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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 559 records · Page 31Linked to original sources
PubMedDate not supplied

Cancer marker assessment: case report on salivary and urinary CEA.

A circadian rhythm is demonstrated for salivary CEA in a clinically healthy man who collected unstimulated saliva samples around the clock for 4 days. Its acrophase occurs around 07:00, slightly later than for patients with colon cancer. A circadian rhythm of borderline statistical significance is found for the urinary excretion rate of CEA determined during the same span by this patient. It has an acrophase occurring around 15:00, differing from that of salivary CEA. Although CEA may have only limited value to assess tumor burden, even when determined in blood, rhythm characteristics of tumor markers such as CEA await applications for guiding treatment timing and for detecting earliest chronome alterations not only in the case of an overt cancer but as a feature of predisease and/or disease risk elevation.

Aged↗
PubMedDate not supplied

Toward a chronome of superfused pike pineals: about-weekly (circaseptan) modulation of circadian melatonin release.

In continuous darkness for about 5.5 days in eleven replications, the pineal shows neither only a decreasing trend nor only a damped circadian rhythm; there is an infradian modulation: after an initial decline, melatonin production increases again, with a pattern compatible with the assumption, for at least one cycle, that a built-in pineal "week" has a larger extent of predictable change than that of a pineal "day". Melatonin release from the isolated pike pineal reveals a circadian rhythm which, on the average, is damped, but demonstrable in the second half of a time series covering 5.5 days (P < 0.05). At fixed environmental temperatures of 10, 15, 19 or 20 degrees C (the latter two pooled), single and population mean cosinor analyses reject the assumptions of zero circaseptan and circadian amplitudes in the chronome of the pineal from the pike (Esox lucius L.). The circaseptan pattern is confounded by possible trends. The time series analyzed are brief, yet validate, by a one-way analysis of variance in plexograms as well as by cosinor, an about-weekly pattern, if not (yet) rhythm, on the basis of 745 determinations. The circaseptan- and circasemiseptan-to-circadian amplitude ratios are numerically larger than unity, on the average (2.014; 95% confidence interval, CI: 1.120 to 3.641 and 1.107; CI: 0.724 to 1.693, respectively). A positive correlation of the urinary excretion rate of a major breakdown product of melatonin of a cancer patient with a circulating cancer marker serving as a gauge of disease progression lends an oncologic perspective to the amplitude ratios of melatonin release in vitro here reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗
PubMedDate not supplied

Spectral differences between epitopes in the cronomes of salivary CA130 and CA125.

Ovarian tumor markers CA125 and CA130 are here investigated in the search for harbingers of an elevated cancer risk or pre-cancer. A circadian rhythm of large amplitude is demonstrated for salivary CA125 and CA130 of a clinically healthy 28-year-old woman (AP). The circadian rhythms of both markers found in AP have a pattern similar to that of a patient (EH) with a müllerian cancer involving the ovary, with high values in the early morning and low values in the afternoon. Whereas acrophases occur approximately at the same circadian stage in both AP and EH, the MESOR and circadian amplitude are higher in EH as compared to AP. The circadian rhythm of salivary CA130 of AP is similar to that of other clinically healthy women. CA130 concentrations are lower than CA125 concentrations in unstimulated saliva (before rinsing of the mouth) in this clinically healthy woman (AP), and in other women studied herein. This difference between CA130 and CA125 concentrations is observed irrespective of circadian stage and irrespective of the concentration range of CA125 at the outset. After rinsing of the mouth, a statistically significant decrease in both CA130 and CA125 concentration is observed in AP and in another healty woman (GC) who collected saliva both before and after rinsing of the mouth.

Adult↗
PubMedDate not supplied

Metachronanalysis of circannual and circasemiannual characteristics of human suprachiasmatic vasopressin-containing neurons.

We here test for and detect anticipated about-yearly (circannual) changes in the volume and number of vasopressin-containing neurons in the human suprachiasmatic nucleus. We then resolve inferential statistical parameters quantifying the extent and timing (the amplitude and acrophase) of the circannual rhythm previously missed by data inspection and classical biometry. We parametrize about-half-yearly changes previously validated by non-parametric statistical tests. New dynamic circannual and circasemiannual endpoints thus become available for basic investigation and the assessment of disease risk elevation and/or chronoprotopathology. It was earlier demonstrated that the circannual rhythms of prolactin and TSH are prominent classifiers of individuals at high versus low familial and other risk for developing breast or prostate cancer. Any neurocrine or neural mechanisms contributing to this classification are now amenable to study, on a population basis, with the dynamic hypothalamic rhythm characteristics yielded by this metachronanalysis.

Cell Count↗
PubMedDate not supplied

Chronobiologic aspects of urinary gonadotropin peptide (UGP).

When using urinary gonadotropin peptide (UGP) as a marker for ovarian cancer, a circadian rhythm of large amplitude is best assessed for improving preanalytic quality control, for specifying how often and when to sample and for resolving chronobiologic endpoints. In a patient (EH, 73 y) with an ovarian (Müllerian) adenocarcinoma, overall high UGP values occurred consistently around 07:00 (standard deviation, SD = 2 h), similar to the timing observed in a presumably healthy woman. The circadian rhythm of EH averages in amplitude about 45% of the daily mean value (SD = 15%). The results indicate the desirability of deriving time-specified reference limits in health for an improved diagnostic value of UGP. The circadian UGP pattern awaits tests of applications for a chronodiagnosis of ovarian cancer, for optimizing treatment efficacy by timing according to rhythms, and conceivably for detecting earliest precancer risk.

Aged↗
PubMedDate not supplied

Physical chemistry and the biologic week in the perspective of chrono-oncology.

The computation of spectra and cross-spectra yielding coherences suggests that there exist certain relationships between rhythmicities and electromagnetic fields that are external to the biologic structure studied. Models are here provided which may prompt further investigation by allowing at least tentative, quantitative temporal insights into physico-chemical aspects of the biologic week. On the basis of empirical data, a computation of the oscillating frequency during the diffusion of ions in a magnetic field can be performed. The frequency of some ions found in cells (Ca2+, K+, Na+, Mg2+) and of some proteins (albumin, hemoglobin) can be calculated given the diffusion constant in cells, the magnetic field strength, the relative molecular mass and the effective charge. For a field of 10(-9) Tesla, the oscillating period of K+ is about 180 hours, that of Ca2+ about 160 hours, that of Na+ about 150 hours and that of Mg2+ about 145 hours; the period lengths of albumin and hemogiobin are of the order of 30 and 40 days. Without a consideration of any receptors, the results seem to represent, at least numerically, realistic components in the time structure investigated by chronobiology.

Blood Chemical Analysis↗
PubMedDate not supplied

Chronome of urinary 6-sulfoxy-melatonin excretion, circulating CA125, cancer progression and therapeutic response.

The longitudinal follow-up of a patient with an advanced adenocarcinoma of the ovary sheds new light on the involvement of the pineal in carcinogenesis. The changes in the circadian MESOR of 6-sulfoxy-melatonin following a course of chemotherapy may differ in relation to the success or failure of treatment, yet the MESOR does not correlate with tumor burden assessed by circulating CA125. By contrast, the ratio of circaseptan-to-circadian amplitudes involving two chronome components correlates with the cancer marker. To that extent, the study reveals a critical about 7-day (circaseptan) aspect of the pineal involvement in cancer progression. This information could be exploited in designing schedules of melatonin administration to cancer patients.

Adenocarcinoma↗
PubMedDate not supplied

Circasemiseptan (about-half-weekly) and/or circaseptan (about-weekly) pattern in human mitotic activity?

This review and metachronanalysis was prompted by the presence of a circasemiseptan pattern (P < 0.05) found by population-mean cosinor in published data characterizing murine malignant growth after treatment with cyclophosphamide (1-4). For cancer chronotherapy (5-9), the analyses serve to suggest the desirability to extend the focus beyond circadian aspects of drug timing and drug effect to a broader view that takes into account as much of the body's make-up in time as is practical. Among the different components of a chronome (the time structure of rhythms with different frequencies and trends in a given variable), the 3.5-day patterns (circasemiseptans) and the 7-day patterns (circaseptans) are more readily accessible to measurement and thus to manipulation and optimization than infradians with even lower frequencies; they may also be pertinent to the scheduling of infusions covering several days, particularly those using drug administration devices, some of which are programmable. Should circaseptans and circasemiseptans characterize the host as well as the tumor, the drug administration schedule could be optimized for both treatment efficacy and host tolerance, with a view of infradian as well as of circadian and ultradian rhythms.

Chronobiology Phenomena↗
PubMedDate not supplied

X-irradiation chronosensitivity and circadian rhythmic proliferation in healthy and sarcoma-carrying rats' bone marrow.

Mitotic activity of bone marrow and tumor of sarcoma-bearing rats and of bone marrow of healthy controls is circadian periodic. Whereas the circadian rhythm in mitotic activity of bone marrow is similar for intact and tumor-bearing rats, with a peak occurring shortly after the onset of the dark (activity) span, the circadian rhythm in mitotic activity of tumor has a much smaller amplitude and a different acrophase occurring late in the dark span. This difference in acrophase of mitotic activity of bone marrow and tumor has important implications for scheduling the administration of oncotherapy. For the tumor model examined herein, it suggests the possibility to achieve concomitantly near maximal efficacy and near minimal myelotoxicity, a result awaiting further investigation in humans with different kinds of malignancies.

Animals↗
PubMedDate not supplied

Chronometaanalysis: circasemiseptan (3.5-day) pattern in mitotic activity of murine sarcoma after treatment with cyclophosphamide.

This note focuses attention upon infradians in mitotic activity of a murine sarcoma. Starting on day 8 after the inoculation of mice with a sarcoma, three different doses of cyclophosphamide, one dose at three different circadian times, were injected and tumor was sampled with serial independence, mostly at 12-hour intervals during the 4 ensuing days. A metachronanalysis of these heterogeneous data, collected for a different purpose with different doses and at different circadian times, reveals the presence of a circasemiseptan pattern (P < 0.05 by population-mean cosinor). Without a longitudinal replication, the result is described only as a pattern rather than as a (recurring) rhythm, characterizing malignant growth after treatment with cyclophosphamide. For cancer chronotherapy, the analyses serve to suggest the desirability to replace exclusive focus upon circadian aspects of drug timing and drug effect by a broader view that takes into account as much of the chronome as is practical. Among the different components of a chronome (i.e., the time structure of rhythms with different frequencies and trends in a given variable), the circasemiseptans (and circa-septans) are more readily accessible than infradians with even lower frequencies; they may also be pertinent to the scheduling of infusions covering several days, particularly those using drug administration devices, some of which are programmable. Since circaseptans and circasemiseptans may characterize the host as well as the tumor, infradian drug administration schedules could be sought that optimize both treatment efficacy and host tolerance.

Animals↗
PubMedDate not supplied

Toward salivary-urinary chronosensitivity testing: chronomes of OVX1, M-CSF and CA130.

Several rhythmic components were previously mapped for salivary and/or urinary CA125 and CA130. On the background of such reference standards, OVX1 and M-CSF were assayed on 242 urine samples and 160 saliva samples provided by a 71-year-old patient with a Müllerian/ovarian adenocarcinoma. Serum OVX1 correlates with serum CA125 (P = 0.002); when circulating CA125 concentrations decreased (from 122 to 14 U/ml), the urinary excretion rate of OVX1 decreased (P = 0.005), whereas the urinary excretion rate of CA125 increased (P < 0.001). Salivary OVX1 and urinary M-CSF show ultradian variations (with a frequency of one cycle in 14-17 hours), which could be utilized to guide treatment timing targeted first to optimize treatment efficacy and as a second consideration to minimize treatment toxicity.

Aged↗
PubMedDate not supplied

Circadian rhythm of sister chromatid exchanges in human chromosomes.

Since sister chromatid exchange (SCE) relates directly to DNA synthesis which is circadian periodic, this study examines whether a circadian rhythm also characterizes SCEs. In 4-hourly blood samples collected for 48 hours on three diurnally active, nocturnally resting subjects with no family history of chromosome aberrations or instability, a circadian rhythm is demonstrable with an acrophase occurring around 14:45. The circadian amplitude is only of the order of 10% of the MESOR in untreated cultures or in cultures exposed to cefodizime. It remains more or less unchanged in cultures exposed to mitomycin-C, while the MESOR increases by about a factor of 2. In studies of human chromosome aberrations, the circadian rhythmicity of SCE should be taken into consideration.

Adult↗
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The pineal gland and cancer.

The pineal gland is considered today as one of the main organs involved in the transduction process which converts environmental light information into an endocrine response. The gland and its hormone melatonin seem to be important chronoimmunomodulators, and a reduction of the latter was associated with experimental and clinical immunodeficiencies and over the control of the neoplastic process. Moreover, melatonin can be an oncostatic or oncostimulating hormone, depending on the timing of its administration. The melatonin circadian rhythm is altered in cancer patients, and this rhythm could be modified as a consequence of certain therapies. Also Electromagnetic Fields (EMF) can affect the pineal function, perhaps working as synchronizers or, as this paper proposes, also through action of the "antenna effect" suggested for artificial human models, with a major energetic transfer over the cephalic area. The pineal could play an important role in the appearance and development of some forms of apparently EMF-related cancers.

Animals↗
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From Pavlov's time coding and conditioned reflexes to a chronophysiology of human nutrition.

Chronobiology, including chronophysiology, is now a hot area of multidisciplinary research. The paper outlines the contribution of I. P. Pavlov's ideas concerning time coding and time structures; conditioning is considered as a full account of how rhythms come about. Are mentioned some principals and advances of chronobiology and chronobiometry, with special emphasis on the chronophysiology of digestion. Finally is reminded the motto of quantitative chronobiology "measure what is measurable in time, hence meaningfully, and render equally significantly measurable what as yet is not."

Chronobiology Phenomena↗
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[Chronobiology in medicine and surgery].

Chronobiology studies predictable variations, rhythms and trends in all forms of life. Each physiologic variable or system in an organism has a time structure which is genetically anchored and capable of being expressed in the absence of external cycles. However, it is normally adjusted by geophysical changes. Chronobiology quantifies rhythms by providing measures of amplitude and timing (phase and period), and a mean more precise than the arithmetic mean. The correct measurement of biological rhythms has led to considerable advances in the understanding of their underlying mechanisms of generation and expression. The use of information on rhythms is opening new opportunities in the prevention, diagnosis and treatment of disease. Chronobiology is also effective in the improvement of the quality of life by teaching self-help to the healthy individual.

Blood Pressure↗