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Biomedical subjects

F Levi

Publications and source records attributed to F Levi.

At least 361 records · Page 20Linked to original sources
PubMed1982

Circadian time dependence of cisplatin urinary kinetics.

Free platinum urinary excretion kinetics after a 30-min infusion of 60 mg/m2 IV cis-diamminedichloroplatinum (C) were studied during 51 monthly courses of C therapy in 11 patients suffering from a variety of advanced malignancies. Each patient received half of his or her treatment course at 6:00 A.M. and 6:00 P.M. Initial treatment time was randomly assigned and subsequent treatment times were alternated. Each C infusion was accompanied by 4100-ml 5% dextrose and 0.45% NaCl solution given intravenously. Evening C infusion resulted in greater urine output, lower peak urinary platinum concentrations, and lower areas under the curve of cisplatin concentration. While the normal circadian rhythm characteristics of body temperature were not altered by changing the C infusion time, the circadian rhythm characteristics of urine volume 1 mo after treatment were significantly disrupted by morning, but not by evening, C. We conclude: (1) that since the kinetics of certain drugs may be affected by the time of administration, kinetic studies should be performed and reported in a time-qualified fashion, and (2) that it is reasonable to expect that, since kinetic parameters are important in determining drug toxicity and effect, these too may vary predictably during the day.

Adult↗
PubMed1982

[Not Available].

Explore the source record for details and available documents.

History, Modern 1601-↗
PubMed1982

Cisplatin urinary pharmacokinetics and nephrotoxicity: a common circadian mechanism.

Renal toxicity and urinary pharmacokinetics following a nonlethal dose (5 mg/kg) of cisplatin were investigated in female F344 (Fischer) rats that were on a standardized light-dark schedule, with water freely available. Circadian timing of drug administration had a major effect on the BUN increase (P less than 0.01), the urine volume increase (P less than 0.025), and the urinary concentration of cisplatin following drug administration (P less than 0.01). Renal toxicity was positively correlated with the peak urinary concentration of cisplatin and with the area under the curve of urinary concentration over the first 20 hours after drug administration (P less than 0.01). Drug administration near the normal circadian maximum of urinary volume prior to treatment resulted in the least renal toxicity, lowest peak, and smallest area of urinary concentration of cisplatin.

Animals↗
PubMed1980

[Evaluation of the comprehensiveness of a cancer register from death certificates].

The comparison of cancer prevalence with cancer mortality can lead under some hypotheses to an estimate of registration rate. A method is proposed, where the cases with cancer as a cause of death are divided into 3 categories: (1) cases already known by the registry (2) unknown cases having occured before the registry creation date (3) unknown cases occuring during the registry operates. The estimate is then the number of cases in the first category divided by the total of those in categories 1 and 3 (these only are to be registered). An application is performed on the data of the Canton de Vaud. Survival rates of the Norvegian Cancer Registry are used for computing the number of unknown cases to be included in second and third category, respectively. The discussion focusses on the possible determinants of the obtained comprehensiveness rates for various cancer sites.

Humans↗
PubMed1980

Chronotherapy of mammary cancer in rats.

Two studies were performed on female Fischer rats, housed 2/cage with food and water ad libitum in rooms maintained at 24 degrees C and with lights on daily for 8 hours (LD 8:16). In each study 192 rats were innoculated subcutaneously with 13762 mammary adenocarcinoma. Of these, 168 received chemotherapy, separate groups being treated at 1 of 6 different circadian stages. As controls, 24 tumour-bearing rats received saline while 24 rats without tumours received therapy. Chemotherapy consisted of 0.8 mg/kg Adriamycin (ADR) i.p. daily from day 11 to day 19 post tumour inoculation (except for days 16 and 17) followed by 1.6 mg/kg phenylalanine mustard (PAM) p.o. 3 times weekly beginning on day 20. In study-I PAM treatment was continued until 50% of the treated tumour-bearing rats died. In Study-II a 50% overall reduction in mean tumour size was not achieved before regrowth, presumably due to differences in the source of the rats, tumour-heterogeneity and/or other factors. At 50% overall tumour size reduction in the first study there was a statistically significant effect of treatment-timing on tumour size and on percent remission. The greatest reduction in mean tumour size and the highest percentage remission was observed in rats treated at the onset of darkness (activity), a timing similar to that observed in previous studies for optimal tolerance of ADR and PAM by the host. No deaths were observed in treated rats without tumours. When the drug combination used was sufficiently active against the tumour, the therapeutic index (selective toxicity) was improved by timing therapy according to circadian rhythms in the tumour-host system. This effect was achieved with doses not lethal to the nontumourous host. The presumption by others that chronotherapy depends on the use of toxic doses does not here apply.

Adenocarcinoma↗
PubMedDate not supplied

Circaseptan (about-7-day) bioperiodicity--spontaneous and reactive--and the search for pacemakers.

A built-in (genetically determined) about-7-day (circaseptan) period comes to the fore as a desynchronized feature of human time structure in the urinary excretion of 17-ketosteroids by a clinical healthy man: during several years following an endocrine intervention (the self-administration of testosterone suppositories), a circaseptan rhythm (which during the preceding decade had revealed a period of precisely 7 days) deviated slightly, yet with statistical significance, from the environmental week. A second line of evidence for an intrinsic circaseptan component stems from the demonstration of statistically significant differences in timing of a circaseptan rhythm in springtail oviposition. A third line of evidence documents prominent circaseptan rhythmicity after the application of a single stimulus (devoid in itself of any circaseptan information). Such single stimulus induction, amplification and/or synchronization also documents the clinical and biologic importance of built-in circaseptan rhythms that were previously often misinterpreted as being purely reactive: a circaseptan spectral component is remarkably prominent in mammalian organ transplant rejection, both in the clinic and in the laboratory. In the latter case, in the absence of any weekly cycles in hospital routine, including treatment schedules, circaseptan components characterize the rejection of the rat kidney, pancreas and heart. Much additional information here reviewed reveals the occurrence of periods of about 7 days. Their implications for transplant and other chronoimmunology as well as biology in general, and their clinical applications in drug treatment, include the need to weld circaseptan timing to circadian timing and dosing. A dramatic documentation of this need stems from the circumstance that pretreatment for one week with the same total dose of the same substance (a polysaccharide - Lentinan) accelerates or retards cancerous growth (hence shortens or lengthens survival) as a function of interactive circaseptan and circadian rhythms.

17-Ketosteroids↗
PubMedDate not supplied

Female thyroid cancer: the role of reproductive and hormonal factors in Switzerland.

We conducted a study on 91 women with thyroid cancer and 306 controls in hospital for acute nonneoplastic, non-hormone-related disorders in order to investigate the role of reproductive and hormonal factors in the etiology of epithelial thyroid cancer in the Canton of Vaud, Switzerland. Non-significant increases in cancer risk with an increasing number of full-term pregnancies (odds ratio, OR, after allowance for age and previous benign thyroid disease = 1.6, for > or = 3 vs. 0 full-term pregnancies, 95% confidence interval, CI: 0.7-3.6) and spontaneous abortions (OR = 2.0 for > or = 2 vs. 0 spontaneous abortions, 95% CI: 0.7-5.2) were seen. A significantly elevated OR (2.8, 95% CI: 1.1-7.2) was found in those women whose first pregnancy ended with an abortion. Whereas most other reproductive, menstrual and hormonal factors examined did not seem to affect the risk of thyroid cancer significantly, a clue emerged of an association between thyroid cancer and artificial menopause (OR = 6.3, for women who underwent artificial menopause vs. premenopausal women, 95% CI: 1.7-23.2). Although not necessarily causal, the relationship between the risk of epithelial thyroid cancer and the occurrence of spontaneous abortions and artificial menopause deserves attention in future studies, in the light of the high incidence of thyroid cancer in young and middle-aged women.

Abortion, Spontaneous↗
PubMedDate not supplied

Mortality from Hodgkin's disease and other lymphomas in Europe, 1960-1990.

Trends in mortality from Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL) in the whole of Europe and in two broad European geographic areas (Western and Eastern Europe) were reviewed over the period of 1960-1990, on the basis of official death certifications derived from the World Health Organization database. Between the early 1960s and 1990, HD mortality in the whole of Europe declined from 2.1 to 0.9/100,000 males (-58%), and from 1.1 to 0.5/100,000 (-56%) females. The decline was larger in Western Europe (around 65%), but appreciably smaller in Eastern Europe (around 30%). In contrast, mortality from NHL increased in males from 2.2 to 4.2/100,000 (+93%), and in females from 1.2 to 2.6/100,000 (+112%). These upward trends were larger in Western (over 100%) than in Eastern Europe (around 80%). The declines in HD were larger and the increases in NHL were smaller in populations below age 65. When all lymphomas were considered together, an increase was observed in both sexes (from 4.3 to 5.1/100,000 males; from 2.4 to 3.1/100,000 females) that was comparable in various areas of the continent. These data confirm a major impact of newer integrated diagnostic and therapeutic approaches in reducing HD mortality, while indicating that this impact has been delayed and limited in Eastern Europe. The upward trends in mortality from NHL probably reflect both real increases in incidence and better case ascertainment and certification, but are inconsistent with a noticeable impact of newer therapies on mortality from NHL. It is also conceivable that the introduction of immunophenotypic and immunogenotypic characterization of lymphomas has selectively eliminated from HD a worse-prognosis subset previously classified on the basis of Sternbergoid cells, which has been subsequently classified as NHL. This would have increased survival and decreased mortality from HD, while increasing incidence and mortality from NHL to an extent which is unknown but worth considering.

Adolescent↗
PubMedDate not supplied

Trends in skin cancer incidence in Neuchâtel, 1976-98.

AIMS AND BACKGROUND: Limited data are available on trends in skin cancer incidence. This paper examines trends of the three major histotypes of skin cancer in an environment favorable for skin cancer registration. METHODS: Trends of skin cancer incidence by histotype in the Swiss Canton of Neuchâtel (165,000 inhabitants) were analyzed on the basis of 4,455 incident cases of basal cell, squamous cell carcinoma, and malignant melanoma registered over the period 1976-1998. RESULTS: Trends over the last decade considered tended to be downwards for squamous cell carcinoma in both sexes, were still on the rise for basal cell carcinoma, and leveled off for malignant melanoma in both sexes. CONCLUSIONS: Different trends were confirmed in this population between skin cancer histotypes related to cumulative intense sun exposure (squamous cell carcinoma) and those mainly related to more complex patterns of exposure to sunlight (basal cell carcinoma and malignant melanoma).

Female↗
PubMedDate not supplied

Phase II trial of chronomodulated infusion of 5-fluorouracil and folinic acid in metastatic colorectal cancer.

Forty three patients with metastatic colorectal cancer (MCC) received a daily administration of 5-fluorouracil (600 mg/m2/d at the first course, 700 mg/m2/d at the second and 800 mg/m2/d at the third course), and l-folinic acid (150 mg/m2/d) or dl-folinic acid (300 mg/m2/d) both chronomodulated from 22:00 to 10.00 am with peak delivery rate at 4.00 for 5 days every 21 days. Only severe mucositis and diarrhea occurred in 19 courses (5.7% Gr 3; 0.6% Gr 4) in 14 patients. Objective response (OR) was evaluated in 40 patients because of one toxicity and two early progressions. No OR was observed in the 15 previously-treated patients versus 28.5% (8/28) partial responses in chemotherapy naïve patients; overall the median survival was 13 months. These results without toxicity and with low OR rate indicate the necessing of a more intensive treatment and confirm the place of oxaliplatin in the chemotherapy of MCC.

Adult↗
PubMedDate not supplied

Cancer-associated alteration of circadian rhythms in carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in humans.

A circadian rhythm of serum concentrations of two tumor markers (CEA and AFP) was demonstrated in individuals not suffering from cancer. These rhythms exhibited a diurnal peak with a nocturnal dip. They disappeared in cancer groups. However, in some cancer subjects, a circadian activity was still detectable, but with quite different characteristics (time of peak, amplitude) of rhythms when compared to controls. The importance of such findings is discussed with regard to the circadian kinetics of cancer cells, to time scheduled cancer treatments and to the detection of cancer.

Carcinoembryonic Antigen↗
PubMedDate not supplied

Dosing time and sex-related differences in the pharmacokinetics of cefodizime and in the circadian cortisol rhythm.

Two g cefodizime i.v. administration at 00:00, 06:00, 12:00 and 18:00 respectively, to 8 male and 8 female, young healthy volunteers, has shown: 1. a sex-related difference in both plasma (AUC) and total cumulative excretion of the agent with larger values in females than in males; 2. a dosing time-related difference in plasma (AUC) with the largest values for Rx at 00:00 and lowest for Rx at 18:00 in both males and females; 3. a dosing time-related difference in urinary concentration of cefodizime with largest values for Rx at 06:00 and lowest for Rx at 12:00. These urinary changes were highly correlated with changes in AUC for each dosing time; 4. no dosing time-related changes were observed for plasma T1/2 as well as cumulative urinary excretion of cefodizime; 5. curve patterns of plasma cortisol had similar aspects for both control and Rx at 00:00 with no sex-related differences. Curve patterns differed from control for other dosing times (p less than 0.005 to p less than 0.001 with ANOVA tests).

Adult↗
PubMedDate not supplied

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↗