Search PubMed⌕ Search

Biomedical subjects

L E Scheving

Publications and source records attributed to L E Scheving.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Mean circadian cosinors of vital signs, performance of blood and urinary constituents in patients with leprosy.

We have herewith examined the characteristics of circadian rhythms in patients with lepromatous leprosy, active or inactive, allowing a comparison with corresponding properties of rhythms in healthy subjects mapped earlier. Group results were illustrated by cosinor plots, produced directly on microfilm by computer. Eventually such reference standards in the form of cosinors, among other displays, notably of waveform, may be individualized and carried on a person's health record. Such a quantitative assessment of an individual's rhythms in health may serve for rigorous comparison with any changes accompanying increased susceptibility or occult or overt disease.

Adult↗
PubMedDate not supplied

Chronobiologic lead study cost-effectively assesses circadian-circaseptan intermodulation in murine pineal melatonin content.

The investment into the design of a study is usually and unfortunately proportional to the available information, i.e. the less one knows the more one is tempted to skimp and perform a minimal 'pilot' study. This is particularly true with respect to chronobiology. On the contrary, at the outset of a study, when the information available regarding a given problem is minimal or zero, the investment into a first study should be near-maximal. Accordingly, the often wasted 'pilot study' should be replaced by a rigorous chronobiologic lead study. The promise of such a chronobiologic 'guide, leading along a difficult or unknown course' is illustrated by the validation with statistical significance of an about-weekly (circaseptan) and an about 24-h (circadian) rhythm in the melatonin content of the murine pineal. Work around the clock on 48 female Lewis/S rats was avoided. Replication of 6 different circadian times on different comparable animals on consecutive days assessed a circaseptan rhythm more prominent than the concomitantly demonstrated circadian, at no added cost for experimental animals beyond those often used for circadian study and with no work around the clock.

Animals↗
PubMedDate not supplied

Circadian influence on the immunization of mice with live Bacillus Calmette-Guérin (BCG) and subsequent challenge with Ehrlich ascites carcinoma.

Non-specific immunostimulation with Bacillus Calmette-Guérin (BCG) is of current interest in the treatment of cancer. The main objective of the series of experiments described in this paper was to evaluate the influence the host's circadian system has on a. the stimulation of the immune system with BCG and b. the subsequent efficiency of that stimulated immune system against the Ehrlich Ascites Carcinoma (EAC). There was a circadian rhythm in the length of survival time in non-immunized mice challenged with the EAC. Mice receiving an EAC challenge during the middle of the light period survived significantly longer than those challenged with the EAC around the time of transition from dark to light. Mice immunized with BCG and challenged with EAC also demonstrated a circadian rhythm in the length of survival 30 days after EAC challenge with 86% survivors in the mice treated at 10(00) and 60% survivors in the mice treated at 07(00). The same relationship was also observed 70 and 80 days after EAC challenge. Eighty days after EAC challenge, a circadian rhythm was apparent in the frequency of solid tumors at the site of the initial EAC injection. The highest incidence of solid tumors occurred at 13(00). A circadian rhythm was found in the increase in body weight between the first and second BCG or saline injections. Rectal temperatures recorded on the 8th, 12th and 16th day after EAC challenge were characterized by circadian rhythmicity. In the mice without development of ascites, the peak temperature consistently occurred at 01(00). In the mice with ascites there was a phase advance in the rectal temperature rhythm of 3 h so that the peak in the rhythm consistently occurred at 22(00). In the mice with ascites a further finding was an increasing hypothermia as the ascites continued to develop; however, this hypothermia was not detectable during the time of the peak (10(00)) in the temperature rhythm. The mice which did not die by the 80th day after EAC challenge were challenged again with 5.0 x 10(6) EAC cells, and during the next 46 days circadian variations were observed in the numbers of mice which survived. Similar changes were observed during an additional 46 days after a third EAC challenge of 41.5 x 10(6) cells.

Animals↗
PubMedDate not supplied

Chronochemotherapy: L 1210 leukemia and beyond.

In cancer and other therapeutic research, an interpretation of median survival times can and should take cure into account. With this qualification, an analysis of recently published data provides further statistically significant evidence in favor of cancer chronotherapy as compared to homeostatic therapy.

Animals↗
PubMedDate not supplied

Nomifensine chronopharmacology, schedule-shifts and circadian temperature rhythms in di-suprachiasmatically lesioned rats--modeling emotional chronopathology and chronotherapy.

Some emotional disorders are associated with alterations of biological rhythm characteristics ('echronism'). Chronotherapy aims empirically to 1. optimize the kind and timing of conventional psychopharmacologic treatment and, need be, to use such old or new molecules in the rational endeavor to 2. correct (disease-determining) rhythm alteration directly. With respect to the first aim, a reduction by timing of undesired pharmacodynamic effects, as well as an amplification of empirically desired ones, can be dramatically illustrated by circadian rhythms in tolerance to many drugs affecting the central nervous system of rodents. A more rational approach is aimed at correcting ecchronism. The new antidepressant drug, nomifensine, achieves this task in rats with bilateral suprachiasmatic lesions, exhibiting in the telemetered core temperature an echronism of varying degrees. In this model system for the chronobiotic treatment of ecchronism, the properly timed administration of nomifensine speeds the adjustment of bilaterally (suprachiasmatically) lesioned rats to a shift in the synchronizing light-dark schedule. With methodologic provisions, notably for treatment timed by pertinent marker rhythms, nomifensine deserves clinical tests in psychochronotherapy.

Animals↗
PubMedDate not supplied

Circadian ACTH 1-17 effects on murine tritiated thymidine incorporation into DNA of thymus, bone marrow and spleen; also on total splenic RNA and DNA.

The importance of administration time along the 24-h scale is shown for a potent corticosteroidogenic adrenocorticotropin analogue, ACTH 1-17 (Synchrodyn 1-17). This molecule affects the incorporation of [3H]TdR into DNA (DNA synthesis) in the thymus, bone marrow and spleen, and total RNA and DNA of spleen in CD2F1 mice, standardized in light alternating with darkness at 12-h intervals. As a function of timing, the same dose of ACTH 1-17 at one time increases, at another time decreases (in each case with statistical significance) and at still another time elicits no response in DNA synthesis or in total RNA and DNA of spleen. Effects upon DNA synthesis are recorded with doses of 0.02 IU/kg body weight. The most marked effect with 20 IU/kg body weight is a decrease of DNA synthesis seen (4 h) after administration of ACTH 1-17 late in the dark span and early in the light span. The effect of ACTH 1-17 on the thymus is more prominent than that on bone marrow and spleen. Time-dependence also characterizes placebo effects by comparison to values in untreated controls. At the cellular level responses to ACTH 1-17 or placebo are characterized by critical interactions of treatment kind with treatment timing as well as interval-to-kill-time. The study documents the need to time-specify, in several ways, responses to ACTH 1-17 and suggests more broadly that 'increases' and 'decreases' may have to be complemented by changes in endpoints of rhythms in all those endocrine studies that involve rhythmic variables and rhythm-dependent effects upon these variables.

Adrenocorticotropic Hormone↗
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↗
PubMedDate not supplied

Synthetic adrenocorticotropin for optimizing murine circadian chronotolerance for adriamycin.

An attempt to pre-set the circadian rhythm in murine chronotolerance for adriamycin (ADR) given i.p. or i.v. with ACTH was performed in three studies. In CDF1 mice standardized in LD12:12, it was demonstrated that 1) the circadian rhythm in murine chronotolerance for ADR exhibits a different timing depending upon whether the intravenous or intraperitoneal route is used for the administration of this anticancer agent; 2) ACTH or saline pretreatment does not enhance optimal circadian-stage-qualified ADR tolerance, whatever its route of injection, with any of the circadian stages and schedules explored; 3) near-optimal tolerance can be achieved by a fixed 'best' interval (among those investigated) between ACTH and ADR, irrespective of circadian stage. Tolerance equivalent to optimal circadian-stage-qualified ADR tolerance results from the administration of ACTH 1-17 (HOE433 = Synchrodyn) 24 hours before ADR injection; 4) and acrophase advance of over 6 hours of the tolerance rhythm results from ACTH 1-17 administration at 6 HALO. The acrophase changes do not directly account for an optimal ADR tolerance at a fixed interval of 24 hours after ACTH 1-17. Thus, ACTH may be considered a potential relative chronizer of murine chronotolerance for ADR.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Chronobiology of human blood pressure in the light of static (room-restricted) automatic monitoring.

Systematic 24-h automatic physiologic monitoring has obvious merits, even without rhythmometry. It can lead more readily to the recognition of odd-hour blood pressure elevation (e.g., of 'evening' or 'morning' hypertension). Such a condition can constitute an initial diagnosis or it may be found under treatment that may seem to be satisfactory if its effects are assessed only on the basis of a conventional check at a casual, possibly 'wrong' time. The mere inspection of a 24-h record, however, does not necessarily allow one to make objective quantitative global statements as to a change in pattern, e.g., after a given intervention. This paper illustrates how by rhythmometry, some of the uncertainties of a subjective interpretation of a record may be removed by practitioners of medicine, as well as basic scientists interested in mechanisms of blood pressure variability. This is possible since a large part of blood pressure variability can be accounted for by its circadian periodic behavior. We herein present a methodology for data collection and analysis that allows the objective quantification of blood pressure rhythm parameters in health and disease and the derivation of reference standards for such parameters. The chronobiologic approach thus makes it possible to define 'hypertension' objectively, and to distinguish between 'mesor-' and 'amplitude-hypertension', i.e., between an elevation in overall mean and one in the predictable extent of variability. Moreover, chronobiology has shown that mesor-hypertension may be preceded by an elevation in circadian amplitude only (amplitude-hypertension). Parameter tests readily allow the assessment, in relation to an objective reference standard, of these conditions, with a defined probability. Similarly, response to drug or non-drug therapy can be established and a given intervention optimized by timing treatment. Using chronobiologic tools in cardiovascular research provides new insights into possible mechanisms underlying mesor- and amplitude-hypertension. The teaching of the chronobiology of blood pressure and autorhythmometry in schools has been proven to be feasible and has been recommended as a step toward self-help for health care.

Adolescent↗
PubMedDate not supplied

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↗
PubMedDate not supplied

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↗