Chronobiology in laboratory medicine.

A critical amount of information has accumulated over the last decades to allow the application of chronobiology to clinical and laboratory medicine. The tasks faced in laboratory medicine include the quantitative measurement of the multifrequency human time structure in health and disease. For this purpose, it is essential to choose an adequate sample size in order to obtain meaningful results and quantitative endpoints which can be interpreted by inferential statistical techniques. No statistical technique is applicable for all purposes and it is essential that the assumptions underlying each technique and its limitation are well known to the investigator. The multifrequency nature of the human time structure has to be kept in mind in order to avoid erroneous results. Time qualified reference ranges have to be established for high amplitude rhythms. Circadian and/or circannual rhythm alterations have been described as group phenomenon in subjects with epidemiologically determined risk states for common diseases, but will require much further studies for the application to individual subjects. Rhythm parameters are new endpoints in the evaluation of the human time structure in health. Alterations of these parameters may occur as cause or as consequence of disease. Recognition of rhythm abnormalities in disease are critical for a meaningful application of chronopharmacology. Time dependent changes in pharmacokinetics and pharmacodynamics have to be taken into account in the interpretation of drug level determinations. A considerable degree of individuality of timing has been documented in some frequencies. This individuality and the rhythm abnormalities found in disease require the study of reference or marker rhythms. If the complexity of the human time structure is clearly understood and its study pursued in a critical manner with quantitative endpoints, chronobiology opens a new dimension in laboratory and clinical medicine.