But, taking this view, it is clear that, apart from the constitutional and local factors above postulated, tophi and, alike, the arthritic phenomena of gout, demand for their production the intrusion of some further element, some _tertium quid_, vital and biological. To this end, therefore, we purpose reviewing tophi in their _clinical_ aspects, as herein possibly we may find some further clue to their exact mode of genesis. CLINICAL EVOLUTION OF TOPHI As to the clinical characters that mark the genesis and maturation of tophi not a little conflict of opinion seems to obtain. Do tophi arise painlessly or not? Do the uratic depositions occasion any local inflammatory reaction? Or, are they merely concomitants or sequels thereof? With what wearisome iteration has the same question been propounded in regard of _gouty arthritis_. Are the attacks of pain and inflammation due to deposits, or do the deposits take place at the site of inflammation? But, restricting our enquiries to tophi, we may remind the reader that Aretæus, writing in the second century, A.D., made the following observations: “Callosities also form in the joints; at first they resemble abscesses, but afterwards they get more condensed, and the humour being condensed is difficult to dissolve; at last they are converted into hard white tophi (Πῶροι στερροὶ λευκοὶ), and over the whole there are small tumours like _vari_ and larger, but the humour is thick white and like hailstones” (Περὶ Αρθριτιδος). To our mind, it would be difficult to emulate, much less to surpass, the succinct and, as we believe, accurate picture here drawn of the various stages that mark the life history of tophi. It will be noted that Aretæus says that in their initial stages they “resemble abscesses,” and, turning to the writings of the elder Garrod and others, we find abundant evidence that it is so. Discussing the more frequent incidence of tophi in the hands than in the feet, Garrod describes the physical characters presented by tophi in the making as seen in one of his examples of gout. “On the dorsal surface of the second phalangeal joints of three fingers, small rounded protuberances were observed, the skin over them being red; these bulgings appeared soft, as if containing a thick fluid, but not the slightest indication of white matter could be seen through the skin; they might have been either gouty concretions in their early stage of formation or some other form of swelling; from a simple inspection I could form no opinion as to their true nature, but their history convinced me that they arose from a deposit of urate of soda. Upon puncturing one of the little swellings, full light was thrown upon the case, as a thick white fluid immediately exuded, a drop of which placed, under the microscope, with the use of polarised light, gave the appearance represented in Fig. 1; the crystals were proved by analysis to consist of urate of soda.”