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About-weekly variations in nocturia
• ELSEVIER
Biomedicine & Pharmacotherapy58 (2004) S140-S144
BIOMEDICINE PHARMACOTH ERAPY
www.elsevier.com/locate/hiopha
About-weekly variations in nocturia Germaine Corndlissen a,*, David E. Axelrod b, Franz Halberg a ~Halberg Chronobiology Center, Universtity of Minnesota, MMC 8609, 420 Delaware St. S.E., Minneapolis, MN 55455, USA bDepartment of Genetics and The Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway NJ 08854, USA
Abstract The aim of this study was to assess components of variation in nocturia and to determine any putative geomagnetic influence. A 54-year old man with benign prostatic hyperplasia had recorded for about 4 years the number of times he awoke each night to urinate. The data have been reanalyzed for chronomics, the mapping of time structures (chronomes), involving the computation of least squares spectra of the urinary record and of environmental variables recorded during the same 4-year span. In addition to the previously reported monthly variation, other periodicities have been documented, including two separate components with periods of one week and of a near-week. The precise 7-day period may be a mainly exogenous resonance with external influences such as a weekly social schedule, whereas the near-week may be a partial resonance with natural changes in geomagnetics, reflecting in part changes in other non-photic natural environmental factors. © 2004 Elsevier SAS. All rights reserved. Keywords: Benignprostatic hyperplasia; Chronomics;Circaseptan; Geomagneticactivity;Nocturia
1. Introduction
2. Subject and methods
Urine volume used in diagnostics [ 1], is characterized by prominent about-yearly, about-monthly, about-weekly and about-daily changes [2], among a host of urinary variables, which have been considered as markers for optimizing the scheduling of cancer therapy [3]. A similar approach could be followed for the treatment of benign prostatic hyperplasia. The accuracy of a diagnosis of this condition, as already suggested in relation to the circadian rhythm [4], could be further improved by the consideration of other periodic components characterizing uroflowmetry and/or the severity of symptoms. Moreover, the same time structure may also shed new light on putative physical environmental factors influencing urine volume. Because weekly rhythms had previously been reported in urine volume, we surmised that a weekly rhythm might also occur in nocturia. The availability of a four-year record of the number of times that a man with benign prostatic hyperplasia awoke each night with the urge to urinate provided the opportunity to test this hypothesis.
The symptoms that led to the diagnosis of benign prostatic hyperplasia at 54 years of age were previously reported [5]. In part, they include the following: digital rectal examination, urodynamics, sonogram, and prostate specific antigen. This report is not based on new symptoms but on reanalysis of the record, which gives new insights to the variation of the symptoms with time.
*Correspondingauthor. E-mail address: [email protected](G Com~lissen). © 2004 Elsevier SAS. Tous droits rdserv~s.
The reanalyzed data [5] consist of the number of times that a man with benign prostatic hyperplasia, 54-year old at the start of recording, awoke each night with the urge to urinate. The 1549 values ranging from 0 to 4 were recorded during the span from 4 October 1994 to 30 December 1998. A least squares spectrum was calculated by cosinor for these data and for the daily values of the geomagnetic index Kp (http: //www.sec.noaa.gov/Data/Geomag.html) recorded during the same span. The cosinor method consists of the separate least squares fit of cosine curves with fixed frequencies [6] ranging here from 1 cycle in 4 years to 1 cycle in 3 days. Major anticipated components were further resolved nonlinearly [6], with the period considered as an added parameter in the model. Given a trial period corresponding to the spectral peak in the linear least squares spectrum,
G. Corn6lissen et a l . / Biomedicine & Pharmacotherapy 58 (2004) S140-S144
S141
Table 1. Major periods of nocturia a n d g e o m a g n e t i c activity* Least Squares Spectrum of Nocturia in 54-year old Man Diagnosed with Benign Prostatic Hyperplasia
................. i~'~)
0.16
.......................
~
Circatrigintan
'7= 0.12
~0.16
[
Pefied
~
(7 days and .6.87 days)
.
.
.
.
ii!(~:~
...............:i~,~ [ ...........
-
1
=
......................
8
....
5~:;~ N ~ ;
.................
3~.~
........................ .............. ':
~:~)
~
(9~
.
.
.
.
.
.
.
c~) ...................... .
.
.
.
.
.
.
........................
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.
.
.
.
.
.
.
.
.
o i ~
. .............
@ : ~ i ~ i :s; .......... i~o;oi o:z~i ................
.............. ................... [
Amplitude
....................
.............
..... ~~i
.............
Period
~9~o,~ c D ........................
. ~
.........
Kp
AmjJilude
.....................
Circaseptan
Circannual
0,14
~ . .......................... Noctu~a
Tria Perod
(]#:3i
~:3i
. . . . . . . ....... ..................... ~ ~9i 5:42j ..............
I
0,06 685 ~
687
0.11
6879
.............:..~....~.~9 . .................... s:~), ....................... ...........i~:~ ~:~i.............. ~~:~ .................... i..........
I i
.....................i
Assessedconcomlttant[
0
20
40
60
80
100
~
014
. o~9~ . . .....................~:~ _
....................................... .........
.....: ................
120
Frequency (cycles in 52 weeks)
Fig. 1. Anticipated spectral peaks resolved with their uncertainties by linear-nonlinear rhythmometry (see text). In particular, two separate components in the circaseptan range deserve further study. Their relative prominence, gauged by the amplitude difference in nocturia, may be aligned with a similar difference in geomagnetic activity [10,11]. The 6.87-day period is similar to the natural geomagnetic activity and the 7-day period is probably anthropogenic [19], yet in each case there is only a frequency and no phase synchronization, pointing to resonance without phase lock-in.
point and 95% confidence intervals are derived for the period, as well as for the MESOR (time structure or chronome-adjusted mean value), the amplitude (half the extent of predictable change within a cycle) and the acrophase (timing of overall high values recurring in each cycle) of the tested spectral component.
*CI: Confidence interval. Although the 95% CIs of the circannual periods of nocturia and Kp partly overlap, the behavior of the two variables differs in that for nocturia, the period is not statistically significantly different from one year, but for Kp it is statistically significantly longer than one year (when series longer than 4 years are analyzed). The difference in behavior also related to the fact that nocturia is characterized primarily by an aboutyearly variation, whereas Kp has a much more prominent half-yearly variation, which is not detected for nocturia.
The approximately monthly period, previously reported [5], is detected as a period of 26.2 days. A period of approximately a year is also detected in the original data and a period of 1.33 years is found to characterize changes in relative prominence of the 7-day component assessed over consecutive weeks as the percentage rhythm (R2).
4. Discussion 3. Results
The cyclic variation of the severity of nocturia is displayed in Fig. 1. There are two distinct statistically significant major periods of about a week (circaseptan), one of about a month (circatrigintan), and one of about a year (circannual). The numerical data are summarized in Table 1. There are also minor (smaller amplitude) peaks of longer and shorter periods, perhaps harmonics and subharmonics. The weekly variation is resolved into two separate components, one slightly shorter and the other not statistically significantly different from 7 days (6.869 and 7.007 days, respectively). The weekly period was confirmed by Fourier analysis [5], which makes no a priori assumptions of period length during analysis. Fourier analysis also detected two components (6.85 and 7.01 days) to the weekly variation. The 7-day component seems to be synchronized with the weekly calendar (e.g. higher on weekends) when the entire four-year series is analyzed (Fig. 2a). Fig. 2b indicates, however, that the 7-day component is not always higher on weekends: whereas higher values are found on weekends during some times of the year (January), higher values may also be found during the middle of the week at other times of the year (June).
About-weekly and yearly periods of intensity of nocturia (number of times a man awakened with the urge to urinate) have been discovered, and an approximately monthly period previously reported has been confirmed by a different method of analysis. There are several possible m e c h a n i s m s that could account for the physiological weekly, monthly, yearly and 1.33-yearly periods. The rhythms may be endogenous or may be resonating with, if not coupled to one or multiple external signal(s). Further evidence for endogenous 7-day physiological periods [3] is provided, i.a. by Hiibner's studies [7] of the unilaterally nephrectomized rat, showing prominent about 7-day variations in DNA labeling and mitosis, and by many other examples of single stimulus amplification (induction?) of circaseptans [3]. Further evidence is provided by periods deviating slightly but statistically significantly from exactly 7 days for a number of urinary variables, notably the excretion of 17-ketosteroids of a healthy man for the last 3 years of a 15-year record, while his urine volume remained 7-day synchronized with a strict 7-day living routine (after the self-administration of a large dose of testosterone) [8]. These results led one of us (FH) to coin the term 'circaseptan' to indicate that an about-weekly rhythm may be built-in just like the circadian rhythm, for which he originally found
S142
G. Corn#lissen et al. / Biomedicine & Pharmacotherapy 58 (2004) S140-S144
Circaseptan Patterns of Nocturia in 54-year old Man Diagnosed with Benign Prostatic Hyperplasia
Differing Patterns of Nocturia at Different Times of Year Reveal More Than a Weekend Effect*
g2~3: January
Mean + SE
~,
Z8 F='L948 P=0.079 2A=0.57 P=0.O10
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~= 1.7 - : F=4,021; P<0:001
.~_ t:6
1.3-
)
24 4 8
Z2
96
i20 1~
z
168
1.o
SUN
Time (ho:ursi 0 = OOiO0 on sunday)
MON
TUE
WED
THU
FRI
SAT
Time (Day of Week)
z3~
z~2. 1,: 2,0-
June 2.8.
F=2.046 2=0065
-~ Z2
o z OI. 9 .~!18
T
'*~ '1.9 4
~ i:7
F:3.253 P=0.004
O 0 23;5 47~ 70"7 94i2 ii7"814t 3 16429
=
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o 1.3 1.0
SUN
MON
TUE
WED
THU
FRI
&a,T
Tim~ (Day of Week) * Resulting in part from the interaction of at least two seoarate circsseDtan components
b Fig. 2. (a) Circaseptan patterns of nocturia in 54-year old man diagnosed with benign prostatic hyperplasia. Plexograms, obtained by stacking the nocturia data covering about 4 years over a single idealized cycle for each ciraseptan period (168 hours=7.00 days, top; 164.8 hours=6.87 days, bottom). One-way analyses of variance (testing for equality of means) validate each circaseptan component resolved by linear-nonlinear rhythmometry. The 7-day period (top) shows higher activity on Sundays and Saturdays, and is consistent with differences in weekend and workweek schedules. (b) Differing patterns of nocturia at different times of year reveal more than a weekend effect*. Plexograms determined for specific times of the year, January (top) and June (bottom), rather than during the entire 4 years, indicate that the 7-day pattern may change, with high values occurring sometimes (June) on a work day rather than on the weekend (January). Differences in weekly pattern may be contributed to by the presence of a second near-week component. Results from one-way analyses of variance and from the single cosinor are shown, the latter as double amplitudes (extent of predictable change within a cycle; dashed curves).
the period to differ slightly but statistically significantly from precisely 24 hours, like an uncoupled oscillator or the beating of the heart in vitro after all nervous connections are severed [9]. There is also the precedent of the presence of both a 7-day synchronized and a 'free-running'component with a period slightly shorter than 7 days in a 25-month record of geomagnetic Pc pulsations recorded in Antarctica, some 600 km away from the closest habitation [10]. The near but not precise 7-day period suggests a possible influence of natural non-photic solar effects, mediated via changes in geomagnetic disturbances [11]. The precise 7-day component may be a gauge of global magnetic pollution reaching the remote locally unpolluted Antarctic stand-alone magnetometer. Among the possible external signals for the weekly variation in nocturia is the weekly variation in activity between the weekend and the work days [3]. Although nocturia is
characterized by a 7-day component resembling the social week, the presence of a second near-week component influences the 7-day pattern, so that the phase of nocturia along the scale of the week differs e.g. between the months of January and June. It is thus unlikely that the weekly variation in social activity alone suffices to account for the weekly variation in nocturia. Moreover, since in the geomagnetic index Kp a similar pattern was not found, any geomagnetic pull of the subject's nocturia may influence only the frequency and not the phase, a further argument for the resonance of an endogenous component, rather than solely an environmental effect. This finding qualifies a possible direct effect of the nearweekly variation in geomagnetic activity [11] upon nocturia. Table 1 lists the periods found in nocturia and in intensity changes of the index of geomagnetic activity, Kp. There are similar weekly and monthly periods for variations in pla-
G. Corndlissen et al. / Biomedicine & Pharmacotherapy 58 (2004) S140-S144
Least Squares Spectra of Nocturla and Kp I
--Nocturia
. . . . Kp
0.20
~
702 ~ (700;704) 0.16
days
|
0.12
/'
t 0.t8
688 (688:690) da~/s
,, 701 '~' (699; 702) ' / il days w 687 , :685; 8 sg)
0.14
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,0.10 3
'~
'
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i
0,08
/ 0.04
t: ~"',,v/ J \
f
,~
\
v
.0.04 - 0.02
O,OO 50
0.00 51
52
53
54
55
Frequency (cycles in 52 weeks)
Fig. 3. Similarity in the circaseptan range of spectra on nocturia and the planetary geomagnetic index Kp, both with more than a single about 7-day component. One component in nocturia corresponds to the social week. It is almost certainly societal, of anthropogenic origin. It is close to a spectral peak for the geomagnetic index Kp, which is characterized by a period slightly but statistically significantly longer than precisely 7 days (52 cycles in 52 weeks, vertical line), as gauged by its 95% confidence interval. The next peak to the right corresponds to a component with a period of 6.87 (nocturia) or 6.88 (Kp) days, also resolved by nonlinear least squares. The about 6.88-day component in Kp, albeit wobbly, is almost certainly natural environmental, as reported earlier [11,19], and may pull, if not synchronize, a built-in component of similar period length in nocturia.
S143
elements of time structures shared between physiology and physics. About 1.3-year cycles reported by Richardson [15] and Mursula and Zieger [ 16] to characterize changes in solar wind speed measured by satellites, have indeed been found in biota, notably in the case of longitudinal series of blood pressure and heart rate covering 6 to 37 years [17,18]. Whatever the mechanism(s) causing the variation in nocturia, the knowledge that symptoms of nocturia are not constaut over time, but vary periodically with time, could be used to improve diagnosis and assessment of therapy. Chronomics [11,19], as a new science on an old topic, provides new transdisciplinary information with basic and eventually clinical applications, for instance for the optimization of treatment timing (chronotherapy), as discussed for the case of cancer chronotherapy [3]. Circaseptan timing can account for, or at least contribute to the difference between inhibiting and enhancing a malignant growth [3,20].
5. Acknowledgments Support for this study was provided by the US National Institutes of Health (GM-13981), the University of Minnesota Supercomputing Institute, and the Dr h.c. (mult.) Earl E. Bakken fund.
netary geomagnetic activity and variations in nocturia (Fig. 3). Also, there are two weekly periods for both geomagnetic activity and nocturia. These similarities are not sufficient, however, to conclude that there is a cause and effect relationship between the variation in geomagnetic activity and the variation in nocturia. Such a conclusion would require independent evidence pointing to a mechanism through which nocturia could be influenced by geomagnetic fields. There is already evidence that humans can respond to changes in geomagnetic activity, with or without 60-Hz magnetic fields, e.g. in terms of the amount of overnight urinary excretion of a melatonin metabolite [12]. Additional evidence for human response to geomagnetic storms has recently been reviewed [13]. It has also been conclusively shown that birds detect geomagnetic fields and use them, together with other clues, for orientation [ 14].
References
Among the possible external signals for monthly rhythms of nocturia could be the period of menstruation of the man's wife [5]. Another possibility is that the monthly nocturia is responding to the monthly period in geomagnetic activity, as described above. A putative influence of geomagnetics on nocturia, as such or as a reflection of the influence of other non-photic environmental factors, is supported by evidence at multiple frequencies, as separate signatures of a global phenomenon. Apart from major about-weekly and aboutmonthly changes in nocturia coinciding with changes in geomagnetics, the about 1.3-year modulation of the circaseptan prominence of nocturia is another sign of matching
[6]
[1]
[2]
[3] [4]
[5]
[7]
[8]
[9]
McConnel JD. Epidemiology, etiology, pathophysiology, and diagnosis of benign prostatic hyperplasia. In: Walsh PC, Retik AB, Vaughan E, et al., Eds. Campbell's urology, 7th Ed. Philadelphia: W.B. Saunders; 1998. p. 1429-52. Sothern RB, Simpson H, Leach C, Nelson WL, Halberg F. Individually assessable human circadian, circaseptan and circannual urinary rhythms (with temporal compacting and editing procedures), In: Haiberg F, Scheving LE, Powell EW, Hayes DK, Eds. Proc. XIII Int. Conf. Int. Soc. Chronobiology, Pavia, Italy, Sept. 4-7, 1977. Milan: I1Ponte; 1981. p. 363-71. Halberg F. The week in phylogeny and ontogeny: opportunities for oncology. In vivo 1995;9:269-78. Golomb J, Lindner A, Siegel Y, Korczak D. Variability and circadian changes in home uroflowmetry in patients with benign prostatic hyperplasia compared to normal controls. J Urol 1992; 147:1044-7. Axelrod DE. A monthly period of symptoms associated with benign prostatic hyperplasia. Urology 2000;55:436iv-436vi. Corn~lissen G, Halberg F. Chronomedicine. In: Armitage P, Colton T, Eds. Encyclopedia of biostatistics, vol. 1. Chichester, UK: John Wiley & Sons Ltd; 1998. p. 642-9. Htibner K. Kompensatorische Hypertrophic, Wachstum und Regeneration der Rattenniere. Ergebnisse der allgemeineu Pathologic und pathologischen Anatomic 1967; 100:1-80. Halberg F, Engeli M, Hamburger C, Hillman D. Spectral resolution of low-frequency, small-amplitude rhythms in excreted 17-ketosteroid; probable androgen induced circaseptan desynchronization. Acta Endocrinol (Kbh) 1965;103(Suppl.):5-54. Halberg F, Corn61issen G, Katinas G, Syutkina EV, Sothern RB, Zaslavskaya R, et al. Transdisciplinary unifying implications of circadian findings in the 1950s. J Circad Rhythms 2003;1:2. http:// www.JCircadianRhythms.com/content/pdf/1740-3391/l/2.pdf
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G. Corn~lissen et al./Biomedicine & Pharmacotherapy 58 (2004) S140-S144
[10] Corn61issen G, Engebretson M, Johnson D, Otsuka K, Burioka N, Posch J, et al. The week, inherited in neonatal human twins, found also in geomagnetic pulsations in isolated Antarctica. Biomed Pharmacother 2001:55(Suppl. 1):32-50. [11] Corn61issen G, Hillman D, Katinas GS, Rapoport S, Breus TK, Otsuka K, et al. Geomagnetics and society interact in weekly and broader multiseptans underlying health and environmental integrity. Biomed Pharmacother 2002;56(Suppl. 2):$319-26. [12] Burch JB, Reif JS, Yost MG. Geomagnetic disturbances are associated with reduced nocturnal excretion of a melatonin metabolite in humans, Neurosci Lett 1999;266:209-12. [13] Corn61issen G, Halberg F, Breus T, Syutkina EV, Baevsky R, Weydahl A, et al. Non-photic associations of heart rate variability and myocardial infarction. J Atmos Solar-Terr Phys 2002;64:707-20. [14] Wiltschko, Wiltschko R. Magnetic orientation in birds. In: Johnston RF, Ed. Current ornithology, vol. 5. 1988. p. 67-121. [15] Richardson JD, Paularena KI, Belcher JW, Lazarus AJ. Solar wind oscillations with a 1.3-yearperiod. Geophys Res Lett 1994;21:1559~0.
[16] Mursula K, Zieger B. The 1.3-year variation in solar wind speed and geomagnetic activity. Adv Space Res 2000;25:1939-42. [17] Halberg F, Corn61issen G, Schack B. Self-experimentation on chrohomes, time structures; chronomics for health surveillance and science: also transdisciplinary civic duty? Behav Brain Sci http:// www.bbsonline.org/Preprints/Roberts/Commentators/Halberg.htmi [18] Corn61issen G, Masalov A, Halberg F, Richardson JD, Katinas GS, Sothern RB, et al. 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? Hum Physiol 2004;30(2):86-92. [19] Halberg F, Corn61issen G, Bingham C, Hillman D, Katinas G, Sampson M, et al. Season's appreciations 2001. Neuroendocrinol Lett 2002;23:170-87. [20] Halberg F, Corn61issen G, Wang ZR, Wan C, Ulmer W, Katinas G, et al. Chronomics: circadian and circaseptan timing of radiotherapy, drugs, calories, perhaps nutriceuticals and beyond. J Exp Ther Oncol 2003 ;3:223~50.
Biomedicine & Pharmacotherapy58 (2004) S140-S144
BIOMEDICINE PHARMACOTH ERAPY
www.elsevier.com/locate/hiopha
About-weekly variations in nocturia Germaine Corndlissen a,*, David E. Axelrod b, Franz Halberg a ~Halberg Chronobiology Center, Universtity of Minnesota, MMC 8609, 420 Delaware St. S.E., Minneapolis, MN 55455, USA bDepartment of Genetics and The Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway NJ 08854, USA
Abstract The aim of this study was to assess components of variation in nocturia and to determine any putative geomagnetic influence. A 54-year old man with benign prostatic hyperplasia had recorded for about 4 years the number of times he awoke each night to urinate. The data have been reanalyzed for chronomics, the mapping of time structures (chronomes), involving the computation of least squares spectra of the urinary record and of environmental variables recorded during the same 4-year span. In addition to the previously reported monthly variation, other periodicities have been documented, including two separate components with periods of one week and of a near-week. The precise 7-day period may be a mainly exogenous resonance with external influences such as a weekly social schedule, whereas the near-week may be a partial resonance with natural changes in geomagnetics, reflecting in part changes in other non-photic natural environmental factors. © 2004 Elsevier SAS. All rights reserved. Keywords: Benignprostatic hyperplasia; Chronomics;Circaseptan; Geomagneticactivity;Nocturia
1. Introduction
2. Subject and methods
Urine volume used in diagnostics [ 1], is characterized by prominent about-yearly, about-monthly, about-weekly and about-daily changes [2], among a host of urinary variables, which have been considered as markers for optimizing the scheduling of cancer therapy [3]. A similar approach could be followed for the treatment of benign prostatic hyperplasia. The accuracy of a diagnosis of this condition, as already suggested in relation to the circadian rhythm [4], could be further improved by the consideration of other periodic components characterizing uroflowmetry and/or the severity of symptoms. Moreover, the same time structure may also shed new light on putative physical environmental factors influencing urine volume. Because weekly rhythms had previously been reported in urine volume, we surmised that a weekly rhythm might also occur in nocturia. The availability of a four-year record of the number of times that a man with benign prostatic hyperplasia awoke each night with the urge to urinate provided the opportunity to test this hypothesis.
The symptoms that led to the diagnosis of benign prostatic hyperplasia at 54 years of age were previously reported [5]. In part, they include the following: digital rectal examination, urodynamics, sonogram, and prostate specific antigen. This report is not based on new symptoms but on reanalysis of the record, which gives new insights to the variation of the symptoms with time.
*Correspondingauthor. E-mail address: [email protected](G Com~lissen). © 2004 Elsevier SAS. Tous droits rdserv~s.
The reanalyzed data [5] consist of the number of times that a man with benign prostatic hyperplasia, 54-year old at the start of recording, awoke each night with the urge to urinate. The 1549 values ranging from 0 to 4 were recorded during the span from 4 October 1994 to 30 December 1998. A least squares spectrum was calculated by cosinor for these data and for the daily values of the geomagnetic index Kp (http: //www.sec.noaa.gov/Data/Geomag.html) recorded during the same span. The cosinor method consists of the separate least squares fit of cosine curves with fixed frequencies [6] ranging here from 1 cycle in 4 years to 1 cycle in 3 days. Major anticipated components were further resolved nonlinearly [6], with the period considered as an added parameter in the model. Given a trial period corresponding to the spectral peak in the linear least squares spectrum,
G. Corn6lissen et a l . / Biomedicine & Pharmacotherapy 58 (2004) S140-S144
S141
Table 1. Major periods of nocturia a n d g e o m a g n e t i c activity* Least Squares Spectrum of Nocturia in 54-year old Man Diagnosed with Benign Prostatic Hyperplasia
................. i~'~)
0.16
.......................
~
Circatrigintan
'7= 0.12
~0.16
[
Pefied
~
(7 days and .6.87 days)
.
.
.
.
ii!(~:~
...............:i~,~ [ ...........
-
1
=
......................
8
....
5~:;~ N ~ ;
.................
3~.~
........................ .............. ':
~:~)
~
(9~
.
.
.
.
.
.
.
c~) ...................... .
.
.
.
.
.
.
........................
.
.
.
.
.
.
.
.
.
.
o i ~
. .............
@ : ~ i ~ i :s; .......... i~o;oi o:z~i ................
.............. ................... [
Amplitude
....................
.............
..... ~~i
.............
Period
~9~o,~ c D ........................
. ~
.........
Kp
AmjJilude
.....................
Circaseptan
Circannual
0,14
~ . .......................... Noctu~a
Tria Perod
(]#:3i
~:3i
. . . . . . . ....... ..................... ~ ~9i 5:42j ..............
I
0,06 685 ~
687
0.11
6879
.............:..~....~.~9 . .................... s:~), ....................... ...........i~:~ ~:~i.............. ~~:~ .................... i..........
I i
.....................i
Assessedconcomlttant[
0
20
40
60
80
100
~
014
. o~9~ . . .....................~:~ _
....................................... .........
.....: ................
120
Frequency (cycles in 52 weeks)
Fig. 1. Anticipated spectral peaks resolved with their uncertainties by linear-nonlinear rhythmometry (see text). In particular, two separate components in the circaseptan range deserve further study. Their relative prominence, gauged by the amplitude difference in nocturia, may be aligned with a similar difference in geomagnetic activity [10,11]. The 6.87-day period is similar to the natural geomagnetic activity and the 7-day period is probably anthropogenic [19], yet in each case there is only a frequency and no phase synchronization, pointing to resonance without phase lock-in.
point and 95% confidence intervals are derived for the period, as well as for the MESOR (time structure or chronome-adjusted mean value), the amplitude (half the extent of predictable change within a cycle) and the acrophase (timing of overall high values recurring in each cycle) of the tested spectral component.
*CI: Confidence interval. Although the 95% CIs of the circannual periods of nocturia and Kp partly overlap, the behavior of the two variables differs in that for nocturia, the period is not statistically significantly different from one year, but for Kp it is statistically significantly longer than one year (when series longer than 4 years are analyzed). The difference in behavior also related to the fact that nocturia is characterized primarily by an aboutyearly variation, whereas Kp has a much more prominent half-yearly variation, which is not detected for nocturia.
The approximately monthly period, previously reported [5], is detected as a period of 26.2 days. A period of approximately a year is also detected in the original data and a period of 1.33 years is found to characterize changes in relative prominence of the 7-day component assessed over consecutive weeks as the percentage rhythm (R2).
4. Discussion 3. Results
The cyclic variation of the severity of nocturia is displayed in Fig. 1. There are two distinct statistically significant major periods of about a week (circaseptan), one of about a month (circatrigintan), and one of about a year (circannual). The numerical data are summarized in Table 1. There are also minor (smaller amplitude) peaks of longer and shorter periods, perhaps harmonics and subharmonics. The weekly variation is resolved into two separate components, one slightly shorter and the other not statistically significantly different from 7 days (6.869 and 7.007 days, respectively). The weekly period was confirmed by Fourier analysis [5], which makes no a priori assumptions of period length during analysis. Fourier analysis also detected two components (6.85 and 7.01 days) to the weekly variation. The 7-day component seems to be synchronized with the weekly calendar (e.g. higher on weekends) when the entire four-year series is analyzed (Fig. 2a). Fig. 2b indicates, however, that the 7-day component is not always higher on weekends: whereas higher values are found on weekends during some times of the year (January), higher values may also be found during the middle of the week at other times of the year (June).
About-weekly and yearly periods of intensity of nocturia (number of times a man awakened with the urge to urinate) have been discovered, and an approximately monthly period previously reported has been confirmed by a different method of analysis. There are several possible m e c h a n i s m s that could account for the physiological weekly, monthly, yearly and 1.33-yearly periods. The rhythms may be endogenous or may be resonating with, if not coupled to one or multiple external signal(s). Further evidence for endogenous 7-day physiological periods [3] is provided, i.a. by Hiibner's studies [7] of the unilaterally nephrectomized rat, showing prominent about 7-day variations in DNA labeling and mitosis, and by many other examples of single stimulus amplification (induction?) of circaseptans [3]. Further evidence is provided by periods deviating slightly but statistically significantly from exactly 7 days for a number of urinary variables, notably the excretion of 17-ketosteroids of a healthy man for the last 3 years of a 15-year record, while his urine volume remained 7-day synchronized with a strict 7-day living routine (after the self-administration of a large dose of testosterone) [8]. These results led one of us (FH) to coin the term 'circaseptan' to indicate that an about-weekly rhythm may be built-in just like the circadian rhythm, for which he originally found
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Circaseptan Patterns of Nocturia in 54-year old Man Diagnosed with Benign Prostatic Hyperplasia
Differing Patterns of Nocturia at Different Times of Year Reveal More Than a Weekend Effect*
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b Fig. 2. (a) Circaseptan patterns of nocturia in 54-year old man diagnosed with benign prostatic hyperplasia. Plexograms, obtained by stacking the nocturia data covering about 4 years over a single idealized cycle for each ciraseptan period (168 hours=7.00 days, top; 164.8 hours=6.87 days, bottom). One-way analyses of variance (testing for equality of means) validate each circaseptan component resolved by linear-nonlinear rhythmometry. The 7-day period (top) shows higher activity on Sundays and Saturdays, and is consistent with differences in weekend and workweek schedules. (b) Differing patterns of nocturia at different times of year reveal more than a weekend effect*. Plexograms determined for specific times of the year, January (top) and June (bottom), rather than during the entire 4 years, indicate that the 7-day pattern may change, with high values occurring sometimes (June) on a work day rather than on the weekend (January). Differences in weekly pattern may be contributed to by the presence of a second near-week component. Results from one-way analyses of variance and from the single cosinor are shown, the latter as double amplitudes (extent of predictable change within a cycle; dashed curves).
the period to differ slightly but statistically significantly from precisely 24 hours, like an uncoupled oscillator or the beating of the heart in vitro after all nervous connections are severed [9]. There is also the precedent of the presence of both a 7-day synchronized and a 'free-running'component with a period slightly shorter than 7 days in a 25-month record of geomagnetic Pc pulsations recorded in Antarctica, some 600 km away from the closest habitation [10]. The near but not precise 7-day period suggests a possible influence of natural non-photic solar effects, mediated via changes in geomagnetic disturbances [11]. The precise 7-day component may be a gauge of global magnetic pollution reaching the remote locally unpolluted Antarctic stand-alone magnetometer. Among the possible external signals for the weekly variation in nocturia is the weekly variation in activity between the weekend and the work days [3]. Although nocturia is
characterized by a 7-day component resembling the social week, the presence of a second near-week component influences the 7-day pattern, so that the phase of nocturia along the scale of the week differs e.g. between the months of January and June. It is thus unlikely that the weekly variation in social activity alone suffices to account for the weekly variation in nocturia. Moreover, since in the geomagnetic index Kp a similar pattern was not found, any geomagnetic pull of the subject's nocturia may influence only the frequency and not the phase, a further argument for the resonance of an endogenous component, rather than solely an environmental effect. This finding qualifies a possible direct effect of the nearweekly variation in geomagnetic activity [11] upon nocturia. Table 1 lists the periods found in nocturia and in intensity changes of the index of geomagnetic activity, Kp. There are similar weekly and monthly periods for variations in pla-
G. Corndlissen et al. / Biomedicine & Pharmacotherapy 58 (2004) S140-S144
Least Squares Spectra of Nocturla and Kp I
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Fig. 3. Similarity in the circaseptan range of spectra on nocturia and the planetary geomagnetic index Kp, both with more than a single about 7-day component. One component in nocturia corresponds to the social week. It is almost certainly societal, of anthropogenic origin. It is close to a spectral peak for the geomagnetic index Kp, which is characterized by a period slightly but statistically significantly longer than precisely 7 days (52 cycles in 52 weeks, vertical line), as gauged by its 95% confidence interval. The next peak to the right corresponds to a component with a period of 6.87 (nocturia) or 6.88 (Kp) days, also resolved by nonlinear least squares. The about 6.88-day component in Kp, albeit wobbly, is almost certainly natural environmental, as reported earlier [11,19], and may pull, if not synchronize, a built-in component of similar period length in nocturia.
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elements of time structures shared between physiology and physics. About 1.3-year cycles reported by Richardson [15] and Mursula and Zieger [ 16] to characterize changes in solar wind speed measured by satellites, have indeed been found in biota, notably in the case of longitudinal series of blood pressure and heart rate covering 6 to 37 years [17,18]. Whatever the mechanism(s) causing the variation in nocturia, the knowledge that symptoms of nocturia are not constaut over time, but vary periodically with time, could be used to improve diagnosis and assessment of therapy. Chronomics [11,19], as a new science on an old topic, provides new transdisciplinary information with basic and eventually clinical applications, for instance for the optimization of treatment timing (chronotherapy), as discussed for the case of cancer chronotherapy [3]. Circaseptan timing can account for, or at least contribute to the difference between inhibiting and enhancing a malignant growth [3,20].
5. Acknowledgments Support for this study was provided by the US National Institutes of Health (GM-13981), the University of Minnesota Supercomputing Institute, and the Dr h.c. (mult.) Earl E. Bakken fund.
netary geomagnetic activity and variations in nocturia (Fig. 3). Also, there are two weekly periods for both geomagnetic activity and nocturia. These similarities are not sufficient, however, to conclude that there is a cause and effect relationship between the variation in geomagnetic activity and the variation in nocturia. Such a conclusion would require independent evidence pointing to a mechanism through which nocturia could be influenced by geomagnetic fields. There is already evidence that humans can respond to changes in geomagnetic activity, with or without 60-Hz magnetic fields, e.g. in terms of the amount of overnight urinary excretion of a melatonin metabolite [12]. Additional evidence for human response to geomagnetic storms has recently been reviewed [13]. It has also been conclusively shown that birds detect geomagnetic fields and use them, together with other clues, for orientation [ 14].
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Among the possible external signals for monthly rhythms of nocturia could be the period of menstruation of the man's wife [5]. Another possibility is that the monthly nocturia is responding to the monthly period in geomagnetic activity, as described above. A putative influence of geomagnetics on nocturia, as such or as a reflection of the influence of other non-photic environmental factors, is supported by evidence at multiple frequencies, as separate signatures of a global phenomenon. Apart from major about-weekly and aboutmonthly changes in nocturia coinciding with changes in geomagnetics, the about 1.3-year modulation of the circaseptan prominence of nocturia is another sign of matching
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