Clinical Analyses—Common , Determinations

The POCL reaction has been used for trace determinations of hydrogen peroxide, most commonly in environmental and clinical analysis [26-52], The latter applications often include various enzyme systems [34-52], where a number of substrates can be indirectly determined by measuring the hydrogen peroxide that is produced as a by-product in the enzymatic reaction. 

Concern over dioxins originally arose over one particular dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). This was found to produce clinical effects (chloracne) in workers exposed to it through industrial accidents.35 It is also toxic to some species of laboratory animals. A few PCBs have been shown in experimental systems to exert a number of toxic responses similar to those observed for TCDD. In consequence, the total concentrations of both dioxins and PCBs in environmental media, including food, are now commonly determined as part of the same chemical analysis, and each cannot be discussed now without reference to the other. 

Until now, most studies have focused on forensic considerations. However, another exciting application of hair anlysis may be clinical investigations. The determination of plasma or urine concentrations of the monitored drugs is commonly used for that purpose however, such analyses may reflect only the exposure within a few days prior to obtaining the specimen. Hair analysis may represent an appropriate alternative, by providing information on the degree of exposure over a long time scale — weeks or months. 

In clinical chemistry the determination of stable elements by radiochemical methods offers no outstanding advantages over alternative methods, but the use of radioisotopes for determining organic compounds is developing rapidly. In isotope dilution methods (G6), a pure but radioactive form of the compound to be measured is mixed with the sample, a fraction is isolated, and its activity is determined. In radio-metric or derivative analysis (W14), a radioactive reagent is allowed to react with the analyte the labeled compound is separated and its activity is measured. The isotopes commonly used are C,... 

Table 24.1 summarizes the normal range of concentrations of some clinically important constituents in human blood. We should emphasize that these normal ranges are approximations. Table 5.3 summarizes the major electrolyte composition (cations and anions) in blood. The analysis of some of the more commonly determined constituents will be discussed below. The physiological significance of the results is also discussed. 

Gas-liquid chromatography (GLC) is the most commonly used method for the forensic and clinical analysis of ethanol. Cadman and Johns in 1958 first reported a GLC method for determining blood ethanol concentrations. They extracted ethanol from samples prior to analysis by adding equal volume of n-propyl acetate (1ml) to a blood sample (1ml) to extract ethanol. No internal standard was used. A fixed volume of extract (35 pi) was injected into a GL chromatograph equipped with a thermal... 

Perhaps the most common type of problem encountered in the analytical lab is a quantitative analysis. Examples of typical quantitative analyses include the elemental analysis of a newly synthesized compound, measuring the concentration of glucose in blood, or determining the difference between the bulk and surface concentrations of Cr in steel. Much of the analytical work in clinical, pharmaceutical, environmental, and industrial labs involves developing new methods for determining the concentration of targeted species in complex samples. Most of the examples in this text come from the area of quantitative analysis. 

Analytical methods for the determination of one antidepressant and/or its metabolite(s) were usually performed in isocratic mode, with total run times from seconds to a few minutes. However, as previously mentioned, multianalyte procedures are preferable, particularly if the method is intended for clinical or forensic analysis. Gradient separation was usually applied when the most common antidepressants were included in the methodology however, total chromatographic run times varied widely, from 5 to 40 min [57, 76], depending on column length, extraction technique (offline vs. online techniques), biological matrix or the specific application of the method. 

Statistical analyses result in a test statistic being calculated. For example, two common tests that will be introduced in this chapter are the f-test and a test called analysis of variance (ANOVA). The /-tests result in a test statistic called /, and ANOVA results in a test statistic called F. When you read the Results sections of regulatory submissions and clinical communications, you will become very familiar with these test statistics. The test statistic obtained determines whether the result of the statistical test attains statistical significance or not. 

Individually, the cholinesterase inhibitors improve memory in patients with AD. There have been no head-to-head comparisons made of the drugs to determine w hether one is more effective than the others and no trials of agents in combination. The main know n differences are the side effect profiles, titration schedules and the dosing regimens (Table 39.1). The most common side effects of treatment with cholinesterase inhibitors are gastrointestinal and include nausea, vomiting and diarrhea. A meta-analysis of the efficacy and safety of these agents revealed that despite many clinical studies show ing... 

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