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NeuroendocrinologyİLetters incl. Psychoneuroimmunology & Chronobiology,
ISSNİ0172ñ780X Copyrightİ©İ1999 NeuroendocrinologyİLetters

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NEL VOL. 20 1/2
SEASON'S APPRECIATIONS 1998

1999; 20:31–43
Full text pdf (176kb)

Season’s Appreciations 1998
Franz Halberg, Germaine Cornélissen, Mary Sampson, George Katinas & Othild Schwartzkopff
1. Chronobiology Laboratories, University of Minnesota, Minneapolis, MN 55455, USA
2. Yaroslav Mudry Novgorod State University, Novgorod, Russia

Correspondence to:
Franz Halberg, Chronobiology Laboratories, University of Minnesota, 5-187 Lyon Laboratories, 420 Washington Ave. S.E., Minneapolis, MN 55455, USA. TEL:+1 612 624 6976; FAX: +1 612 624 9989
E-MAIL: halbe001@maroon.tc.umn.edu

Key words:
chronome, chrone, chronorisk, circadian-circannual


Our reference values are in the form of 7-day series of hourly or denser around-the-clock data for a minimum of a week, for both genders, from womb to tomb, for ”whites” and ”Asians”.
Paraphrasing an academic engineer (Duechting 1998), breakthroughs in health care depend upon 1. the vision of a leader, 2. the creativity of staff, 3. a friendly work environment, 4. an appropriate technology, 5. an auspicious start time and 6. the adherence to a time line. Indeed, we may not deal with the sum of these ingredients, but with their product.
+ Regarding Item 5, to bring chronobiology into the mainstream, any time is not only auspicious, but overdue, notably if we are sidetracked by unexpected findings prompting our return to excursions into the cosmos (Halberg and Cornelissen 1998; Cornelissen et al. 1999; cf. Halberg 1961, 1964a and b; Halberg et al. 1970). Here, adverse effects characterizing rhythmic, and to that extent predictable, solar-terrestrial and broader interactions with human pathology as well as morphology and physiology can lead to useful results on terra firma as well. Findings made warrant prospectively refined archival studies of human morbidity and mortality in geomagnetically, and geographically differing areas and in space (Halberg and Cornelissen 1998). Results also warrant strategically placed worldwide and extraterrestrial systematic monitoring. The ECG, or at least heart rate, and blood pressure and as-yet opportunistic metabolic, neural and endocrine studies should become systematic. The biological approach will have to be coordinated with physical monitoring to pick up disease risk syndromes and to develop countermeasures for instrumented self-help for risk reduction in health care. Such pre-habilitation is deemed essential in extraterrestrial space, away from hospitals. Longitudinal monitoring for a lifetime of different non-human species and hybrid (combined longitudinal and transverse) monitoring of humans can provide hints of the sites of life’s origins and evolution(s).
Putative effects of magnetic field disturbance upon mortality on earth were found neither by others (Lipa et al. 1976) nor by ourselves, when in 1998 we examined overall mortality from all causes in Minnesota in relation to Schwabe’s about 10.5-yearly (circadecennian) cycle in solar activity (Cornelissen and Halberg, unpublished). This was at variance with long-held claims of magnetic storm effects by Russian (Chizhevsky 1940, 1968; Dubrov 1978; Breus et al. 1989) and other investigators (Duell and Duell 1934, 1935), including subtle geophysical effects reported by prominent physiologists in the U.S. (Brown 1960; Barnwell 1960). Dr. Tamara Breus, however, had given one of us skeptics an opportunity for a chrono-meta-analysis of a data set of over 6,300,000 diagnoses made in response to calls for an ambulance in Moscow during three years of high solar activity (1979-1981) (Breus et al. 1989). With a variety of approaches, ranging from cross-spectral coherence to superimposed epochs, an effect of magnetic storms could be validated on 85,819 cases of myocardial infarctions (Halberg et al. 1991; cf. Halberg et al. 1992; Cornelissen et al. 1993, 1994; Breus et al. 1995), among other effects of interest to space life science (Halberg et al. 1991).
These results were subsequently confirmed by a different method which removed rhythms before the analysis of the heliogeophysical effect and were then extended to an effect of storms upon strokes and to another data set (Villoresi et al. 1994a,b; cf also Feigin, 1997). An effect of magnetic storms was also reported for traffic accidents (Strestik and Prigancova 1986). Why earlier claims, thoroughly reviewed by Dubrov (1978) and Gamburtsev et al. (1994), could not be consistently documented, may have a complex answer, and more than insufficient sample sizes may be involved, although Tamara’s over 6 million cases helped. As one of many pertinent considerations, the solar cycle number and stage may lead to quite different associations (Cornelissen et al. 1998; Halberg and Cornelissen 1998; Halberg et al. 1998; Nikityuk et al. 1998; Sothern et al. 1998; Watanabe et al. 1998). Thus, when a series of automatic half-hourly around-the-clock measurements of heart rate covering 11 years, is correlated with the Wolf numbers (WN), there is a statistically significant positive correlation during the ascending (r=0.535; P=0.001), but not during the descending stage (r=0.078; P=0.556) (20). For another series covering 30 years by up to 6 measurements/day, heart rate was positively correlated with WN during the descending stage of one solar cycle (Jan 1970-Dec 1975: r=0.398; P=0.001) and negatively during the next 2 descending stages (Jan 1982-Dec 1985: r=-0.427; P=0.002, and Aug 1991-Jul 1996: r=- 0.450; P<0.001). A remove-and-replace approach also revealed solar effects upon the amplitude of about 7-day cycles in heart rate (Cornelissen et al. 1996).
Concurrently, a chronobiologic approach can be suggested with respect to the origins and development of life. The study of the timing of circadian rhythms in nucleic acids was a first hint of an RNA world before ours based on DNA (Halberg et al. 1958, 1959; Barnum et al. 1958; Edmunds and Halberg 1981). By 1991 (Halberg et al. 1991; cf. Cornelissen and Halberg 1994; Breus et al. 1995), ontogeny (regarding, e.g., newborns as living fossils) and phylogeny were considered clues to the physical setting in which life came into existence. (Halberg et al. 1990; Cornelissen and Halberg 1994; Diez-Noguera et al. 1996; Thaela et al. 1997; Fanjul-Moles et al. 1998; cf also Halberg and Conner 1961; Schweiger et al. 1986; Woolum et al. 1998).). A recapitulation, along the lines of the coiner of ecology (Haeckel 1905), originally Haeckel’s Biogenetic Law (”ontogeny recapitulates phylogeny”), much disputed (de Beer 1930; Gould 1977; Alberch 1980; Bonner 1982; McNamara 1982; Halberg et al. 1990, 1998; McKinney & McNamara 1991; Goldbeter 1996; Halberg 1997), has evolved into an evolution of ontogeny discussed by scholars of heterochrony, mostly in terms of morphological characteristics. We in turn have sought the lessons yet to be learned about the evolution of rhythms from their development from the egg, as also advocated subsequently in principle by Prigogine (in the introduction to Goldbeter 1996). These evolutionary topics could all be approached empirically by systematic coordinated physical and physiological monitoring, i.e., by what developed into an agenda for BIOCOS, presented at a meeting at the International Union of Physiological Sciences, endorsed by the Russian Academy of Medical Sciences (Halberg et al. 1998) and proceeding on back burners, to be implemented on an appropriate scale.
+ About Item 3, the work environment is ideal; it is the world at large, motivating a small team, cooperating with quite a few local and many other friends, most of them apparent from the bibliography. Elsewhere, one of us (Halberg 1963) indicated that productivity is inversely proportional to the funds at one’s disposal. By that criterion, we should be most productive. We are not distracted, but stimulated to derive more fun from our findings.
+ With respect to Item 2, our creativity must be judged by the reader of our bibliographies.
A U.S. physicist, former coordinator of the International Solar- Terrestrial Energy Program, interested in breaking down disciplinary barriers (Roederer 1985), wanted to initiate a Solar Activity and the Biosphere (SABIO) project. We cite him verbatim (Roederer 1995): ”If confirmed, the implications of solar variability-induced effects of biota and human health, however small, could be far-reaching. Leaving aside the potential impact on preventive medicine, health care and insurance, they would be of basic importance to chronobiology”. We add that chronobiology could spawn two budding fields that depend upon coordinated physical and biological monitoring, notably on humans: chronoastrobiology and, to those astronauts who explore space, chronobioastronautics. The extension of the data for learning more about our origins and for venturing further is the task of BIOCOS. This may be the road leading to the next item:
+ Regarding Item 4, the appropriate technology for closing the loop between available diagnostic and therapeutic devices is desirable for a mainstream chronomedicine (Cornelissen et al. 1999). Interest by both the public and private sectors will be essential to transfer the monitoring technology, now sufficiently miniaturized from mice to human beings.
+ Item 6 is a problem. We are general practitioners of chronomedicine, tackling whatever problem comes our way, and are not good in adhering to timelines, except for being at it 7 days a week for many hours each day.
+ For Item 1, we are fortunate to have Earl E. Bakken as the mentor of a future center. He has already made the implantable pacemaker into a reality. This invaluable device in health care is a sine qua non for the rehabilitation of many of the sick. Earl also had an early encounter with what developed into chronobiology and may now help this established discipline to reach the mainstream. His vision, implementable by chronomedicine, is action to improve the health-related quality of life (Bakken 1998). Earl advocates the use of multiple modalities ranging, as he puts it, from high touch to high tech, from bedside manner and placebo effects of use to the patient in their own right to the action of externally provided molecules and devices. Most, if not all, treatments have or should have some ingredients from high touch and more and more treatments will involve high tech as engineering becomes chronobiomimetic.
High touch effects can gain greatly from the monitoring and other methods of chronomedicine, which provide entry into the otherwise- ignored normal range, and thus seek to pick up subtle effects. Earl has a vision, which we share, of making integrated health care into a chronomedical reality. Our name for the road to the realization of this vision is pre-habilitation. The Minnesota center in chronomedicine has as its goal to assure that the benefit from splitting the normal range of variation will not take another hundred years ! The center’s focus is directed at a scenario eloquently described elsewhere in a different context (Whitaker 1998):

You’re a vibrant 52-year-old executive, avid tennis player, loving husband and father. Then, in an instant, a stroke irrevocably tears apart the entire fabric of your life. You now can’t walk without assistance. Your left arm is crippled and your speech is slurred. When your friends and business associates come to visit you, they can hardly believe it’s you. You are a shadow of your former self, unable to work, walk without great difficulty or even carry on a conversation. You must drag yourself up stairs. And you face what seems like an eternity of gruelling therapy to merely regain a fraction of your lost function. Now let me ask you a question — If you could avoid this by taking a few simple precautions, wouldn’t you do it ? [Stroke] strikes half a million Americans [and, we add, many more around the world] every year, killing 150,000 people, 20% within the first month. Depressingly, only 10% of people who have a stroke ever resume completely normal function.

The chronobiologist asks: If you could avoid stroke, which in the worst massive case may even leave you unable to clean, feed, dress or otherwise care for yourself, by investing into a week of somewhat obtrusive monitoring, along with other simple precautions, wouldn’t it be worth it ? The chronomedical initiative is to motivate the public and the health care provider, in this order of priority, to focus on the concept of pre-habilitation, not only with respect to stroke and to other vascular conditions, but with attention paid to all possible risks, so that the person saved from a stroke does not end up with another crippling or painful disease. The chronobiology center will accordingly focus on disease risk syndromes and thereby will strive to achieve the change in health care from after-the-fact endeavors to the detection of elevated disease risk and its lowering by treatment, pre-habilitation.

The reduction of too much variability in blood pressure and the augmentation of too little heart rate variability will be the major immediate goals. We will focus on circadian blood pressure overswinging or CHAT, short for circadian hyperamplitudetension, and upon an excessively low standard deviation of heart rate, a CAHRV, a chronome alteration of heart rate variability. For the purpose of diagnosing these conditions, the availability of reference values from peers of both genders, all ages and different ethnic groups, eventually with outcomes, will be critical. For this purpose first and foremost, the data store accumulated over the past 50 years must be organized while at the same time invaluable accumulating records of much broader scope are to be catalogued and archived. Equally important is the continuance and systematic extension of the collection of time-specified reference values around the world from womb-to-tomb. This is under way in the context of the ongoing projects on the Biosphere and the Cosmos (BIOCOS). This endeavor gained momentum from Dr. Kuniaki Otsuka’s now- international, originally Asian Chronome Ecologic Study of Heart Rate Variability (ACEHRV).
These ongoing projects provide invaluable reference standards for blood pressure, heart rate and other ECG indices, some derived from beat-to-beat 7-day or, when need be, longer ECG records. Invaluable data may continue to accumulate cost-free due to our function as a design and data analysis center. By such planning and analytical endeavors, the center is likely to have further opportunities to bring chronobiology into the mainstream of health care. Its goals include the collection and organization of data on the variability of indices of risks competing with vascular disease risk. Endocrine gauges of cancer and emotional disease risk have been the result of coordinated international studies (Halberg et al. 1981). In the course of these endeavors, major focus will also be placed, whenever possible opportunistically, on the underlying mechanisms that may lead to new treatment modalities, involving physical approaches, such as the manipulation of electricity and magnetism.
We will be available to test new technology aimed at closing the loop between available and yet-to-be-developed diagnostic and treatment devices with a view of their use where they are most needed such as in missions in space where neglect of the limits to acceptable blood pressure and heart rate variability may have consequences such as those of the neglect of limits of O-rings to acceptable temperatures, leading to the Challenger disaster (Feynman 1988). Focus upon this dividend from chronoastrobiology could provide both a model for health care on earth and also basic data on the origins of life, an intellectual dividend for center staff (Dorman et al. 1993; Doarn et al. 1998).
The bottom line of our endeavors, the detection and treatment of disease risk syndromes, notably stroke prevention, is to be implemented locally as well as by as many as possible in a network of about 100 co-investigators worldwide. The first line of treatment for stroke prevention will be timed relaxation methodology (Watanabe et al., 1996a, b) to be applied before drug treatment. For this purpose and more broadly, chronobiologic self-help in health care, including family- and self-monitoring of vital signs, is to be taught and implemented as far as possible. This educational endeavor of the local public in different age groups will also constitute a major goal of the new center.
We thank Dana Johnson and his committee, Phil Regal and Dave Hunter in particular, for batting for a chronobiology center at the University of Minnesota. We appreciate the guidance to pertinent literature offered by Howard Burchell and again by Earl Bakken.With Salvador Sanchez de la Peña, the associate editor, we thank the editor-in-chief, the cardiologist Mircea Dumitru of Geronto- Geriatrics, for a Chronome-Geriatrics, and look forward to meeting Mircea in person. We also look forward to meeting Dr. Michael Fossel (1998), editor-in-chief of the Journal of Anti-Aging Medicine, whose enthusiasm, for which we are grateful, exceeds ours: in introducing our paper on CHAT he wrote a special note, paraphrasing our presentation by saying that we recommend to ”avoid flying blind” in dealing with blood pressure and, we add, with any other variable.
Whether or not our plans are realized in Minnesota, we thank all of our past, present and future teachers (= editors = co-authors = referees = students = readers, in particular), who may help others and us to avoid flying blind, so that every day in 1999 and in the new millennium may be for them a chronobiologically qualified holiday.
Support:
U.S. Public Health Service (GM-13981); National Heart, Lung, and Blood Institute, National Institutes of Health (HL-40650), University of Minnesota Supercomputer Institute, Dr. h.c. Dr. h.c. Earl Bakken Fund and Dr. Betty Sullivan Fund, and Mr. Lynn Peterson (United Business Machines, Fridley, Minnesota, USA).
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Nikityuk BA, Balakireva MV, Cornelissen G, Halberg F (1998) Similarities and differences in the 112-year time course of birth weight between the sexes. Reports of Morphology (Vinnitsa State Medical Univ. n.a. Pirogov) 4 (1): 91
Otsuka K (ed.) (1998) Chronome & Janus-medicine: Heart Rate Variability (HRV) and BP Variability (BPV) from a viewpoint of chronobiology and ecology. Medical Review, Tokyo
Otsuka K, Cornelissen G, Breus T, Chibisov SM, Baevsky R, Halberg F (1998) Altered chronome of heart rate variability during span of high magnetic activity. Abstract 10, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998
Otsuka K, Cornelissen G, Halberg F (1997) Circadian rhythmic fractal scaling of heart rate variability in health and coronary artery disease. Clinical Cardiology 20: 631-638
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Other Publications In 1998
1. Cornelissen G., Sothern R.B., Halberg Francine, Halberg Franz. 7- year (circaseptennian) patterns in psychology and biology ? Psychological Reports 82: 483-487, 1998.
2. Rhodus N., Raab F., Cornelissen G., Little J., Schaffer E., Halberg F. Chronobiologic vs. conventional blood pressure (BP) monitoring of dental patients. J. Dent. Res. 77: 255 (AADR Abstract 1195), 1998.
3. Zaslavskaya R., Tokbaeva K., Teibloom M., Halberg F., Cornelissen G. Time-organization of hemodynamics in hypertensive patients in West Kazakstan. Proceedings, VIII International Symposium, Ecologo-Physiological Problems of Adaptation, Moscow, January 27-30, 1998, pp. 139-140.
4. Zaslavskaya R., Zhumabaeva T., Teibloom M., Halberg F. Chronopharmacodynamics of propranolol of prolonged action- betakep in hypertensive patients. Abstract, 6th International Symposium on Hypertension in the Community: Screening, Investigation and Therapy, Geneva, Switzerland, February 8-11, 1998, p. 59.
5. Otsuka K., Cornelissen G., Halberg F., Yamanaka T., Nakajima S., Kubo Y., Shinagawa M., Hotta N., Hasebe T., Omori K., Watanabe Y., Ohkawa S. Vagal tone and various assessments of complexity of heart rate variability in healthy Japanese subjects. Therapeutic Research 19: 265-275, 1998.
6. Siegelova J., Fiser B., Dusek J., Dobsak P., Cornelissen G., Halberg F. Cirkadianni kolisani kardiovaskularnich velicin. Abstract, Nove Trendy ve Funkcni Diagnostice a Rehabilitaci, Slavnosti Pracovni Schuze, 75 Let, Brno 27. unora 1998, p. 12.
7. Otsuka K., Ohkawa S., Cornelissen G., Halberg F. Factors regulating circadian rhythmicity of cardiovascular events. 1. Role of the autonomic nervous function. Progress in Medicine 18: 319-326, 1998. [In Japanese.]
8. Halberg F., Cornelissen G., Otsuka K., Schwartzkopff O. Can the nomenclature for HF and LF/HF ECG power be replaced in a chronome context ? In: Chronome & Janus-medicine: Heart Rate Variability (HRV) and BP Variability (BPV) from a viewpoint of chronobiology and ecology, Otsuka K. (ed.), Kyowa, Tokyo, 1998, pp. 126-134.
9. Singh R., Singh R.K., Mahdi A.A., Misra S., Rai S.P., Singh D., Cornelissen G., Halberg F. Studies on circadian periodicity of urinary corticoids in carcinoma of the breast. in vivo 12: 69- 74, 1998.
10. Raab F.J., Schaffer E.M., Guillaume-Cornelissen G., Halberg F. Interpreting vital sign profiles for maximizing patient safety during dental visits. JADA 129: 461-469, 1998.
11. Hellbruegge T., Halberg F., Staudt F. In memoriam: Professor Dr. Rudolf C.H. Engel. Sozialpaediatrie, Kinder- und Jugendheilkunde 20: 120, 1998.
12. Thaela M.-J., Jensen M.S., Cornelissen G., Halberg F., Noeddegaard F., Jakobsen K., Pierzynowski S.G. Circadian and ultradian variation in pancreatic secretion of meal-fed pigs after weaning. J. Animal Science 76(4): 1131-1139, 1998.
13. Halberg F., Cornelissen G., Otsuka K., Zhao Z.Y., Delyukov A., Gorgo Y., Wang Z.R., Rawson M.J., Holte J., Schwartzkopff O. Chronobiological approaches to integrative anthropology illustrated by heart rate variability (HRV) and geomagnetics. Reports of Vinnitsa State University 2: 254-255, 1998.
14. Tarquini B., Tarquini R., Perfetto F., Cornelissen G., Halberg F. Cord blood leptin concentration as a gauge of chronorisk. Reports of Vinnitsa State University 2: 242-243, 1998.
15. Cornelissen G., Halberg F., Wetterberg L., Tarquini B. Meta- chrono-analysis of human pineal weight reveals circannual chronome component. Reports of Morphology (Vinnitsa State Medical Univ. n.a. Pirogov) 4 (1): 87, 1998.
16. Nikityuk B.A., Balakireva M.V., Cornelissen G., Halberg F. Similarities and differences in the 112-year time course of birth weight between the sexes. Reports of Morphology (Vinnitsa State Medical Univ. n.a. Pirogov) 4 (1): 91, 1998.
17. Shemerovsky C.A., Cornelissen G., Halberg F. Circadian rhythm of defecation and chronorisk of constipation. In: Biomedical and Biosocial Problems of Integrative Anthropology, International Academy of Integrative Anthropology, St. Petersburg, 1998, pp. 251-253. [In Russian.]
18. Rodriguez C., Revilla M.A., Revilla M., Revilla E., Cornelissen G., Arechiga H., Halberg F. El perfil cronobiológico de tensión arterial y de frecuencia cardiaca en un grupo familiar, determinado mediante monitorizacion automática. Gac. Med. Mex. 134: 15-26, 1998.
19. Revilla M. Jr, Rodriguez C., Revilla M. Sr, Revilla E., Cornelissen G., Halberg F. Chronobiologic self-help starts in the family with blood pressure and heart rate monitoring. EuroRehab 8: 41-59, 1998.
20. Siegelova J., Fiser B., Dusek J., Cornelissen G., Halberg F. Circadian variability of rate pressure product in hypertension with enalapril therapy. Abstract, Investigator-Initiated Satellite Symposium to 17th Scientific Meeting, International Society of Hypertension: Renin-angiotensin-aldosterone system: Where to block it ?, Prague, Czech Republic, June 4, 1998, p. 6.
21. Halberg F., Cornelissen G., Sonkowsky R.P., Lanzoni C., Galvagno A., Montalbini M., Schwartzkopff O. Chrononursing (chronutrics), psychiatry and language. New Trends in Experimental and Clinical Psychiatry 14: 15-26, 1998.
22. Otsuka K., Halberg F. Chronobiological approach in cardiology. Medical Specialist in Cardiology 6: 69-73, 1998.
23. Otsuka K., Cornelissen G., Shinagawa M., Kubo Y., Ohkawa S., Halberg F. Chronomes (rhythms, chaos and age and disease trends) of heart rate variability (HRV) in patients with coronary artery disease (CAD). Abstract, 23rd Annual Conference, International Society for Computerized Electrocardiology, Keystone, Colorado, April 18-23, 1998.
24. Otsuka K., Shinagawa M., Kubo Y., Ohkawa S., Cornelissen G., Halberg F. Age, gender and circadian rhythmicity and heart rate variability. In: New Aspects of ECG Informations from the Viewpoint of Time and Space, Toyama J., Watanabe Y. (eds.), Life Medicom, Nagoya, 1998, pp. 335-364. [In Japanese.]
25. Cornelissen G., Halberg F. Chronomedicine. In: Encyclopedia of Biostatistics, Armitage P., Colton T. (editors-in-chief), v. 1, John Wiley & Sons Ltd., Chichester, UK, 1998, pp. 642-649.
26. Otsuka K., Cornelissen G., Halberg F. Circadian amplitude- hypertension as a risk factor of ischemic stroke and nephropathy. Vrach, issue 4, 9-11, 1997. [In Russian.]
27. Cornelissen G., Syutkina E.V., Halberg F., Otsuka K., Wang Z.R., Wan C.M., Garcia Alonso L., Portela A., Delmore P., Fink H., Bingham C., Gaziano E., Grigoriev A.E., Abramian A.S., Mitish M.D., Yatsyk G.V., Teibloom M., Maggioni C., Tereshenko L.I., Lipatova T.Yu, Logvinenko I., Zaslavskaya R.M. Chronobiologic blood pressure self-monitoring ”up front” and until cure or death. Human Physiology 24: 118-125, 1998. [In Russian.]
28. Halberg F., Cornelissen G., Syutkina E., Schwartzkopff O. [Chronobiology, chronodiagnostics, chronoprophylaxis and chronotherapy for everyone.] Medical Market
29: 13-15, 1998. [In Russian.] 29. Siegelová J., Fiser B., Dusek J., Kadanka Z., Moran M., Cornelissen G., Halberg F. Sleep apnea syndrom[e] and circadian blood pressure variability: the effect of CPAP therapy. Abstract, XVI Martin Days of Respiration with international participation, Martin, Czech Republic, September 16-17, 1998, p. 26.
30. Otsuka K., Ohkawa S., Cornelissen G., Halberg F. Ambulatory and home blood pressure monitoring. Pharma Medica 16: 33-39, 1998. [In Japanese.]
31. Halberg F., Cornelissen G. Chronomedicine in the footsteps of Gennady Gubin in Tyumen, Siberia, Russia, and beyond. In: Creative Portraits: Professor G.D. Gubin. Vector, Tyumen, 1998 (? no year given for book as a whole: this contribution dated 1997), pp. 43-52. [In Russian.]
32. Halberg F. Dedication: September 1995. Giovanni Dell’Acqua’s chronobiologic lessons, humanistic legacies and resulting developments worldwide and in a budding cosmobiology. Docta tempestiva, tradita, evolutionesque Johannis de Aqua in ludo Ferrarense, Romano, terrestre, cosmicoque. Acta med. rom. 36: 118-126, 1998.
33. Otsuka K., Nishimura Y., Kubo Y., Shinagawa M., Watanabe H., Cornelissen G., Halberg F. Chronos and chaos: heart rate variability in healthy Japanese. The Autonomic Nervous System (Tokyo) 35: 271-279, 1998.
34. Halberg F. Season’s appreciations 1997. In: Proc. 3rd International Symposium of Chronobiology and Chronomedicine, Kunming, China, October 7-12, 1998, pp. 4-15.
35. Halberg F., Cornelissen G. Chronoastrobiology. In: Proc. 3rd International Symposium of Chronobiology and Chronomedicine, Kunming, China, October 7-12, 1998, pp. 128-142.
36. Cornelissen G., Watanabe Y., Sothern R.B., Grafe A., Bingham C., Halberg F. Dangers of correlation analyses assessing solar cycle stage-dependence of human blood pressure and heart rate. In: Proc. 3rd International Symposium of Chronobiology and Chronomedicine, Kunming, China, October 7-12, 1998, p. 143.
37. Sothern R.B., Cornelissen G., Bingham C., Watanabe Y., Grafe A., Halberg F. Solar cycle stage: an important influence on physiology that must not be ignored. In: Proc. 3rd International Symposium of Chronobiology and Chronomedicine, Kunming, China, October 7-12, 1998, p. 144.
38. Watanabe Y., Cornelissen G., Sothern R.B., Nikityuk B., Bingham C., Grafe A., Halberg F. Numerical counterparts to sunspot cycles in human blood pressure and heart rate variability. In: Proc. 3rd International Symposium of Chronobiology and Chronomedicine, Kunming, China, October 7-12, 1998, p. 145.
39. Masalov A., Cornelissen G., Halberg F., Otsuka K., Syutkina E.V., Zhao Z.Y., Delyukov A., Tarquini B. Rhythms, chaos, human heart rate variability and open-heart surgery: circaseptan and circasemiseptan amplification. In: Proc. 3rd International Symposium of Chronobiology and Chronomedicine, Kunming, China, October 7-12, 1998, p. 146.
40. Halberg F., Cornelissen G., Zue Z.N., Zhao Z.Y., Carandente F., Carandente O., Schwartzkopff O. Chronobiology, an evolving scientific discipline, and chronomedicine, a medical specialty. In: Proc. 3rd International Symposium of Chronobiology and Chronomedicine, Kunming, China, October 7-12, 1998, pp. 159-171.
41. Delyukov A., Gorgo Y., Cornelissen G., Otsuka K., Zhao Z.Y., Halberg F. Examination of putative relation of heart rate to extra-low-frequency perturbations of atmospheric pressure. Abstract, 33rd World Congress, International Society of Medical Hydrology and Climatology, Karlovy Vary, Prague, Luhacovice, Czech Republic, October 4-11, 1998, pp. 275-276.
42. Halberg F., Schwartzkopff O., Cornelissen G. Wertvoll. [Review of the book Chronobiologie und Chronomedizin by Hildebrandt G., Moser M., Lehofer M.] Deutsches AErzteblatt: AErztliche Mitteilungen 38: B-1797, 1998 [18. September].
43. Cornelissen G., Halberg F., Breus T.K., Watanabe Y., Sothern R., Haus E., Kleitman E., Wendt H.W., Bingham C. An origin of biologic week on the basks of the data of human heart rate variations over the solar activity cycle. Biofizika 43: 666-669, 1998. [In Russian.]
44. Cornelissen G., Halberg F., Obridko V.N., Breus T.K. Quasi-11- year modulation of global and spectral features of geomagnetic disturbance. Biofizika 43: 677-680, 1998. [In Russian.]
45. Cornelissen G., Otsuka K., Chen C-H., Kumagai Y., Watanabe Y., Halberg F. Nonlinear relation of the circadian blood pressure ampliutde to cardiovascular disease risk. Abstract 7, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
46. Garcia Alonso L., Garcia Penalta X., Cornelissen G., Halberg F. About-yearly and about-monthly variation in neonatal height and weight. Abstract 14, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
47. Halberg F., Cornelissen G., Watanabe Y. From time-unspecified measurements to chronobiological specialties such as chronomedicine and chronoastrobiology: challenges for manufacturing. Abstract 6, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
48. Ikonomov O., Stoynev A., Penev P., Peneva A.V., Cornelissen G., Samayoa W., Halberg F. Circadian rhythm of blood pressure and heart rate in uncomplicated healthy human pregnancy. Abstract 13, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
49. Isaacson P., Lee R., Cornelissen G., Schwartzkopff O., Halberg F. Chronomes of oxygen saturation and heart rate in health and after coronary artery bypass grafting. Abstract 11, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
50. Katinas G.S., Cornelissen G., Homans D., Rhodus N., Siegelova J., Machat R., Halberg F. Individualized combination chronotherapy of coexisting CHAT and MESOR-hypertension includ- ing diltiazem HCl. Abstract 8, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
51. Otsuka K., Cornelissen G., Breus T., Chibisov S.M., Baevsky R., Halberg F. Altered chronome of heart rate variability during span of high magnetic activity. Abstract 10, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
52. Rawson M.J., Cornelissen G., Holte J., Katinas G., Eckert E., Halberg F. Circadian and circaseptan components of blood pressure and heart rate during depression. Abstract 12, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
53. Siegelova J., Fiser B., Dusek J., Placheta Z., Cornelissen G., Halberg F. Circadian variability of rate pressure product in essential hypertension with enalapril therapy. Abstract 3, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
54. Watanabe Y., Cornelissen G., Halberg F., Otsuka K., Ohkawa S-I., Kikuchi T. Need for chronobiologic reference values (chronodesms) smoothed over age: a problem awaiting a BIOCOS solution. Abstract 9, Neinvazivni metody v kardiovaskularnim vyzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
55. Halberg F. [Vazeni pratele / Dear Friends / Sehr geehrte Freunde.] Catalogue, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998, pp. 8-12.
56. Fanjul Moles M.L., Cornelissen G., Miranda Anaya M., Prieto Sagredo J., Halberg F. Larger infradian vs. circadian prominence of locomotor activity in young vs. older crayfish. Abstract, VI Convegno Nazionale de Cronobiologia, Chianciano, Italy, November 27-28, 1998, p. 65.
57. Germanó G., Cornelissen G., Damiani S., Halberg F. Antihypertensive drug vs. placebo effect assessed chronobiologically. Abstract, VI Convegno Nazionale de Cronobiologia, Chianciano, Italy, November 27-28, 1998, p. 42.
58. Hardeland R., Cornelissen G., Halberg F. Coexisting circaseptan and circadian patterns in the motility of Euglena gracilis Klebs in continuous darkness. Abstract, VI Convegno Nazionale de Cronobiologia, Chianciano, Italy, November 27-28, 1998, p. 66.
59. Katinas G., Cornelissen G., Chen C.H., Rhodus N., Schaffer E., Halberg F. Systolic blood pressure (SBP) speed and acceleration relate to the SBP-MESOR and the left ventricular mass index (LVMI). Abstract, VI Convegno Nazionale de Cronobiologia, Chianciano, Italy, November 27-28, 1998, p. 30.
60. Schwartzkopff O., Cornelissen G., Halberg F. Differences in the time structures (chronomes) of blood pressure (BP) and heart rate (HR). Abstract, VI Convegno Nazionale de Cronobiologia, Chianciano, Italy, November 27-28, 1998, p. 31.
61. Watanabe Y., Halberg F., Cornelissen G., Sothern R., Otsuka K., Ohkawa S., Kubo Y. Spectral differences among human circulatory variables and similarities with solar and/or geomagnetic signa- tures. Abstract, VI Convegno Nazionale de Cronobiologia, Chianciano, Italy, November 27-28, 1998, p. 43.
62. Woolum J.C., Cornelissen G., Halberg F. Chronometaanalysis: enucleation changes the infradian-circadian amplitude ratio of Acetabularia. Abstract, VI Convegno Nazionale de Cronobiologia, Chianciano, Italy, November 27-28, 1998, p. 64. 63. Halberg F., Sánchez de la Peña S., Cornelissen G., Gubin D., Otsuka K., Halberg Francine, Ikonomov O., Stoynev A., Madjirova N., Schwartzkopff O. Time structures, chronomes, broaden the base of gerontology and geriatrics / Estructuras temporales, cronomas, la base amplia de la gerontologia y geriatria. Geronto-Geriatrics 1: 25-46, 1998. [In English and Spanish.]
64. Bennett T., Cornelissen G., Halberg F., Delmore P., Siegelova J., Kubo S. New invasive and non-invasive hardware-software systems for long-term and short-term assessment of hemodynamic changes. Part II: Implanted hemodynamic monitors reveal broad chronomes potentially useful for guiding therapeutic interventions. Scripta medica 71: 177-181, 1998.
65. Chen C.H., Cornelissen G., Halberg F. Left ventricular mass index (LVMI) as ”outcome” related to circadian blood pressure (BP) characteristics (abstract). Scripta medica 71: 183-190, 1998.
66. Cornelissen G., Halberg F., Otsuka K., Watanabe Y., Kumagai Y., Uezono K., Kawasaki T., Weber M., Drayer J.I.M., Siegelova J. Age trends in circadian characteristic of heart rate and heart rate variability in health. Scripta medica 71: 191-198, 1998.
67. Loeckinger A., Herold M., Cornelissen G., Fiser B., Siegelova J., Halberg F. Circaoctohoran frequency desynchronization from atriopeptin of endothelin-1 in the healthy human circulation. Scripta medica 71: 199-207, 1998.
68. Siegelova J., Cornelissen G., Dusek J., Fiser B., Watanabe Y., Otsuka K., Halberg F. Diagnosis and assessment of treatment effects: a single 24-hour blood pressure monitoring profile. Scripta medica 71: 209-213, 1998.
69. Weydahl A., Cornelissen G., Halberg F., Siegelova J., Kumagai Y., Otsuka K. Chronobiologic optimization of exercise physiology and practice guided by heart rate variability. Scripta medica 71: 215-229, 1998.

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Copyright © Neuroendocrinology Letters 1999
All rights reserved. No part may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or ortherwise, without prior written permission from the Editor-in-Chief.