Julia Halberg

Chronobiologic blood pressure assessment with a cardiovascular summary, the sphygmochron

Chronobiology deals with rhythmic patters that occur in all forms of life [1–5, 7–33, 35–38, 40–44, 47]. Virtually all organisms exhibit approximately daily (circadian) cycles. In human beings, prominent rhythms are found in blood pressure, circulatory pulse, body core and surface temperature and in chemical variables of blood, urine, and tissues. (Fig. 1). The medical section of this new science explores the relationships of rhythms to prediction, prevention, diagnosis, and treatment of diseases. Several decades of research worldwide have established that medical diagnoses can be subject to a much higher proportion of false positives (e. g., “office hypertension”) and false negatives (e. g., “odd-hour” hypertension) when only single samples are taken at arbitrary times of the day instead of taking rhythms into account. Radiation, chemotherapy, and other treatments have been shown to have markedly different efficacy and safety depending upon the pattern of administration within the day. Without modern engineering tools, chronobiology had to rely on manual measurement series that were cumbersome to collect and required methods of analysis that were not generally available. Modern bioengineering with microcomputers can bring the findings of chronobiology on circadian and other rhythms into the mainstream of medicine. Chronobiology can thus provide new dimensions to an individualized, positive assessment of health complementing the current negative approach relying solely on the absence of unusual values or overt disease.

Chronobiology, Radiobiology and Steps Toward the Timing of Cancer Radiotherapy

Radiotherapists and most radiobiologists approach the organism and its responsiveness, e.g., its radiosensitivity, as a more or less constant entity. Radiotherapy is hence scheduled during ‘regular’ working hours on weekdays only, as a function of practicality. In the past few decades, however, a quantitative science, chronobiology, has developed. This science shows that the host harboring a malignancy and some malignancies themselves are dynamic entities. Human and other hosts exhibit recurrent changes. These can be assessed by inferential statistical means. Thus, a variety of bioperiodicities is uncovered. Their frequencies range from 1 cycle in less than 20 hours (ultradians), over one in about 24 hours (circadians) to one cycle in more than 28 hours (infradians). Infradians include changes with a frequency of 1 cycle in about a week (circaseptans) or in about a year (circannuals), as well as about 30-day cycles (circatrigintans). These latter cycles are found in menstrually cycling women (but also years before the first and decades after the last menstruation); furthermore, circatrigintans are also found in men (66).

The Sphygmochron for Chronobiologic Blood Pressure and Heart Rate Assessment in Cancer Patients

Chronobiometry (11, 15), a subdiscipline of chronobiology*, serves, among other uses, for cardiovascular assessment of a cancer patient. This approach is advocated for everyone, in order to obtain individualized reference standards in health. The assessment of a reliable chronobiologic mean (the midline-estimating statistic of rhythm, briefly the MESOR) is particularly pertinent in the case of heart rate for patients with cancer who are treated with doxorubicin, where it can serve as a gauge of cardiotoxicity. The purpose of this chapter is to introduce the chronobiologie approach to the measurement of blood pressure and heart rate and to distinguish it from any conventional 24-hour ambulatory monitoring. The 24-hour profile (carried out without chronobiologie analyses) is a valuable yet incomplete substitute for the conventional casual spotchecks, currently practiced for convenience rather than at pertinent times.

Multi-purpose monitoring of carbon dioxide in closed organism-environment systems

Carbon dioxide output monitoring from biosatellites and the analysis of such data by circadian rhythmometry can serve the double purpose of (1) documenting an interesting aspect of circadian system behavior in extraterrestrial space while (2) gauging at the same time an important function of the life support system. Groundwork here analyzed shows circadian CO2 output endpoints and an acrophase-map of other rhythmic variables in the mouse.

A Tribute to Franz Halberg, MD

Dr Franz Halberg, a towering figure in cardiovascular research who founded and developed the new science of modernized chronobiology, passed away a month shy of 94 years of age on June 9, 2013. The chronobiological vocabulary and ambulatory monitoring methods were his original conceptions. Dr Halberg’s international stature and contributions to hypertension research through chronobiological methods were monumental, and we pay our respects to this outstanding scientist, educator, and scientific father and his dedication to the advancement of heart attack and stroke victims, hypertension research through chronobiological methods in individual monitoring, analyses, and interpretation in variations as a function of Time. In the early stages of his professional life, his keen observations of biological variations in living beings enabled him to find periodicities shared between biological systems and their broad environments, influenced by the sun and the cosmos, leading to chronomics (broad time structures beyond circadian rhythms). Biological time structures (clock hours) and chronomes are considered essential parameters in blood pressure monitoring, as well as in neurohormonal rhythms and other organs/systemic variations. The impact Dr Halberg had in science stemmed not only from his original findings but also from his vision of their implications that led beyond a scientific breakthrough to a new way of thinking as a truly great scientist. His lifetime of hard work after his medical education and training seeking optimal configurations of the time structure has contributed to some of the greatest advancements in the modern scientific world and standardized clinical practice, especially in hypertension. His research on timing guided by the circadian clock observed early changes in blood pressure and heart rate variability, especially large fluctuations in amplitudes and shift changes in peak hours among heart attack and stroke victims, and cancer patients. The changed rhythms can be detected during subclinical stages by ambulatory monitoring, …

Chapter 26 Toward the chronobiology and chronomics of the intestine

Publisher Summary Chronomics, a computer-aided data collection and analysis, map time structures, chronomes, in the alimentary canal and elsewhere. Chronomics complement chronobiology, as genomics complement genetics. This chapter introduces the conceptual and methodological steps underlying the time-microscopic mapping of the normal range of variation in general, and in the gut in particular. With chronobiologic provisions and safeguards, chronomics can map an integrative internal–external collateral hierarchy for physiological coordination that replaces the illusion of a master clock serving for constancy. The naked eye is an important tool, but if used alone, it has severe limitations. A ubiquitous phase-adjusting mechanism with subtractive coupling, effects upon the circadian amplitude, the suprachiasmatic nuclei (SCN), has particular pertinence for the alimentary canal. On a restricted diet, the gut overrides the hypothalamus in collateral rather than up/down hierarchy, a basic finding that awaits time-microscopic manipulation in various applications.

Cardiovascular rhythms, their adjustment to schedule change and shift work

With illustrative chronobiologic methodology, the rules of rhythm shifting by work schedule manipulation are reviewed with reference to self-measured or ambulatory blood pressure and heart rate. The literature on the cardiovascular performance of shift workers studied with miniaturized devices or by self-measurement is reviewed and the systolic blood pressure status of 36 police officers presented. 53% of these officers had blood pressure excess. The cosinor approach defines blood pressure characteristics and their deviation with respect to those of healthy peers by fitting cosine curves for assessing static and dynamic parameters. Some of these chronobiologic endpoints are introduced in the minicourse to stimulate their use in particular for individuals under a burden such as police work on shifting schedules.<<ETX>>

Franz Halberg, MD (5 July 1919–9 June 2013) – In Appreciation

On Sunday morning June 9, 2013, one of the greatest scientists of the 20th and 21st centuries left us. His close associates also lost a very staunch friend and a mentor who never ceased to inspire. Franz Halberg’s passing shy of his 94th birthday leaves a void that cannot be filled. Franz Halberg (Figure 1) will be remembered for founding the fields of quantitative chronobiology, chronomics, and chronobioethics. These new transdisciplinary scientific disciplines could not have flourished without Franz Halberg’s unveiling of lawful variations as a function of TIME within the physiological range and his vision that they had far-reaching implications. Toward this goal, he not only gathered a critical mass of data himself, but with a steadily increasing network of colleagues worldwide, he also developed inferential statistical methods for their analysis and interpretation. By adding TIME to the existing body of knowledge in all of biology and medicine, and by recognizing the crucial role this new element plays in all matters of life, Franz Halberg developed the new science of chronobiology. By insisting on an inferential statistical foundation, details of a rich time structure were revealed akin to the finer spatial resolution obtained with a microscope. His methodical scrutiny of periodicities shared between biological systems and their broad environment, seen (photic) and unseen (non-photic) influences from the Sun and the cosmos led to chronomics in a way reminiscent of discoveries enabled by the advent of the telescope. Franz Halberg was born on July 5, 1919 in Bistritz, Romania, where he received his elementary and secondary schooling. In 1943, he received his medical degree from the University of Cluj in Koloszvar. He became a citizen of Austria and worked in the Department of Anatomy at the University of Innsbruck from 1946 to 1948, first as a Scientific Assistant and later as a University Assistant. There, Franz studied the adrenal. In 1948, he immigrated to the United States, where he continued this work at Harvard Medical School with a World Health Organization fellowship in clinical endocrinology. He also held a position of Assistant in Medicine at the Peter Bent Brigham Hospital in Boston. In 1949, he joined the staff at the University of Minnesota Medical School, which saw his breakthrough experiments that led to the important discovery that circadian rhythms are partly endogenous and can be manipulated by environmental synchronizers, notably the lighting and feeding schedules. Franz coined the term circadian, after documenting that biologic rhythms tip the scale between health and