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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 127 records · Page 7Linked to original sources

Rhythms of isolated platelet glutathione, aging, and the internal evolution of species.

Platelet integrity upon reinfusion after storage for varying periods of time constitutes a clinical problem requiring chronobiologic study. For such a study, total glutathione (GSH) served as an index. Blood from healthy volunteers drawn at 0800 was mixed with citrate-citric acid-dextrose (CCD) and centrifuged at 100g to obtain platelet-rich plasma (PRP), transferred to sterile containers, and maintained under ordinary laboratory conditions at room temperature in casually alternating light (L) and darkness (D), in LD 16.8, in continuous light (LL), or in continuous darkness (DD). In 5-ml aliquots of PRP mixed with 500 microliter of 0.34 M EDTA and recentrifuged for 15 min at 200g, a circadian rhythm of GSH per 10(9) platelets was found. The fit to 4-hr data of a linear trend and a 24-hr cosine yields similar acrophases (phi) under the various conditions investigated. With 360 degrees = 24 hr and with 95% limits in parentheses, the acrophases for PRP from a male donor stored in LD, LL, or DD are -64 degrees (-20 degrees, -107 degrees), -67 degrees (-28 degrees, -106 degrees), and -74 degrees (-35 degrees, -112 degrees), respectively. The corresponding values for platelets from a female donor in LD, LL, and DD are -49 degrees (-17 degrees, -80 degrees), -82 degrees (-50 degrees, -113 degrees), and -68 degrees (-29 degrees, -107 degrees), respectively. Six of six best-fitting circadian periods are longer than 24 hr, a result in keeping with a possibly free-running circadian rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Evolution↗

Consistent synchronization and circaseptennian (about-7-yearly) modulation of circannual gonadal index rhythm of three marine invertebrates.

A circannual rhythm in mean gonadal weight, expressed as percentage of overall body weight, is quantified by cosinor and linear-nonlinear least-squares rhythmometry in three marine invertebrates. Data series from the purple sea urchin (Strongylocentrotus purpuratus), a mollusk, the black chiton (Katharina tunicata), and the ochre sea star (Pisaster ochraceus), exhibiting circannual periods of 368, 361, and 365 days, have relatively tight 95% limits of 356-387, 356-367, and 359-371 days, respectively, when scrutinized by nonlinear least-squares rhythmometry. These limits overlap a precise year (365.25 days). This findings supports the occurrence of a 1 year-synchronized circannual rhythm in these marine invertebrates. For the ochre sea star, the about-yearly timing of greatest gonadal weight in relation to body mass, analyzed for a circannual rhythm by the fitting of a 1-year cosine to the data, remains virtually identical within 30 years. The 95% confidence intervals of the acrophase for mean gonadal weight (as percentage of body weight), range from March 3 to April 12 in the 1950s and from March 8 to April 12 in the 1980s. A MESOR (midline-estimating statistic of rhythm) difference may relate to geographic factors (Pacific Grove, California, from January 1954 to December 1958 vs. Terrace Point near Santa Cruz, California, from December 1978 to June 1985) that in turn may reflect a different food supply and/or temporal factors, e.g., it may result from changes in the ecology of the sea. A possible circaseptennian rhythm is only suspected in the data from the ochre star (P = 0.14); it is rigorously described for the purple sea urchin (P less than 0.001) and also detected in the black chiton (P = 0.029) in time series covering 9.5 years, from September 1953 to April 1963 for the purple sea urchin and from January 1957 to September 1966 for the black chiton. Least-squares rhythmometry (with trial periods between 1 and 15 years in 6-month increments) resolves the two (circannual and circaseptennian) components concomitantly below the 3% level of statistical significance. Nonlinear least-squares rhythmometry validates a period of 7.01 years for the purple sea urchin, although within broad 95% limits (ranging from 5.58 to 10.41 years). The life span of these marine invertebrates is not determined. One deals with a population rhythm sampled with serial independence.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Chronobiologic view of molt and longevity of Folsomia candida (Collembola) at different ambient temperatures.

A reanalysis of data published earlier indicates that the springtail, Folsomia candida, kept in continuous darkness, lengthens its intermolt interval (stadia) with age. At an environmental temperature of 21 degrees or 26 degrees C, the early stadia show an about-half-weekly or circasemiseptan interval and later stadia an about-weekly or circaseptan intermolt interval. At 15 degrees C, early stadia are about circaseptan, lengthening to nearly circadiseptan with aging. Our own studies of Folsomia candida at 23 degrees C show that the incidence of molting in 24 springtails observed at 3-hr intervals for 17 days is characterized by a prominent circadian rhythmicity and an infradian periodicity with a period of about 3 days. Both components are statistically highly significant (P = 0.001) when assessed concomitantly by least-squares rhythmometry.

Aging↗

Life span of springtail on 12-hr shifts at varying intervals of 12-hr alternation in ambient temperature.

The effect of shifts at different intervals of a regimen of quasioptimal and nonoptimal ambient temperatures alternating at 12-hr intervals was tested on the springtail, Folsomia candida. Life span data demonstrate that shifts of the temperature regimen can be optimized to prolong life rather than to shorten it or to leave it unaffected. Optimal shift intervals are 7 days apart, in keeping with the results on effects of shifts of a regimen of alternating light and darkness in a giant alga, Acetabularia mediterranea, and in the face fly, Musca autumnalis.

Acetabularia↗

Circadian change of dichlorvos lethality (LD 50) in the cockroach in LD 14:10 and continuous red light.

To examine a possible circadian change in LD 50, male, nonvirgin female, and virgin female American cockroaches, Periplaneta americana, were standardized on a regimen of light for 14 hr, alternating with darkness for 10 hr (LD 14:10); they were tested for their sensitivity to an organophosphorus insecticide, dichlorvos, on this regimen and on a regimen providing for 1 added day's maintenance in continuous red light (RR). A marker rhythm in locomotor activity was established using running wheels for the three groups of cockroaches in LD 14:10. Series, consisting of the number of impulses per hour from each of ten roaches per group, were fitted with a 24-hr cosine curve; the zero amplitude assumption was rejected by single cosinor for all series (P less than 0.001) and by population-mean cosinor for each group. Individual circadian acrophases (phi) differed by 18 degrees, 13 degrees, and 6 degrees in the three groups. Group phis were -49 degrees, -48 degrees, and -47 degrees; (360 degrees identical to 24 hr; 0 degrees = light off), i.e., they were within 2 degrees (8 min) of each other with confidence intervals of 6 degrees, 5 degrees, and 11 degrees, respectively. In three separate groups (males and virgin and nonvirgin females) of 480 roaches each, susceptibility to dichlorvos was tested; six doses were applied, each to 10 roaches, 3 hr apart for 24 hr. The phis reflecting maximal resistance to the insecticide were at -200 degrees, -194 degrees, and -203 degrees, i.e., within 9 degrees of each other. Assuming sinusoidality, times of highest susceptibility (-20 degrees, -14 degrees, and -23 degrees) led the acrophase of the activity rhythm by about 2 hr.

Animals↗

Daily spot-checking versus chronobiologic monitoring of human differential surface (rib versus breast) temperature.

A healthy, physically active woman, 35 years of age, living in Minneapolis, automatically monitored her skin surface temperature (ST) 3 inches above each nipple and on a rib below each breast for almost 3 months. In this paper a portion of that period is analyzed, namely, from October 24, 1984 (day 1 of menstruation) to November 16, 1984 (day 1 of next menstruation). On both sides, the differences between the skin surface temperature over the rib and over the breast (rib-breast DST) were calculated for each hour. The DST starts with a negative value on day 1, then becomes less negative up to around day 6, when the DST becomes positive. The means of DST during certain hours show extremely variable patterns. Even by using DST along with changes in activity and environmental temperature, circadian rhythms must be assessed. Around the clock monitoring is more reliable than a daily 1-hr mean check at a fixed time of the day. On the left side, DST mesors have a first macroscopic peak around days 8-10, another on day 14, and still others later in the cycle. On the right side, DST mesors follow a similar pattern, changing from negative to positive values. Peaking at day 10 is not as marked on the right side as on the left. The peak on day 14 is clear for both sides. With around the clock monitoring and the computation of the mesor of the differences between the temperatures at the two sites, an increase around the "estimated" ovulation time may be expected if care is also taken to account for the effects of periods of exercise and/or environmental changes.

Adult↗

Circadian variability of blood pressure and heart rate in newborns and cardiovascular chronorisk.

At present, neonates are being given screening tests for relatively rare diseases, such as phenylketonuria. The time has come to give emphasis to assessing the risk for major handicapping diseases, such as coronary heart disease, stroke, and certain diseases of the kidney. Modern technology for blood pressure and heart rate monitoring and data analysis provides noninvasive means to determine when preventive measures are indicated.

Blood Pressure↗

Two circadian rhythms and an infradian rhythm in human cardiac arrhythmia?

Circadian and infradian rhythmometry can and should be applied for the "isolation" of components in a broad spectrum of rhythms with different frequencies that can characterize the occurrence, among other pathologies, of ischemia in the electrocardiogram (ECG). Analyses of data from the literature on the recurrence of cardiac ischemia in a 12-day electrocardiographic record show two phase-drifting, internally and externally desynchronized, circadian rhythmic components and an infradian about-half-weekly modulation. ECGs covering spans much longer than 12 days are indicated in order to distinguish transient phase-drifts from long-maintained desynchronization. To assess the importance of such phenomena for diagnosis, prognosis, and treatment, a recording with accompanying as-one-goes analyses of data is indicated.

Arrhythmias, Cardiac↗

Altered circadian plasma cortisol and aldosterone group rhythms in Cushing's syndrome versus obesity and health.

According to textbooks, Cushing's syndrome (CS) is associated with a loss of the circadian rhythmicity in circulating cortisol. Documented cases of a persisting rhythm in CS are regarded as an exception. Herein, we show that a circadian rhythmicity in plasma cortisol, albeit of much reduced amplitude and with altered timing, remains a group characteristic of patients with CS, characterized further by a circadian rhythm in circulating aldosterone. In Lubochna, Czechoslovakia, 28 patients with CS, 120 patients with obesity imitating CS, 70 subjects with simple obesity, and 19 nonobese controls were sampled at 0800, 1600, 2000, 0000, and again at 0800 on the following day. In Rome, five women and three men with CS and 27 women and 30 men in clinical health gave blood for aldosterone determinations at 0600, 0800, 1200, 1800, 2000, and 0000. Results were first analyzed by single cosinor and then summarized by population-mean cosinor. A group rhythm was demonstrated for all categories of subjects by the methods employed, although, compared to health and even to simple obesity or Cushing-imitating obesity, the amplitude of the rhythm in CS was much reduced. Subgrouping according to etiology and individualized assessment in practice are mandatory. The scope of this group rhythm assessment, however, is merely to document that as a general rule the circadian rhythms in circulating cortisol and aldosterone persist in CS documented by surgery or at autopsy.

Aldosterone↗

Circadian urinary characteristics of adolescents: sensitive dynamic indices complement mean values as new physiologic endpoints.

To introduce the study of physiologic urinary rhythms into secondary education, six girls and 11 boys, 14-18 years of age, collected urine at about 3-hr intervals for 24 hr. The volume and the excretion in urine of creatinine, potassium, and sodium were determined. Blood pressure was measured during the same 24-hr span to teach the students some elements of chronobiologic sampling and analysis in the context of evaluating the risk of developing a high blood pressure later in life. Herein, we examine on urinary excretory rates whether dynamic chronobiologic endpoints such as the amplitude (A) and/or acrophase (phi) may complement the more static mesor (M) in distinguishing groups of adolescents. In a comparison of the two sexes, dynamic characteristics of the urinary excretion of sodium and of the ratio of sodium/potassium do not separate the two groups, while the M does so. The reverse holds true for the excretion of potassium. In the case of urinary creatinine, the circadian A in itself is an index suggesting a "sex" difference; whereas in urinary volume, the M alone, and to a lesser extent the combination of (M, A, phi), yields a P value below the 5% level. The groups are rather small and heterogeneous; a study of ethnicity is beyond our scope. These qualifications notwithstanding, results indicate the need for testing multiple chronobiologic characteristics in comparing groups whether one's interest in the future relates to ethnicity, sex, or other factors. Such studies of urinary rhythms of high-school students serve for instruction and research and to instill responsibility for self-help in preventive health care.

Adolescent↗

Diurnal stage of circadian rhythm of plasma zinc in healthy and psoriatic volunteers.

The characteristics of circadian variation of human plasma zinc concentrations in health and psoriasis are compared by the cosinor method. Sequential measurements of plasma zinc were performed at 0800 (fasting), 1000 (1 hr after breakfast), 1330 (1 hr after lunch), and 1900 (1 hr after supper) on groups of 20 patients with psoriasis, a disorder in which zinc metabolism may be disturbed, and 16 clinically healthy individuals. The limited sampling notwithstanding, groups showed a statistically significant circadian rhythm when analyzed by the cosinor method with the least-squares fit of a 24-hr cosine curve. The rhythm's timing in the clinically healthy group was similar to that derived by the same cosinor method from much denser series (covering the entire 24-hr span) published earlier by others. The diurnal portion of the circadian rhythm of human plasma zinc differed in the two groups investigated; this difference was not seen in the mean fasting plasma zinc concentrations. Circadian studies may reveal differences between groups that are not apparent by conventionally used single fasting estimates. More generally, in future studies of zinc, e.g., in skin disease, sampling time and the subjects' routine should be strictly standardized as a minimum, and rhythm characteristics should be quantified as an optimum.

Adult↗

Chronobiologic monitoring and analysis for anesthesiologists: another look at a chronoanesthetic index.

A circadian rhythm in anesthetic index is quantified by the single cosinor method in data published earlier. Although the double circadian amplitude, a measure of the extent of predictable change, is only 14%, the assumption of no rhythm (zero amplitude) is rejected at the 1% level of statistical significance. It seems likely that, in the absence of noise, the amplitude of the rhythmic change in the response to the anesthetic will be larger. The broader importance of chronobiology for anesthesiologists is also indicated. Hardware and software for the monitoring of a patient's vital signs before, during, and after surgery provide refined dynamic endpoints from the analysis of data series and lead to time-specified reference values that improve even the interpretation of time-specified single values.

Anesthetics↗

Oral and cervical temperatures as marker variables for chronoradiotherapy of patients with cervical cancer.

Oral and cervical temperatures were measured every 30 min during the time the patients were awake (0800-2200) and hourly during the night in 28 women with stage II-III cervical cancer. Data series averaged over all patients were analyzed to determine the circadian rhythmic pattern of temperatures from both sites as well as of the difference in temperature between the two sites. The characteristics of the 24-hr component, notably the amplitude-acrophase pair, were found to differ between the two sites (P less than 0.001). Harmonics of the 24-hr component were found to contribute with statistical significance to the circadian waveform. Accordingly, the acrophase is compared to the macrophase (time of maximal value) and orthophase (time of maximal value assumed by a multiple component model). The relative merits of these different endpoints should be assessed as a function of clinical outcome.

Body Temperature↗

Strain differences in circadian drinking behaviors of ethanol and water in rats.

Voluntary drinking responses to an alternating three-bottle, two-choice paradigm to tap water or to 5% ethanol were measured in adult male Fisher (Fshr; N = 14) and spontaneously hypertensive (SP; N = 16) rats for 6-9 days. All animals were singly caged and housed separately in isolation chambers. The animals received light from 0600 to 1800 (CST) daily (LD 12:12) or remained in constant darkness (DD) at room temperature (23 degrees C). Food was freely available. Water and ethanol bottles were changed daily, and volumes of the respective fluids consumed by each rat were measured. A dim red light (approximately 0.5 lux) was used in handling animals in the dark. SP rats demonstrated significant (P less than 0.05) circadian drinking patterns of water and ethanol consumption under LD and DD lighting conditions. Fshr rats, however, exhibited a circadian pattern (P less than 0.02) only with regard to water consumption under an LD 12:12 lighting schedule; they did not exhibit circadian patterns of drinking water (P less than 0.054) in DD or ethanol in LD (P less than 0.24) or in DD (P less than 0.67) conditions. Volumes of ethanol consumption were also greater (P less than 0.05) in SP rats than in Fshr rats. It is concluded that differences exist in circadian drinking behaviors for both water and ethanol intake in two strains of rats. Perhaps variation in circadian patterns is an evolutionary mechanism that programs behavior over an appropriate time span for differences in physiological needs of nocturnal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗

Perinatal malnutrition, suprachiasmatic nuclear lesioning, and circadian-ultradian aspects of spontaneous behavior of albino rats.

The effect of reducing the dietary protein content at different stages of development was investigated. A group of control rats was fed a diet with 25% protein throughout the entire study. Four other groups were fed only 6% protein in a diet isocaloric with the control diet. In an "intrauterine"-deprivation (prenatal) group, the feeding of the low protein diet was limited to the span from mating to delivery. In a "postnatal"-deprivation (lactation) group, the reduced protein diet was limited to the 25 days allowed for lactation. In a "perinatal"-deprivation group, the low-protein diet was fed during both the pregnancy and the 25 days after birth. Protein deprivation in a "preperinatal" group started 1 month before mating and continued throughout gestation and lactation to day 25 after birth. Except for the perinatal group, consisting of two animals, other groups consisted each of three or four rats. Behavioral variables--activity, rest, eating, drinking, exploring, grooming, curling up, and lying down--were studied in rats from each group at 90 days of age for 3 days at consecutive near-12-min intervals for observation spans of 1 min. Two animals subjected to bilateral suprachiasmatic lesions, subsequently validated histologically, and two sham-operated controls were also investigated. Both the population-mean and the single cosinor methods were used for data analysis in conjunction with linear least-squares spectra. Cosinor methods allow the rejection of the zero-amplitude assumption on a group basis for the intact controls (P = 0.007), the intrauterine malnutrition group (P = 0.034), the lactation group (P = 0.059), the preperinatal group (P = 0.055), and on an individualized basis for the two animals constituting the perinatal group (P = 0.007 and 0.002). These results by population-mean cosinor are complemented by the single cosinor demonstration of rhythms for most animals and variables investigated. The results demonstrate, on an individualized basis, the persistence of circadian rhythms under differently timed conditions of protein malnutrition. The data on the behavior of rats with bilateral lesions of the suprachiasmatic nuclei show a circadian to ultradian variance transposition. In most behaviors, there are prominent ultradian rhythms, which, however, require study over longer spans with dense observations on additional animals.

Animals↗

Individualized principal component analysis of endocrine circannual variability.

The technique of principal component (PC) analysis (PCA) of multivariate observations is a method that allows dimension reduction of multivariate data for further analysis. It is here introduced as a means of selecting chronobiologically important variables that can be further studied by an analysis of variance. The use of PCA is illustrated for a study of major temporal sources of human endocrine variability. Contributions to temporal variability by seven steroidal and six nonsteroidal hormones are compared in samples available at 100-min intervals for 24 hr in three seasons for each of three clinically healthy individuals: an adolescent woman, a menstrually cycling woman, and a postmenopausal woman. On an individualized basis, it is ascertained that the first principal component, a new variable, is primarily determined by steroids and that PCA can single out variables displaying interseasonal (circannual) differences validated as statistically significant by a subsequent analysis of variance. The variables here scrutinized and identified as contributing to the PC, however, need not all differ with statistical significance along the scale of the seasons. The steroids contributing the first principal component are DHEA-S and an estrogen in all three individuals studied, cortisol and aldosterone in two of them, and 17-OH progesterone in one case.

Adolescent↗

Circatrigintan rectal temperature and endocrine rhythms of clinically healthy, menstrually cycling women.

Rectal temperatures were measured automatically every 10 min for part or most of two menstrual cycles in ten clinically healthy young women, 20-30 years of age, with a wearable instrument, the Polychronor. Occasional malfunction of the instrumentation resulted in corresponding gaps in the series. Data were examined by chronograms, plexograms, and chronobiologic serial sections computed with the fit of a 24-hr period, population-mean cosinor, and linear-nonlinear least-squares analyses. Single cosinor-derived circadian parameters were next fitted with a cosine curve of a period equal to the number of days of the corresponding intermenstruum. Second-order infradian inferential statistics were calculated next; the first day of menstruation was used as acrophase reference. A population-mean cosinor at the intermenstrual period yields a temperature acrophase of -279 degrees, with the 95% confidence interval extending from -254 degrees to -312 degrees. Since the intermenstruum differs in different subjects and/or in different menstrual cycles of a given woman, this acrophase corresponds to different time intervals from the first day of menstruation in different cases. This acrophase thus indicates the relative timing within the menstrual cycle of overall high rectal temperatures. On four subjects in four stages of their menstrual cycle, plasma was also obtained at 2-hr intervals around the clock. Ten hormones were determined. The sparse endocrine sampling along the menstrual cycle notwithstanding, a circatrigintan rhythm in all hormones investigated was demonstrated for a woman 26 years of age. At the period corresponding to the intermenstrual interval, the acrophases for T3, cortisol, FSH, testosterone, DHEA-S, T4, and LH occurred before the circatrigintan rectal temperature acrophase, whereas the acrophases for prolactin, estradiol, and progesterone occurred near or shortly after the rectal temperature acrophase. Whereas earlier circatrigintan mapping of adult women had been summarized on a group basis, this study allows individualized circatrigintan rhythm assessment. Circatrigintan, like circadian and circannual, acrophase and amplitude relations do not necessarily imply causal relations, yet they are an indispensable quantitative reference standard for the study of basic mechanisms and for diagnosis and intervention, including endeavors in planned parenthood that might take into account the organism's dynamics with multiple frequencies.

Adult↗

Bootstrapped potential circadian harbingers if not determinants of cardiovascular risk.

Among 12 endocrine variables in blood from clinically healthy adult women sampled systematically around the clock and the year, discriminant analysis methods have singled out certain hormones in certain seasons as classifiers for a high or low risk of developing diseases associated with a high circadian rhythm-adjusted mean (midline estimating statistic of rhythm, MESOR, M) of blood pressure, i.e., risk of M-hypertension (RMH). Before extending the labor intensive, costly data base, showing circadian changes with RMH, we reanalyzed available data by circadian bootstrapping, complementing earlier circannual bootstrapping. Differences in circadian M for aldosterone in all four seasons and for TSH in spring and summer (the only seasons checked), but not for the cortisol M checked in spring and summer, are validated, as are differences in circadian amplitude for TSH in spring and summer and aldosterone in spring. Identification of classifiers provides cost-effective, time-specified endocrine checks complementing the targeted automatic monitoring of blood pressure as part of a system of chronobioengineering for health maintenance.

Adolescent↗