Laboratory medicine concept

Source Adapted from Zane HD. Immunology—Theoretical and Practical Concepts in Laboratory Medicine, Saunders Philadelphia, 2001. 

Abstract The concept of total allowable error , investigated by Westgard and co-workers over a quarter of a century for use in laboratory medicine, comprises bias as well as random elements. Yet, to minimize diagnostic misclassifi-cations, it is necessary to have spatio-temporal comparability of results. This requires trueness obtained through metrological traceability based on a calibration hierarchy. Hereby, the result is associated with a final uncertainty of measurement purged of known... 

The concept of measurement traceability provides probably the most important strategy to achieve standardisation in laboratory medicine aimed at comparable measurement results regardless of the method, the measurement procedure (test kit) and of the laboratory where the analyses are carried out. 

The complete traceability chain as presented here is valid only for those measurable quantities, which can have a value, expressed in SI units. When primary or secondary calibrators are not available the traceability chain for many measurands in laboratory medicine ends at a lower level, e.g. at the manufacturer s standing measurement procedure. In a situation where a manufacturer detects a new diagnostic marker and defines the measurable quantity by establishing a measurement procedure for this marker, the manufacturer s measurement procedure will form the top of the traceability chain. Nevertheless even in this simple situation the principles of the traceability concept are applicable. 

Traceability is not really a new fundamental concept in the field of laboratory medicine. Many years before the concept traceability had been mentioned in general chemical metrology, reference measurement procedures and reference materials had been established in clinical chemistry. Some basic experimental work for the development of reference measurement procedures and reference materials had already been undertaken in expert laboratories. 

To assess errors associated with laboratory results in a systematic way, the uncertainty concept has been introduced in laboratory medicine. According to the ISO Guide to the Expression of Uncertainty in Measurement ( GUM )> uncer-... 

The realisation that every laboratory determination that is carried out is associated with both random and systematic errors has had a major impact on laboratory medicine in the last thirty years. It is also at the heart of quality control and quality assurance procedures which are primarily concerned with understanding the sources of such errors and their suppression or minimisation (Whitehead, 1977 Aitio, 1981 Taylor, 1987). However, it has been pointed out by Broughton (1983) that all laboratories may carry out some form of "quality control" but this is often designed to give retrospective reassurance rather than provide prospective action. The dual concepts of bias and precision in laboratory medicine are well known, but not always appreciated even by users of reference materials (Taylor. 1985 Taylor, 1987). By definition an unbiased result should be the "true" result, but in practice this is hardly ever achieved. The nearest approach to a true value is generally obtained by using a certified reference material and a definitive method, but these ideals are unobtainable in the case of most trace metal analyses. 

This was not the case outside of Europe By 1300 Chinese and Indian alchemists were actively engaged in iatrochemistry—the application of alchemy to medicine—but iatrochemistry did not fully evolve in Europe until 200 years later. Chinese and Indian alchemical writers also devoted much thought to the proper design of a laboratory, another concept that did not appear in European alchemical literature until about 1500. For example an Indian treatise of this period, the Rasaratnasamuchchaya, contains the following description ... 

As with all branches of science, polymer chemistry is continually advancing. New topics in polymer chemistry which involve new concepts, new polymers or novel uses for existing materials are being studied in research laboratories throughout the world. In this chapter, some of the more important of these developments are described including the use of polymers in medicine, electronically conducting polymers, and polymer liquid crystals. 

Harmonization of pharmacopeial standards as a practical matter began at the International Congresses of Pharmacy between 1865 and 1910 [2], but the first formal attempt can be traced to 1902. Both USP President Horatio C. Wood, M.D., and Frederick M. Power, Ph.D., an American chemist of the Wellcome Chemical Research Laboratories of London, were appointed by the U.S. Secretary of State as delegates to represent the United States government at the International Conference for the Unification of the Formulae for Heroic Medicines, a conference of 19 countries from Europe and North America [3]. The second conference occurred in 1918. The 3rd in 1925 was attended by 31 countries from all continents except Asia and Australia. They drafted a new International Convention, which came in force in 1929. It revised the 1902 agreements on 77 heroic medicines and introduced the concept of maximum dose. It also requested that the League of Nations create a permanent secretariat of pharmacopeias [4]. Andrew G. DuMez, Ph.D., represented the USP, and was officially appointed by the U.S. Public Health Service to represent the United States at this conference [4,5]. An expert committee of the League of Nations planned a third conference for 1938, but it was never convened because of World War II [2]. 

Eijkman was director of the Geneeskundig Labora-torium (medical laboratory) in Batavia from 1888 to 1896, and during that time he made a number of important discoveries in nutritional science. In 1893 he discovered that the cause of beriberi was the deficiency of vitamins, not of bacterial origin as thought by the scientific community. He discovered vitamin B, and this discovery led to the whole concept of vitamins. For this discovery he was given the Nobel Prize in physiology or medicine for 1929. 

More than 15 additional trace elements are considered by some investigators to have a potentially important role in human medicine. A review by Nielsen considers these in detail and discusses emerging concepts of essentiality. For some such as lead, cadmium, arsenic, aluminum, and nickel, the clinical laboratory will primarily consider them as toxic elements (see Chapter 35). Others, such as lithium and fluoride, are classified as pharmacologically beneficial and monitoring of dosage may be required. Some elements can be considered nutritionally beneficial and are reported to produce restorative health effects at lower dosages. Evidence comes mainly from animal studies when dietary depletion of the element is combined with other metabohc, hormonal, or physiological stressors. ... 

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