SOME EARLY OBSERVERS OF ALBUMINURIA By WILLIAM DOCK, M. D.

Peter Bent Brigham Hospital

BOSTON, MASS.

N 1694 a century before Wells (1811) melancholy, hard-living but healthy,” who and Blackall (1813) published their developed dropsy, and after all else had observations on dropsy and albuminuria, failed was treated with permanent drains, IFrederick Dekkers described the effect inserted on a needle, as shown by his illus­ of heat and acetic acid on certain types of tration. He mentions the fact that the urine urine, and in 1764, sixty-two years before of these patients frequently contains much Bright’s classical work on nephritis, Dom­ sediment, especially after boiling and adds: enico Cotugno described a typical case of acute nephritis, with anasarca, and large I can scarcely pass by the fact that the waters of consumptives and emaciated people quantities of a heat-coagulable substance, are clear and translucent, when unboiled. But “ovi albumini persimilem,” in the urine. I have also found that these when placed on the Cotugno’s observation is remarkable in fire, soon become milky, really smelled like that he was testing for albumin, whose milk, and had the taste of sweet milk; when a probable presence in cases of dropsy he had drop or two of acetic acid were added to this, deduced from experiments on the body and it was then placed in the cool air, shortly fluids from dropsical cadavers. a white rennet, namely, the caseous part, sank Dekkers (1648-1720) was a pupil of to the bottom, and the oily or buttery part Sylvius and for thirty years Professor of floated up, and there was a sweet whey, quite Medicine in the University of Leyden. homogeneous, free of the different parts now; His claim to the discovery of albuminuria wherefrom we might conclude that this urine was first brought forward by Wilhelm is a kind of clear and very thin or watery chyle, Leube (“Ueber die Bedeutung der Chemie or nourishing fluid. in der Medizin,” Berlin, 1884). He con­ It is futile to speculate on the character tributed to Paul Barbette’s “Praxis Barbet- of the “oily particles,” though it seems likely tiana” and wrote a medical textbook, that Dekkers’ imagination was too much “ Exercitationes Practicae Circa Medendi taken by the similarity between the appear­ Methodum” which dealt with disease under ance of the boiled urine and milk. It is eight headings as determined by the type evident that the acetic acid was added to of therapy. This was published in Leyden confirm the notion that this fluid was milk, in 1694, and went through several editions- and the reaction so accorded with his ideas in Latin, French and Dutch. The illustra­ that he made no further study of it. In fact, tions reproduced here are from the Dutch it is not apparent from his description that edition of 1717, printed by Johannes de many specimens were examined, nor does Vivie in Leyden, a copy of which, from the he link up this albuminuria with dropsy, collection of the late Dr. F. J. Lutz, was but rather regarded it as a frequent occur­ obtained from the library of the Washington rence in wasting diseases. University School of Medicine, St. Louis. Cotugno, or Cotunnius, was born in In the fifth chapter of this book he discusses 1736, became Professor of Anatomy at cathartics, and especially their effect upon Naples in 1766 and died in 1822. He gave dropsy. The discussion is chiefly in case- a very good description of the intestinal histories, among them that of “a woman lesions of typhoid fever, the pustules of forty years old, mother of five children, smallpox, and described the nasopalatine nerve, the cerebrospinal fluid and the the nature of the cerebrospinal fluid. Prior internal ear. Since the World War Italian to his time it had been thought that the otologists have hailed him as the original fluid in the subarchnoid was a post-mortem propounder of the theory of sound-percep­ artefact, the space being filled during life tion which is known by Helmholtz’s, name. with “vapor” or even being a mere vacuum. His celebrated contemporary, von Haller, To prove that this was artefact his oppo­ nents had stated that the spinal fluid was ' not coagulable by heat, while that obtained from the ventricles of the brain was coagula­ ble. Cotugno found that in most of his experiments, as in those of Bellinius, Brun- nerus, Boerhaave and de Haen, the fluid of the ventricles, like that of the spinal cord, evaporated entirely, without forming any coagulum. He attributed his critics’ results to their having obtained the ventricular fluids from hydrocephalics and gave the

Frederik Dekkers (1648-1720) describes him as “a brilliant man, keen and shrewd in the most detailed investigations.” His experiments on coagulability of vari­ ous body fluids were part of a study of sciat­ ica, which was published with the title “De Ischiade Nervosa Commentarius,” and dedicated to his teacher, Gerhard van Swieten. This was first published in Naples in 1765, and went through at least five subsequent editions, in Vienna, Venice and Naples. The copy on which this account is The Insertion of a Wick for the Drainage of Ascites. From Dekkers’ “Exercitationes Medicae Practicae based was printed in Venice in 1782, and Circa Medendi Methodum, Observationibus Illustra- was obtained from the collection of Dr. tae, 1673. George Dock, to whom I am indebted for following discussion of inflammatory valuable suggestions in preparing this study. exudates: In this work he ascribes sciatica to a Thus I shall show that all the humors of the dropsy of the dural sheaths of the roots of body which, when secreted naturally from the the sciatic nerves and discusses at length blood, are not coagulable, frequently become coagulable from serious disturbances. I shall twelve pints of concentrated urine in a night. begin with urine, which everyone knows is not However, since the sick man himself admitted coagulable but which was seen to coagulate that his drinking had been very slight, it was in those experiments of ours which I am about certain that the enormous quantities of urine to describe. were being drawn especially from waters col­ A soldier, twenty-eight years old, was lected in the dropsy. Although this was shown stationed for many years at mild and very damp by the decrease in the distention of the body, it seemed best to settle this question by a definite experiment, heating the urine. For I had often conclusively shown that the fluid collected beneath the skin of such dropsical cadavers contained material capable of coagu­ lation and I hoped that if the sick man passed such fluid by way of the urine, coagulation would be seen if the material which flowed out were heated; which, as I had anticipated, was

Domenico Cotugno (1736-1822) Baiae. About the.end of August he was seized with an intermittent quotidian fever, which strangely broke out in dropsy in five days. At the beginning of September he was brought to my Sanatorium and intrusted to my care. He was suffering at this time with immense watery swellings of his whole body, and over­ whelmed by the hitherto daily attacks of fever; the dropsy seemed to increase daily, shortly before the paroxysms. The excreta were dry, there was but little urine and he was wholly cast down in mind. Then followed the effects of treatment with ipecac, Peruvian bark and rhubarb, Title Page of “De ischiade nervosa commentarius” by squill pills and sassafras decoctions: Domenico Cotugno. proved by experiment. For with two pints of this But the urine flowed much less and finally urine exposed to the fire, when scarcely half the dropsical swelling seemed to grow . . . evaporated, the remainder made a white mass, In this case it seemed best to use cream of tartar, already loosely coagulated like egg albumen. . . whose effect in provoking urine, without acceler­ Thus it was shown for the first time that urine, ating the pulse, I have shown in other experi­ which no one had shown to be coagulable if ments. By this remedy the output of urine was from healthy people, can at some time contain increased so that the sick man passed ten or a coagulable substance. He then discusses the fluids present in inflammation blocked the lymphatics the the serous cavities and states that when rapid pulse of fever forced the lymph into normally clear they are different from lymph the intercellular spaces and serous cavities, in that they are not coagulable, as he had where it might coagulate. “Nor have those shown often in cadavers and five times in pathologic ligaments, which we have often the pericardial fluid of living dogs, and as seen, after such inflammations binding Malpighi had shown in the pericardial either the pericardium to the heart, or the fluid of a live cow. Those fluids which did pleurae to the lungs, any other origin.” coagulate were entirely different in char­ So perfect was Cotugno’s theory that acter, “of a new color, concentrated and he missed the entire significance of albumin­ yellow and far from a pure watery colorless­ uria, as we understand it, and having ness.” These he regarded as inflammatory, discomfited the critics of his notions on as in the cerebrospinal fluid of hydroceph­ cerebrospinal fluid, made no further obser­ alus, the pleural and pericardial effusions vations on this phenomenon. Those who read of dropsy. “The hydrocele of the sheath of his work, notably Erasmus Darwin, who the testis, the fluids of which are coagulable, quoted him in his “Zoonomia,” approved is wont to be preceded by an inflammation his theory. Those accidentally discovering of the testis.” He gave a rather simple albumen in the urine of nephritis, were more theory of these processes, based on the sup­ impressed than Cotugno, who had predicted position that blood consisted of three parts, its presence, investigated further and estab­ “one red, which is composed of innumerable lished the importance of this condition. minute discs; another yellow which is We may. conclude by saying of Cotugno, hardened at the fire; and finally, the pure as Blackall does of Dr. Darwin: aqueous.” The red part was confined to the arteries and veins, the yellow passed This great author would, without doubt, have modified his opinion, had he made any into the lymphatics, while the .aqueous experiments, and would have ascertained that also went through fine pores into the serous the coagulation of which he speaks, takes place cavities, pulmonary and oral surfaces. That long before the boiling heat; that it is not a which came in contact with the air evapo­ temporary relief, but a continued symptom of rated and could be seen condensing in cold dropsies through their whole course; and that weather, the part that entered the serous the curative effort of nature is urine not loaded sacs remained as a pure, clear fluid, but when with serum, but almost devoid of it.