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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 55 records · Page 3Linked to original sources
PubMed1990

Longitudinal chronobiologic blood pressure monitoring for assessing the need and timing of antihypertensive treatment.

To examine the need for antihypertensive therapy and its timing, a 46 year-old woman with a 10-year history of "mild to moderate hypertension," treated for that span with 50 mg of hydrochlorothiazide per day, usually taken before retiring, carried out a study in a series of stages. Throughout the first 8 stages, she monitored her blood pressure and heart rate at 15-minute intervals around the clock for 70 consecutive days. In the first two stages, her medication was continued for a total of 10 days, of which the last 7 days constituted a double-blind study start. For the next 25 days, she was placed on a placebo once in the evening. For the ensuing week, she received three tablets per day (in the morning, noon and evening), with all three being placebo. Thereafter, for consecutive 7-day spans, she was placed on treatment, only in the morning, only at noon or only in the evening, with placebo at other times. The desirability of one vs. another treatment was assessed by a comparison of slopes fitted to the daily MESORs; on that basis, the morning or noon treatment appeared to be possibly superior to the evening treatment. Eventually the patient was taken off medication; 5 months later her sphygmochrons, based on two-to-six day monitoring, were acceptable by current standards. The slope of MESORs may be a useful endpoint to assess the need for medication, to optimize its timing or to establish the likelihood that medication is not needed. This approach should, however, be based on several (rather than a single) double-blind alternation of drug and placebo treatments for spans that are the longer the smaller the extent of apparent blood pressure elevation. Thus, in the case of apparent mild MESOR-hypertension, the blood pressure MESOR changes following the change in medication should be assessed during spans longer than one week. In the particular case studied, it seems possible that the patient had taken medication for 10 years, perhaps without justification. In cases of very mild blood pressure elevation, it seems desirable, by self-measurement or preferably automatic measurement, to take the patient off medication for spans measured in weeks or preferably months rather than days, in order to rule in or rule out the need for treatment, on the basis of repeated blood pressure profiles, to be compared eventually with reference standards from peers at low familial and personal risk of developing high blood pressure.

Antihypertensive Agents↗
PubMed1989

Some aspects of the chronobiology of nutrition: more work is needed on "when to eat".

Chronobiology involves the objective resolution with modern hardware and software of biologic time structure, now known to characterize most, if not all, body functions; it is also the science of timely intervention, a challenge to nutritionists. At all ages, yet the sooner the better, starting preferably in the womb but at least immediately after birth, the application of the principles of chronobiology requires the study of nutrition. In many cases, e.g., in the case of an increased risk of developing high blood pressure later in life, dietary preventive interventions should eventually precede drug treatment. That such intervention should take place at the earliest individualized recognition of risk seems reasonable and is an aim of chronobiologic research. In any event, a mathematical rhythm spectrum becomes evident in any variable measured with sufficient density over an appropriately long span; it constitutes the fabric of all life. In the science and practice of nutrition today, "cherchez le contrôle" (i.e., the provision of a control) requires the assessment of a multifrequency rhythmic structure.

Animals↗
PubMed1989

Infradian modulation of liver nucleic acid and lipid content of adult female Lewis/S rats.

Infradian modulation with periods of 168 h and 120 h characterizes the RNA, DNA and lipid content of the liver in adult female Lewis/S rats. Multilinear analysis shows that the fit of an infradian cosine curve with these periods is statistically significant below the 5% level (P = 0.011; P = 0.007 and P = 0.013) and that they account for 19.0, 22.7 and 20.1% of the overall variability, respectively.

Activity Cycles↗
PubMed1989

Circadian and ultradian characteristics of plasma growth hormone in children with normal and short stature.

Circadian and ultradian variations characterize plasma growth hormone (GH) in 40 boys and 10 girls of short stature, and 15 boys and girls of normal stature, 6-14 yr of age, living on a diurnal waking (approximately 07:00 to approximately 22.00), nocturnal resting routine. Blood was drawn at about 3-h intervals during a 24-h span and serum stored frozen at -60 degrees C until radioimmunoassay for GH concentration. A linear least-squares spectrum analysis of those data reveals the anticipated statistically significant circadian rhythm as the principal spectral feature for all groups. Prominent components with a period of 12 h were also found for the groups of short boys and short girls, and of 8 h for short boys. A parameter comparison indicates similar circadian characteristics between short and normal children, whether one compares boys (p = .52, .30 and .84 for comparison of rhythm-adjusted means (M), amplituedes (A) and acrophases (phi), respectively), girls (p = .65, .37 and .92), or all children (p = .53, .31 and .87). These results notwithstanding, studies of GH responses to GH-releasing hormone in children with short stature and healthy controls should be extended to evaluate any possible difference in terms of gender and circadian or ultradian timing.

Adolescent↗
PubMed1989

Chronobiology, growth hormone and healthy and malignant growth.

Chronobiology, the computer-aided science (logos) of life (bios) in time (chronos), provides novel concepts, tools and facts for those concerned with mitosis, growth and growth hormone (GH). GH concentrations in human plasma demonstrate a statistically significant circadian rhythm on a 6h as well as on a 24h rest-activity cycle. On a 24h routine of light (L) and darkness (D), alternating at 12h intervals, and in continuous D, circadian mitotic rhythms in mice persist as a feature of growth or regeneration. A circadian cell cycle commences with an increase in phospholipid labeling, followed by an increase in cytoplasmic RNA formation, preceding, in regular sequences, an increase in nuclear DNA formation and the next mitotic peak in those cells that are dividing in a growing or regenerating (reversibly "post-mitotic') rodent liver. About 5-day (presumably estral) and about 7-day (circaseptan) components as well as circadians are resolved as a spectrum of mitotic rhythms in rodent cornea. The effects of hormones such as GH or a synthetic ACTH analogue, ACTH 1-17, depend upon the circadian cell cycle stages when the agent is administered. No effect or statistically significant effect can be the result only of 1) the timing of a fixed dose of GH or 2) of the timing of the samples taken to investigate any effect. For both the timing of administration and the assessment of effects, a multifrequency spectrum of rhythms, if taken into account, can provide (in lieu of a considerable and often formidable source of variation) a new critical dimension of growth and development.

Adolescent↗
PubMed1987

Autometrically and automatically monitored, iatrogenous, inhalant-decongestant-associated high blood pressure quantified by rhythmometry.

Blood pressure and heart rate were oscillometrically monitored with an automatic Nippon Colin instrument (Komaki, Japan) and were also self-measured by a 20-year-old man treated with an inhalant-decongestant containing an adrenergic and a corticosteroid analog. The subject also collected 24-hr urines for aldosterone determination. An elevation of urinary aldosterone excretion was observed compared to the usual value range of a peer group. After removal of the drug, urinary aldosterone dropped as did urinary potassium, whereas plasma potassium rose. Chronobiologic serial sections, carried out to follow the time course of blood pressure and heart rate, showed decreasing trends in MESOR after discontinuance of treatment. A decrease in the hyperbaric index, a measure of blood pressure excess over 24 hr, was also observed. Another subject treated with the same and a third treated with a similar inhalant-decongestant, who also monitored their blood pressures automatically and/or with self-measurements, showed similar effects: a decrease in blood pressure after removal of treatment and an increase in blood pressure when (for testing only) treatment was briefly resumed.

Adult↗
PubMed1986

Does Gonyaulax polyedra measure a week?

Cell communication was investigated in Gonyaulax polyedra by mixing two cultures grown on opposite lighting regimens, as reported in a companion paper. Herein, using the same data, 7-d (circaseptan) rhythms are also shown to characterize the luminescence of this cellular organism. A fraction of a culture of G. polyedra, grown in 12 h of light (L), alternating with 12 h of darkness (D), was exposed for 3 d to an LD-shift by 11 h. The circadian glow rhythm was compared under free-running conditions (LL) for cultures previously kept on the two differing LD regimens and for mixed cultures. A circaseptan modulation of the circadian amplitude is detected in cultures that had not undergone an LD shift and in some of the mixed cultures, but not in the shifted cultures. A statistically significantly lower circaseptan amplitude (less than 50%) and acrophase advance of over 120 degrees or 56 h (p less than 0.001) characterizes the mixed cultures, as compared to the original unshifted cultures, a finding that could mean that G. polyedra communicates along a circaseptan frequency. Whether a prior phase-shift known to affect circaseptan behavior in another unicell, Acetabularia mediterranea, led to an alteration of the time structure of G. polyedra remains an interesting subject for further study in this model, a model attractive to students of unicellular rhythms and underlying mechanisms that henceforth should be studied at multiple circadian and circaseptan frequencies. Circadian and circaseptan interrelations can both serve as markers for mechanisms of intercellular communication.

Animals↗
PubMed1979

Circadian variation in urinary melatonin in clinically healthy women in Japan and the United States of America.

Urinary melatonin excretion is lower in East-Asian (Japanese) than in North-American (whites of mixed ethnic origin) women. Moreover, a statistically significant circadian rhythm is demonstrated by population-mean cosinor in the data pool from both groups of women. Furthermore, statistical significance characterizes interactions of effects from geographic differences (between ethnic groups) with temporal factors. Such spatio-temporal interactions await further scrutiny with a view inter alia of carcinogenesis as it is influenced by a spectrum of intermodulating rhythms.

Adult↗
PubMed1979

Circannual rhythms in progesterone receptor levels and functions.

Studies in this laboratory on the nuclear binding sites (acceptors) for progesterone receptor in the developed chick oviduct have resulted in the detection of seasonal variations in the levels and functions of the receptor. Cytosol preparations obtained from the chick oviducts during the winter/spring period between January and May display reduced receptor levels as well as a loss of the capacity of the receptor to bind to nuclear "acceptor" sites in vitro. The binding of [3H]P-R to whole chromatin or purified acceptor proteins reannealed to DNA display the same rhythm. No such rhythm is detected for the binding of P-R to pure DNA. Computer analysis of the data, using least squares method to fit the data to cosine curves, shows a significant fit indicating a circannual rhythm in P-R binding to the acceptor protein-DNA complex but not to pure DNA. The nuclear binding in vivo, achieved by injecting [3H]progesterone into the wing vein and analyzing the radioactivity localized in the oviduct nuclei, also displays a similar rhythm. These results support that native nuclear acceptor sites for progesterone in the chick oviduct represent protein-DNA complexes and not pure DNA. The failure of P-R to bind the nuclear acceptor sites in vivo and in vitro during this period can be explained by the two subunit hypothesis of Schrader and O'Malley, whereby one of the two subunits is absent or inactive during this period.

Animals↗