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ABSTRACT: Exploring any non-photic as well as photic components in the spectrum of the incidence pattern of suicides, we find gender differences in Minnesota, USA, and Australia, notably in the para-annual range of the spectrum. A trans-tridecadal BEL cycle (also more liberally referred to as para-tridecadal) with a period of about 35 years is found in data pooled from both genders and separately for both men and women in Finland (1969-2007). When fitted separately as a single component, the estimated period and its 95% confidence interval (CI) (in years) is 35.5 [26.7, 44.3] overall, 36.4 [25.3, 47.5] for males, and 38.9 [28.5, 49.3] for females, with respective amplitudes (N/100,000) of 170 [119, 222], 145 [98, 192], and 29 [18, 40]. Differences between a Schwabe cycle and an about 7-year component (possibly a harmonic of the Hale cycle) characterizing suicide patterns of Finnish men and women, respectively, remain to be examined in longer series. In Bulgaria (1929-1945), a far-transyear with a period of about 1.3 years is noteworthy as is a quinmensal component with an about 5-month period. In France (1979-2008), in males and females, suicides are characterized by about 10.0-year and 10.1-year cycles, respectively. In Japan (1987-1999), an about 12.7-year component is detected, albeit with a broad uncertainty. A better understanding of the origin of these patterns, notably in terms of the relative contribution of non-photic and photic (daily and yearly) cycles, may lead to better prediction of incidence dynamics and to novel interventions for the prevention of major depression and suicide.
World Heart Journal. 01/2011; 3(1-1556-4002):31-42.
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ABSTRACT: Administration of glucocorticoids is effective and necessary in various diseases, but the appearance of side effects may compromise
its results. Timing as well as dosing designed to obtain, for the highest number of patients, maximal beneficial effects with
minimal undesired effects, is particularly pertinent to long-term corticosteroid therapy, in view of the rhythms exhibited
by the endogenous secretion of adrenal cortical and coordinating hormones, primarily ACTH. In experimental animals, properly-timed
circadian treatment can be preferred to alternate-day treatment for avoiding certain side effects. To secure the desired effect
each day rather than only on alternate days, a chronobiologically correct corticosteroid therapy seeks the best compromise
between timing for most of the desired and least of the undesired effects. This was the aim in the design of a chronopluricorticoid
drug, with the time specification on its label. The clinical use of this preparation allowed the inferential statistical demonstration
of a rhythmic circadian organization maintained during therapy, while the pharmacological results gained were similar to those
obtained by the conventional administration of larger doses of corticoids.
International Journal of Clinical & Laboratory Research 04/1983; 13(2):203-217.
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ABSTRACT: Summary 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 thenormal 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 pressure 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 time. The
authors suggest the introduction of AR in thecurriculum 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. If this is not the case, it may be useful to modify some features of these
rhythms, e.g. by shifting meal times, so as to obtain an optimal therapeutic index.
La Ricerca in Clinica e in Laboratorio 01/1976; 6(3):207-250.
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ABSTRACT: This review provides evidence that the bioengineering community needs to develop cost-effective, fully unobtrusive, truly ambulatory instrumentation for the surveillance of blood pressure and heart rate. With available instrumentation, we document a disease risk syndrome, circadian blood pressure overswinging (CHAT, short for circadian hyper-amplitude-tension). Circadian hyper-amplitude-tension is defined as a week-long overall increase in the circadian amplitude or otherwise-measured circadian variability of blood pressure above a mapped threshold, corresponding to the upper 95% prediction limit of clinically healthy peers of the corresponding gender and age. A consistently reduced heart rate variability, gauged by a circadian standard deviation below the lower 5% prediction limit of peers of the corresponding gender and age, is an index of a separate yet additive major risk, a deficient heart rate variability (DHRV). The circadian amplitude, a measure of the extent of reproducible variability within a day, is obtained by linear curve-fitting, which yields added parameters: a midline-estimating statistic of rhythm, the MESOR (a time structure or chronome-adjusted mean), the circadian acrophase, a measure of timing of overall high values recurring in each cycle, and the amplitudes and acrophases of the 12-hour (and higher order) harmonic(s) of the circadian variation that, with the characteristics of the fundamental 24-hour component, describe the circadian waveform. The MESOR is a more precise and more accurate estimate of location than the arithmetic mean. The major risks associated with CHAT and/or DHRV have been documented by measurements of blood pressure and heart rate at 1-hour or shorter intervals for 48 hours on populations of several hundred people, but these risks are to be assessed in a 7-day/24-hour record in individuals before a physical examination, for the following reasons. (1) The average derived from an around-the-clock series of blood pressure measurements, computed as its MESOR, the proven etiopathogenetic factor of catastrophic vascular disease, can be above chronobiologic as well as World Health Organization limits for 5 days or longer and can be satisfactory for months thereafter, as validated by continued automatic monitoring. The MESOR can be interpreted in light of clock-hour-, gender-, and age-specified reference limits and thus can be more reliably estimated with a systematic account of major sources of variability than by casual time-unspecified spot checks (that conventionally are interpreted by a fixed and, thus, rhythm, gender-, and age-ignoring limit). With spot checks, in a diagnostically critical range of "borderline" blood pressures, an inference can depend on the clock-hour of the measurement, usually providing a diagnosis of normotension in the morning and of hypertension in the afternoon (for the same diurnally active, nocturnally resting patient!). Long-term treatment must not be based upon the possibility of an afternoon vs a morning appointment. Moreover, the conventional approach will necessarily miss cases of CHAT that are not accompanied by MESOR hypertension. (2) Circadian hyper-amplitude-tension indicates a greater risk for stroke than does an increase in the around-the-clock average blood pressure (above 130/80 mm Hg) or old age, whereas (3) CHAT can be asymptomatic, as can MESOR hyptertension. (4) Deficient heart rate variability, the fall below a threshold of the circadian standard deviation of heart rate, an entity in its own right, is also a chronome alteration of heart rate variability (CAHRV). Deficient heart rate variability can be present together with CHAT, doubling the relative risk of morbid events. In each case--either combined with CHAT or as an isolated CAHRV--a DHRV constitutes an independent diagnostic assessment provided as a dividend by current blood pressure monitors that should be kept in future instrumentation designs. CHAT and DHRV can be screened by systematic focus on variability, preferably by the use of automatic instrumentation and analyses, which are both available (affordably) for research in actual practice, in conjunction with the Halberg Chronobiology Center at the University of Minnesota.
Biomedical Instrumentation & Technology 36(2):89-122.
Biomedical Instrumentation & Technology 36(3):183-97.