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Biomedical subjects

F Levi

Publications and source records attributed to F Levi.

At least 343 records · Page 19Linked to original sources
PubMed1987

Aspects of chronopharmacology and chronotherapy in pediatrics.

Pediatric chronopharmacological findings until now have been limited to circadian changes in children from ages 6 to 15 years. This means that data in newborns and even in infants of 1 year are not available and other bioperiodicities with periods of about-1-year (infradian rhythms) have not been explored in older children. Biologic time-related changes have been documented for phenytoin and theophylline with regard to pharmacokinetics, for orciprenaline with regard to bronchodilation, and for corticosteroids as well as anticancer agents with regard to their effectiveness. Despite the limited number of experiments performed to date, it is already possible to state that a chronopharmacological approach provides better precision in pharmacologic study than the conventional approach not using time-related data and better therapeutics can be achieved with the help of chronopharmacological facts since appropriate timing in administration of medicine usually enhances its desired and/or reduces its undesired effects.

Adrenal Cortex Hormones↗
PubMed1986

[Colorectal polyps and cancers by sub-site: epidemiologic findings in Geneva and Vaud].

The present study is a comparative analysis of the adenomatous polyps and colorectal cancers, registered during a determined period within the population of the cantons of Geneva and Vaud. The analysis is particularly based on the polyp/cancer ratio by sub-site. Histological type as well as age and sex of the patient are taken into consideration.

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↗
PubMed1985

[Barrett esophagus. Retrospective study of 258 cases].

Barrett's esophagus, nearly always an acquired disease, is neither rare nor a curiosity, having been diagnosed in 258 out of 2573 patients with reflux esophagitis. It was associated with esophageal adenocarcinoma in 29 cases (11.2%) and with non-esophageal cancer in 72 cases (27.9%).

Adenocarcinoma↗
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

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

[Nycthemeral change in the anticoagulant effect of heparin given at a constant rate by the intravenous route].

Six subjects with venous thromboembolism volunteered for this prospective study. Heparin was administrated intravenously at a constant rate with an infusion pump. The activated partial thromboplastin time (A.P.T.T.) and thrombin time (T.T.) were measured every 4 hrs. for 48 hrs. These coagulation tests exhibited a nycthemeral variation with a large amplitude which was reproducible from one day to the next and statistically validated by the cosinor method (p less than 0.001). All patients had a nocturnal peak of A.P.T.T. and T.T. on both days. In four patients this peak for A.P.T.T. exceeded the upper desired limit.

Aged↗
PubMed1984

[Clinical chronopharmacokinetics].

Circadian (approximately or equal to 24 hours) and other endogenous biological rhythms, detectable at all levels of organisation, constitute a temporal structure in all species, including man. Circadian, circannual, and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical and chemical agents, including medications and foods, are rather common phenomena. A better understanding of periodic and thus predictable changes in drug effects can be attained through consideration of three complementary concepts: the chronopharmacokinetics of a drug (rhythmic changes in its pharmacokinetics), the chronesthesy (rhythmic changes in susceptibility of target biosystems to the drug), and the chronergy (the drug-integrated overall effects). The chronopharmacokinetics of many drugs have been evaluated in man (tables I-IV) including sodium salicylate, aspirin, indomethacin (fig. 1), sustained-release indomethacin, paracetamol (acetaminophen), phenacetin, amidopyrine, theophylline sustained-release theophylline (fig. 2), aminophylline, sustained-release aminophylline, digitalis, propranolol, clorazepate, hexobarbitone (hexobarbital), diazepam, midazolam, lithium, phenytoin (diphenylhydantoin), nortriptyline, ethanol, erythromycine , ampicillin, sulfasymazine , sulphanilamide, cis-diammine-dichloroplatinum (fig. 3), mequitazine (fig. 4), d-xylose, ferrous sulphate, potassium chloride, hydrocortisone and prednisolone, among others. The roles presumably played by circadium rhythms in drug metabolizing liver enzymes (fig. 5), and kidney function are summarized, and the practical implications of chronopharmacokinetics, aiming both to improve in a quantitative manner the metabolic fate of a drug and its effectiveness, are discussed.

Anesthesia↗
PubMed1983

Circadian and seasonal changes in ACTH-induced effects in healthy young men.

The effects of the ACTH 1-17 analogue (100 micrograms i.m.) as a function both of time of day (7.00, 14.00 and 21.00 h) and season (winter versus summer) were determined on a set of physiological variables: urinary 17-hydroxycorticosteroids, oral temperature, grip strength (right and left hands), peak expiratory flow and self - rated fatigue. Six young healthy males took part in the study in January-February 1980 and June-July 1981. They were synchronized with a diurnal activity from 7.00 to midnight and a nocturnal rest. Urine was collected every 3 to 4 hours, at fixed clock hours over 72 h (winter) and 48 h (summer). There was a one week interval between each ACTH test or placebo control. Variables were measured according to the same schedule. 24 h urinary 17-OHCS excretion was maximum for ACTH injected at 7.00 in winter and 14.00 in summer, and the minimum occurred after ACTH given at 21.00. The highest peak of urinary 17-OHCS was found after ACTH at 7.00 both in winter and in summer. It is likely that the maximal stimulation of glucocorticoid secretion occurs when ACTH is administered around the beginning of the activity span. Both in winter and summer the injection of ACTH at 7.00 was followed by the greatest decrease in self-rated fatigue (24 h mean) and the largest increase (24 h mean) both in grip strength and peak expiratory flow (bronchial patency) in comparison with other times of ACTH administration (14.00 and 21.00 h).

17-Hydroxycorticosteroids↗
PubMed1983

Aspects of clinical chronopharmacology.

Circadian (congruent to 24 h), circannual (congruent to 1 year) and other biological rhythms of endogenous origin, detectable at all levels of organization, constitute a temporal structure in all animal species, including man. Circadian, circannual and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical as well as chemical agents including medications and foods are rather common phenomena. Modern chronopharmacology investigates drug effects: (a) as a function of biological timing, and (b) upon parameters characterizing the endogenous bioperiodicities. A better understanding of periodic and thus predictable changes in drug effects can be attained through consideration of three complementary concepts: the chronokinetics of a drug (rhythmic changes in its pharmacokinetics); the chronesthesy (rhythmic changes in susceptibility of target biosystems to this drug), and the chronergy (the drug integrated overall effects). One of the aims of chronopharmacology is solving problems of drug optimization. Knowledge of those administration times coinciding with best effectiveness or tolerance is required to optimize both timing(s) and dosage(s) of a medication. Illustrative examples of both experimental and clinical investigative chronopharmacology are corticosteroids and anticancerous agents.

Adult↗
PubMed1982

Antibody-dependent cellular cytotoxicity against drug-induced antigens in L5178Y mouse lymphoma.

In vivo treatment with antineoplastic compounds has been reported to lead to the expression of new antigenic specificities which were not detected on parental cells, and which were transmissible as a genetic character. The current study is concerned with antibody-dependent cellular cytotoxic (ADCC) activity in serum of syngeneic mice challenged with LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. LY/DTIC target cells coated with LY/DTIC-immune serum were specifically lysed by virgin lymphocytes. The genetic background of the effector cells, whether syngeneic, allogeneic or xenogeneic, did not produce significant differences in the percentage of target-cell lysis. ADCC activity was reduced when the immune serum was added directly to the incubation medium, without precoating. Although sera from individual animals exhibited different levels of ADCC activity, they nevertheless followed the general trend of the pooled sera. Peak activity of ADCC was obtained in the sera collected on Days 8 and 30 after LY/DTIC cell challenge. The ADCC activity elicited by LY/DTIC cells may contribute to the rejection of drug-altered tumour cells.

Animals↗