Adaptive and nonadaptive consequences of chemical inhibition of intercellular communication.

Intercellular communication is a fundamental process in multicellular organisms developed to orchestrate homeostatic control of mitotic and differentiation processes in pre- and postmitotic cells. Endogenous and exogenous chemicals can, via a series of mechanisms, interfere with intercellular communication between and within various tissues. The responses to the inhibition of non-gap-junctional and gap-junctional communication can be either adaptive or nonadaptive depending on the mitigating circumstances. The inhibition of gap-junctional communication appears to be one of the sequelae of a membrane-triggered response to many natural and man-made pharmacological chemicals. The biological consequences of inhibited intercellular communication might include teratogenesis (embryo or fetal toxicity), tumor promotion, reproductive toxicology, and neuroendocrine-related disorders.

A scale for assessing the severity of diseases and adverse drug reactions. Application to drug benefit and risk.

Physicians were interviewed to assess their willingness to risk adverse drug reactions among patients. These untoward reactions were ranked according to severity and weighted against the primary illness being treated. A specially designed questionnaire in the form of a matrix was used. Severity was divided into seven classes denoted by progressively increasing numerical scores, W1 to W7, whose values could be calculated from analysis of the completed questionnaires. The questionnaires presented several cases, in each of which an illness of specified severity was to be treated with a drug whose untoward reactions differ in severity from that of the primary illness. Each case involved a different permutation of the severities. Analysis of the completed questionnaires yielded the mean values of the scores which were found to range from W1 = 1.00 (the mildest case) to W7 = 817 (the most serious case). It is our opinion that this type of scale is preferable to nonnumerical descriptions of severity such as "mild" or "serious," since, when combined with data on frequency of occurrence, a numerical scale permits a determination of expectation of both benefit and risk.