[Effectiveness of diagnostics and treatment of complicated hypertensive disease taking into account results of 3 day arterial pressure monitoring].

UNLABELLED: Empirical choice of antihypertensive therapy (AGT) for patients with complicated hypertensive disease (HD) encounters difficulties due to high variability of arterial pressure (AP) and inadequate response to intake of medicines. The objective methods for the choice of AGT methods are absent. AIM: To evaluate effectiveness ofthe choice of AGT taking account of AP profile calculated based on the analysis of results of 3 day AP monitoring in patients with complicated HDfor whom the empirical prescription of medicines does not give the desirable result. MATERIALS AND METHODS: The study included 51 patients aged 56 +/- 19 yr with HD 18 +/- 13 yr in duration without adequate control of AP despite combined AGT AD was measured (BPLab, Nizhni Novgorod) every 30 min for 3 days, the AP profile was calculated by special FORM-based algorithm. Peak time and magnitude were calculated, the first and second derivatives of the process were determined, AGT was prescribed at the computed AD maximum points. RESULTS: Systolic and diastolic AP decreased within 2 weeks after AGT The number of patients with enhancedAP in the daytime and at night and those with highly variable AP decreased from 33 to 11% (chi2 = 8.4, p < 0.005), from 61 to 33% (chi2 = 10.1, p < 0.005), from 51 to 26% (chi2 = 8.2, p<0.005) respectively. The number ofpatients with inadequate lowering of night-time AP and those with abnormally high fluctuations of AP decreased from 53 to 24% (chi2 = 9.3, p < 0.005) and from 31 to 15%, (p < 0.005) respectively. The frequency of intake of AGT drugs did not change. CONCLUSION: Approximation of real AP circadian profile fluctuations based on results of 3 day monitoring is a sensitive diagnostic tool facilitating the choice of rational AGT for patients with markedly altered circadian rhythms when empirical prescription of AGT does not ensure desired control ofAP

COSMIC INHERITANCE RULES: IMPLICATIONS FOR HEALTH CARE AND SCIENCE.

Countering the trend in specialization, we advocate the trans-disciplinary monitoring of blood pressure and heart rate for signatures of environmental cyclic and other variabilities in space as well as terrestrial weather on the one hand, and for surveillance of personal and societal health on the other hand. New rules (if confirmed novel laws) emerge as we recognize our inheritance from the cosmos of cycles that constitute and characterize life and align them with inheritance from parents. In so doing, we happen to follow the endeavors of Gregor Mendel, who recognized the segregation and independent assortment of what became known as genes. Circadians, rhythms with periods, τ, between 20 and 28 hours, and cycles with frequencies that are higher (ultradian) or lower (infradian) than circadian, are genetically anchored. An accumulating long list of very important but aeolian (nonstationary) infradian cycles, characterizing the incidence patterns of sudden cardiac death, suicide and terrorism, with drastically different τs, constitutes the nonphotic (corpuscular emission from the sun, heliogeomagnetics, ultraviolet flux, gravitation) Cornélissen-series.

[Several-day arterial pressure and heart rate monitoring in patients with paroxysmal atrial fibrillation].

Patient N presented with a well-apparent abnormality of chronological structure of heart beat biorhythms despite the absence of subjective complaints throughout the six-month long observation period. It was shown that AP peaks were associated with a significant decrease of circadian index (CI), i.e. the development of a rigid daily heart contraction rhythm. The reduction of CI as a specific indicator of stability of the daily cardiac contraction rhythm gave evidence of altered vegetative regulation of cardiac function during hypertension. Rigidity of the daily heart contraction rhythm increased with increasing severity of the disease. Smoothing of the circadian rhythm profile suggests depletion of adaptive reserve and the development of the "denervated" heart phenomenon. Cardioversion created a tendency towards normalization of circadian index.

CHRONOMICS AND GENETICS.

The mapping of time structures, chronomes, constitutes an endeavor spawned by chronobiology: chronomics. This cartography in time shows signatures on the surface of the earth, cycles, also accumulating in life on the earth's surface. We append a glossary of these and other cycles, the names being coined in the light of approximate cycle length. These findings are transdisciplinary, in view of their broad representation and critical importance in the biosphere. Suggestions of mechanisms are derived from an analytical statistical documentation of characteristics with superposed epochs and superposed cycles and other "remove-and-replace" approaches. These approaches use the spontaneously changing presence or absence of an environmental, cyclic or other factor for the study of any corresponding changes in the biosphere. We illustrate the indispensability of the mapping of rhythm characteristics in broader structures, chronomes, along several or all available different time scales. We present results from a cooperative cartography of about 10, about 20, and about 50-year rhythms in the context of a broad endeavor concerned with the Biosphere and the Cosmos, the BIOCOS project. The participants in this project are our co-authors worldwide, beyond Brno and Minneapolis; the studies of human blood pressure and heart rate around the clock and along the week may provide the evidence for those influences that Mendel sought in meteorology and climatology.

Why continued surveillance? Intermittent blood pressure and heart rate abnormality under treatment.

Several opinion leaders have monitored their blood pressure systematically a sufficient number of times a day for chronomic (time structural) analyses, from the time of encountering chronobiology until their death; they set an example for others who also may not wish to base treatment on single spotchecks in a health care office. Such self-measurements, while extremely helpful, were not readily feasible without a noteworthy interruption of activities during waking as well as of sleep. New, relatively unobtrusive instrumentation now makes monitoring possible and cost-effective and will save lives. Illustrative results and problems encountered in an as-one-goes self-survey by GSK, a physician-scientist, are presented herein. Both MESOR-hypertension and CHAT (circadian hyper-amplitude-tension) can be intermittent conditions even under treatment, and treatment is best adjusted based on monitoring, rather than "flying blind".

Prokaryotic and eukaryotic unicellular chronomics.

An impeccable time series, published in 1930, consisting of hourly observations on colony advance in a fluid culture of E. coli, was analyzed by a periodogram and power spectrum in 1961. While the original senior author had emphasized specifically periodicity with no estimate of period length, he welcomed further analyses. After consulting his technician, he knew of no environmental periodicity related to human schedules other than an hourly photography. A periodogram analysis in 1961 showed a 20.75-h period. It was emphasized that "... the circadian period disclosed is not of exactly 24-h length." Confirmations notwithstanding, a committee ruled out microbial circadian rhythms based on grounds that could have led to a different conclusion, namely first, the inability of some committee members to see (presumably by eyeballing) the rhythms in their own data, and second, what hardly follows, that there were "too many analyses" in the published papers. Our point in dealing with microbes and humans is that analyses are indispensable for quantification and for discovering a biologically novel spectrum of cyclicities, matching physical ones. The scope of circadian organization estimated in 1961 has become broader, including about 7-day, about half-yearly, about-yearly and ex-yearly and decadal periodisms, among others. Microbial circadians have become a field of their own with eyeballing, yet time-microscopy can quantify characteristics with their uncertainties and can assess broad chronomes (time structures) with features beyond circadians. As yet only suggestive differences between eukaryotes and prokaryotes further broaden the perspective and may lead to life's sites of origin and to new temporal aspects of life's development as a chronomic tree by eventual rhythm dating in ontogeny and phylogeny.

Time microscopy for all kinds of data including circadian clock biology.

Data showing a rhythm to the naked eye prominently, barely or not at all were described as kinds A, B and C, respectively. Here, we document good agreement between estimates of maxima and minima with eyeballing and with the addition of point and interval estimates of parameters in kind A data. We also construct a chart that provides estimates of uncertainties that can be obtained objectively while they are more difficult to quantify subjectively; again there is agreement. Interval as point estimates of rhythm characteristics and parameter comparisons are useful in charting all kinds of data and become indispensable as we proceed from kind A to kind C data. Illustrations included herein from molecular biology apply equally to all aspects of transdisciplinary science.

Incidence of sudden cardiac death, myocardial infarction and far- and near-transyears.

We analyzed cycles with periods, tau, in the range of 0.8-2.0 years, characterizing, mostly during 1999-2003, the incidence of sudden cardiac death (SCD), according to the International Classification of Diseases, 10th revision (ICD10), code I46.1. In the tau range examined, only yearly components could be documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong Kong, in the latter two locations based on relatively short time series. By contrast, in Minnesota, USA, we found only a component with a longer than (= trans) yearly (transyearly) tau of 1.39 years; the 95% confidence interval (CI) of the tau extended from 1.17 to 1.61 years, falling into the category of transyears (defined as a tau and a 95% CI between 1.0 and 2.0 years, with the limits of the 95% CI of the spectral component's tau overlapping neither of these lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of about 1-year in length was present, and in addition, one with a tau of 1.69 year with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far-transyears being defined as having a tau with a CI between 1.20 and 2.0 year, with the CI overlapping neither of these lengths. In the Czech Republic, there was also a calendar-yearly tau and one of 1.76 years. In the latter two geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes were of similar prominence. The taus are only candidate transyears; the 95% CIs of their taus overlap the 2-year length. When a series on SCD from 1994 to 2003 from the Czech Republic was analyzed, the 95% CI of the transyear's tau no longer overlapped the 2-year length. Transyears were also found in the Czech Republic for myocardial infarctions (MI), meeting the original transyear definition in both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from the Czech Republic, a near-transyear was also found, meeting the definition of a period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along with a far-transyear, defined as a tau between 1.2 and 2.0 years, again with the 95% CI covering neither of these lengths. Herein, we discuss near- and far-transyears more generally in the light of their background in physics and the concept of reciprocal cyclicities.

Chronomics, neuroendocrine feedsidewards and the recording and consulting of nowcasts--forecasts of geomagnetics.

A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5-20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on antiphasic lighting regimens happened to start on the day after the second extremum of a moderate double magnetic storm gauged by the planetary geomagnetic Kp index (which at each extremum reached 6.3 international [arbitrary] units) and by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter on the first day of the sampling. Neuroendocrine chronomes (specifically circadian time structures) differed during magnetically affected and quiet days. The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude and tended to advance in acrophase, while the MESOR and amplitude of the hypothalamic circadian melatonin rhythm were higher during the days with the storm. The circadian parameters of circulating corticosterone were more labile during the days including the storm than during the last three quiet days. Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a mechanism underlying physiological and probably also pathological associations of the brain and heart with magnetic storms. Investigators in many fields can gain from at least recording calendar dates in any publication so that freely available information on geomagnetic, solar and other physical environmental activity can be looked up. In planning studies and before starting, one may gain from consulting forecasts and the highly reliable nowcasts, respectively.

AMBULATORY BLOOD PRESSURE MONITORING: THE NEED OF 7-DAY RECORD.

The need for systematic around-the-clock self-measurements of blood pressure (BP) and heart rate (HR), or preferably for automatic monitoring as the need arises and can be met by inexpensive tools, is illustrated in two case reports. Miniaturized unobtrusive, as yet unavailable instrumentation for the automatic measurement of BP and HR should be a high priority for both government and industry. Automatic ambulatorily functioning monitors already represent great progress, enabling us to introduce the concept of eventually continuous or, as yet, intermittent home ABPM. On BP and HR records, gliding spectra aligned with global spectra visualize the changing dynamics involved in health and disease, and can be part of an eventually automated system of therapy adjusted to the ever-present variability of BP. In the interim, with tools already available, chronomics on self- or automatic measurements can be considered, with analyses provided by the Halberg Chronobiology Center, as an alternative to "flying blind", as an editor put it. Chronomics assessing variability has to be considered.

UNTREATED TRANSIENT LONGER THAN 7-DAY CHAT, CIRCADIAN HYPER-AMPLITUDE TENSION, IN A 7-YEAR PERSPECTIVE.

The case report presented herein aims at promoting the awareness in medical, notably cardiological, practice of the importance of, first, collecting at least a week-long record of around-the-clock measurements of blood pressure (BP) and heart rate (HR) (and a much longer record if the 7 day record so indicates) and, second, of analysing the data chronobiologically in the light of reference values specified as a function of time, gender and age as a minimum. In addition to diagnosing deviations in a chronome (time structure)-adjusted mean value, a chronobiological approach identifies abnormalities in the variability of BP and/or HR, gauged by the circadian characteristics (double amplitude and acrophase, measures of the extent and timing of predictable change within a cycle) and by the standard deviation. A woman in presumably good health was 60 years of age at the start of intermittent monitoring over a 7 year span. The case report illustrates the extent to which a decision based on single BP readings and even on 24 hour averages may be misleading. Treatment based on an initial week-long monitoring may benefit from continued long-term monitoring.

MOVING LEAST SQUARES SPECTRA SCRUTINIZE CHRONOMICS IN AND AROUND US.

As an extension of the chronobiological serial section, gliding spectra illustrate the changing time structure (chronome) of physiological, physical and/or other variables in a given frequency range. For this purpose, least squares spectra are computed over a specified interval (much shorter than the observation span) that is progressively displaced by a given increment throughout the entire record. Results can be displayed either as 3D charts or as surface charts, displaying the estimated amplitudes, percentage rhythms or ordering P-values at each trial period for each interval. The procedure is illustrated for the record of Wolf numbers as a gauge of solar activity and for the number of marriages and divorces in Japan during the past century. Major components in these time series show deviations in period length and relative prominence over time. Particularly in the case of non-stationary time series, gliding spectra offer themselves as useful tools to examine changes in time structure beyond a specific spectral component.

CIRCANNUAL VARIATION IN HUMAN DIASTOLIC BLOOD PRESSURE DURING CONSECUTIVE SOLAR CYCLES.

Putative circadecadal modulations of a circannual variation in diastolic blood pressure are explored in a still accumulating 35 year record of self-measurements by a clinically healthy man. Analyses of monthly means by gliding spectra, one-way analysis of variance (ANOVA), and cosinor were carried out after removing data collected during travel across time zones or during illness. An about yearly change in diastolic blood pressure may or may not be detected with statistical significance by cosinor or ANOVA, apparently as a function of solar cycle number and/or stage. It appears to be, however, 1 year synchronized in the entire span analysed as a whole. A given variable such as diastolic blood pressure may be characterized by multifrequency rhythms that may intermodulate, so that findings in different stages of cycles with the lowest (e.g., circadecadal) frequency mapped may determine different outcomes in cycles with higher frequencies, such as circannuals.

CIRCAMULTISEPTAN ASPECT OF SUDDEN DEATH: COMPETING SOCIO-ECOLOGICAL SYNCHRONIZERS: ALCOHOL AND MAGNETICS?

In order to investigate infradian aspects of sudden death, the daily incidence of 70,531 cases recorded in response to a call for an ambulance during 3 years (1979-1981) in Moscow, Russia, were re-analysed, focusing on multiseptans (components with periods of 7 days and/or multiples thereof). Apart from a prominent yearly and half-yearly variation in the daily incidence of sudden death, least squares spectra revealed the presence of about-weekly and two-weekly components. The about 15.2-day variation was validated by nonlinear least squares and shown to differ in period length from that found in the local index of geomagnetic activity, K. This result suggests that apart from any geomagnetic influence on sudden death, changes in lifestyle (such as alcohol consumption) associated with the twice-a-month salary schedule may affect the occurrence of sudden death. Such a component is not prominently seen for the incidence of other cardiovascular conditions recorded in the same database. The weekly pattern of sudden death, peaking on Saturdays, also differs from those of other cardiovascular conditions, characterized by a higher daily incidence on Mondays. The possibility to now record events in cardioverter-defibrillators offers an opportunity to explore broad chronomes of potentially lethal arrhythmia that may lead to a better understanding of underlying triggers, so that novel countermeasures may be designed and implemented.

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.

[Study of circadian (diurnal) rhythm of intraocular pressure in healthy persons and patients with glaucoma]. / Issledovanie tsirkadiannoi (okolosutochnoi) ritmiki vnutriglaznogo davleniia v norme i u bol'nykh glaukomoi.

35 patients (65 eyes) were examined; 10 patients (18 eyes) were without glaucoma or ophthalmic hypertension, and 25 patients (47 eyes) had an open-angle glaucoma of stages I-III. Glaucomatous patients were divided into 2 groups: patients of one group were examined in hospital (26 clinical studies), and those of another group were examined in policlinics (21 clinical studies). The studies resulted in elaborating a nearly daily rhythm correlating with the modern chronological-and-biological recommendations, i.e. 9 measurements during 4 days were made in hospital and 11 measurements during 5 days were made in policlinics. Such tonometry method was proven to have advantages before Maslennikov's daily tonometry. It was established that the cyclic nature of fluctuations of intraocular pressure (IOP) is individual not only for each person but also for each eye. The obtained data support the advisability of measuring the IOP by using the chronological-and-biological method in diagnostically complicated situations, at so-called glaucoma with pseudo-normal IOP, and in choosing the treatment schemes for patients with glaucoma.

Near 10-year and longer periods modulate circadians: intersecting anti-aging and chronoastrobiological research.

Biological cycles with relatively long and some unusual periods in the range of the half-week, the half-year, years, or decades are being discovered. Their prior neglect constituted a confounder in aging and much other research, which then"flew blind" concerning the uncertainties associated with these cycles when they are not assessed. The resolution of more about 10-year and other cycles, some reported herein, replaces the admission of complete unpredictability, implied by using the label "secularity." Heretofore unaccounted-for variability becomes predictable insofar as it proves to be rhythmic and is mapped systematically to serve as a battery of useful reference values. About 10-year cycles in urinary 17-ketosteroid excretion and in heart rate and its variability, among others, are aligned with cycles of similar length in mortality from myocardial infarction. Associations accumulate between cycles of natural physical time structures, chronomes such as the 10.5-year (circadecennian) Schwabe and the 21-year (circavigintunennian) Hale cycles of solar activity, and chronomes in biota. There are about 50-year (circasemicentennian) cycles in mortality from stroke in Minnesota and in the Czech Republic and also in human morphology at birth, the latter result reducing the likelihood that these cycles are purely human made. Associations among large populations warrant long-term systematic coordinated sampling of natural physical and biological variables of interest for the design of countermeasures against already documented elevated risks of stroke, myocardial infarction, and other catastrophic diseases, notably in elderly adults. New findings will be introduced against the background of the documented value of mapping rhythms in medicine and gerontology. In both these fields, rhythms promise the seeming paradox of better care for less.

About 8- and approximately 84-h rhythms in endotheliocytes as in endothelin-1 and effect of trauma.

Population densities (PD) of capillaries (C) and endotheliocytes (E) were determined in pinnal dermis of C57BL mice before and after trauma. Moving (and overall) least-squares spectra before trauma detected in EPD (versus CPD) pronounced 3.5-day (circasemiseptan) and 8-h oscillations corresponding to components of the endothelin-1 chronome in human blood plasma reported earlier. Circadians were more pronounced in CPD. After trauma, circasemiseptan oscillations appeared also in CPD; their period gradually shortened and in two weeks split into about 2.5- and about 4.5-day oscillations; and circadian components became very pronounced. The pre-traumatic chronome was not restored within three weeks following trauma.