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Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 505 records · Page 28Linked to original sources

Circadian and circatrigintan respiratory and related intermodulations in the crab Barytelphusa guerini.

Respiration and related physiologic variables in different tissues of Barytelphusa guerini and the respiration of this freshwater crab as a whole are closely synchronized in phase and in frequency along the circadian scale, in the face of large differences in circadian amplitude. A very close timing of most of the 36 variables examined in 2 separate circadian profiles and a modulation of some of these variables in added profiles as a function of lunar stage are clearly demonstrable, statistically significant and illustrative of time relations at 2 interacting frequencies.

Animals↗

Chronobiological serial sections for core temperature monitoring after transplantation of the murine pancreas.

In order to study any early sign of rejection of pancreas transplantation, rhythmometry was carried out on female adult inbred Lewis rats. Animals previously kept in continuous light, more or less synchronized in frequency by cyclic human activities, were transferred to a regimen of light (L) and darkness (D) alternating at 12-h intervals in single cages at the room temperature of 24 +/- 1 degrees C, with food and water ad libitum. At this time under ether anesthesia, temperature transensors were implanted in healthy rats and rats rendered diabetic by the administration of streptozotocin. Some of the diabetic rats were left untreated; casual blood sampling showed gross hyperglycemia. Other rats were treated by pancreatic grafts from ethionine-prepared donors, either by isografts (in rats of the Lewis strain) or by allografts (of the pancreas from inbred Fischer rats transplanted to Lewis rats). Intraperitoneal temperature was telemetered at 10-min intervals for 3 weeks following transplantation. Urine volumes were determined from rats housed in metabolic cages. Data were analyzed rhythmometrically. Chronobiological serial sections and single cosinors served this purpose. Following sensor implantation and transfer to an LD 12:12 regimen, the adjustment of the thermal acrophase consistently near the middle of the daily dark span occurred within approximately 7 days in healthy rats and in streptozotocin-diabetic rats cured by isograft. Thermal acrophase adjustment was slower for animals rendered diabetic by streptozotocin and left untreated or for animals thus rendered diabetic which had rejected the pancreatic allograft (as documented by hyperglycemia in casually sampled blood). The eventual synchronization of the circadian temperature rhythm of allografted rats differed from one rat to the other and, for some allografted animals, from the consistent synchronization of the circadian rhythm in telemetered intraperitoneal temperature of diabetic and non-diabetic Lewis rats. The acrophase of the circadian rhythm in urine volume of healthy rats or of a rat with a pancreatic isograft (which cured a prior streptozotocin-induced diabetes) differed with statistical significance from those of rats with untreated diabetes, some in this state after the rejection of a pancreatic allograft. Both urine volume and core temperature are ready marker rhythms, not only for rats but also for human beings. Both variables can be self-monitored by the cooperation of instructed but not necessarily extensively educated patients. Temperature, in particular, can also be monitored with automatic devices and alterations of certain of its rhythm characteristics may signal changes preceding fever. The use of such admittedly unspecific yet eminently practical and possibly informative marker rhythmometry awaits clinical testing.

Animals↗

Circadian rhythm in murine reticuloendothelial function.

Six separate groups, each composed of 15 comparable inbred female CBA mice, standardized in light daily from 0700 to 1900, alternating with darkness, maintained with food and water available ad libitum, were tested at 4-h intervals for a 24-h span for the phagocytic index, determined 3, 6, 9 and 12 min after the injection of a carbon suspension. By an analysis of variance and the single cosinor method applied to these data a circadian rhythm was demonstrated, with a double amplitude of 20% and an acrophase during the second half of the daily light span. These results extend the scope of immunologic circadian rhythms to the reticuloendothelial system as a feature of a bioperiodic defense mechanism, most active during the habitual rest light span of nocturnally active mice.

Animals↗

Prolactin and breast skin temperature rhythms in postmenopausal women with primary breast cancer.

Plasma prolactin and cortisol were determined and breast skin temperatures measured in 8 postmenopausal diurnally active-nocturnally resting women, 7 with primary breast cancer and 1 with benign breast disease. In all subjects, prolactin peaked during the early morning hours. Cortisol and oral temperature served as internal physiological markers of anticipated rhythmicity in adrenocortical function and metabolism. In all patients studied, the tumour site had an increased mesor (midline-estimating statistic of rhythm) and reduced amplitude of the circadian breast skin temperature rhythm when compared to a similar site on the contralateral breast. Thermal asymmetry was also observed between left and right breasts. A cancer, if in the left breast, may reinforce lower amplitude and perhaps a higher mesor (associated with the healthy left breast in these particular patients), whereas if it is located in the right breast, it tends to nullify inter-mammary differences in mesor and amplitude. Screening for breast cancer appears to require subjects being monitored on at least two occasions before thermal abnormalities due to tumour or preneoplasia become discernible.

Aged↗

Chronobiologic serial sections of several orders.

The chronobiologic serial section is described. Its applicability to the analysis of nonequidistant data is emphasized. Its ability to detect and quantify multiple components is discussed and exemplified on simulated series with various amounts of additive Gaussian noise. This least-squares method is discussed in the context of a number of complementary procedures such as complex demodulation and linear-nonlinear least-squares rhythmometry.

Animals↗

Construction of rhythm-specified reference intervals and regions, with emphasis on 'hybrid' data, illustrated for plasma cortisol.

Time-specified reference intervals, so-called chronodesms for the interpretation of single samples, have heretofore been proposed for longitudinal data, consisting of repeated samples from a single individual, and for transverse data: single time-specified samples from many individuals. Herein the problem of dealing with hybrid data, namely time series of data collected on a group of subjects, is considered for a derivation of reference intervals that take into account both inter- and intra-individual variability. The formulae are applied to cortisol data (72 samples from each of 10 healthy young adult North American women) with interpretation from both Bayesian and frequentist viewpoints. The provision of reference limits for both single samples and paired rhythm characteristics offers the opportunity of introducing an overdue time-specification and time-structure evaluation into microscopic chronobiology and through it into medical, veterinarian and other practice.

Adult↗

Higher corticosterone values at a fixed single timepoint in serum from mice "trained" by prior handling.

Results of "training" rodents for bioassay of synthetic corticosteroids are not consistent with expectations presumably based upon earlier implied claims stemming, perhaps, from over behavioral patterns displayed by handled as compared to nonhandled rodents (or the observer's wishful thinking?). At the timepoints investigated, "habituation" of mature mice and rats by exposure to handling, injection and killing procedures results in statistically significantly increased corticosterone concentrations. For younger animals the elevation in corticosterone concentration may also be applicable; although, it is not known to what extent we are dealing with an effect of "habituation" and/or age. Lowest hormone concentration occurred in the groups of mice housed undisturbed in an animal chamber separate from the room housing mice subjected to habituation. The results of this study suggest that for certain rodents kept in L from 0600 to 1800 "habituation" for 1 week, at least at the circadian stage corresponding to 0800, is not only ineffectual (in eliminating the rise in serum corticosterone associated with handling) but detrimental to the evaluation of synthetic corticosteroid potency by bioassay (to the extent that such a rise in exaggerated rather than reduced). In these acute experiments, methylprednisolone was more suppressive than dexamethasone and the water soluble ester-salts less suppressive than the 21-hydroxy bases. These results suggest the possibility of important differences in the distributive stage and/or the metabolism of these compounds--factors affecting the speed of onset of the desired as well as undesired effects.

Adrenal Cortex Hormones↗

Combined chronochemotherapy of L1210 leukemic mice using 1-beta-D-arabinofuranosylcytosine, cyclophosphamide, vincristine, methylprednisolone and cis-diamminedichloroplatinum.

When cyclophosphamide, 1-beta-D-arabinofuranosylcytosine, vincristine, methylprednisolone (P) and cis-diamminedichloroplatinum (CP) were administered to mice previously given injections of 4.5 or 5 million L1210 leukemia cells, the effectiveness of the 5-drug combination was influenced by the stage of the circadian system at the time of injection. By applying what we refer to as the chronobiological approach (timed treatment), in comparison with a homeostatic (time unqualified) approach, fewer deaths and less weight loss were found, as the result probably of lower drug toxicity. Despite a cure rate that ranged from 24 to 48% as a function of CP timing in the first study, the overall acute drug toxicity (ranging from 20 to 76%) was unacceptable as a treatment protocol. In a second study, by lowering dosages of all drugs but still administering the drugs in a chronobiological manner, death due to acute drug toxicity was reduced to zero while the percentage of cures ranged from 44 to 88% in animals treated with P at different circadian stages. In both studies the homeostatic approach was unsatisfactory because of overwhelming drug toxicity.

Animals↗

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↗

Competing circadian effects of methylprednisolone and rat weight, light chains, immunocytoma size and survival.

Eighty-four singly housed LOU rats, 43 males and 41 females, were studied (under conditions standardized for rhythmometry) for the effect of methylprednisolone sodium succinate (MP) upon a transplantable immunocytoma. Body temperature was monitored as a host reference rhythm while light chain excretion and tumor size were monitored to determine an effect upon the tumor. The MP, dissolved in a sweet solution, was consumed by the rats without any statistically significant shift in acrophase of the circadian temperature rhythm. Time dependent effects of MP treatment were observed with respect to 1) tumor size decrement and 2) the survival of treated animals, as compared to untreated animals.

Animals↗

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↗

Circadian murine ouabain chronotolerance revisited.

Data published earlier on a possible circadian variation in murine susceptibility to intravenously-administered ouabain and analyzed by conventional biometric methods, were reanalyzed by cosinor procedures. A statistically significant circadian rhythm could thus be demonstrated, contradicting the earlier conclusion that there was no circadian rhythm in susceptibility to ouabain when injected intravenously. Results from this reanalysis agreed with those from previous investigations in which ouabain was injected intraperitoneally or subcutaneously. Thus, a circadian rhythm characterizes murine susceptibility to ouabain given via 3 different routes.

Animals↗

Plexo-serial linear-nonlinear rhythmometry of blood pressure, pulse and motor activity by a couple in their sixties.

A Nippon-Colin (model BP-203X) instrument was used for longitudinal monitoring of systolic and diastolic blood pressure and pulse, at 10-min or other intervals for 26 days and for a shorter span, by a healthy woman, 60 years of age, and her husband, 61 years of age, both following their usual routine in an academic setting and at home. Due to the quasi-portable nature of the instrument, it was possible on most mornings to bring it from the home by car to the laboratory at the University and to return it to the home on most evenings, for about 2 months. The sturdy instrument withstood transportation and functioned flawlessly for the spans investigated. While the lack of true portability is definitely a handicap of the instrument which precludes it from use in sports and during ambulation, the circumstance that measurements during certain excessive activities away from a given site are not feasible can lead to a more standardized assessment of the blood pressure profile in subjects who pursue sedentary occupations. The procedures of linear-nonlinear rhythmometry applied to the data from the woman covering 26-day spans each and her husband covering 3 days, partly at 10-min and 3-min intervals, respectively, reveal the feasibility of quantifying parameters of circadian rhythmicity rather consistently. Spans as short as 48-h, invariably for the case of systolic blood pressure and usually for the case of diastolic blood pressure, though with lesser consistency for heart rate, sufficed to assess the circadian rhythmic component of this couple in their sixties and may constitute an individualized reference standard for blood pressure monitoring by the elderly with a view of assessing blood pressure rhythm alteration before it may become pathogenetic.

Blood Pressure↗

Circadian and circannual aspects of the complement cascade - new and old results, differing in specificity.

Single cosinor analyses of several elements in the complement cascade suggest the occurrence of circadian rhythms in this immunochemical system. Some earlier results, obtained with less specific methods and reported as properdin, on reanalysis also reveal circadian and circannual rhythms in the aspects of immunology represented. The topic of the complement cascade as a whole is briefly reviewed in the content of modern knowledge.

Adult↗