Cumulative Subject selectivity

These studies demonstrated that DNA-binding can be a reliable probe of metabolic activation. In contrast to studies of metabolites per se, which usually involve large numbers of metabolite intermediates, DNA-binding monitors only chemically reactive metabolites. Also, if there is no selective repair of specific adducts, DNA-binding monitors the cumulative production of metabolites over time, while direct measurement of metabolites can show the metabolite spectrum only at the time observed. This can be particularly critical for studies of activation of complex chemicals such as polycyclic aromatic hydrocarbons whose primary metabolites are subject to secondary and tertiary metabolism (8). 

Patrignani P, Filabozzi P, Patrono C Selective, cumulative inhibition of plate-let thromboxane production by low-dose aspirin in healthy subjects. J. Clin. Invest 2-1366,1982... 

We now come to the subject of simplified reaction-center complexes, which have been found to be particularly valuable for the study of various components along the electron-transport chain in photosystem I. The basic strategy used for obtaining simplified PS-I reaction-center complexes was to selectively remove the components one-by-one cumulatively along the electron-carrier sequence, starting from the terminal end of the chain. 

Figure 1 shows a hypothetical tolerance frequency distribution, f(D)dD, along with its corresponding cumulative distribution, P(D). Thus, when the response is quantal in nature, the function P(D) can be thought of as representing the dose-response either for the population as a whole, or for a randomly selected subject. The notion that a tolerance distribution, or dose-response function, could be determined solely from consideration of the statistical characteristics of a study population was introduced independently by Gaddum (2) and Bliss (3). 

FIGURE 5—4 Frequency distribution curves and quantal concentration-effect and dose-effect curves. A. Frequency distribution curves. An experiment was performed on 100 subjects, and the effective plasma concentration that produced a quantal response was determined for each individual. The number of subjects who required each dose is plotted, giving a log-normal frequency distribution (colored bars). The gray bars demonstrate that the normal frequency distribution, when summated, yields the cumulative frequency distribution—a sigmoidal curve that is a quantal concentration-effect curve. B. Quantal dose-effect curves. Animals were injected with varying doses of sedative-hypnotic, and the responses were determined and plotted. The calculation of the therapeutic index, the ratio of the to the ED q, is an indication of how selective a drug is in producing its desired effects relative to its toxicity. (See text for additional explanation.)... 

The selection of structural materials and welding methods shall be based upon codes and standards acceptable to the Regulatory Body. Consideration shall be given to the potential cumulative effects of radiation on materials likely to be subjected to significant radiation fields. 

These are critical and selective reviews published at intervals containing extensive bibliographies. Each volume has an author and subject index and there are occasional cumulative indexes of chapter titles and authors. 

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