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Biomedical subjects

E Halberg

Publications and source records attributed to E Halberg.

At least 55 records · Page 3Linked to original sources
PubMedDate not supplied

Chronobiology: a frontier in biology and medicine.

On the occasion of Franz Halberg's 70th birthday, some of his many achievements are reviewed. We provide a historical background to the development of chronobiology; offer insight into the current state of this new science; and sketch the promise of this discipline for health care and cure. As a tribute to Franz Halberg, in an era of fast-growing technology, an attempt is made to describe his perspective of tomorrow's medicine and biology. The many students he trained throughout his productive career face the challenge of deserving the trust he placed in them and of further implementing his vision. A leader in social pediatrics put it aptly: it will take several generations of researchers to study and master his life's work.

Animals↗
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Magnetic resonance spectroscopy and ambulatory cardiovascular monitoring noninvasively gauge timing of phosphate metabolism and circulation.

Circadian changes in high-energy phosphate metabolism of the human forearm and the relative independence of these metabolic changes from the circulation were noninvasively demonstrated and quantified by combining nuclear magnetic resonance spectroscopy (MRS), ambulatory blood pressure and heart rate monitoring and chronobiologic time series analysis.

Adenosine Diphosphate↗
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Chronomodulatory infradian synchronization by placebo or ACTH 1-17 of Musca autumnalis mortality on shifted lighting regimens.

The face fly, Musca autumnalis, exposed to shifts of an LD16:8 lighting schedule at varying intervals, whether previously untreated or given placebo or ACTH 1-17 treatment, before the initiation of shifts, exhibits an infradian frequency response in mortality. At overall 50% mortality, a periodicity of approximately 4.5 days is found for flies exposed to placebo or ACTH 1-17 as a response to the shift interval. As compared to controls, the mortality of flies treated with placebo or ACTH 1-17 is delayed. Not all shift schedules are detrimental; some are actually beneficial.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Chronosynergistic effects of lighting schedule-shift and cefodizime on plasmacytoma growth and host survival time.

Lighting regimen shifts can modify the effects of cefodizime, for the purpose of a chronoimmunomodulation. Two experiments were carried out on male and female LOU rats inoculated subcutaneously with plasmacytoma cells. Some rats were kept on their original LD12:12 regimen, whereas others, after tumor implantation, were subjected every second day to 6-h shifts, instituted, in alternation, as advance or delay. Daily treatment with cefodizime or placebo started when, overall, about 50% of the animals had developed a palpable tumor. A subgroup of animals contributed daily smears for the determination of the estrus cycle and further provided core temperature and activity data by telemetry. In Experiment I, the repeated shifting of the LD regimen was associated with survival time prolongation (p less than 0.05), irrespective of drug administration. Moreover, in those (female) rats repeatedly exposed to shifts of the lighting schedule, cefodizime was found to prolong survival time (p less than 0.05). The effects of cefodizime vs placebo on survival time were found to be circadian stage-dependent. In Experiment II, differing from Experiment I in the initial conditions before the institution of the shifts, cefodizime treatment was associated with a prolongation of survival time of the female rats kept on a fixed LD12:12 regimen. Both male and female rats again showed a circadian stage-dependence of the cefodizime effect. These results suggest that interactions between synchronizers of rhythms (such as shifts of the lighting regimen, the latter simulating the daily routine) and immunomodulating agents such as cefodizime may be optimized to improve treatment strategies against cancer and other diseases.

Animals↗
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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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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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Toward a chronopsy: part II. A thermopsy revealing asymmetrical circadian variation in surface temperature of human female breasts and related studies.

A thermorhythmometric analysis was carried out on data from a patient who underwent a prophylactic subcutaneous mastectomy, subsequently to a preoperative mammogram revealing clustered small calcifications in the left breast. The patient self-measured surface temperature of each breast, above and below the nipple, at intervals of 75 +/- 10 min for 59 h while awake. In one location of each breast, the recording thermistor-probe was insulated for 21.5 h while other probe locations remained uninsulated. The overall rhythm-adjusted average surface temperature and the extent of predictable circadian variation differed with statistical significance when the two breasts were compared. The left breast exhibited a higher rhythm-adjusted mean temperature and a lower extent of predictable circadian variation, as compared to the contralateral breast. The interbreast differences of surface temperature also demonstrated a statistically significant rhythm. A review on results of rhythmometry of breast temperature was also carried out. The thermorhythmometric findings here reported must not necessarily be regarded as indicative of cancer; they may be found in non-cancerous subjects and may or may not reflect early pathology. The objective of this publication is to suggest that non-invasive mammary thermorhythmometry may complement clinical histopathology. This subject may exemplify a new principle awaiting scrutiny with much more extensive sampling and much longer follow-up, namely that chronopathology including chronoprotopathology, alongside established diagnostic procedures, may provide an indication for prophylactic intervention.

Adult↗
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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

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↗
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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↗
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Toward a chronopsy: part I. A chronobiologic case report and a thermopsy complementing the biopsy.

A prophylactic bilateral subcutaneous mastectomy, following a preoperative mammogram revealed clustered small calcifications in the left breast. In order to investigate the merits of thermorphythmometry, the patient self-measured surface temperature of each breast, above and below the nipple, while awake. In the case here presented, bilateral subcutaneous mastectomy followed by extensive histologic scrutiny of both breasts revealed no indication of malignancy. Bilateral fibrocystic disease with calcification and lobular hyperplasia was found. As compared to the contralateral sites, the atypical epithelial proliferation was more abundant in the mammographically and thermorhythmometrically 'abnormal' area of the left breast.

Body Temperature Regulation↗
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Toward a chronopsy: Part III. Automatic monitoring of rectal, axillary and breast surface temperature and of wrist activity; effects of age and of ambulatory surgery followed by nosocomial infection.

Data of core and breast surface temperature and motor activity collected automatically with ambulatory devices, reveal circadian rhythms of different prominence in these various potential chronobiologic markers. Chronobiologic serial sections further allow the study of any alterations of the circadian rhythm parameters following ambulatory surgery. An approach using miniaturized instrumentation and methods of time series analysis may signal the danger of postoperative complications and, if it prompts timely preventive measures, may increase the safety of ambulatory surgery in particular.

Ambulatory Surgical Procedures↗