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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 451 records · Page 25Linked to original sources
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Professor John Mills.

Explore the source record for details and available documents.

History, 20th Century↗
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Hyperbaric indices (HBI) assess the extent and timing of deviant blood pressure in patients under treatment.

Fourteen patients provided data from ambulatory monitoring at 7.5-min intervals for 24h. Rhythm characteristics and measures of blood pressure excess (hyperbaric indices along the 24-h scale) are presented in mmHg/h. A 10-year projection of blood pressure excess exceeded the 1,000,000 mmHg/h limit for systolic blood pressure in 4 cases and for diastolic blood pressure in 1 case. In such cases, additional treatment is urgently indicated, whether or not the mean blood pressure is near or even below the limits indicated by current guidelines.

Blood Pressure↗
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Circadian systolic and diastolic differences (CSDD) and circadian modulation of 1.7-h ultradians.

In 24-h ambulatory blood pressure profiles there is overlap between the lowest systolic and the highest diastolic pressure in over 90% of the cases. An overlap is observed in about 75% of the cases when considering 90% ranges. The prominence of the 1.7-h ultradian component varies as a function of circadian stage and is found to be most prominent around mid-sleep.

Activity Cycles↗
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Intermittent automatic chronobiologic monitoring complements daily self-measurements.

The self-measurement of blood pressure for circadian rhythm assessment has been used for the evaluation, 'as one goes', of the effectiveness of treatment for high blood pressure (among other purposes). Even in a setting of high technology, with miniaturized ambulatory fully automatic recorders available, it is cost-effective to combine self- with automatic blood pressure measurement, to check on both the adequacy of treatment and the need for it. These aims were followed by an 81-year-old physician practicing autorhythmometry for over a decade.

Aged↗
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Further steps toward a neonatal chronocardiology.

The study of 53 series of blood pressures at half-hour intervals from clinically healthy full-term newborns during the first days of life reveals various classifiers correlating with a history of high blood pressure: the circadian amplitude of diastolic blood pressure, the 50% range of systolic blood pressure and the standard deviation of heart rate.

Cardiovascular Diseases↗
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Bootstrapping and added data discriminate, at low blood pressures, neuroendocrine risk of developing mesor-hypertension.

Under room-restricted conditions in a clinical research center, blood pressure and circulating aldosterone and TSH, sampled along 24-h and seasonal scales, reveal differences between small groups of young adult clinically healthy women at high or low risk of developing a high blood pressure. In view of the small sample sizes, data on additional age groups were added and both the original and the extended samples were further analyzed by bootstrapping. Monte Carlo procedures thus applied support the validity of the rhythm-stage-dependent endocrine and blood pressure differences as a function of the risk of developing a high blood pressure.

Aldosterone↗
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Melatonin circadian-stage-dependently delays breast tumor development in mice injected daily for several months.

Breast tumor incidence is compared in C3CF1 mice, receiving at one of 6 different circadian stages, daily injections of melatonin or of a vehicle or no treatment, the latter in a slightly cooler environment. Results are summarized when approximately 33% of all animals have a breast tumor. Vehicle treatment increases tumor incidence. This environment-handling-vehicle effect is reduced by injecting melatonin, as indicated by life table analysis. A circadian-stage-dependence of the melatonin effect is suggested by the statistical significance of a 12-h component fitted to the tumor incidence data. The administration time of melatonin is an indispensable complement to dosing, notably when effects upon tumorigenesis are involved.

Animals↗
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Chronomodulatory effect of cyclosporine upon survival of DBA mice with L1210 leukemia.

A circadian stage-dependent anti-tumor effect of cyclosporine was tested on 268 female DBA mice, 9-10 weeks of age. The mice were kept in 6 different environmental chambers on regimens of 12h of light alternating with 12h of darkness, staggered by 4h: they were inoculated intraperitoneally with 2 X 10(5) L1210 cells at one of 6 different circadian stages. At the same circadian stage, starting 48h after inoculation, for 4 days, each mouse received the vehicle, a fixed dose of cyclosporine (15 mg/kg b.w.), a varying dose of cyclosporine 5, 10, 20 and 25 mg/kg b.w.) or no treatment. Cyclosporine prolonged survival time in a circadian stage dependent fashion (p less than 0.01), as shown by an analysis of variance and by cosinor analysis (mesor = 8.45h; amplitude = 5.45h; acrophase = 12 HALO). Cyclosporine thus acts, in a feed-sideward, as a chronomodulator of the interaction between the tumor and its host.

Animals↗
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Cosinor demonstration of circatrigintan (circavigintan) biorhythm in cell component volume of female urethral ejaculate.

In urethral expulsions of a multipara, aged 37 years, induced by digital stimulation over a time span of almost one and a half 26-day menstrual cycle, the volume of desquamated cellular component changed, according to two nearly identical versions of cosinor, with the period of 22-27 days, with the acrophase between 17th and 23rd day of menstrual cycle and with the amplitude between 0.5 and 1.2 ml/day. The issue testifies to periodic quantitative changes in squamous cells of vaginal type in female urethra, large paraurethral ducts and trigone of the bladder during menstrual cycle, with maximal desquamation during its secretory phase. A link on stop function of urethral epithelium and thus on female miction problems is suggested.

Adult↗
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Chronobiologic quantification of nocturnal low-dose dopamine effect on circadian rhythms of thyroid-related hormones and prolactin (PRL).

Six clinically-healthy young men provided plasma samples every 30 min for 24 h (from 09:00-09:00 on 2 occasions. TSH, free T3 and free T4 were determined in the 30-min samples, while prolactin was determined in samples 1-3h apart. During the first test span, each man received an infusion of physiologic saline between 21(00)-01(00). Upon re-sampling several weeks later, 3 men received a low dose of dopamine (0.1 microgram/kg/min) and 3 men received a high dose (1.0 microgram) over the same hours (21:00-01:00). The least-squares fit of a 24-h cosine to each data series described a statistically-significant circadian rhythm (p less than 0.01) for each subject on each day of study. While overall group comparisons revealed no significant difference in mesor for any hormone studied, some intra-individual differences in rhythm parameters between saline and dopamine infusion were found. Dopamine Rx produced a statistically-significant increase in amplitude for PRL and T4 and an advance in acrophase for TSH, T3 and T4, but a delay for PRL. Studies measuring hormones of interest for the 24th immediately preceding and the 24th immediately following dopamine infusion at varying circadian stages (rather than only between 21:00-01:00) are warranted and have to be individualized--one of the points of this paper. The other main point is that data reduction to a mean and a standard deviation entails loss of information that can be recovered by chronobiologic methods, here used only as a model, in view of the limitations of the sampling design on hand.

Circadian Rhythm↗
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Chronobiologic lead study cost-effectively assesses circadian-circaseptan intermodulation in murine pineal melatonin content.

The investment into the design of a study is usually and unfortunately proportional to the available information, i.e. the less one knows the more one is tempted to skimp and perform a minimal 'pilot' study. This is particularly true with respect to chronobiology. On the contrary, at the outset of a study, when the information available regarding a given problem is minimal or zero, the investment into a first study should be near-maximal. Accordingly, the often wasted 'pilot study' should be replaced by a rigorous chronobiologic lead study. The promise of such a chronobiologic 'guide, leading along a difficult or unknown course' is illustrated by the validation with statistical significance of an about-weekly (circaseptan) and an about 24-h (circadian) rhythm in the melatonin content of the murine pineal. Work around the clock on 48 female Lewis/S rats was avoided. Replication of 6 different circadian times on different comparable animals on consecutive days assessed a circaseptan rhythm more prominent than the concomitantly demonstrated circadian, at no added cost for experimental animals beyond those often used for circadian study and with no work around the clock.

Animals↗
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Ultradian chronomodulation by melatonin of a Placebo effect upon human killer cell activity.

The effect of melatonin injection evaluated earlier with respect to placebo-treated controls is reevaluated, also with reference to spontaneous changes in natural killer cell activity. This effect consists, first, of stimulation of natural killer cell activity over and above any changes brought about by placebo (saline). After 6 h, the melatonin effect appears to be an inhibition as compared to values from placebo-treated subjects, or no effect as compared to values from untreated subjects. In this case, amplification and attenuation of the placebo effect by melatonin are found within the relatively short span of 1/4 of a day, rather than within a day or a week. An ultradian 'feed-sideward' by melatonin may be aligned with the corresponding previously reported circadian and infradian chronomodulation.

Activity Cycles↗
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Hardware and software for (and results from) chronobiologic approaches to cancer treatment and prevention.

Chronobiology, aided by modern automatic instrumentation for the monitoring of marker rhythms and the administration of complex therapeutic schedules on the one hand and, on the other hand, by appropriate software for data analysis, exploits the organism's time-structure along several frequency scales. Available evidence shows that several modes of treatment, namely radiotherapy, chemotherapy and immunotherapy, can all be improved by timing. Even more important is the mapping of rhythms in health, for a comparison of rhythm characteristics between individuals at low or high risk with respect to a given disease; it may ultimately lead to a rational chronobiologic approach to cancer prevention.

Chronobiology Phenomena↗