Circatrigintans

By 1657, Santorio's aphorisms comment on changes in body weight of one or two pounds, recurring about once a month in a mature man in a perfect state of health, who observed the utmost moderation in living. An extremely unusual case of a man who bled from his thumb about once a month is recorded, as is a purpura of the calf recurring for six years in a 60-year-old man with Morbus maculosus Werlhofii. Circatrigintans characterize the frequency of neutrophil leukocytes with "androgen-induced" nuclear appendages. In a variety of life forms, variables related not only to the reproductive tract but also to other organ systems of individuals of both genders show overt or covert cycles in the range of about 30 days. These changes can be demonstrated and validated, e.g., by the nonlinear least squares fit of a cosine curve with a 30-day period or (in cycling women) with a period corresponding to that of the menstrual cycle length (without or with the concomitant fit of harmonics).

Human circatrigintans are ubiquitous: an acrophase chart shows the timing of overall high values and its 95% confidence interval for each variable investigated (Figure 10/I). The relatively tight horizontal 95% confidence intervals attest to the statistical significance of the circatrigintan component of the chronome in a variety of physiological variables. In this chart, 360 degrees represent one menstrual cycle and 0deg. the first day of menses. The results serve, among others, as a map for the sequencing of events during the menstrual cycle. This sequence of events can be quite different on the circatrigintan scale as compared to that along the circadian scale, as seen for the case of the systolic blood pressure and heart rate of a clinically healthy woman (Figure 10/IV): whereas systolic blood pressure peaks during the follicular stage of the menstrual cycle, heart rate peaks later, perhaps shortly after ovulation. This is revealed by the nearly opposite direction of the vectors that indicate a nearly antiphasic time relation validated by non-overlapping elliptical 95% confidence regions around their tips. This circatrigintan systolic blood pressure vs. heart rate allophase contrasts with the relatively close, albeit different, phase relation existing between these two variables along the circadian scale, as also indicated by the cosinor plots (Figure 10/IV, bottom). A circatrigintan rhythm of systolic blood pressure persists during pregnancy (Figure 10/II), as does a desynchronized circaseptan, pointing perhaps to interrelations between these two chronome components.

A circatrigintan was found in the urinary excretion of 17-ketosteroids by a healthy man (Figure 10/III), consistently during 15 years, persisting when the subject's wife was in menopause. An increase in the circatrigintan amplitude of 17-ketosteroid excretion by a healthy man coincides with the start of a rather massive androgen self-administration and might relate to a male sex gland cycle. Circatrigintans can be the major chronome components in human prematurity, as in the case of the blood pressure of a boy in whom they can exceed the prominence of circadians and circaseptans.

Circatrigintan alterations are associated with the presence of disease and risk elevation, as revealed by the least-squares spectrum of breast surface temperature of a woman with breast cancer (Figure 10/VA). The amplitudes at different frequencies of breast surface temperature characterizing the cancerous right breast are shown below those of the healthy left breast. The large peak around 24 hours in the healthy breast surface temperature is not detected in the cancerous breast temperature: a much smaller peak is found at a shorter (21-hour) circadian period. The result could be interpreted as a circadian desynchronization associated with breast cancer, an oversimplification since the infradian domain of the breast surface temperature spectrum is also altered. Another interpretation recognizes that an infradian component with an about-28-day and one with an about-7-day period characterize the healthy breast but not the breast with cancer. Instead of the circatrigintan and the circaseptan peaks, two other infradian peaks have appeared, one at a period of about 84 hours and another at one of 42 hours. These results could be interpreted as a spectral change due to a circaseptan frequency multiplication; this too would be an oversimplified restriction of focus only on the infradian domain of the mathematical rhythm spectrum.

From the viewpoint of an integrated chronome, a third hypothesis can be formulated, based on the recognition that the 84- and 42-hour components are not only harmonics of the 7-day synchronized (168-hour) circaseptan, but also subharmonics of the desynchronized (21-hour) circadian. Accordingly, the spectral change in surface temperature of the cancerous breast involves a concomitant infradian frequency multiplication and a desynchronized circadian frequency division ("demultiplication"), thereby achieving a spectral compromise yielding new infradian and circadian components bearing a harmonic relation to each other and to the environmentally synchronized circaseptan component of the healthy breast in the same patient. An inter-relation of several components of the chronome is further corroborated by the results on breast surface temperature showing a circatrigintan-to-circaseptan variance transposition from healthy breasts to breasts at a high risk for developing cancer (Figure 10/VB), supporting the foregoing hypothesis of a coordination among several chronome components.