Search PubMedSearch

Biomedical subjects

F Halberg

Publications and source records attributed to F Halberg.

At least 91 records · Page 5Linked to original sources

Longitudinal chronobiologic blood pressure monitoring for assessing the need and timing of antihypertensive treatment.

To examine the need for antihypertensive therapy and its timing, a 46 year-old woman with a 10-year history of "mild to moderate hypertension," treated for that span with 50 mg of hydrochlorothiazide per day, usually taken before retiring, carried out a study in a series of stages. Throughout the first 8 stages, she monitored her blood pressure and heart rate at 15-minute intervals around the clock for 70 consecutive days. In the first two stages, her medication was continued for a total of 10 days, of which the last 7 days constituted a double-blind study start. For the next 25 days, she was placed on a placebo once in the evening. For the ensuing week, she received three tablets per day (in the morning, noon and evening), with all three being placebo. Thereafter, for consecutive 7-day spans, she was placed on treatment, only in the morning, only at noon or only in the evening, with placebo at other times. The desirability of one vs. another treatment was assessed by a comparison of slopes fitted to the daily MESORs; on that basis, the morning or noon treatment appeared to be possibly superior to the evening treatment. Eventually the patient was taken off medication; 5 months later her sphygmochrons, based on two-to-six day monitoring, were acceptable by current standards. The slope of MESORs may be a useful endpoint to assess the need for medication, to optimize its timing or to establish the likelihood that medication is not needed. This approach should, however, be based on several (rather than a single) double-blind alternation of drug and placebo treatments for spans that are the longer the smaller the extent of apparent blood pressure elevation. Thus, in the case of apparent mild MESOR-hypertension, the blood pressure MESOR changes following the change in medication should be assessed during spans longer than one week. In the particular case studied, it seems possible that the patient had taken medication for 10 years, perhaps without justification. In cases of very mild blood pressure elevation, it seems desirable, by self-measurement or preferably automatic measurement, to take the patient off medication for spans measured in weeks or preferably months rather than days, in order to rule in or rule out the need for treatment, on the basis of repeated blood pressure profiles, to be compared eventually with reference standards from peers at low familial and personal risk of developing high blood pressure.

Antihypertensive Agents

Control of a murine plasmacytoma with doxorubicin-cisplatin: dependence on circadian stage of treatment.

In anticipation of the development of clinical chronotherapy and in order to pick clinical test times for doxorubicin and cisplatin trials, two large studies were performed on rats bearing a transplanted plasmacytoma. The circadian timing of each of two anticancer drugs given at precisely equal dose intensities was expected to improve therapeutic benefit over conventionally given (time-unqualified) treatment. In each chronotherapeutic study, maximal benefit and minimal toxic effects were found when cisplatin was administered in the middle to latter part of the daily activity (dark) span, while doxorubicin was administered near the end of the daily resting (light) span for these nocturnally active rodents living on a 12-hour-12-hour or 8-hour-16-hour light-dark schedule. This was true whether doxorubicin or cisplatin was given first and whether there was a lag of only a few hours or a few days between the administration of these two agents.

Animals

Circaseptan (about 7-day) modulation of circadian rhythm in corneal mitoses of Holtzman rats.

An infradian modulation with a 168 h or circaseptan period characterizes epithelial corneal mitoses in adult female and male Holtzman rats, standardized at 24 +/- 1 degree C and approximately 50% relative humidity on six different sequences of light (L) alternating every 12 h with darkness (D). To approximate sampling over a 24 h LD span by convenient sampling within a single hour, the LD 12:12 regimen was staggered by 4 h in the six environments. Bedding was changed 3 days before each day of killing. During each of eight or 12 consecutive days, male and female rats, respectively, were killed and the eyeballs were removed. Mitotic indices in the cornea were determined separately for each eye and the data were analyzed by linear and nonlinear least-squares rhythmometry. For a prominent circadian component of mitotic activity, the 95% confidence interval (CI) of the period extends from 23.6 to 24.3 h for the data from males and from 23.7 to 24.2 h for those from female rats. The circadian amplitude is larger in males as compared to females. The peaks in the 24 h cosine functions best approximating the data, the circadian acrophases, are at -64 degrees or -48 degrees, i.e., 4 h 16 min or 3 h 12 min from lights-on in male and female rats, respectively. In the data from the two genders, the 24 h synchronized circadian acrophases are thus only 16 degrees, i.e., 1 h and 4 min apart. A test for an anticipated circaseptan (7-day) period shows that this particular infradian periodicity is superimposed upon the circadian one in data from both genders.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Some aspects of the chronobiology of nutrition: more work is needed on "when to eat".

Chronobiology involves the objective resolution with modern hardware and software of biologic time structure, now known to characterize most, if not all, body functions; it is also the science of timely intervention, a challenge to nutritionists. At all ages, yet the sooner the better, starting preferably in the womb but at least immediately after birth, the application of the principles of chronobiology requires the study of nutrition. In many cases, e.g., in the case of an increased risk of developing high blood pressure later in life, dietary preventive interventions should eventually precede drug treatment. That such intervention should take place at the earliest individualized recognition of risk seems reasonable and is an aim of chronobiologic research. In any event, a mathematical rhythm spectrum becomes evident in any variable measured with sufficient density over an appropriately long span; it constitutes the fabric of all life. In the science and practice of nutrition today, "cherchez le contrôle" (i.e., the provision of a control) requires the assessment of a multifrequency rhythmic structure.

Animals

Infradian modulation of liver nucleic acid and lipid content of adult female Lewis/S rats.

Infradian modulation with periods of 168 h and 120 h characterizes the RNA, DNA and lipid content of the liver in adult female Lewis/S rats. Multilinear analysis shows that the fit of an infradian cosine curve with these periods is statistically significant below the 5% level (P = 0.011; P = 0.007 and P = 0.013) and that they account for 19.0, 22.7 and 20.1% of the overall variability, respectively.

Activity Cycles

Circadian and ultradian characteristics of plasma growth hormone in children with normal and short stature.

Circadian and ultradian variations characterize plasma growth hormone (GH) in 40 boys and 10 girls of short stature, and 15 boys and girls of normal stature, 6-14 yr of age, living on a diurnal waking (approximately 07:00 to approximately 22.00), nocturnal resting routine. Blood was drawn at about 3-h intervals during a 24-h span and serum stored frozen at -60 degrees C until radioimmunoassay for GH concentration. A linear least-squares spectrum analysis of those data reveals the anticipated statistically significant circadian rhythm as the principal spectral feature for all groups. Prominent components with a period of 12 h were also found for the groups of short boys and short girls, and of 8 h for short boys. A parameter comparison indicates similar circadian characteristics between short and normal children, whether one compares boys (p = .52, .30 and .84 for comparison of rhythm-adjusted means (M), amplituedes (A) and acrophases (phi), respectively), girls (p = .65, .37 and .92), or all children (p = .53, .31 and .87). These results notwithstanding, studies of GH responses to GH-releasing hormone in children with short stature and healthy controls should be extended to evaluate any possible difference in terms of gender and circadian or ultradian timing.

Adolescent

Chronobiology, growth hormone and healthy and malignant growth.

Chronobiology, the computer-aided science (logos) of life (bios) in time (chronos), provides novel concepts, tools and facts for those concerned with mitosis, growth and growth hormone (GH). GH concentrations in human plasma demonstrate a statistically significant circadian rhythm on a 6h as well as on a 24h rest-activity cycle. On a 24h routine of light (L) and darkness (D), alternating at 12h intervals, and in continuous D, circadian mitotic rhythms in mice persist as a feature of growth or regeneration. A circadian cell cycle commences with an increase in phospholipid labeling, followed by an increase in cytoplasmic RNA formation, preceding, in regular sequences, an increase in nuclear DNA formation and the next mitotic peak in those cells that are dividing in a growing or regenerating (reversibly "post-mitotic') rodent liver. About 5-day (presumably estral) and about 7-day (circaseptan) components as well as circadians are resolved as a spectrum of mitotic rhythms in rodent cornea. The effects of hormones such as GH or a synthetic ACTH analogue, ACTH 1-17, depend upon the circadian cell cycle stages when the agent is administered. No effect or statistically significant effect can be the result only of 1) the timing of a fixed dose of GH or 2) of the timing of the samples taken to investigate any effect. For both the timing of administration and the assessment of effects, a multifrequency spectrum of rhythms, if taken into account, can provide (in lieu of a considerable and often formidable source of variation) a new critical dimension of growth and development.

Adolescent

Circadian and circannual rhythms of several enzymes of lysosomal origin in human plasma.

The circadian and circannual group rhythms in the plasma concentrations of the following lysosomal enzymes were studied in women and men: beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, beta-D-glucosidase, beta-D-galactosidase, alpha-D-galactosidase, alpha-L-fucosidase and alpha-D-mannosidase. The circadian rhythm was detected in all the tested enzymes of women, and only in alpha-D-galactosidase, beta-D-glucosidase, alpha-D-mannosidase and beta-D-N-acetylglucosaminidase of men. A statistically significant difference between genders in the circadian rhythm was exhibited by beta-D-galactosidase, beta-D-glucosidase, beta-D-N-acetylglucosaminidase, beta-D-glucuronidase, alpha-D-galactosidase and alpha-L-fucosidase. A circannual rhythm was detected in all the tested enzymes, with the exception of beta-D-glucuronidase and beta-D-N-acetylglucosaminidase, without any statistically significant difference between genders. The group rhythms of some of the enzymes (alpha-D-galactosidase, beta-D-glucosidase, beta-D-galactosidase) showed similar values of both circadian and circannual acrophases, suggesting that they may be subjected as a group to the same chronobiological coordination. The chronobiological rhythms of lysosomal enzymes were different from those of lactate dehydrogenase and alpha 1-antitrypsin, indicating that these rhythms are not merely reflecting fluctuations of the water content of plasma. No in-phase relationship was observed between the circadian and circannual rhythms of plasma cortisol and those of the tested lysosomal enzymes, excluding a direct chronobiological relationship between this hormone and lysosomal enzymes.

Acetylglucosaminidase

Ten-year-replicated circadian profiles for 36 physiological, serological and urinary variables in healthy men.

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs--blood pressure (systolic, diastolic, pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components--albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components--calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed for serum Ca, cholesterol, Cl, CO2, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically significant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Circadian stage-dependent effect of ACTH and melatonin on protein synthesis by rat adrenal cells.

The objective of the present study was to determine the circadian effects of melatonin and two different ACTH preparations: a synthetic heptadecapeptide with adrenocorticotrophic action (Synchrodyn 1-17, HOE 433) and a natural ACTH (Acthar, Armour). Both ACTH preparations acted in a circadian stage-dependent fashion affecting the MESOR and the amplitude of total protein synthesis of rat adrenal cells. The results also indicated interaction of melatonin with the rhythmic action of ACTH. We conclude that circadian adrenocortical organization also modulates protein synthesis.

Adrenal Glands

[Blood levels of dehydroepiandrosterone sulfate (DHEA-S) and the risk of breast cancer].

In North American women at low or high risk of developing breast cancer, as assessed by an epidemiologic questionnaire, the plasma concentration of dehydroepiandrosterone sulfate shows a statistically significant circannual variation. In adolescents, in all seasons, circulating dehydroepiandrosterone sulfate is a classifier of the risk of developing breast cancer, a relatively low concentration of this hormone being associated with an increased risk.

Adolescent

Neuro-steroids: 3 beta-hydroxy-delta 5-derivatives in rat and monkey brain.

The rat brain accumulates pregnenolone (P) as the unconjugated steroid, the sulfate ester (S) and fatty acid esters (L). P + PS do not disappear from rat brain after combined adrenalectomy (adx) and castration (orx). PL does not serve a source of P after adx + orx. P is metabolized by several rat brain regions to progesterone and to PL. Brain microsomes contain the acyl-transferase which converts P to PL using endogenous substrates. Brain P and dehydroepiandrosterone (D) undergo a prominent circadian variation with their acrophases at the beginning of the dark span. The circadian variation of brain D persists after adx + orx. The monkey brain (Macaca fascicularis) also accumulates P and D. Adrenal suppression with dexamethasone for 4 days does not decrease the concentrations of brain P and 3rd ventricle CSFP and D. The concentrations of brain D are decreased to a much smaller extent than plasma D. D inhibits the aggressive behavior of castrated male mice exposed to lactating female intruders. This is not the case for DS or androst-5-ene-3 beta, 17 beta-diol. The D analog 3 beta-methyl-androst-5-en-17-one, which is not estrogenic and cannot be metabolized to testosterone or estradiol, is as active as D in inhibiting the aggressive behavior of castrated mice.

Adrenal Glands

Circadian rhythm of gastric acid secretion in active duodenal ulcer: chronobiological statistical characteristics and comparison of acid secretory and plasma gastrin patterns with healthy subjects and postvagotomy and pyloroplasty patients.

Twenty-one male patients with active duodenal ulcer underwent hourly 24-hr gastric acid collections under controlled, calorically deprived conditions. The 24-hr hourly acid secretory output for the group displayed a statistically significant (p less than 0.001) rhythm, with peak rates occurring during the evening hours and low rates during the early morning hours, by population-mean cosinor statistical analysis. Population-mean cosinor analysis also verified the occurrence of a significant (p = 0.034) circadian rhythm in unstimulated acid secretion in a group (N = 14) of healthy male subjects similarly studied and reported previously. In contrast, population-mean cosinor analysis confirmed the absence of any detectable circadian rhythm in unstimulated acid secretion in a group (N = 17) of postvagotomy and pyloroplasty patients studied 2-11 years after surgery. Population-mean cosinor analysis of 4-hr plasma gastrin determinations, obtained in all groups during the 24-hr gastric acid collection, revealed an absence of any detectable circadian rhythm in plasma gastrin. This latter finding is compatible with the interpretation that the circadian rhythm of unstimulated gastric acid secretion, observed in the clinically healthy and active ulcer groups, is unrelated to changes in plasma gastrin levels. The employment of quantitative chronobiological inferential statistical techniques is important to the analysis of any time-dependent measurement in gastrointestinal function, of which gastric acidity is one example.

Adult

The gerontological decline of the renin-aldosterone system: a chronobiological approach extended to essential hypertension.

The circadian (about 24-hr) oscillating function of the renin-angiotensin-aldosterone system (RAAS) was investigated as a function of age in clinically healthy participants and in essential hypertensive patients. A peculiar age-related decline in the RAAS circadian mesor (rhythm-adjusted mean) and amplitude (variability from mesor) was found in the essential hypertensive patients. This finding suggests a nonphysiologic evolution in the tonic (24-hr mean level) as well as phasic (oscillating amplitude) circadian activity of the RAAS with increasing age. A relative hyperreninemic aldosteronism characterized the aged essential hypertensive patients.

Adolescent