Circadian and ultradian extrasystole rhythms in healthy individuals at elevated versus lowland altitudes.

We defined chronobiologic norms for supraventricular and ventricular single extrasystoles (SV and VE, respectively) in healthy older males in lowland areas. The study was extended to higher altitudes, where hypobaric hypoxia was expected to increase extrasystole frequency, while perhaps not changing rhythmicity. In healthy men (lowland n = 37, altitude n = 22), aged 49-72 years, mean numbers of SVs and VEs were counted over a 24-h period. Cosinor regression was used to test the 24-h rhythm and its 2nd-10th harmonics. The resulting approximating function for either extrasystole type includes its point, 95% confidence interval of the mean, and 95% tolerance for single measurement estimates. Separate hourly differences (delta) between altitude and lowland (n = 59) were also analysed. Hourly means were significantly higher in the mountains versus lowland, by +0.8 beats/h on average for SVs, and by +0.9 beats/h for VEs. A relatively rich chronogram for VEs in mountains versus lowland exists. Delta VEs clearly display a 24-h component and its 2nd, 3rd, 4th and 7th harmonics. This results in significantly higher accumulation of VEs around 8.00 a.m., 11.00 a.m. and 3.00 p.m. in the mountains. The increase in extrasystole occurrence in the mountains is probably caused by higher hypobaric hypoxia and resulting sympathetic drive. Healthy men at elevated altitudes show circadian and several ultradian rhythms of single VEs dependent on the hypoxia level. This new methodological approach--evaluating the differences between two locations using delta values--promises to provide deeper insight into the occurrence of premature beats.

500-year periodicity of political instability in the history of ancient Egypt and China. Androgens at work?

UNLABELLED: DISCOVERY: A periodicity of 500 years has been discovered in the political history of ancient Egypt and documented by means of inferential statistics. Periods of chaos and waning of central power (some of them called "intermediate periods") recurred every 500 years. DATA & METHODS: Input for the computation is the mean duration of ruling dynasties calculated per each half century. Fisher's periodogram analysis and Halberg's cosinor regression have been used. A highly significant (p < 0.00002) periodicity of approximately 500 years has been found. Data are taken from two different historians and results for low and middle chronology are being compared. FURTHER RESULTS: Lability of dynastic power in ancient Egypt as well as China between 3000 and 500 B. C. culminated each 500 years synchronously. No local events, confined to Egypt or China alone, can serve as an explanation. The rhythm of "dark ages" seems to continue beyond Egyptian and ancient Chinese history into the modern era and seems to be world-wide. HISTORICAL BACKGROUND: It is a surprising fact, that this periodicity has been known already to the priests of Babylon, who ascribed this to the maleficient influence of god Nergal. The same periodicity has been described by the Chinese philosopher Mencius in the 3rd century B.C. and attributed to the will of tian (heaven). Egyptians elevated their war god Seth every 500 years and European kings assumed masculine nicknames. CONCLUSION: This recurring cultural pattern of aggressiveness and strife resembles overall traits of male psyche or mid-life crisis. We suggest to look for an unknown cosmophysical factor impacting the neuroendocrine system of man by raising the levels of androgens periodically. EXPLANATION HYPOTHESES: Sun impacts global weather on Earth, but there is no known significant periodicity of 500 years in solar activity. The Wheeler weather cycle almost fits the cycle of Egyptian political history. But his cold-dry periods seem to lag behind the periods of social destabilization and hence can not cause them. An alternative view (based on idealistic rather than materialistic presuppositions) is, that periodic long-term shifts of archetypes take place within the collective unconscious of mankind independently of external environment.

Solar activity, revolutions and cultural prime in the history of mankind.

BACKGROUND: Russian astronomer A.L. Tchijevsky published in the twenties of 20th century a study comparing the approximately 11-year cycling of "sunspot activity" and "historical process", analyzed globally since the 5th century B.C. to the 19th century A.D. According to him, phenomena of societal "excitation", as revolutions, occurred synchronously with the solar maxima, and, oppositely, those of peaceful activities of masses, as science and arts, with the solar minima. Recently, Slovak philosopher E. Páles describes periodic fluctuation of historical events in mutually distant geographic areas during more than three millennia. The period lengths, however, are longer, one of the most pronounced being around 500 years. THE QUESTION was therefore posed: does a similar correlation with sunspot activity, as found for 11-year cycles, exist also in the 500-year cycling? MATERIAL AND METHODS: The historical data consisted of two time series concerning revolutions in Europe and China, and of eight time series from activities in science and arts registered from five geographic areas. For the comparison, parallel time series of sunspot (Wolf) numbers, available since IInd century B.C., were constructed. Using periodic regression function, the times of peaking were estimated for each data set. RESULTS: In agreement with Tchijevsky's hypothesis, revolutions culminated near to solar maxima while cultural flourishing usually distinctly near to solar minima. This conclusion is based on the level of statistical significance alpha=0.05. CONCLUSION: Solar impact on geomagnetic field could be one of elucidating mechanisms. Recently, electromagnetic influencing of brain function has been realized artificially.

Cerebral infarction versus solar and geomagnetic activity: a cross-regression study.

BACKGROUND: In the course of occurrence of cerebral infarction, cerebral hemorrhage and subarachnoidal hemorrhage episodes, periodicities resembling those found in the solar and geomagnetic activity were observed by Kovác and Mikulecký in 2005. OBJECTIVES: To investigate putative relationships between two indices of solar activity and one index of geomagnetic activity on one side and the occurrence of cerebral infarction on the other. METHODS: In addition to the 192 monthly cases out of 6100 new cases of cerebral infarction that occurred between January 1989 and December 2004, monthly averages for Wolf numbers, solar flares index and Ap index were included in the analysis. The cross-correlation between each cosmo-geophysical variable on the one hand and the number of new cases of the disease on the other was computed. The quadratic regression with the chosen time delay was also studied using, separately, the Wolf numbers, solar flares and Ap index as the explanatory variable and the number of cases of cerebral infarction as the responding variable. RESULTS: Significantly negative correlation coefficients between the monthly means of the Wolf numbers, of solar flares and of Ap index on the one hand and monthly numbers of new cases of the disease on the other were found for the delays between -6 and +17 months. The cross-regression results for the delay of +5 months (infarction delayed after each cosmo-geophysical variable by 5 months) displayed a linear decrease except for the Wolf numbers where the parabolic decrease of cases was significant. CONCLUSIONS: An increased intensity of the studied cosmo-geophysical parameters appears to be significantly connected with decreased occurrence of cerebral infarctions, and vice versa. This effect seems to last up to 17 months. The results are supported by a few similar findings in the literature. Putative cosmo-biomedical connections warrant further study to verify them in larger samples and longer time scales. If confirmed, their mechanisms should be elucidated.

Familial occurrence of myoclonic epilepsy syndrome and acute intermittent porphyria.

OBJECTIVES: Myoclonic epilepsy (ME) syndrome is not rare in north-eastern Europe; it is also seen in various forms. Familial occurrence of ME syndrome and acute intermittent porphyria (AIP) was observed in three siblings. The following report was aimed the differentiation between co-morbidity of two different disorders or presence the epileptic seizures within the clinical picture of latent AIP. MATERIAL AND METHODS: A case report of three siblings who suffered from seizures, myoclonias, ataxia and minor psychological changes since the age of 8 and 9 years is described in the following report. RESULTS: The clinical picture most resembled that of "Baltic myoclonus" (dentate-rubral degeneration or dyssynergia cerebellaris myoclonica -- Ramsay-Hunt syndrome) with epilepsy and/or a benign form of progressive myoclonic epilepsy (PME). The possibility of juvenile myoclonic epilepsy (JME) and other aetiological factors, as less probable causes of ME syndrome, were considered. After 15 years of the treatment by anti-epileptic drugs in all three siblings, AIP was discovered. CONCLUSION: Our interest lies in the differentiation of co-morbidity of two different disorders or presence of epileptic seizures as the clinical picture of latent AIP. We propose that the AIP attacks were caused by long-term administration of anti-epileptic drugs. At the same time we suggest it is a coincidence that the two independent genetic abnormalities coexist in the subjects (benign form of degenerative cerebral disease and AIP).

Multinucleate cells (MNC) as sensitive semiquantitative biomarkers of the toxic effect after experimental fibrous dust and cigarette smoke inhalation by rats.

Changes in the counts of binucleate (BNC) and multinucleate cells (MNC) in cell mixtures from lung tissue and bronchoalveolar lavage fluid (BALF) as well as in proportions of four types of BALF cells: Alveolar macrophages (AM), lymphocytes, polymorphonuclears (PMN), BNC and in total BALF protein were followed in a study comparing the toxicity of wollastonite with that of amosite asbestos in Fischer 344 rats. Both of the fibrous dusts were inhaled every second day at 30 or 60 mg/m3 air combined with daily exposure to cigarette smoke at 30 mg of total particulate matter (TPM)/m3 air for 1 h. The exposures lasted 175 days. Both, proportions of BNC as well as of MNC in lung cell mixtures rose significantly after exposure to cigarette smoke only. After inhalation of wollastonite the BNC proportions in all except the lower dust exposure group compared to controls showed a significant rise with the maximal factor value of 2.1 in the higher dust plus smoke exposure group. Wollastonite caused only marginal changes in MNC and other inflammation parameters. After inhalation of amosite at comparing to controls the proportion of BNC rose 8 times in the 30 mg/m3 and 11 times in the 60 mg/m3 exposure group, respectively. The effect of smoking was additive. The proportions of MNC were 39 times higher in the 30 mg/m3 and 41 times higher in the 60 mg/m3 amosite exposure group than in controls. In the higher exposure group the effect of smoking was synergic in that the MNC proportion rose about 58 times over control values from 0.05% up to about 3.0% (99% confidence interval--CI = 2.7-3.3%). The other followed inflammation parameters showed the presence of inflammation in the lung. It could be concluded that wollastonite at the same inhalation exposure concentration caused in rats less toxic effects than amosite, and, that the number of MNC, as well as BNC in lung cell mixtures and in BALF may serve as an important semiquantitative biomarker of inflammation.

Seasonality of births and childhood inflammatory bowel disease.

PURPOSE: In some geographical areas, including Slovakia, children with diabetes mellitus type 1 are born more often in summer than in late autumn and winter. Does this also apply to another autoimmune disorder - inflammatory bowel disease - in Slovakia? BASIC PROCEDURES: The month of birth was recorded for 30 boys and 36 girls with Crohn disease and 23 boys and 40 girls with ulcerative colitis. The monthly numbers of births were adapted to the length of the given month, divided by the number of boys or girls born in the whole Slovak children population in the same calendar month in comparable years, transformed to moving averages from three successive values each, and expressed as the fraction of the yearly total, which was equal to 1. According to the null hypothesis, there should be equal probability (1/12) of being born in any month. The significance of departures from this value was evaluated with cosinor regression using two sinusoidal functions with period lengths of 12 and 6 months. The most illustrative measure is the relation of the corridor of 95% confidence for the total approximating function to the midline estimating statistic of rhythm (the mesor) (1/12). Significant departures up or down are recognized as nonoverlapping of the mesor straight line by the confidence corridor. MAIN FINDINGS: These were similar to those reported for childhood diabetes mellitus type 1. In our sample of Crohn disease, the number of births was markedly higher between June and October and lower between December and March. In ulcerative colitis, there was a slight increase between June and August and a decrease between December and February. PRINCIPAL CONCLUSIONS: The seasonal effect on births of children with later childhood-onset Crohn disease is similar to that described for diabetes mellitus type 1, i.e., maximal frequency of births in summer.

Chronobiological aspects of adult-onset Crohn disease.

PURPOSE: To study the time course of Crohn disease and its signs. To compare the results with the world literature and draw conclusions for practice. BASIC PROCEDURES: Fifty-six patients were studied retrospectively: 31 males aged 19-48 years with disease duration 1-8 years, and 25 females aged 21-65 with disease duration 1-13 years. The disease was active (Crohn disease activity index > 150) in 25 patients and inactive in 31. Plasma levels of interleukin-6 (normal upper value 8 pg/ml) were investigated with radioimmunoassay. Bone mineral density was measured as the T-score (normal range between -1 and 0 standard deviations) in the forearm using dual-energy X-ray absorptiometry. The seasonality of births of the patients in relation to the total Slovak population and seasonality of severity of three important disease signs were examined with Halberg cosinor regression. The dependence of the signs on age and duration of disease was evaluated using quadratic regression. Results are presented as 95% confidence intervals (for means) and 95% tolerance intervals (for individuals). The level of statistical significance was set at alpha = 0.05. MAIN FINDINGS: Significant seasonality in births was found: decreased frequency in May-June and increased frequency in September-January. Significant spring elevation of interleukin-6 levels, accompanied by significant spring rise of the disease activity index and by decrease of bone density, is described. Among patients with active disease, interleukin-6 levels significantly increased up to the age of 41 years, whereas linear increase of disease activity during aging was on the borderline level of significance in the same subgroup. No significant age trend was encountered in T-score for either subgroup. The same was true for interleukin-6 and disease activity versus duration. Significant decrease in T-score paralleled disease duration up to seven years in the subgroup with active disease. PRINCIPAL CONCLUSIONS: The course of Crohn disease is influenced by time, including the seasons of the year. However, this does not find full agreement in the world literature, probably because of geographic, socioeconomic and epidemiologic differences, as well as varying approaches in method. In practice, regular monitoring of the time course is necessary in provision of appropriately timed treatment.

Chronoastrobiology: proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and ontogenetic memories.

"Chronoastrobiology: are we at the threshold of a new science? Is there a critical mass for scientific research?" A simple photograph of the planet earth from outer space was one of the greatest contributions of space exploration. It drove home in a glance that human survival depends upon the wobbly dynamics in a thin and fragile skin of water and gas that covers a small globe in a mostly cold and vast universe. This image raised the stakes in understanding our place in that universe, in finding out where we came from and in choosing a path for survival. Since that landmark photograph was taken, new astronomical and biomedical information and growing computer power have been revealing that organic life, including human life, is and has been connected to invisible (non-photic) forces, in that vast universe in some surprising ways. Every cell in our body is bathed in an external and internal environment of fluctuating magnetism. It is becoming clear that the fluctuations are primarily caused by an intimate and systematic interplay between forces within the bowels of the earth--which the great physician and father of magnetism William Gilbert called a 'small magnet'--and the thermonuclear turbulence within the sun, an enormously larger magnet than the earth, acting upon organisms, which are minuscule magnets. It follows and is also increasingly apparent that these external fluctuations in magnetic fields can affect virtually every circuit in the biological machinery to a lesser or greater degree, depending both on the particular biological system and on the particular properties of the magnetic fluctuations. The development of high technology instruments and computer power, already used to visualize the human heart and brain, is furthermore making it obvious that there is a statistically predictable time structure to the fluctuations in the sun's thermonuclear turbulence and thus to its magnetic interactions with the earth's own magnetic field and hence a time structure to the magnetic fields in organisms. Likewise in humans, and in at least those other species that have been studied, computer power has enabled us to discover statistically defined endogenous physiological rhythms and further direct effects that are associated with these invisible geo- and heliomagnetic cycles. Thus, what once might have been dismissed as noise in both magnetic and physiological data does in fact have structure. And we may be at the threshold of understanding the biological and medical meaning and consequences of these patterns and biological-astronomical linkages as well. Structures in time are called chronomes; their mapping in us and around us is called chronomics. The scientific study of chronomes is chronobiology. And the scientific study of all aspects of biology related to the cosmos has been called astrobiology. Hence we may dub the new study of time structures in biology with regard to influences from cosmo- helio- and geomagnetic rhythms chronoastrobiology. It has, of course, been understood for centuries that the movements of the earth in relation to the sun produce seasonal and daily cycles in light energy and that these have had profound effects on the evolution of life. It is now emerging that rhythmic events generated from within the sun itself, as a large turbulent magnet in its own right, can have direct effects upon life on earth. Moreover, comparative studies of diverse species indicate that there have also been ancient evolutionary effects shaping the endogenous chronomic physiological characteristics of life. Thus the rhythms of the sun can affect us not only directly, but also indirectly through the chronomic patterns that solar magnetic rhythms have created within our physiology in the remote past. For example, we can document the direct exogenous effects of given specific solar wind events upon human blood pressure and heart rate. We also have evidence of endogenous internal rhythms in blood pressure and heart rate that are close to but not identical to the period length of rhythms in the solar wind. These were installed genetically by natural selection at some time in the distant geological past. This interpretive model of the data makes the prediction that the internal and external influences on heart rate and blood pressure can reinforce or cancel each other out at different times. A study of extensive clinical and physiological data shows that the interpretive model is robust and that internal and external effects are indeed augmentative at a statistically significant level. Chronoastrobiological studies are contributing to basic science--that is, our understanding is being expanded as we recognize heretofore unelaborated linkages of life to the complex dynamics of the sun, and even to heretofore unelaborated evolutionary phenomena. Once, one might have thought of solar storms as mere transient 'perturbations' to biology, with no lasting importance. Now we are on the brink of understanding that solar turbulences have played a role in shaping endogenous physiological chronomes. There is even documentation for correlations between solar magnetic cycles and psychological swings, eras of belligerence and of certain expressions of sacred or religious feelings. Chronoastrobiology can surely contribute to practical applications as well as to basic science. It can help develop refinements in our ability to live safely in outer space, where for example at the distance of the moon the magnetic influences of the sun will have an effect upon humans unshielded by the earth's native magnetic field. We should be better able to understand these influences as physiological and mechanical challenges, and to improve our estimations of the effects of exposure. Chronoastrobiology moreover holds great promise in broadening our perspectives and powers in medicine and public health right here upon the surface of the earth. Even the potential relevance of chronoastrobiology for practical environmental and agricultural challenges cannot be ruled out at this early stage in our understanding of the apparently ubiquitous effects of magnetism and hence perhaps of solar magnetism on life. The evidence already mentioned that fluctuations in solar magnetism can influence gross clinical phenomena such as rates of strokes and heart attacks, and related cardiovascular variables such as blood pressure and heart rate, should illustrate the point that the door is open to broad studies of clinical implications. The medical value of better understanding magnetic fluctuations as sources of variability in human physiology falls into several categories: 1) The design of improved analytical and experimental controls in medical research. Epidemiological analyses require that the multiple sources causing variability in physiological functions and clinical phenomena be identified and understood as thoroughly as possible, in order to estimate systematic alterations of any one variable. 2) Preventive medicine and the individual patients'care. There are no flat 'baselines', only reference chronomes. Magnetic fluctuations can be shown statistically to exacerbate health problems in some cases. The next step should be to determine whether vulnerable individuals can be identified by individual monitoring. Such vulnerable patients may then discover that they have the option to avoid circumstances associated with anxiety during solar storms, and/or pay special attention to their medication or other treatments. Prehabilitation by self-help can hopefully complement and eventually replace much costly rehabilitation. 3) Basic understanding of human physiological mechanisms. The chronomic organization of physiology implies a much more subtle dynamic integration of functions than is generally appreciated. All three categories of medical value in turn pertain to the challenges for space science of exploring and colonizing the solar system. The earth's native magnetic field acts like an enormous umbrella that offers considerable protection on the surface from harsh solar winds of charged particles and magnetic fluxes. The umbrella becomes weaker with distance from the earth and will offer little protection for humans, other animals, and plants in colonies on the surface of the moon or beyond. Thus it is important before more distant colonization is planned or implemented to better understand those magnetism-related biological- solar interactions that now can be studied conveniently on earth. (ABSTRACT TRUNCATED)

Periodic emergence of great poets in the history of Arabia & Persia, China and Japan.

A periodicity of about 500 years has been discovered in the history of poetry and documented by means of inferential statistics. Great poets of Arabia, Persia, China and Japan emerged periodically every 500 years. Moreover, the waves of poetic creativeness in the West and in the East have been synchronous for the last 3000 years. It is a surprising fact, that this periodicity has been known already before 800 B.C. to the priests of Babylon, who ascribed it to the influence of goddess Inanna. A set of psychological symptoms typical for pubescence recurs on a global (worldwide) scale during these historical epochs every 500 years. One possible explanation would be to search for a cosmophysical factor, which impacts the neuroendocrine system of men.

Tree-stem diameter fluctuates with the lunar tides and perhaps with geomagnetic activity.

Our initial objective has been to examine the suggestion of Zürcher et al. (Nature 392:665­666, 1998) that the naturally occurring variations in stem diameter of two experimental trees of Picea alba were related to near simultaneous variations in the lunisolar tidal acceleration. The relationship was positive: Lunar peaks were roughly synchronous with stem diameter peaks. To extend the investigation of this putative relationship, additional data on stem diameter variations from six other tree species were gathered from published literature. Sixteen sets of data were analysed retrospectively using graphical representations as well as cosinor analysis, statistical cross-correlation and cross-spectral analysis, together with estimated values of the lunisolar tidal acceleration corresponding to the sites, dates and times of collection of the biological data. Positive relationships were revealed between the daily variations of stem diameter and the variations of the lunisolar tidal acceleration. Although this relationship could be mediated by a 24.8-h lunar rhythm, the presence of a solar rhythm of 24.0 h could not be ruled out. Studies of transpiration in two of the observed trees indicated that although this variable was not linked to stem diameter variation, it might also be subject to lunisolar gravitational regulation. In three cases, the geomagnetic Thule index showed a weak but reciprocal relationship with stem diameter variation, as well as a positive relationship with the lunisolar tidal force. In conclusion, it seems that lunar gravity alone could influence stem diameter variation and that, under certain circumstances, additional regulation may come from the geomagnetic flux.

Rotor-type hyperbilirubinaemia has no defect in the canalicular bilirubin export pump.

BACKGROUND: The cause of Rotor syndrome (RS), a rare-familial conjugated hyperbilirubinaemia with normal liver histology, is unclear. We hypothesized that RS can be an allelic variant of Dubin-Johnson syndrome, caused by mutation in ABCC2, and investigated ABCC2 (gene) and ABCC2 (protein) in two patients with RS. METHODS: A 57-year-old male presented with a 5-year history of predominantly conjugated hyperbilirubinaemia (170 micromol/l). Urinary porphyrin excretion was increased; cholescintigraphy revealed no chromoexcretion. A 68-year-old male presented with lifelong conjugated hyperbilirubinaemia (85 micromol/l). Bromosulfophthalein elimination was typical for RS. Both patients had histologically normal liver, without pigment. ABCC2 expression was investigated by confocal fluorescence microscopy. ABCC2 was sequenced from genomic DNA and cDNA, and exon deletions/duplications were sought by comparative genomic hybridization on a custom micro-array. RESULTS: In both patients, ABCC2 was expressed unremarkably at the apical membrane of hepatocytes and no sequence alterations were found in 32 exons, adjacent intronic regions and the promoter region of ABCC2. CONCLUSIONS: Rotor-type hyperbilirubinaemia is not an allelic variant of ABCC2 deficiency.