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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 487 records · Page 27Linked to original sources
PubMedDate not supplied

Interrelationships of oxygen consumption and insecticide sensitivity.

The circadian rhythms of oxygen consumption and insecticide sensitivity (to dichlorvos, a rapid-acting organophosphate) in adult confused flour beetles (Tribolium confusum du Val) were determined using a LD 12:12 lighting regimen and other standardized conditions. Analysis included fitting a 24 h cosine curve to the data to estimate rhythm characteristics. Relationships between rhythms in oxygen consumption and insecticide sensitivity were evaluated on the basis of each rhythm's acrophase (timing of high point). The acrophase of oxygen consumption occurred on the average about 3 h after the middle of the daily dark span. Maximum insecticide sensitivity, based upon the reciprocal of the LC70, occurred about 2 h earlier. Although the times are fairly close, the difference between the two acrophases was statistically significant.

Animals↗
PubMedDate not supplied

Perspectives in chronobiology of air pollution.

In a series of experiments, male and female Sprague Dawley rats, kept in light (L) from 06(00) to 18(00) alternating with darkness (LD 12:12) inhaled different concentrations of carbon monoxide (50-1,700 ppm) at each of two test times, 12 h apart. A decrease in flow of CO2 (VCO2) resulting from CO inhalation was greater in the active dark (D) than resting light (L) span. Experimental hypoxic mortality of male and female mice also shows circadian variations, being greater in the D than in the L span. Moreover, a difference of mortality was observed betwen hypoxic exposures performed at 12(00) (in LD or DL) and hypoxic exposures performed at 00(00) (in LD or DL). Such results await tests of any extent to which they model responses of human beings to air pollution. In human beings any external environmental circadian, circaseptan and circannual variations in air pollution as such may serve to variable extent as socioeconomic synchronizers of innate rhythms with a corresponding frequency, rather than as solely generators of time patterns in any physiopathologic response to air pollution.

Air Pollution↗
PubMedDate not supplied

Circadian ACTH 1-17 effects on murine tritiated thymidine incorporation into DNA of thymus, bone marrow and spleen; also on total splenic RNA and DNA.

The importance of administration time along the 24-h scale is shown for a potent corticosteroidogenic adrenocorticotropin analogue, ACTH 1-17 (Synchrodyn 1-17). This molecule affects the incorporation of [3H]TdR into DNA (DNA synthesis) in the thymus, bone marrow and spleen, and total RNA and DNA of spleen in CD2F1 mice, standardized in light alternating with darkness at 12-h intervals. As a function of timing, the same dose of ACTH 1-17 at one time increases, at another time decreases (in each case with statistical significance) and at still another time elicits no response in DNA synthesis or in total RNA and DNA of spleen. Effects upon DNA synthesis are recorded with doses of 0.02 IU/kg body weight. The most marked effect with 20 IU/kg body weight is a decrease of DNA synthesis seen (4 h) after administration of ACTH 1-17 late in the dark span and early in the light span. The effect of ACTH 1-17 on the thymus is more prominent than that on bone marrow and spleen. Time-dependence also characterizes placebo effects by comparison to values in untreated controls. At the cellular level responses to ACTH 1-17 or placebo are characterized by critical interactions of treatment kind with treatment timing as well as interval-to-kill-time. The study documents the need to time-specify, in several ways, responses to ACTH 1-17 and suggests more broadly that 'increases' and 'decreases' may have to be complemented by changes in endpoints of rhythms in all those endocrine studies that involve rhythmic variables and rhythm-dependent effects upon these variables.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Individualized cosinor assessment of circadian hormonal variation in third trimester human pregnancy.

Two clinically healthy pregnant women were studied in a single 24-h span during the third trimester. Blood drawn every 20 min was assayed for cortisol (F), dehydroepiandrosterone sulfate (DHEA-S), estriol (E3), and prolactin (PRL). Blood drawn hourly was assayed for progesterone (P), human placental lactogen (HPL) and 15alpha-hydroxyestriol (E4). Breast temperature (BT) was continuously monitored. Single cosinor analysis demonstrated statistically significant circadian rhythms for plasma concentrations of F, DHEA-S, and BT for both subjects, and of E3 for one subject. Statistically significant circadian rhythms in plasma concentrations of P, HPL, E4 or PRL could not be demonstrated in our third trimester subjects. However, analysis of data from subjects sampled at earlier gestational ages revealed highly significant PRL circadian rhythms. These results suggest that plasma concentrations of PRL show a progressive decrease in circadian amplitude despite a progressive increase in mesor with advancing gestational age. Frequent sampling and cosinor data analysis permit identification of circadian rhythms in BT. The use of BT as a potential marker for rhythms in plasma concentration of certain hormones awaits further scrutiny. The demonstration of several circadian endocrine rhythms in individual subjects in the third trimester of human pregnancy facilitates the usefulness of such marker rhythms.

Body Temperature↗
PubMedDate not supplied

Time-varying effects in mice and rats of several synthetic ACTH preparations.

Circadian stage-dependent effects characterize synthetic ACTH 1-17 preparation (HOE 433 = Synchrodyn 1-17), tested in mice and rats, with reference notably to corticosterone and aldosterone production in vitro and to the behavior of rhythms in these two corticoids as an aspect of the adrenal cortical pacemaker of the circadian system. The possibility to advance or delay the rhythm in serum corticosterone by ACTH 1-17 also is demonstrated, as is a differential behavior of the circadian rhythm in serum aldosterone. Differences in timing of circadian corticosterone and aldosterone responses also are described and await further scrutiny for ultradian and infradian (notably circannual) modulation.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Synthetic adrenocorticotropin for optimizing murine circadian chronotolerance for adriamycin.

An attempt to pre-set the circadian rhythm in murine chronotolerance for adriamycin (ADR) given i.p. or i.v. with ACTH was performed in three studies. In CDF1 mice standardized in LD12:12, it was demonstrated that 1) the circadian rhythm in murine chronotolerance for ADR exhibits a different timing depending upon whether the intravenous or intraperitoneal route is used for the administration of this anticancer agent; 2) ACTH or saline pretreatment does not enhance optimal circadian-stage-qualified ADR tolerance, whatever its route of injection, with any of the circadian stages and schedules explored; 3) near-optimal tolerance can be achieved by a fixed 'best' interval (among those investigated) between ACTH and ADR, irrespective of circadian stage. Tolerance equivalent to optimal circadian-stage-qualified ADR tolerance results from the administration of ACTH 1-17 (HOE433 = Synchrodyn) 24 hours before ADR injection; 4) and acrophase advance of over 6 hours of the tolerance rhythm results from ACTH 1-17 administration at 6 HALO. The acrophase changes do not directly account for an optimal ADR tolerance at a fixed interval of 24 hours after ACTH 1-17. Thus, ACTH may be considered a potential relative chronizer of murine chronotolerance for ADR.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Circadian-stage-specified effects of a synthetic short chain ACTH-1-17 (HOE 433) on blood leukocytes and corticosterone secretion in mice.

A synthetic short chain ACTH, ACTH-1-17 (HOE 433 = Synchrodyn 1-17), beta-ala1, lys17 corticotropin (1-17)heptadecapeptide-4-N-butylamide, was tested for activity at the anticipated circadian stage of highest adrenal corticosterone responsiveness (22-HALO) in BALB/c mice. Statistically significant dose-response relations were demonstrated both in vitro (corticosterone production by adrenals incubated in Krebs-Ringer solution) and in vivo (increases in the serum corticosterone concentration). Leukocyte counts in mice injected with this ACTH showed statistically significant decreases (as compared to controls) for all kinds of cells except the neutrophil and medium-sized lymphocyte.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Comparative effects of meal timing on circadian rhythms of plasma insulin and skin surface temperature in non-human primates.

Circadian rhythms of plasma immunoreactive insulin and skin surface temperature were demonstrated in a group of African green vervets. Alteration in the timing of a single daily meal of fixed calorie content resulted in an acrophase shift of plasma immunoreactive insulin for the group of animals and in an acrophase shift of skin surface temperature in 7 or the 8 animals studied. The acrophase shift of skin surface temperature was considerably less then the shift of acrophase of plasma immunoreactive insulin, which closely approximated the shift in meal timing. The results of this study are compared with results of similar studies in human beings.

Animals↗
PubMedDate not supplied

Mesor-hypertension: hints by chronobiologists.

Circadian systems are intermodulated by networks of specialized neural, hormonal and cellular functions, with time structures that are interdependent. In cardiovascular pathophysiology, circadian and ultradian rhythms of clinical interest have been demonstrated. Cardiac output, heart rate, arterial pressure and blood volume are the best known. Systolic and diastolic blood pressure and heart rate have circadian patterns in health and therefore arterial pressure cannot be evaluated by a single measurement during a 24-h span. With correct monitoring for at least 48-h it is possible to detect the mesor-hypertension and the possible amplitude-hypertension that precedes the mesor-hypertension. Prolonged elevation of blood pressure can cause irreparable harm to sensitive tissues. To quantify the damage, the concept of hyperbaric impact has been introduced. This is a measure of the excess load exerted upon the arterial walls. Studies of the beta-blocker penbutolol with correct automatic monitoring have shown the persistence of the physiological circadian variation in the cardiovascular parameters during penbutolol administration. The so-called elimination of the circadian rhythm in blood pressure, which would not really be desirable, was not seen in any of our patients, whose cardiovascular parameters were monitored continuously, day and night, while taking penbutolol. The amplitudes of the rhythms were always prominent. A phase shift, a delay of about 100 degrees, was demonstrated in the heart rate of one 63-year-old mesor-normotensive woman.

Blood Pressure↗
PubMedDate not supplied

Variability of human blood pressure with reference mostly to the non-chronobiologic literature.

The voluminous literature on the variability encountered in 24-h recordings of human blood pressure in health is here presented by reference to selected clinical articles. Most references are cited by number for the sake of brevity, with a few cited by author when this appears to be of particular interest. Reports of work on laboratory animals are included when the findings are directly pertinent as background to studies on human beings. Results from semiautomatic and automatic direct and indirect measurements are briefly reviewed and aligned with results from work in which blood pressure was self-measured or measured conventionally by staff. The considerable and not generally recognized range of human blood pressure variability is thus extracted from the literature. An apparently limited extent of variation is shown to result mostly from the averaging of data from individuals constituting the groups investigated. Once variation is overwhelmingly documented and recognized as a fact, the different ways in which variations are presented and utilized by different author-investigators gain in importance. In a number of studies, methods of time series analysis are used. Thus, major attention can be paid to the extent to which predictable changes, so-called rhythms, characterize the data. Circadian rhythms are found to be quite prominent. By the assessment of these rhythms and about-yearly (circannual) ones, one quantifies health and individualized risk as well as disease. Otherwise 'unmanageable' variability, reviewed herein, can be resolved by relatively simple inferential statistical procedures as a set of new endpoints. A formidable foe thus becomes a powerful friend: the rhythm characteristics can be used in cardiovascular physiology and epidemiology, and preventive and curative medicine. Long-term blood pressure monitoring is no longer a mere research tool and a curiosity for the practitioner of medicine. Results from such monitoring should immediately be used in the clinic, in the school and at home. Automatic blood pressure monitoring, cost-effectively used in combination with self-measurement, as needed, may become a routine procedure if data collection can be wedded to appropriate analyses yielding new endpoints as sensitive gauges of health.

Adolescent↗
PubMedDate not supplied

Chronobiology of human blood pressure in the light of static (room-restricted) automatic monitoring.

Systematic 24-h automatic physiologic monitoring has obvious merits, even without rhythmometry. It can lead more readily to the recognition of odd-hour blood pressure elevation (e.g., of 'evening' or 'morning' hypertension). Such a condition can constitute an initial diagnosis or it may be found under treatment that may seem to be satisfactory if its effects are assessed only on the basis of a conventional check at a casual, possibly 'wrong' time. The mere inspection of a 24-h record, however, does not necessarily allow one to make objective quantitative global statements as to a change in pattern, e.g., after a given intervention. This paper illustrates how by rhythmometry, some of the uncertainties of a subjective interpretation of a record may be removed by practitioners of medicine, as well as basic scientists interested in mechanisms of blood pressure variability. This is possible since a large part of blood pressure variability can be accounted for by its circadian periodic behavior. We herein present a methodology for data collection and analysis that allows the objective quantification of blood pressure rhythm parameters in health and disease and the derivation of reference standards for such parameters. The chronobiologic approach thus makes it possible to define 'hypertension' objectively, and to distinguish between 'mesor-' and 'amplitude-hypertension', i.e., between an elevation in overall mean and one in the predictable extent of variability. Moreover, chronobiology has shown that mesor-hypertension may be preceded by an elevation in circadian amplitude only (amplitude-hypertension). Parameter tests readily allow the assessment, in relation to an objective reference standard, of these conditions, with a defined probability. Similarly, response to drug or non-drug therapy can be established and a given intervention optimized by timing treatment. Using chronobiologic tools in cardiovascular research provides new insights into possible mechanisms underlying mesor- and amplitude-hypertension. The teaching of the chronobiology of blood pressure and autorhythmometry in schools has been proven to be feasible and has been recommended as a step toward self-help for health care.

Adolescent↗
PubMedDate not supplied

Assessment of the risk of mesor-hypertension.

A small number of selected (rather than randomly picked) women of three age groups was extensively sampled in two geographic locations. Data on twelve of the plasma hormones in addition to those on some systemic variables, including blood pressure (BP), determined around the clock and along the calendar were here analyzed further. The risk of developing certain diseases was assessed by epidemiologically designed questionnaires. The risk of cerebro-, reno-, cardiovascular disease was here approached by focus upon the risk of developing a high rhythm-adjusted mean (mesor) of BP. The risk of mesor-hypertension (RMH) for a selected group of young adult women was inversely correlated with the circannual amplitude (a measure of the extent of predictable since rhythmic change along the scale of a year) and the circannual mesor of plasma aldosterone. These indices are costly in several ways since it takes at least a year and quite a few samples to estimate them reliably. In the attempt to reduce sampling requirements to one or at most two plasma samples, a chronobiologic pattern discrimination analysis was undertaken on the original data from the subgroup of young adult women. Data were normalized by the sample standard deviation of each variable and processed according to proximity (so-called nearest neighbor) rules, for dimension reduction and classification. For each variable, each subject's samples were classified by reference to those of all others. The results objectively identify certain variables for further testing on larger, properly stratified and randomized cohorts followed preferably for a life-time and also illustrate the computer method of pattern discrimination used. Pattern discrimination not only singles out plasma aldosterone as the primary classifier for RMH, but shows further the circannual- and circadian-stage dependence of the classification. The clock-hour for optimal classification of RMH by aldosterone and by hormonal co-classifiers changes with the season. Furthermore, the relation between the circadian mesor of aldosterone concentration and RMH is an inverse one in summer, fall and winter, but a direct one in spring. A validated inverse relation to RMH of the circannual amplitude and mesor as well as any added differences in acrophase or waveform of aldosterone as a function of circannual stage all contribute to the change in sign of the relationship between aldosterone and RMH observed in spring. The latter change renders mandatory the specification as to clock-hour and season of any spot-check for risk assessment, whether it is based upon single or multiple samples.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMedDate not supplied

Testing period for single cosinor: extent of human 24-h cardiovascular 'synchronization' on ordinary routine.

A clinically healthy woman monitored her systolic and diastolic blood pressure and pulse for 26 days at approximately 10-min intervals, with interruptions. Data over subspans of varying length were analyzed by single cosinor. A method for testing a period assumed to characterize data analyzed by single cosinor was introduced and programmed to compute a 95% confidence interval for the circadian period. Statistically significant deviations from precisely 24 h were found. The likelihood of their occurrence was found to vary as a function of the length of the interval analyzed. Under ordinary conditions in health, the circadian period may vary around 24 h, indicating that strict frequency-synchronization with the environment need not occur on a short-term basis. Deviations from an average circadian period may be brought about in part by infradian components modulating the circadian rhythm and by day-to-day changes in waveform.

Blood Pressure↗
PubMedDate not supplied

Circadian systolic and diastolic hyperbaric indices of high school and college students.

Apparently healthy North American (mostly Minnesotan) students, 117 boys and 147 girls, 14-21 years of age, self-measured blood pressure at 1 h or longer intervals for spans ranging from 24 h over several weeks to much longer spans. Each series was analyzed for a circadian rhythm by the single cosinor fit of a 24-h cosine curve. The mesor, amplitude and acrophase thus obtained were used for the determination of a mean acrometron, i.e. the mean of the sum of mesor + amplitude for each individual investigated. A circadian hyperbaric impact (HBI) was then computed as the tension-time product represented by the area under the fitted cosine curve and above the acrometron as a critical value. A highly skewed distribution of these HBIs was found: the HBI for systolic and diastolic blood pressure equalled 0 in 64 and 49 of the series on boys and 78 and 72 of the series on girls, respectively. Individuals singled out as outliers by the HBI are recommended for traking, some with and some without eventual intervention. The overall HBI is a step toward assessing the values that may lie above some group reference value, assuming a fixed rather than a likely-changing threshold for the damaging effect and further assuming the linearity of any impact, if not damage, along the scales of pressure and time. The overall HBI, based on such unvalidated approximations, will have to be complemented by an index related to the changes that lie outside a chronodesm with focus both upon the pressures that are too low as well as upon those that are too high.

Adolescent↗
PubMedDate not supplied

Breast skin temperature rhythms in relation to ovulation.

Breast skin temperatures have been monitored at 30-min intervals throughout wake-span for the whole or part of the menstrual cycle of women aged 20-37 years using both manual and automatic (chronobra) methods of measurement. Circadian breast skin temperature rhythms have been mathematically characterized and rhythm parameters assessed in relation to the estimated time of ovulation. Data generally indicate that there is a peri-ovulatory rise in breast temperature. Computer simulation and practical experiments, based on changes in the residual sums of squares from target values obtained for days in the cycle prior to ovulation, have indicated that this peri-ovulatory increase in temperature is possibly detectable within 24 h. The use of the chronobra and associated statistics may be of value in signalling the onset of the infertile phase of the menstrual cycle.

Adult↗
PubMedDate not supplied

Timing of medical diagnosis and treatment: clino-circadian quantification of suppression by dexamethasone of the adrenal cortical cycle in healthy men.

The inhibitory effect exerted upon the cyclic activity of the adrenal cortex by a synthetic steroid analog (dexamethasone-21-phosphate) administered at different circadian stages, has been studied previously. Reexamination of the same data by microscopic methods herein provides two sets of objective quantitative endpoints for further studies, namely 1. the characteristics of a rhythm isolated from a superimposed trend as well as noise, and 2. the endpoints of the trend itself. These endpoints quantify the effect of dose and, with the appropriate dose, the optimal timing for a given purpose may also be found.

Adrenal Cortex↗