Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. VI. Isolation and properties of permeability factor and its inhibitor in human plasma.
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Biomedical subjects
Publications and source records attributed to A A MILES.
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An examination is made of the arguments for and against measuring the agglutinating potency of standard antisera in terms of "units" instead of in terms of serum "titre".
All types of tuberculin, crude and pure alike, have in the past been assayed by "matching" the skin reactions they produce in sensitized animals with those produced by the International Standard for Old Tuberculin; furthermore, a variety of sensitizing antigens have been used. Such "matching" assays are not easy to analyse statistically.An assay is described, based on the linear relationship between the diameter of the skin reaction and the logarithm of the dose of tuberculin. This type of assay is shown to be precise. It eliminates the need for preliminary titrations and provides information about the slope of the dosage-response lines, and it yields fiducial limits of error from the internal evidence of the assay.Using this method, a comparative study is made of the effects of varying both sensitizing antigens and test allergens. It is shown that there is sufficient heterogeneity among these different types of tuberculins to make invalid their comparison in terms of a single standard, namely, the International Standard for Old Tuberculin.
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The relation between the biological activity of drugs, expressed in terms of international units, and their therapeutic efficacy is neither simple nor constant, varying with the patient, the disease, and the drug, together with a number of other factors. Yet clinicians and pharmaceutical manufacturers understandably demand as simple a relation as possible between unitage and efficacy. The authors examine the implications of that demand and consider how far bio-assay in terms of units can be adapted to meet it. For this purpose they select three substances whose standardization is under consideration by the WHO Expert Committee on Biological Standardization: adsorbed diphtheria toxoid, delay insulin, and corticotrophin. In their conclusions, they consider that unitage should be regarded simply as a statement of the amount of active principle present, and that it should be taken as an indication of efficacy only when the efficacy depends on the content of active principle. Where different dosage-response relationships of an active substance, and of the same substance compounded to increase efficacy, entail the establishment of a standard for the "compound", the unitage of that compound must be expressed in terms of the number of units of starting material compounded. Finally, they consider that unitage, apart from indicating the amount of active substance, cannot be very useful to the clinician in his estimate of a drug's efficacy.
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