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Biomedical subjects

A Reinberg

Publications and source records attributed to A Reinberg.

At least 73 records · Page 4Linked to original sources
PubMed1986

Chronobiology and asthma. I. Day-night differences in bronchial patency and dyspnea and circadian rhythm dependencies.

The symptoms of allergic asthmatic patients typically worsen during the night, especially during the early morning hours. Although 24-hour variations in the environment contribute to the intensification of the asthmatic condition nocturnally, environmental changes themselves do not fully explain the temporal aspects of this disease. Circadian (about 24-hour) rhythms in critical bioprocesses constitute significant contributory factors. The exacerbation of asthma during the night represents the changing status of biological functioning due to circadian rhythms in bronchial patency; airways hyperreactivity to acetylcholine, histamine, and house dust; and plasma cortisol, epinephrine, histamine, and cyclic AMP, among others.

Asthma↗
PubMed1986

Ultradian, circadian and circannual rhythms of blood glucose and injected insulins documented in six self-controlled adult diabetics.

The aim of the study was to document during one to two years individual rhythmic patterns in blood glucose and injected insulin in self-controlled insulin dependent (C-peptide negative) diabetics with home blood glucose monitoring. Two females and four males with diurnal activity from 0700 to 2300 self-determined their blood glucose three to six times a day over a period of 12-27 months. Circadian and ultradian rhythms were analysed for each subject on a monthly basis to document annual rhythms. Blood glucose (BG) estimated circadian acrophases were located between 2200 and 0300 for all patients and months with few exceptions. A correlation was found between circadian mesors and amplitudes of BG in four subjects. Annual changes in BG were validated for each subject with large interindividual differences in peak times. The individual mean of injected insulin (II) varied from 40 to 80 iU with annual changes validated for each subject. A group pattern was observed with a peak time either in the autumn (four patients) or in the summer (two patients). A circadian rhythm of II was detected in almost all monthly means and for all patients. Locations of computed peak time phi of II exhibited a great stability for a given individual but large interindividual differences. Thus the rather constant phi location of BG for all subjects contrasted with interindividual differences in phi locations of II. These results suggest that rhythmic changes in BG and II should be recognized when forming a realistic strategy for timing and dosing time(s) of insulin.

Activity Cycles↗
PubMed1986

Interindividual differences in the circadian hematologic time structure of cancer patients.

The complete hematologic blood cell count of 11 patients with advanced cancer were determined on 14 occasions, every 4 hr over 36-48 hr. Oral temperature was also measured at the same times as blood sampling. Five patients had breast cancer, five had ovarian cancer and one a leiomyosarcoma. Circadian rhythms were detected by the cosinor method for seven hematologic variables (red blood cells, hemoglobin, hematocrit, white blood cells, neutrophils, lymphocytes, platelets) and for oral temperature in the whole group of patients. All acrophases were located between 1300 and 1700 hr, except for lymphocytes (2100 hr). A rhythm with a period of 8 hr was validated for lymphocytes and monocytes. Validated or estimated amplitudes and acrophases were closely similar in both breast and ovarian cancer subgroups. Individual cosinor analyses documented large differences from patient to patient, which were accounted for by differences in performance status. Thus, subjects with poor performance status and rapidly progressive disease had very few validated rhythms as compared to those patients with good performance status. As a result a statistically significant correlation was found between the number of validated hematologic circadian rhythms and the performance status (r = -0.88; P less than 0.01).

Adult↗
PubMed1986

[Circadian and seasonal changes of the inducer:suppressor ratio (OKT4+:OKT8+) in venous blood of healthy adults].

Circadian and seasonal variations in the T helper: T suppressor-cytotoxic ratio were investigated in peripheral blood from five healthy young men. Mononuclear cells were isolated on Ficoll-Paque gradient, then incubated with OKT4 and OKT8 monoclonal antibodies. Plasma cortisol was determined in four of these seven time series. Large interindividual differences were documented and statistically validated for the 24-hr.-means of total lymphocytes, OKT4+:OKT8+ ratio, and of plasma cortisol (both total and free). For a pooled data, a circadian rhythm was demonstrated by cosinor (p less than 0.001) for total lymphocytes (acrophase at 1.00 hr.), total plasma cortisol (acrophase at 10.30 hrs.) and free plasma cortisol (acrophase at 9.50 hrs.), but not for OKT4+:OKT8+ ratio. This index however exhibited a statistically significant circadian rhythm in April and August, but not in November. Its double-amplitude exceeded 80% of the 24-hour-mean and its acrophase was localized at 6.40 hrs. in April and at 22.30 hrs. in August. Its 24-hr-mean was higher in August as compared to April and November. The circadian rhythm in the OKT4+:OKT8+ ratio did not seem to be related to that of plasma cortisol. Both circadian and seasonal variations need to be taken into account when investigating the regulations of immune variables such as T helper: T suppressor-cytotoxic ratio.

Adult↗
PubMed1986

Circadian rhythms in effects of hypnotics and sleep inducers.

Chronopharmacology involves the investigation of drug effects as a function of biological time and the investigation of drug effects on rhythm characteristics. Three new concepts must be considered: (a) the chronokinetics of a drug, embracing rhythmic (circadian) changes in drug bioavailability (or pharmacokinetics) and its excretion (urinary among others); (b) the chronaesthesia of a biosystem to a drug, i.e. circadian changes in the susceptibility of any biosystem to a drug (including organ systems, parasites, etc.); skin and bronchial chronaesthesia to various agents have been documented in man; and (c) the chronergy of a drug, taking into consideration its chronokinetics and the chronaesthesia of the involved organismic biosystems. The term chronergy includes rhythmic changes in the overall effects and in the effectiveness of some drugs. Clinical chronopharmacology is useful for solving problems of drug optimization, i.e. enhancing the desired efficiency of a drug and reducing its undesired effects. Circadian rhythms can be demonstrated in various effects of drugs on sleep, anaesthesia and related processes. For example, in the rat the duration of sleep induced by substances such as pentobarbital, hexobarbital, Althesin (alphaxadone and alphadoline in castor oil) is circadian system stage-dependent. Time-dependent changes of liver enzymes (e.g. hexobarbital oxidase) play a role in these circadian rhythms. The clinical chronopharmacokinetics of benzodiazepines have been documented in man. Chronopharmacologic methods can be used to study desired and undesired hypnotic effects of substances. Such is the case of new antihistamines (anti-H1), which do not induce sleepiness, in either acute or chronic administration. Pertinent also is the problem of intolerance to shift-work. Intolerant shift-workers are subject to internal desynchronization between at least two rhythms (e.g. activity-rest cycle and body temperature). Clinically these workers suffer from sleep disturbances, persistent fatigue and are regular users of sleeping pills, which is also a symptom of intolerance. However, over the long-term, these drugs are of no help to intolerant shift-workers.

Adaptation, Physiological↗
PubMed1986

Differences between young and elderly subjects in seasonal and circadian variations of total plasma proteins and blood volume as reflected by hemoglobin, hematocrit, and erythrocyte counts.

Circadian and seasonal rhythms in total plasma proteins were documented in healthy young men (around 24 years old), and in elderly subjects (both sexes), including senile-dementia patients in their eighties. The concentration of plasma proteins within a given group changed predictably (7-13%), depending on the hour of sampling and the season. Concentrations decreased noticeably around 04:00 h, then peaked around 08:00 h (shortly after waking). The 24-h mean concentrations of total plasma proteins were lower in the elderly groups than in the young men. But the seasonal variations of the 24-h mean values were strikingly larger in the elderly groups (7-8 g/L) than in the young men (2-5 g/L). Moreover, the circadian profiles of plasma proteins differed from the profiles of hematocrit, hemoglobin, and erythrocyte counts. Evidently, circadian variations of blood volume may not be the only element accounting for the variations of plasma protein concentrations. We suggest that the rhythms in plasma protein concentrations be taken into account when reference values are set. Circadian and seasonal variations in plasma proteins may also significantly affect the transport and binding of drugs, especially in the aged.

Adult↗
PubMed1985

Circadian changes in anticoagulant effect of heparin infused at a constant rate.

Six patients with venous thromboembolism were treated with heparin, administered intravenously by a constant infusion pump. The initial daily dose of heparin was adjusted to keep the activated partial thromboplastin time, sampled at 0800, between 1.5 and 2.5 times the control level. Once that level was obtained, this dose was kept constant. Anticoagulation was thereafter measured, every four hours for 48 hours, by activated partial thromboplastin time, thrombin time, and coagulation factor Xa inhibition assay. The results of all three coagulation tests showed a circadian variation in the six patients. Maximum values were achieved at night and minimum values in the morning. These circadian variations were reproduced for two consecutive days. Differences between night and morning values reached almost 50% for activated partial thromboplastin time, 60% for thrombin time, and 40% for factor Xa inhibition assay. This circadian variation resulted from two rhythms, a circadian rhythm lasting 24 hours and an ultradian rhythm lasting 12 hours, which were detected by cosinor analysis for each coagulation test (p less than 0.01). A circadian rhythm was detected individually in most of the patients for each coagulation test (p less than 0.05). All patients had a nocturnal peak in activated partial thromboplastin time on both days. In four patients this peak exceeded the upper desired limit of activated partial thromboplastin time. These rhythms should be taken into account when evaluating the dosage of heparin to be administered.

Aged↗
PubMed1985

Circulating CALLA-positive lymphocytes exhibit circadian rhythms in man.

Common acute lymphoblastic leukemia antigen (CALLA) is a polypeptide with a molecular weight of 100,000 daltons (P100). It has been mainly found on the membrane of leukemic lymphoblasts, but not on that of normal circulating lymphocytes. Circadian rhythmicity in circulating CALLA-positive (CALLA+) lymphocytes was investigated in five healthy male subjects. Blood was sampled every 4 h for 24 h in each subject. Seven times series were obtained (three for the same subject). Leukocyte and differential counts were determined, and mononucular cells (greater than 95% lymphocytes) were isolated in Ficoll-Paque gradient. CALLA+ cells were characterized with both J5 and VILA1 monoclonal antibodies. Other T- and B-cell subpopulations were also determined in the same samples. Up to 1160 +/- 498 (mean +/- 1 S.E.M) J5-labelled CALLA+ lymphocytes per mm3 were found in peripheral blood at night. At this time, circulating VILA1-labelled CALLA+ lymphocytes also reached their peak although with a much lower number (66 +/- 14 cells/mm3). A circadian rhythm (with a period identical to 24h) was statistically validated with several methods for the number of J5-labelled cells, that of VILA1-labelled cells and the J5: VILA1 ratio. The count of J5-labelled CALLA+ cells was correlated with that of total lymphocytes, total T (OKT3+) and inducer T (OKT4+) cells (p less than 0.01), but neither with suppressor/cytotoxic cells (OKT8+) nor with B cells (SIg+, B1+, B2+, or HLA-Dr+). No correlation was found between any of these lymphocyte subpopulation and the count of VILA1-labelled CALLA+ cells. Such results further support the hypothesis that VILA1 and J5 monoclonal antibodies do not bind to the same epitope of the CALLA molecule. The large nocturnal increase in circulating J5-labelled CALLA+ lymphocytes may be accounted for by a release of immature presumably T lymphocytes in the peripheral blood.

Adult↗
PubMed1985

Circadian rhythm in tolerance of mice for the new anthracycline analog 4'-O-tetrahydropyranyl-adriamycin (THP).

A statistically significant circadian rhythm in tolerance of 226 male B6D2F1 mice synchronized with LD 12:12 for 4'-O-tetrahydropyranyl-adriamycin (THP) was demonstrated. Four intravenous dosages (18, 25, 32 and 40 mg/kg) and six different dosing times (3, 7, 10, 14, 19 and 23 hr after light onset-HALO) were compared. Survival rate, body weight loss and leukopenia depended on both the dose and time of injection. The overall survival rate varied between 83% (light-rest span) and 56% (dark-activity span) (chi2 = 17; d.f. = 2; P less than 0.001). Maximal body weight loss occurred 4-5 days after drug injection. Total leukocyte counts were determined on these days. Both body weight loss and leukopenia were reduced by approximately 100% in those mice injected in their late rest span (7-10 HALO) as compared to those treated in the middle of their activity span (19 HALO). Circadian rhythms in day-60 survival rate, body weight loss and leukopenia were statistically validated by cosinor analysis, with estimated peak times (acrophases) occurring respectively at 7:30, 9:20 and 8:40 HALO. Minor cardiac lesions consisting of diffuse vacuolization and loss of muscular striation were observed in histologic sections from 3/32 hearts (16 controls, 16 treated). All three corresponded to THP given at 19 (2/2 mice) or 23 HALO (1/4 mice). Thus lethal, hematologic and possibly cardiac tolerance for THP were largely optimized by administering the drug to mice in their late span (7-10 HALO).

Animals↗
PubMed1985

Timing optimizes sustained-release indomethacin treatment of osteoarthritis.

Chronopharmacologic studies of indomethacin have indicated that time of dosing influences tolerance and effectiveness. A double-blind, crossover chronotherapeutic trial was undertaken in 66 subjects with osteoarthritis of the hip or knee who were treated with an indomethacin sustained-release (ISR) oral preparation once a day. Varying the ISR dosing time resulted in a quadrupling of tolerance and a doubling of analgesic effectiveness. Three dosing times (8 a.m., noon, and 8 p.m.), each tested during 1-wk spans and randomized for sequencing, were compared in each subject. Subjects self-rated pain intensity every other hour before (1 to 2 days) and during each week of treatment. Morning dosing was associated with a 32% incidence of undesirable effects, whereas the comparable rate was 7% for evening dosing. Ninety-five percent of the subjects reported increased drug effectiveness with a change in ISR ingestion time. The time of dosing that resulted in optimal effectiveness differed among subjects. This was explainable by large interindividual differences in the circadian variation of self-rated pain intensity. Evening dosing was most effective in subjects with predominantly nocturnal or morning pain; conversely, morning or noon dosing was most effective in subjects with greater afternoon or evening pain. The differences that resulted from varying the timing of the identical ISR dose in the same subject greatly exceeded those reported for other nonsteroidal anti-inflammatory drugs.

Adult↗
PubMed1985

Circadian rhythms in competitive sabre fencers: internal desynchronization and performance.

During a 7-10 day span, circadian rhythms of sleep-wake, self-rated fatigue and mood, oral temperature, eye-hand skill and right and left hand grip strength were investigated in eight subjects: five males (21-28 years of age), members of the French sabre fencing team selected for the 1984 Olympic Games in Los Angeles, and three females (19-26 years of age) practicing fleuret (foil) fencing as a sports activity. On the average six measurements/day/variable/subject were performed. The single cosinor method showed that a circadian rhythm was detectable for only 26 out of the 56 time series (46.4%). Power spectrum analysis gave almost the same figure (19 out of 48: 39.5%) with regard to rhythms with tau = 24 hr indicating that with one exception (subject JFL) rhythms were internally desynchronized including differences tau between right and left hand grip strength rhythms for three subjects. Results suggest: (a) a physiologic synchronization of circadian rhythms may be a predictor of good performance; (b) however, internal desynchronization as shown previously may be a trivial phenomenon and thus does not imply in itself alterations of either health or performance; (c) chronobiologic methods should be recommended for a better understanding of changes in performance by those participating in competitive and other sports.

Adult↗
PubMed1985

Effects of cyclic (nocturnal) total parenteral nutrition and continuous enteral nutrition on circadian rhythms of blood lipids, lipoproteins and apolipoproteins in humans.

The aim of the present study was to investigate the occurrence and characteristics (acrophase, amplitude) of circadian rhythms of serum total cholesterol, free-fatty acids (FFA), triglycerides, lipoproteins (HDL-, LDL-, and VLDL-cholesterol), apolipoproteins A and B, glucose and total proteins in hospitalized patients fed with 12 h nocturnal total parenteral nutrition (TPN) (from 8 PM to 8 AM) including lipids, patients fed with continuous enteral nutrition over 24 h daily spans, and patients eating 3 meals a day serving as controls. All the subjects were synchronized with diurnal activity and nocturnal rest in the hospital routine. The results showed the following: 1) circadian rhythms of total cholesterol, triglycerides, FFA, HDL-, LDL-cholesterol, apolipoprotein A and total proteins were detected in both TPN patients and controls, rhythms of apolipoprotein B and glucose in TPN patients only; in enteral nutrition patients, rhythms were detected for total proteins, glucose and triglycerides only; 2) a significant shift in triglyceride and FFA acrophases was observed in TPN patients, as compared with controls; 3) 24 h mean of both triglyceride and cholesterol concentrations remained unchanged after one month, in both TPN and enteral nutrition patients. The present approach, by extending results of previous investigations, leads one to conclude that, on both a metabolic and a chronobiological basis, cyclic nocturnal TPN is well-tolerated.

Administration, Oral↗
PubMed1985

Effects of the antiprogesterone steroid RU 486 during midluteal phase in normal women.

UNLABELLED: The antiprogesterone steroid RU 486 (17 beta-hydroxy-11 beta-4-dimethyl-aminophenyl)17 alpha(1-propynyl)estra-4,9-dien-3-one) was given orally to 32 normally cycling women for 4 days, starting on the fourth day of the luteal phase. Uterine bleeding occurred on the third day of RU 486 administration in all 14 women treated with 100 mg/day, in 7 of the 8 women treated with 50 mg, and in 8 of 10 women receiving 25 mg/day. Premature luteal regression induced by RU 486 occurred in 8 women treated with 100 mg/day, in 3 treated with 50 mg, and in 2 receiving 25 mg/day. Plasma LH was measured every 15 min from 0800-1200 h for 5 days in 17 women. Mean LH levels decreased and pulsatile release disappeared in 7 of the 8 women treated with 100 mg, in 2 of 4 receiving 50 mg, and in 1 of 5 treated with 25 mg. RU 486 had no effect when given to 5 women with anovulatory cycles for 4 days starting on day 18 of the cycle. IN CONCLUSION: 1) RU 486, given to normally cycling women at midluteal phase, provokes uterine bleeding. 2) This effect occurs whether or not luteal regression is induced by the compound, indicating that RU 486 acts directly upon the endometrial tissue, very likely at the progesterone receptor level. 3) The drug may impair simultaneously or separately luteal function and gonadotropin secretion in a dose-dependent manner. 4) The lack of antiglucocorticosteroid activity, at the dosage of 100 mg/day, suggests that RU 486 may be useful for fertility control.

Adrenocorticotropic Hormone↗
PubMed1985

The genetic background of circadian and ultradian rhythm patterns of 17-hydroxycorticosteroids: a cross-twin study.

Circadian and ultradian rhythms in urinary excretion of 17-hydroxycorticosteroids were documented individually during an 8-day span in two pairs of young male twins. Studies were performed once at the age of 6 years for dizygotic twins and twice at the ages of 4.3 and 10.3 years for monozygotic twins. Four different methods were used for time-series analyses: chronograms (raw data), best-fitting curves resulting from cosinor analyses, power spectra and correlations of time-qualified data. Estimates of rhythm parameters (prominent periods, acrophases, etc.) as well as shapes of curves were closer in mono- than in dizygotic twins. Both similarities and small differences in rhythm characteristics of monozygotic twins were detected at both ages considered.

17-Hydroxycorticosteroids↗
PubMed1985

Hypothalamo-pituitary regulation of thyrotrophin secretion in chronically catheterized Brattleboro rats.

Plasma TSH rhythms were measured in Brattleboro (DI) and control Long-Evans (LE) rats with an intracardiac catheter allowing repeated sampling in conscious unstressed animals. The TSH response to thyrotrophin-releasing hormone (TRH; 500 ng/100 g body weight) was also determined. Finally, hypothalamic and pancreatic TRH concentrations and TRH-degrading activity (TRH-DA) were measured by specific radioimmunoassay. Long-Evans rats had a 24-h rhythm with a major modulatory 8-h component. In DI rats, only the 24-h rhythm was detected. The mean 24-h rhythm-adjusted mean TSH level was higher in DI than in LE rats (1.38 +/- 0.05 and 1.14 +/- 0.06 micrograms/l respectively, P less than 0.01). The peak TSH response to TRH was significantly increased in DI rats while the pituitary concentration of TSH was also higher (0.93 +/- 0.09 vs 0.39 +/- 0.06 micrograms/mg wet weight in LE, P less than 0.001). Hypothalamic TRH and TRH-DA were similar in both strains. The response to propylthiouracil-induced hypothyroidism was identical in both strains. We conclude that DI rats have a normal pituitary sensitivity to tri-iodothyronine but a central dysfunction in the pituitary environment leading to some alterations of TSH secretion.

Animals↗
PubMed1985

Seasonal variations in socially and legally unacceptable sexual behaviour.

The calendar dates, over the 15-year span 1966-1980, of committed rapes by eight male recidivists and offences of sexually indecent or immoral behaviour by eight other male recidivists were gathered from the files of the Préfecture de Police, Paris, France. Each offender of the first group had committed from two to six rapes, while each offender of the second had committed from two to 16 incidences of indecent behaviour. Although the reported rapes took place during several calendar years, almost all, 18 out of 22 offences, were committed by the eight rape-recidivists during the 4-month span of July-October. Single cosinor analysis of these data revealed a circannual rhythmicity (P less than 0.03) with luminal diameter being 10 August +/- 34 days (the 95% CL). The peak time of indecent sexual behaviour, exclusive of rape, against females occurred during September with secondary peaks in February and June; such offences directed against males peaked in October. 'Bootstrap' and 'Jackknife' methods confirmed seasonality within all data sets, except for the offences of indecent behaviour.

Adolescent↗