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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 91 records · Page 5Linked to original sources
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Ultradian rhythmometry by adaptive line enhancer.

Widrow's adaptive line enhancer (ALE) was applied to human rectal temperatures at 12-min intervals for 9 days. Changes along the scale of 9 days in circadian pattern suggested the occurrence of infradian variation, resolved by analyses of the entire series by linear-nonlinear rhythmometry. Once the original signal is filtered to extract the circadian component, ultradian components appear. A wide peak with a period of about 100 min, seen each day, may reflect a consistent ultradian component. Other peaks at lower ultradian frequencies (around a period of approximately 8 hr) are unsteady and may correspond to harmonics of the partially extracted circadian oscillation. Ultradian components with periods of approximately 131 and approximately 68 min were also suggested independently by population-mean cosinor summarizing data collected over a total of 158 days. Results show the ability of ALE to detect and reconstruct periodic components in noise and to track their changes in frequency, notably when other methods are also used to assess separately the components and the corresponding uncertainties involved.

Biometry↗
PubMed1986

Circadian rhythm of gastric acid secretion in men with active duodenal ulcer.

Twenty-one men with active duodenal ulcer underwent hourly gastric acid and 4-hourly plasma collections under fasting conditions. A statistically significant circadian rhythm was demonstrated for the group by population-mean cosinor analysis, a statistical technique designed for time-dependent measurements, for the 24-hr acid secretory output but not for plasma gastrin concentration. These findings are compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, here observed in most patients of the active ulcer group and previously reported for a group of healthy subjects, does not depend critically upon a circadian-rhythm change in plasma gastrin. Chronobiologic statistical techniques add an important quantitative element to the time-dependent measurement of gastrointestinal function of which one example is gastric acidity, with high rates occurring during the evening and low ones in early morning.

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↗
PubMed1986

Circadian rhythm and diurnal excursion of plasma cortisol in diabetic pregnant women.

The effect of type I and II diabetes in pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol was studied in the second and third trimesters and post partum. Cosignor analysis demonstrated persistence during gestation of the significant circadian rhythm of the nonpregnant state. As previously reported in control pregnancies, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased during gestation while the relative excursion of cortisol (expressed as the percent deviation from the 24-hour mean) was blunted. No significant difference was found between diabetic groups or when diabetic groups were compared with control subjects. Nocturnal hypoglycemia was common among diabetic women during pregnancy and post partum. Although these episodes were usually asymptomatic, the mean concomitant cortisol levels were increased over the corresponding cortisol levels of nonhypoglycemic diabetic and control subjects. We conclude that differences between control and type I and II diabetic subjects in carbohydrate tolerance or glycemic excursion are not explained by differences in cortisol levels or rhythm. The pregnancy-associated blunting of the excursion of cortisol is consistent with an autonomous source of adrenocorticotropin. Asymptomatic nocturnal hypoglycemia is common in insulin-requiring diabetic women and is associated with increased cortisol secretion.

Circadian Rhythm↗
PubMed1986

Schedule-shifts, circadian rhythms and lifespan of freely-feeding and meal-fed mice.

Mice feeding ad lib were subjected to weekly 12-hr shifts of the daily light-dark (LD) schedule beginning at either 7, 20 or 52 weeks of age and continuing until death. Other mice were meal-fed and, from 7 weeks of age until death, experienced weekly 12-hr shifts of the LD schedule alone (with mealtime fixed) or of both the LD schedule and mealtime. Telemetered core temperature data indicated marked differences in response to the different shift conditions and suggested, in the case of meal-fed animals, involvement of a food-anticipatory rhythm. Shifting of the LD schedule had no statistically significant effect on the mean survival time of mice feeding ad lib, regardless of when shifting began. While meal-feeding in itself prolonged life, the added imposition of schedule-shifting had no statistically significant effect on mean survival time, regardless of whether the meal schedule reinforced or opposed shifts of the LD schedule. In the latter case, tenth-decile survival time may have been increased.

Aging↗
PubMed1986

The manpower crisis facing radiation oncology.

Data from several sources document that the number of radiation oncologists being trained is substantially above the number projected as recently as 1983. This paper addresses the manpower crisis facing radiation oncology and includes information on the supply of and need for specialists, as well as possible courses of action given current circumstances.

Internship and Residency↗
PubMed1986

Evidence for a circaseptan and a circasemiseptan growth response to light/dark cycle shifts in nucleated and enucleated Acetabularia cells, respectively.

Nucleated as well as enucleated Acetabularia mediterranea cells were subjected to 14 different patterns of shifts in a regimen of 12 hr of light alternating with 12 hr of darkness in four 30-day long experiments. With one exception, which might be due to a circannual modulation, these experiments showed that nucleated cells had maximal growth rates when a shift was performed every 7th or 15th day. In enucleated cells, maxima were observed on shift schedules that were about 3-4 days rather than about 7 days apart. The results indicate that in the unicellular green alga Acetabularia a rhythm of about 7 days (circaseptan) exists and that removal of the nucleus results in a circaseptan frequency multiplication.

Acetabularia↗