗

Spin-offs from blood pressure and heart rate studies for health care and space research.

Evidence here cited underlies resolutions at international meetings to initiate a chronobiology project for health improvement. This project demonstrates expeditiously the feasibility and the health benefits of incorporating chronomedical considerations in the diagnosis, treatment, and prevention of one (or a few closely related) vascular (and oncological) diseases, that have high awareness and importance in the public perspective. Thereby, chronomedicine should become a mainstream basic and applied speciality leading to continual improvement in national/international health status. Reference data obtained for health care can also serve to give a better understanding of the relationship between the terrestrial biosphere and cosmoi near and far.

Blood Pressure↗

Chronomedical aspects of oncology and geriatrics.

Extensive laboratory evidence on the merits of cancer chronotherapy is validated by the doubling of 2-year disease-free survival rate obtained by the chronoradiotherapy of patients with very advanced perioral cancers and by the quadrupling of the 5-year survival achieved by the chronochemotherapy of patients with advanced ovarian and bladder cancer. Miniaturized monitors for marker rhythmometry of tumor and core temperature recorded over long spans should facilitate the optimization of treatment by timing, while also serving the purpose of earliest intervention. The likelihood of a cure should be increased by focusing upon the now extensively documented tumor marker rhythms that may show time structure (chronome) alterations before exceeding the physiological range (that is otherwise neglected as one of random variation), and before overt symptoms appear.

Aging↗

Immunocytoma effect upon circadian variation in murine urinary excretion of beta-aminoisobutyric acid, beta-alanine, phenylalanine and tyrosine.

Under the conditions of disynchronization by the manipulation of both the alternation of light and darkness and the availability and unavailability of food, circadian rhythms characterize the excretion of several amino acids by inbred LOU rats bearing an immunocytoma. Large amplitude rhythms can be demonstrated for urinary beta-aminoisobutyric acid, beta-alanine, phenylalanine and tyrosine. Under the same conditions of disynchronization, control animals excrete the same compounds also with a marked circadian variation but at an invariably lower average rate. These excretory rhythms, along with those demonstrated earlier for polyamines and light-chains, are of interest as potential markers for the chronotherapy of cancer.

Amino Acids↗

Autorhythmometry: leads from single-sample medical check-ups toward a health science of time series.

Starting from the definition of health as given by the WHO, the authors emphasize that rhythms of biological variables should be taken into account if one is to arrive at a positive and individual definition of the concept of health. The evaluation of a single datum spot check of physiological functions does not permit to quantify health in dynamic terms whereas this may become possible when the rhythmic quality of these variables, according to a spectrum of characteristic frequencies, has been assessed. Rhythmometry provides for appropriate reference standards as regards both the population in general and the physical conditions of the same subject during certain spans in the (prospective) life history (spans selected according to consideration of risk and hence cost and benefit at a given age). The authors therefore stress the importance of rhythmometry, thanks to which the time course and other peculiarities of any biological phenomenon can be evaluated by obtaining serial measurements, objectively quantifying their characteristic features, and working out special models with the aid of computers. Of special interest, particularly for the evaluation of reference standards, is autorhythmometry (AR), to be used at least for certain variables. This is the method by which each subject studies himself, performing a certain number of measurements in the course of the day (or month or year) of his body temperature, blood pressure, cardiac rhythm, grip strength, etc. In AR, the subject takes an active part in the study of his condition of health and it has been shown that in the majority of cases these measurements are done with the utmost accuracy and precision, providing that the purpose of the operations to be performed has been adequately explained. The wide spread use of AR, during more or less extended periods in a lifetime, would permit the assessment of the normal situation for each individual and thus offer the possibility of diagnosing any disorder at its very beginning; it would thus be of great prophylactic value. The authors refer to the example of arterial blood pressure; widely different values for the normal levels can be found in the texts of different authors. They also show that a certain presure may be normal for a given subject at a certain time of day and be a sign of illness for another subject, or even for the same subject at a different ime. The authors suggest the introduction of AR in the curriculum of secondary schools and into the routine for outpatients and inpatients. This practice would increase the availability of information on public health at a lower cost. AR may be very usefully applied to chronotherapy: it is a well-known fact that there are rhythms of sensitivity and therefore rhythms of toxic as well as therapeutic effects for various drugs. These can be dove-tailed in such a way as to work out, for individual cases, a time for administration at which the therapeutic effect is at its maximum and the toxic one at its minimum...

Animals↗

Toward a heart rate and axillary temperature chronome in schizophrenia: gauge of disease severity.

The heart rate and axilliary temperature of 17 patients with schizophrenia were measured every 3 hours during waking for 4 days. In 28 profiles, large inter- and intra-individual variations notwithstanding, relations between the time structures (chronomes) of heart rate and axillary temperature are assessed and further examined from the viewpoint of their bearing on the severity of the patients's condition.

Adult↗

Biological rhythm experimentation: a longitudinal design and analysis.

Certain experiments exploring the relationship between biological rhythms and external factors such as pharmacologic agents are typified by the particular importance of interaction and conditional effect parameters. The category of biological rhythm experiments presented here also necessarily involves a deliberate confounding of periodicity rooms and biological rhythm stages (time points). These features, together with the longitudinal nature of the observations, require special precautions in the experimental design and analysis.

Animals↗

Mean circadian cosinors of vital signs, performance of blood and urinary constituents in patients with leprosy.

We have herewith examined the characteristics of circadian rhythms in patients with lepromatous leprosy, active or inactive, allowing a comparison with corresponding properties of rhythms in healthy subjects mapped earlier. Group results were illustrated by cosinor plots, produced directly on microfilm by computer. Eventually such reference standards in the form of cosinors, among other displays, notably of waveform, may be individualized and carried on a person's health record. Such a quantitative assessment of an individual's rhythms in health may serve for rigorous comparison with any changes accompanying increased susceptibility or occult or overt disease.

Adult↗

Chronobiology in 1975.

UNLABELLED: A spectrum of rhythms with several frequencies importantly characterizes not only the central nervous system but also the neuroendocrines and endocrines, other structures and organs, beyond the level of the cell to subcellular structures; it has a wide bearing since chronobiologic methods and facts relate to both basic research and its bearing on major problems of our day. Perhaps most important, computer analysis of data series allows study of temporal structure, progressive and rhythmic variations in life processes and in their responses to environment and drugs. By such methods coupled to modern data collection and/or self-measurement, chronobiology is particularly promising in the following areas, cited as illustrative rather than comprehensive examples: 1. Work hygiene: optimization of work schedules by adjustment of regular schedules and in particular of shift-work to the individuals' physical and mental rhythms. Experimentally, differences in manner of schedule change can account for the difference between the life span shortening and lengthening. 2. Population control: improved methods for detecting the neural as well as neurohormonal regulation of ovulatory cycles should aid efficient family planning by the recognition of a spectrum of rhythms and its synchronization with socio-ecologic factors acting, perhaps, via olfactory and/or other sensory modalities; 3. Nutrition: optimizing the utilization of ever scarcer food supplies and also the benefit from both oral and parenteral medications by meal timing; 4. Education: providing a do-it-yourself system for monitoring individual health in the context of secondary and adult education and as the basis for preventive health care; and, in another context, taking individual mental rhythms as well as morningness-eveningness into account in teaching and learning; 5. Health care: Any risk, e.g., from blood pressure rhythm alteration (perhaps preceding by years intermittent labile elevation) will be detected earlier and more efficiently by multiple measurements readily obtained by autorhythmometry. Results of such an endeavor provide at any one time indices that can be compared with an individualized rhythmometric reference standard as well as peer group rhythm parameters. The rhythm-determined average is more reliable than the single measurement. Other individualized characteristics of a rhythm, such as measures of extent of change or timing of change, may constitute an early warning signal and could be monitored by self-measured or preferably automatically-collected data. Timely and timed treatment can then be sought to prevent, in the case of blood pressure, elevation and consequent debilitating disease such as coronary infarction and stroke. 6. THERAPY: One can strive toward the more specific correction of any pathogenic rhythm alteration when such can be recognized by modern methods of data collection and data analysis...

Animals↗

Circadian periodicity of plasma lipid peroxides and other anti-oxidants as putative markers in gynecological malignancies.

BACKGROUND: The chronome (from chronos, time, and nomos, rule), or time structure, of lipid peroxidation and anti-oxidant defense mechanisms may relate to prevention and curative chronochemotherapeutic efficacy and management. PATIENTS AND METHODS: Newly diagnosed women with gynecological malignancies (N = 30), 30-60 years of age, and age-matched clinically healthy women (N = 35) provided blood samples every 6 hours for 24 hours under standardized conditions. Plasma malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, and serum ascorbate, urate and high-density lipoprotein cholesterol (HDL-C) concentrations were determined. RESULTS: Each variable underwent circadian variation (p < or = 0.002). Patients differed from controls by their overall chronome-adjusted mean value (MESOR) and by the circadian dynamics in the spectral element of their chronome. CONCLUSION: Chronomes of putative anti- and pro-oxidants should be mapped to explore their putative chemotherapeutic role as markers in cancer chronoprevention and management of established disease.

Adult↗

Circadian relations among cardiovascular variables of young adults.

Every 4 hours for 24 hours, 14 clinically healthy young individuals (6 women and 8 men), 26 +/- 4 years of age, measured systolic (S) and diastolic (D) blood pressure (BP) by sphygmomanometer and heart rate by ECG and did impedance cardiography under usual living conditions. Stroke volume (SV), cardiac output (CO) and total peripheral resistance (TPR) were calculated. Time series of SBP, DBP, HR, SV, CO and TPR were analyzed by single and population-mean cosinor. A circadian cardiovascular rhythm is demonstrated by rejection of the zero amplitude assumption in the population-mean cosinor test for SBP, DBP, HR, SV, CO and TPR (P < 0.01). TPR peaks around 0400 (-61 degrees from local midnight), in antiphase with all other variables, their acrophase occurring around 1600 (-240 degrees). A circadian rhythm of statistical significance or of borderline statistical significance is found for all variables except TPR in women. Circadian rhythm characteristics were otherwise mostly similar in men and women with a statistically significant gender difference found by parameter tests only for the MESOR and amplitude of SBP.

Adult↗

Age, gender and circadian or circasemidian blood pressure and heart rate variation of children.

Systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) of clinically healthy children (24 boys and 15 girls) 3 to 7 years of age were measured with a standard mercury sphygmomanometer at 3-hour intervals for 24 hours in April 1991. The children slept and/or rested from 2100 to 0700 and napped from 1230 to 1530; they had meals at 0730, 1200 and 1800. A statistically significant circadian and about 12-hour (circasemidian) component of variation is documented for SBP and DBP of boys and girls and for HR of boys. No gender difference was found for the circadian and circasemidian components. A positive correlation with age is found for the MESOR and circadian amplitude of SBP and DBP (p < 0.05); a negative correlation with age is found for the MESOR of HR (p < 0.001).

Activity Cycles↗

Multiple resonances among time structures, chronomes, around and in US. Is an about 1.3-year periodicity in solar wind built into the human cardiovascular chronome?

AIMS: Velocity changes in the solar wind, recorded by satellite (IMP8 and Wind) are characterized by a solar cycle dependent approximately 1.3-year component. The presence of any approximately 1.3-year component in human blood pressure (BP) and heart rate (HR) and in mortality from myocardial infarction (MI) is tested and its relative prominence compared to the 1.0-year variation. MATERIALS AND METHODS: Around the clock manual or automatic BP and HR measurements from four subjects recorded over 5 to 35 years and a 29-year record of mortality from MI in Minnesota were analyzed by linear-nonlinear rhythmometry. Point and 95% confidence interval (CI) estimates were obtained for the approximately 1.3-year period and amplitude. The latter is compared with the 1.0-year amplitude for BP and HR records concurrent to the solar data provided by one of us (JDR). RESULTS: An approximately 1.3-year component is resolved nonlinearly for MI, with a period of 1.23 (95% CI: 1.21; 1.26) year. This component was invariably validated with statistical significance for BP and HR by linear rhythmometry. Nonlinearly, the 95% CI for the 1.3-year amplitude did not overlap zero in 11 of the 12 BP and HR series. Given the usually strong synchronizing role of light and temperature, it is surprising that 5 of the 12 cardiovascular series had a numerically larger amplitude of the 1.3-year versus the precise 1.0-year component. The beating of the approximately 1.3-year and 1.0-year components was shown by gliding spectra on actual and simulated data. DISCUSSION AND CONCLUSION: The shortest 5-year record (1998-2003) revealed an approximately 1.3-year component closer to the solar wind speed period characterizing the entire available record (1994-2003) than that for the concurrent 5-year span. Physiological variables may resonate with non-photic environmental cycles that may have entered the genetic code during evolution.

Adult↗

Optimization of the chronotherapeutic index in the experimental animal laboratory.

Large animal studies show that the effects of fixed doses of anticancer drugs vary predictably with multi-frequency rhythms' stages--components of a genetically--anchored, habitat synchronized, cosmically influenced time structure--the chronome. Both the tolerance by the host of the toxic drugs and the treatment's efficacy in killing cancer cells contribute to these changes. Chronotherapy, timing treatment according to the chronome, attempts to first maximize treatment efficacy while also minimizing toxicity, so as to optimize the therapeutic ratio. Outcomes have been improved by several hundred per cent by treating rodents at the "right" time with single or multiple agents under controlled laboratory conditions, and by chronoradiotherapy of human perioral tumors, using tumor temperature as a marker rhythm.

Animals↗

Chronobiologic response modifiers and breast cancer development: classical background and chronobiologic tasks remaining.

Mapping the chronome's multi-frequency (about-daily, -weekly, and -yearly) neuroendocrine and immune rhythms can help determine when potential chronobiologic response modifiers (CBRMs) should be applied. Aimed at shielding in time by manipulating rhythms, CBRMs may be pertinent to all stages of carcinogenesis, from prevention to treatment, by forestalling the neuroendocrine, immunologic or cell cycle-related recurrent susceptibility peaks from getting aligned, favoring cancerous growth. Pituitary/hypothalamic isografts in the virus-free Bagg albino mouse and designs described as heterophasic allow the systematic investigation of the effect of internal shifts among neuroendocrines. Rhythm manipulation by CBRMs can then aim at lowering (breast or prostate) cancer risk by reproducing identified favorable low risk chronome configurations such as a circannual amplitude in blood that is small for TSH and large for prolactin in women and vice versa for men.

Animals↗