Biomedical subjects
W Nelson
Publications and source records attributed to W Nelson.
Circadian acrophase in peak expiratory flow rate and urinary electrolyte excretion of asthmatic children: phase shifting of rhythms by prednisone given in different circadian system phases.
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Rat body composition: sensor implantation and lighting effects.
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Anomalies of the gallbladder; a review with report of four cases.
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STUDIES OF BLOOD VOLUME IN THE TETRALOGY OF FALLOT AND IN OTHER TYPES OF CONGENITAL HEART DISEASE.
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CEOs influencing hiring decisions.
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Chronobiology: a frontier in biology and medicine.
On the occasion of Franz Halberg's 70th birthday, some of his many achievements are reviewed. We provide a historical background to the development of chronobiology; offer insight into the current state of this new science; and sketch the promise of this discipline for health care and cure. As a tribute to Franz Halberg, in an era of fast-growing technology, an attempt is made to describe his perspective of tomorrow's medicine and biology. The many students he trained throughout his productive career face the challenge of deserving the trust he placed in them and of further implementing his vision. A leader in social pediatrics put it aptly: it will take several generations of researchers to study and master his life's work.
Rhythm scrambling: good, bad or indifferent?
The scrambling of rhythms, i.e. their mixing-up or throwing into disorder, on a variety of schedules of lighting and feeding, left the average overall life span of several groups of mice unaffected. One particularly scrambled schedule prolonged 10th-decile survival time. The phase-shifting of rhythms, in a mammalian simulation of shift-work schedules, need not be harmful and can be indifferent or even beneficial. Such findings have important implications for health, performance and safety in human shift-work by both sexes and for the choice of other schedules, such as those for drug treatments or exercise.
The effects of learners on waiting times and patient satisfaction in an ambulatory teaching practice.
Data regarding waiting times and times with nurses and physicians were recorded for 656 patients visiting a large family practice unit. Patients also provided estimates of their own waiting times and ratings of the acceptability of these waits. The data were analyzed to assess whether any differences exist in terms of waiting times, times with providers, and waiting time satisfaction for patients seen by clinical clerks (medical students), resident physicians, and attending physicians. Consultation times were longer for patients seen by learners, but waiting times were shorter for these patients. Importantly, there were no significant differences in terms of patient satisfaction with consultation time or waiting time satisfaction. Thus, while learners made a noticeable impact on consultation time, the overall effect on the patient booking system was marginal, and there was no negative impact on patient wait time satisfaction. To control for unevenness of type of providers assigned to the different services, only intermediate assessments are included in this study. The conclusions should not be generalized for other types of services.
Inhibition of intrinsic pumping activity in ovine mesenteric lymphatics during endotoxic shock.
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Role of the lymphatic circulatory system in shock.
That the lymphatic vessel participates in the regulation of interstitial dynamics through its ability to contract and propel fluid and protein from the extravascular tissues back to the bloodstream has not been fully appreciated. The "lymph pump" appears to be regulated by local physiologic forces as well as neurogenic and humoral factors. We have assessed the effects of hemorrhage and endotoxin on the ability of the lymph vessel to propel fluid in sheep using a model system that permits the quantitation of lymphatic pumping in vivo without the complication of variable lymph inputs. A major blood loss was found to enhance lymphatic contractile activity and fluid pumping. Considering the large reservoir of fluid and protein in the interstitium and lymph, we speculate that stimulation of the "lymph pump" after hemorrhage might help to re-expand the vascular space. On the other hand, the intravenous administration of endotoxin inhibited lymphatic pumping, suggesting that impaired lymph propulsion in sepsis may contribute to edema by reducing the ability of the lymphatic vessel to remove extravasated protein from the tissues.
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.
Methods for cosinor-rhythmometry.
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Strain-difference in circadian murine chronotolerance to the antidepressant drug nomifensine.
The anti-depressant drug nomifensine (8-amino-1,2,3,4-tetrahydro-methyl-4-phenylisoquinoline) was administered at several dose levels to mice of 2 inbred strains at one of 6 circadian times 4h apart under conditions standardized for light-dark synchronized rhythmometry. A circadian rhythm in tolerance to nomifensine reflected by differences in mortality was demonstrated for both C57 and DBA mice. An interstrain difference in tolerance was also observed.
Construction of rhythm-specified reference intervals and regions, with emphasis on 'hybrid' data, illustrated for plasma cortisol.
Time-specified reference intervals, so-called chronodesms for the interpretation of single samples, have heretofore been proposed for longitudinal data, consisting of repeated samples from a single individual, and for transverse data: single time-specified samples from many individuals. Herein the problem of dealing with hybrid data, namely time series of data collected on a group of subjects, is considered for a derivation of reference intervals that take into account both inter- and intra-individual variability. The formulae are applied to cortisol data (72 samples from each of 10 healthy young adult North American women) with interpretation from both Bayesian and frequentist viewpoints. The provision of reference limits for both single samples and paired rhythm characteristics offers the opportunity of introducing an overdue time-specification and time-structure evaluation into microscopic chronobiology and through it into medical, veterinarian and other practice.
Higher corticosterone values at a fixed single timepoint in serum from mice "trained" by prior handling.
Results of "training" rodents for bioassay of synthetic corticosteroids are not consistent with expectations presumably based upon earlier implied claims stemming, perhaps, from over behavioral patterns displayed by handled as compared to nonhandled rodents (or the observer's wishful thinking?). At the timepoints investigated, "habituation" of mature mice and rats by exposure to handling, injection and killing procedures results in statistically significantly increased corticosterone concentrations. For younger animals the elevation in corticosterone concentration may also be applicable; although, it is not known to what extent we are dealing with an effect of "habituation" and/or age. Lowest hormone concentration occurred in the groups of mice housed undisturbed in an animal chamber separate from the room housing mice subjected to habituation. The results of this study suggest that for certain rodents kept in L from 0600 to 1800 "habituation" for 1 week, at least at the circadian stage corresponding to 0800, is not only ineffectual (in eliminating the rise in serum corticosterone associated with handling) but detrimental to the evaluation of synthetic corticosteroid potency by bioassay (to the extent that such a rise in exaggerated rather than reduced). In these acute experiments, methylprednisolone was more suppressive than dexamethasone and the water soluble ester-salts less suppressive than the 21-hydroxy bases. These results suggest the possibility of important differences in the distributive stage and/or the metabolism of these compounds--factors affecting the speed of onset of the desired as well as undesired effects.
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.
Circadian murine ouabain chronotolerance revisited.
Data published earlier on a possible circadian variation in murine susceptibility to intravenously-administered ouabain and analyzed by conventional biometric methods, were reanalyzed by cosinor procedures. A statistically significant circadian rhythm could thus be demonstrated, contradicting the earlier conclusion that there was no circadian rhythm in susceptibility to ouabain when injected intravenously. Results from this reanalysis agreed with those from previous investigations in which ouabain was injected intraperitoneally or subcutaneously. Thus, a circadian rhythm characterizes murine susceptibility to ouabain given via 3 different routes.