. * • » r *.*, '. k 4 ».k\ t »„» r•-••'»•.•»-........... . ^ f.T.:.T;r;%:::;t.:::.: .3;:'.:;i;,.::;:;::i:::::: C{:::i;^.;:;;::;r:;:: ■i JP;*8iifi;i: ; *>•", ■»* • •»:»■» » « « "'ft #■'*■ »»-»»' V-»• vf* ► »•,.*■ » » » r . r « •» #- • » # # »»• i • # # /A? v.w.w. • »-1 V V fiv * #1 • •-«#■ #*r i&i AV BKM&y 0»-'', &&# ^o £~M excreted by the kidneys. 1 " uric acid ) 800 " carbonic acid, excreted chiefly by the lungs. 403 " water, diffused through all the excretions. TRANSITION CHANGES. 63 35 atoms of muscular tissue, 1788 " oxygen,. 14 atoms of solid matter of bile, 82 " urea, .... 1 " uric acid, 800 " carbonic acid, 403 " water, .... In excess, .... Carbon. Nitrogen. Hydrogen. Oxygen. 1680 210* 1365 525 1788 1680 210 1365 2313 700 164 10 800 14 164 4 630 328 4 403 140 164 6 1600 403 1674 6 182 28 1365 2313 1680 210 1365 2313 The 6 atoms of carbon and 28 of nitrogen here unaccounted for, are probably eliminated in combination with the constituents of water, forming some of the less defined elements of the excretion—as com- pounds of ammonia, fatty, coloring, and odorous principles, &c. The sulphur and phosphorus existing in the blood and some of the secretions have not been here taken into consideration, as experi- ments are still wanting to show in what proportion they exist. 40. It is evident that the atoms of worn-out tissues on re-entering the blood are ultimately evolved from the body as well-recognized elements of the excretions. Recent researches have rendered it pos- sible that these effete matters are not at once resolved into urea, uric acid, &c, but undergo a series of transition changes, some of which have been studied with much success. Thus, in the fluids obtained by macerating the tissues of the body in water, the following bodies have already been detected: Creatine, creatinine, inosinic acid, ino- site, lactic acid, hypoxanthine, besides certain ill-defined volatile acids. All these bodies may be regarded as transition stages of the meta- morphoses of worn-out elements of tissues with the constituents of the excretions. The following views of the relation borne by some of these bodies to each other are by no means uninteresting. 41. Creatine is a crystalline body first discovered in the juice of flesh by Chevreul, and more recently submitted to a most masterly examination by that illustrious chemist, to whom we owe so much, Baron Liebig. This substance appears to be the most important pro- duct of the metamorphosis of muscular tissue under the influence of destructive assimilation. I feel little doubt of the correctnesss of the 64 PHYSIOLOGY OF URINE. opinion announced by Heintz, who differs from Liebig, in regarding this body as absolutely excrementitious : indeed, the fact of the copi- ous excretion of creatine by the kidneys fully bears out this view. The relations borne by creatine to several other bodies are very interesting. Thus, if the protein elements of effete muscular tissue in a nascent state come in contact with water and ammonia, which are so frequently the result of the decomposition of animal matter, we should have the elements of creatine, with the evolution of 23 atoms of hydrogen, which probably by their union with oxygen help to keep up the temperature of the body; for— C H N 0 1 atom protein, . . . 40+30+ 5+12 + 18 " water, ... 18 18 + 10 " ammonia, ... 30 10 40+78+15+30 = 5 creatine, .... 40+55+15+30 23 Creatine may be traced to the decomposition of the gelatinous as well as albuminous tissues; for they, in the rearrangement of their nascent atoms, are prone to form glycocoll, and this body requires but the elements of ammonia to form creatine ; for— C H N O 2 atoms of glycocoll, ... 8+ 8+2+6 + 1 " ammonia, . . . 3+1 = 1 " creatine, . . . 8+11+3+6 Creatine has at present been detected only in the juices of the muscular tissues, and hence may be regarded as the exclusive product of their decomposition, brain and nervous matter containing none. Some of the creatine is removed by the kidneys unchanged ; some is converted into an active base, creatinine. This may be prepared artificially by boiling creatine with hydrochloric acid, and differs only from that body in containing less water. C H N O 1 atom creatine, .... 8+11+3+6 —4 " water, .... 44 =creatine,.....8+ 7+3+2 Creatine, boiled with alkalies, is resolved into urea and sarcosin. TRANSITION CHANGES. 65 C H N 0 1 atom creatine, .... 8+11+3+6 — 1 " urea, .... 2+ 4+2+2 = 1 " sarcosin, .... 6+ 7+1+4 It is hence probable that the creatine* found in flesh is, after all, a sort of transition stage between the protein elements and urea; the latter body being formed from the creatine, and not directly from the elements of the tissue. We have, however, the sarcosin to account for; this body has not been found in the urine or other excretions, but as it differs from lactate of ammonia only in the absence of one atom of water, it is not impossible that its elements become thus arranged: C H N 0 1 atom sarcosin, .... 6+7+1+4 + 1 " water, .... 11 = lactate of ammonia, . . . 6+8+1+5 Lactic acid is, as has long been believed, an important constituent of the fluids of the animal economy. Professor Liebig,144 once the opponent of this view, has since become its advocate. It is further interesting to observe that creatine bears a simple relation to uric acid, and under the influence of oxygen, and by union with carbonic acid and ammonia, or their elements, may possibly form this acid. C H N 0 1 atom creatine, . . . . 8+11+3 + 6 2 " carbonic acid, . . . 2+ 4 1 " ammonia, . . . 3+1 6 " oxygen, .... 6 10+14+4+16 —10 atoms water, . . . . 10+ 10 = 1 uric acid, .... 10+ 4+4+ 6 A peculiar acid—the inosinic—has been discovered by Liebig in the juices of flesh, and is in all probability a result of secondary changes; this has not been met with in the excretions, but its constituents are * Mr. Moore, reviewing the works of Bidder and Schmidt, states that creatine, creatinine, and uric acid cannot be regarded as intermediate steps in the formation of urea, as they themselves traverse the renal capillaries undecomposed. But before we fully admit this, we must consider whether their elements would not be more naturally present in the urine in the form of urea. 5 66 PHYSIOLOGY OF URINE. exactly equal to those of acetic acid, oxalic acid, and urea. It is, therefore, in all probability, broken up into these bodies: C H N 0 Acetic acid, .... 4+3+ 3 Oxalic acid, .... 4+ 6 Urea,.....2+4+2+ 2 Inosinic acid, .... 10+7+2+11 42. It is pretty evident that some organs of the body tend to resolve their elements into transition compounds peculiar, or nearly so, to themselves. From some late researches of Professor Scherer,145 it appears that the spleen presents a marked peculiarity. Thus a decoction of this organ in water contains a peculiar body which evi- dently constitutes an early phase in the conversion of the spleen, by metamorphosis, or destructive assimilation, into uric acid. This inte- resting body is deposited mixed with uric acid from the juices of the spleen, and it bears so close a resemblance to xanthine or uric oxide, that Scherer has named it hypoxanthine. C H N 0 1 atom hypoxanthine, .... 5+2+2+1 + 1 " oxygen, . = 1 " uric oxide, + 1 " oxygen, . = £ " uric acid, 5+2+2+2 1 5+2+2+3 Inosite is a very recent addition to our knowledge, for which we are also indebted to Scherer.145 It is a peculiar sugar found in the infusion of muscular tissue, apparently incapable of undergoing vinous fermentation, and consists of C12H12012. This in all pro- bability is a transition stage in the metamorphosis of fat previous to its ultimate conversion into carbonic acid and water. 43. All speculations of this kind, notwithstanding the seductive interest with which they are invested, must be regarded with extreme caution, and, as in every case in which we endeavor to explain vital phenomena by the physical or chemical laws governing dead matter, be admitted as only provisionally correct. Their minute, and even general details, being liable to partial or complete alteration on the detection of a comparatively slight error in the analysis, or even in some cases of a mere difference of opinion regarding an atomic weight. But they are by no means to be idly rejected, for they enable us to group together a series of facts which, without the hypothetical rela- TRANSITION CHANGES. 67 tion now assumed, would scarcely seem to bear much relation to each other. They, moreover, suggest new investigations, and cause the views thus educed to be submitted to further researches, and in thus endeavoring to determine their truth or falsehood, new facts become almost daily elicited. 44. It is an interesting circumstance that an hypothesis involving the fundamental argument on which the relation of the elements of food to those of the blood, so ably advocated by both Mulder and Liebig, are based, was propounded by Anaxagoras, the Ionic philoso- pher, five hundred years before the Christian era. We are best ac- quainted with his views from the criticisms of Lucretius, but who quotes them only to refute them.* Praeterea, quoniam cibus auget corpus, alitque; Scire licet, nobis venas, et sanguen, et ossa, Et nervos alienigenis ex partibus esse: Sine cibos omneis commisto corpore dicent Esse, et habere in se nervorum corpora parva, Ossaque, et omnino venas, parteisque cruoris; Fiet, uti cibus omnis, et aridus, et liquor ipse, Ex alienigenis rebus constare putetur, Ossibus, et nervis, venisque, et sanguine misto. Lucretius, de Rerum Naturd, i, 859-868. In his ignorance of the ultimate chemical composition of bodies, Anaxagorasf based his argument on their minute physical constitu- tion, and hence he assumed that wheat really contained the elements of the blood and tissues ready formed, requiring only atomic aggre- gation in the living organism to convert them into blood and flesh. Lucretius triumphantly inquires why, if this be true, drops of blood are not visible on submitting wheat to the pressure of the mill- stones ?— Conveniebat enim frugeis quoque saepe minutas, Robore quom saxi franguntur, mittere signum Sanguinis, aut alifim, nostro quae corpore aluntur; Cum lapidi lapidem terimus, manare cruorem. lb., 880. 45. The physiological relations borne by the urine to other secre- tions both in regard to quantity and quality, are exceedingly interest- * I have revised these passages from the edition of "Lucretius" by the late head- master of Eton, Dr. Keate, to whose elegant scholarship it is a satisfaction, if it be not presumption, as an old pupil, to bear my humble testimony. f His doctrine was called 'Opowiiepeia. 68 PHYSIOLOGY OF URINE. ing. The fact of this fluid constituting the stream by which a host of noxious ingredients, either formed within the body or derived from without, is washed away, has been already alluded to (30). But there is another very important office which it performs in common with other secretions, depending upon the power possessed by the kidneys, of temporarily compensating for the deficient action of other secreting organs. Thus, so long as the functions of the skin and the kidney bear a normal relation to each other, all goes on as in health, a limpid secretion from the one and insensible exudation from the other an- nounce that a just balance obtains between the two functions. But if the energy of the cutaneous function be increased so that more than a normal amount of fluid escapes from the skin, the kidneys compen- sate for this great loss by secreting a smaller quantity of fluid, so that the urine becomes concentrated, and its specific gravity is increased; and conversely, the bulk of the urine is often greatly increased when the skin is imperspirable. In this way the balance is for a time pre- served, and no greater amount of fluid is drawn from the body than is consistent with health. Again, if the function of the liver be im- paired, either from mechanical or other causes, highly carbonized products are eliminated in the urine (186), the kidneys performing temporarily the function of separating some or all of the elements of bile from the blood, as every case of jaundice teaches us. In these and other analogous modes the quantity and quality of the urine may become so modified as to lead to serious errors; and to induce a sus- picion of the presence of renal disease, when, so far from any exist- ing, the kidneys are really performing their most exalted function of depurating the blood of a noxious, and often even toxic agents. The fact of an excessive or diminished secretion of urine existing in any particular case cannot per se be regarded as indicative of disease of the kidney, any more than the excessive sweating so frequent in rheumatism or phthisis, or the diminished perspiration in fever, can be regarded as evidence of the existence of disease of the skin. In- deed, it is most important not to lose sight of the fact, that the pre- sence of abnormal constituents in the urine, or of healthy constituents in abnormal proportions, by no means indicates the necessary exist- ence of renal disease. In the great majority of cases they really indicate the contrary condition, and rather, as already stated, point out that the kidneys are performing their functions in a manner more conducive to the health of the patient, by drawing off from the blood matter which, if not thus eliminated, would induce disease. CORRECTIONS FOR URINOMETER. 69 Physical Characters of Urine. 46. In the investigation of urine in connection with diagnosis, it is important to notice its physical properties, especially its density or specific gravity, color, consistence, and in some particular cases its optical properties. Almost every one is familiar with the modes of discovering the density of the urine. This may be most readily accomplished by pouring some of the fluid into a cylindrical vessel, and im- mersing in it the little instrument known as the hydrometer, FiS- 14- gravimeter, or urinometer (Fig. 14). This is generally made e|, of glass or metal, and consists of two bulbs {a b) and a nar- £ row stem {ef). The instrument is made sufficiently heavy j£ to cause it to sink to e, when placed in distilled water. Then, j£ as all bodies immersed in fluids displace a bulk equal to •'Jr themselves, it follows that in a fluid denser than water the ^(„m instrument will not sink so deeply, and less of the stem will jf be immersed.7 *The space e to/ is graduated into degrees a\& corresponding to different densities. When such an instru- ment is allowed to float in a vessel of urine, the number on the stem corresponding to the level of the fluid, will indicate very nearly its specific gravity. Thus if the degree 18 be on the surface of the urine, its specific gravity is said to be 1018 (the number 1000 being always added to the number on the stem). This shows that a vessel holding when quite full 1000 grains of distilled water, will contain just 1018 grains of the urine or other fluid under examination. These instru- ments are generally made of unnecessary magnitude. One of rather more than twice the size of the figure will float in a test-tube holding an ounce of urine, and is the most convenient for carriage and ordi- nary use. 47. It is obvious that for the indications of the gravimeter or uri- nometer to be correct, the scale on the stem must not be divided into equal parts, as the density of each stratum of fluid in which the instru- ment is immersed of necessity increases with the depth from the sur- face. A mathematical calculation is thus rendered necessary to com- pensate for the error thus existing in the indications on the stem. We are indebted to Mr. Ackland for the contrivance of a most inge- nious machine for effecting the graduation of the scales of all these instruments, so as to remove this source of error very completely.* * Instruments thus graduated may be procured at Messrs. Home and Thorn- thwaite's, 123 Newgate Street. 70 PHYSIOLOGY OF URINE. He has also ascertained that with glass urinometers, in which the weight of the bulbs, when loaded with mercury and fit for use, varies from 90 to 105 grains, the indications are very nearly correct, even when the temperature of the urine ranges from 60° to 80°, as the dilatation of the glass by the increased temperature nearly compen- sates for the necessarily diminished density of the fluid. Mr. Ack- land has calculated the following table, by which, within a moderate range of specific gravity, even this small error may be compensated. A Table for reducing the indications of a Glass Urinometer to the standard tem- perature (60° Fahr.) when the specific gravity has been taken at a higher tem- perature. No. to be No. to be No. to be Temp. added to the Temp. added to the Temp. added to the indication. indication. indication. 60 •00 69 •80 78 1-70 61 •08 70 •90 79 1-80 62 •16 71 1-00 80 1-90 63 •24 72 M0 81 2-00 64 •32 73 1-20 82 • 2-10 65 •40 74 1-30 83 2-20 66 •50 75 1-40 84 2-30 67 •60 76 1-50 85 2-40 68 •70 77 1-60 Example.—Suppose the urinometer to float in urine of 73° temp, at 21. On referring to the table opposite 73° will be found 1*20, which is to be added to the indication 21, making the true specific gravity=21-+l'2+1000=1022#2. 48. If a urinometer be not at hand, any small and thin stoppered phial may be substituted. For this purpose counterpoise the empty bottle and stopper in a tolerably good balance, with shot or sand. Then fill it with distilled water, insert the stopper, and carefully as- certain the weight of the water it contains. Empty the bottle, fill it with urine, and again weigh it; the specific gravity of the fluid will be readily found by merely dividing the weight of the urine by that of the water. As an example, if the carefully counterpoised phial hold 478 grains of distilled water and 498 of urine, the specific gravity of the latter will be 1*0418, for |f|=l*0418. This process affords much more accurate results than can be obtained by the urinometer or gravimeter just described. Still, as the errors necessarily involved in the indi- cations of the latter are not sufficient to be of any great practical importance, this instrument is generally preferred on account of the very great facility attending its-use. DIURNAL VARIATIONS. 71 49. Much difference of opinion has existed regarding the average density of healthy urine (52), a discrepancy admitting of ready ex- planation by a reference to the state of health of the individual by whom it was secreted, the period of the day at which it was passed, the bulk of the fluid drunk in the course of the day, and the character of the previous ingesta. Nothing can be more absurd than attempting to determine the average state of the density of the urine by the examination of speci- mens voided at different periods of the day. So seriously is the state of this secretion affected by comparatively slight causes, that from a neglect of this caution, a patient told only to "bring his water," might be supposed one day, from its density, to be suffering from diabetes, and on the following he may surprise his medical attendant by presenting him with a specimen as light as spring water (51). In all cases where any approach to accuracy is required, an average sample from the urine passed in 24 hours into the same vessel must be selected: as this is, however, not always practicable, it is better to request the patient to furnish specimens of the urine passed immedi- ately before going to bed (urina chyli), and of that voided on rising in the morning (urina sanguinis). The average density of these two specimens will give a nearer approach to the truth. 50. The law of the density of the morning urine being less than that passed at night holds good in disease, certainly in the majority of cases. A remarkable exception, however, occurs in some neuralgic and hysterical affections, in which, immediately after a paroxysm of the disease, the urine falls to its minimum of density at whatever period of the day it is secreted, often after an hysterical fit being scarcely heavier than pure water. The following table shows the results of some observations on the respective densities of night and morning urine in different diseases : Density of urine passed at Disease. Night. Morning. Urina chyli. Urina sanguinis. 1-027 1-022 Irritable bladder. 1-026 1-022 Haemoptysis. 1-026 1-020 Dyspepsia. 1024 1-024 u 1-024 1-014 u 1-022 1-016 Phthisis. 1-021 1-019 Oxaluria. 1-005 1015 Hysteria. 1-020 1-018 Healthy. 72 PHYSIOLOGY OF URINE. A very curious statement has been made in Germany by Dr. Schweig,11 that the density of urine presents a constant rate of in- crease and decrease during the day, and that cceteris paribus it ranges from 1-017 to 1-022 in the forenoon, 1-023 to 1-028 in the afternoon, 1-019 to 1-028 in the evening, and 1-012 to 1-025 during the night. Taking the night urine alone he states its density to vary through certain limits in a cycle of six days, so that twice in this period its density attains a " high minimum;" on the third and fourth night being higher than on the fifth and second, but then being lower than on the first. Five of these cycles occur, according to Dr. Schweig, in each lunar revolution, counting the night before the new moon as the second day of one of his cycles. The following is the density of night urine taken from an average of 20 such periods: Nights of the Cycle. Density of the Urine. 1........1-022 2........1-017 3........1-019 4........1-020 5........1-019 6........1017 I have not been able to verify these statements, and am inclined to believe that these supposed cycles of daily variation bear a direct relation to the periodicity of the meals (71). 51. It is quite impossible to assign any limits within which the specific gravity of the urine secreted at different periods of the twenty- four hours may possibly range. In addition to the bulk of water eliminated from the circulation by the kidneys in a given time being materially affected by the state of surface (45) and other causes, the amount of fluids drunk will exert an important effect in modifying the density and bulk of the urine. In many persons mere mental anxiety, or the ingestion of a few cups of tea, a glass or two of hock, or a goblet of soda-water, will at once determine the secretion of urine of a density as low as 1-002 or 1-003. The free use of aqueous diluents will also greatly increase the bulk, and in a corresponding degree diminish the density of the urine. And from some recent observations of Professor Liebig it appears probable that the purer the water, the more freely it is absorbed into the blood, and elimi- nated by the kidneys, the presence of small quantities of saline matter considerably retarding its absorption and subsequent excretion (385). It was observed by Becquerel13 that a man whose normal average QUANTITY OF THE URINE. 73 of urine in 24 hours was 30 ounces, passed 56 ounces after swallow- ing about a quart of water in the day. In another case the natural average, or 32 ounces, was raised to 87 ounces after the imbibition of half a gallon of water in the 24 hours. Severe mental emotion, especially a paroxysm of hysteria, will also determine the secretion of pale aqueous urine, of low density (50). A young woman who naturally passed in 24 hours about 35 ounces of urine, voided 86 ounces after the occurrence of an hysteric fit in the course of the day. 52. Dr. Prout's experience led him to assign 1-020 as the average gravity of healthy urine, and this completely agrees with my own observations. From a number of careful observations made by Bec- querel, it appears that the mean density of all the urine passed in 24 hours, and examined by him, was in men 1-0189 and in women 1-0151, the mean in the two sexes being 1-017. Dr. Routh146 has made a very careful and valuable series of researches on the subject, and from an average of eighteen cases he has shown that 1-021 very nearly represents the specific gravity of the urine secreted in 24 hours. 53. The average quantity of urine secreted in 24 hours in this country varies from 30 to 40 ounces; this is Dr. Prout's estimate, and is certainly the most correct. Dr. Routh found in eighteen cases the average quantity did not exceed 35 ounces. It is, however, capable of varying from at least 20 to 50 ounces without exceeding the possible limits of health, the quantity excreted in summer being as a general rule less than during winter, on account of the greater activity of the functions of the skin in warm weather. M. Becquerel regards 43 ounces in men and 47 in women as the most accurate expression of the average quantity of urine. The habitual use of w^ak subacid wines in France will from their diuretic influence sufficiently explain the discrepancy existing between the re- marks of English observers and those of Becquerel. 54. Presuming that in any given class of affections the several in- gredients existing in the urine preserve nearly their normal ratio, it is obvious that if by any means we could appreciate with tolerable accuracy the quantity of solids or "real urine" excreted in a certain time, we should be able to learn, not only to what extent the kidneys are performing their great and important function of depuration, but should also obtain data by which it would be possible to measure, 74 PHYSIOLOGY OF URINE. within certain limits, not only the amount of nourishment required from ingesta, but of the rapidity of the destruction of the effete tis- sues of the body under the influence of the oxygen of the arterial blood (35). In this manner we may recognize the existence of a series of causes influencing the condition of our patients, the detec- tion of which would otherwise have been scarcely possible. It is also possible that we may occasionally obtain some aid in the diagnosis of the localization of the diseased action in the kidneys where those organs are structurally affected; for the researches of Professor Bow- man have shown, that the separation of the water from the blood takes place through the Malpighian tufts, whilst the saline and other cha- racteristic elements of the urine are separated in the tubes by means of epithelial structure. Indeed, epithelial cells have been discovered in urinary deposits actually distended with crystals of uric acid and of oxalate of lime.147 The first element in an inquiry of this kind will be, to obtain a tolerably accurate measure of the quantity of urine secreted in twenty- four hours. Simple as this appears, it in practice is attended with no small difficulty. Not only is it no easy matter to make our pa- tients quite understand what we require, but the loss of urine gene- rally voided during the action of the bowels will frequently prove no small obstacle to our learning the exact quantity secreted. The pa- tient should be told to pass water at noon, and rejecting the portion then excreted, to collect all that he passes up to the same hour the next day, when he should take care to empty his bladder completely. Having thus measured the amount of urine secreted in a given pe- riod, we are yet far from having any satisfactory information as to the proportion of work done by the kidneys in that time, as far as their depurating functions are concerned, the amount of fluid in the renal secretions being liable to serious variations, according to the quantity of fluids drunk, the action of the skin, &c. Thus, a person may, under peculiar circumstances, void, in twenty-four hours, forty ounces of urine, and on the next day but twenty, and yet the amount of depurating duty performed by the kidneys be the same; for the former bulk of urine, if of a density of 1-015, will contain about as much solid matter as half that quantity if of a specific gravity of 1-030. 55. The amount of solid matters existing in the urine can, of course, be discovered by the evaporation of a given quantity to as CALCULATION OF SOLIDS. 75 dry an extract as can be obtained. The practical difficulties attend- ing this process are familiar to every one who has ever performed the task; and, moreover, the time required for its performance would pre- clude its being had recourse to sufficiently frequently to be of any real service. It has, therefore, been proposed to calculate the quantity of solid matter pfesent in the urine from its specific gravity; and for this purpose the following different formulae have been suggested by the late Dr. Henry, Dr. E. Becquerel,8 and Dr. Christison.9 If D = the density or specific gravity of the urine, and A = the difference between 1000 and its density— The quantity of solids in 1000 grs. is, according to Dr. Henry, A X 2-58 " " Dr. Christison, A X 2-33 " " Dr. Becquerel, A X P65 It is true that by formulae of this kind only an approximation to the truth can be gained, in consequence not only of the different densities of the various elements of the urine, but from their not always ex- isting in the same proportion, and therefore are never to be relied on, where great accuracy is required, as in the chemical analysis of the urine. Yet they are of great value in the investigation of disease at the bedside, as affording an approach to a knowledge of the solids removed from the system in a given time, sufficiently accurate for all clinical purposes, either in relation to diagnosis, or indications of treatment. Of these three formulae, that of Dr. Christison has been shown by the researches of Dr. Day10 to be the most exact, and to afford results generally sufficiently accurate for the guidance of the practitioner.* 56. The following table, calculated from Dr. Christison's formula, shows at a glance the quantity of solids and fluid existing in 1000 grains of urine of different densities : * In addition to these we may mention Trapp's formula, the error of which, ac- cording to Vogel, cannot exceed one-tenth in healthy, and one-fifth in morbid urine. If A represents the excess of the specific gravity of urine above that of water (= 1000), the amount of the solid constituents of 1000 parts of that fluid will be represented by 2 A- 76 PHYSIOLOGY OF URINE. Table 1. Speci6c gravity. Solids. Water. Specific gravity. Solids. Water. 1001 2-33 69767 1021 4893 951-07 1002 4-66 995-34 1022 51-26 948-74 1003 699 993-01 1023 53-;VJ 946-41 1004 9-32 990-68 1024 55-92 944-18 1005 11-65 988-35 1025 58-25 941-75 1006 1398 986-02 1026 60-58 939-42 1007 16-31 983-69 1027 62-91 937-09 1008 18-64 981-36 1028 65-24 934-76 1009 2097 979-03 1029 67-57 932-43 1010 23-30 976-70 1030 69-90 930-10 1011 25-63 974-37 1031 72-23 927-77 1012 27-96 97204 1032 74-56 925-44 1013 30-29 969-71 1033 76-89 923-11 1014 3262 967-38 1034 79-22 920-78 1015 34-95 965-05 1035 81-55 918-45 1016 37-23 962-72 1036 83-88 916-12 1017 39-61 960-39 1037 86-21 913-79 1018 41-94 958-06 1038 88-54 911-46 1019 44-27 955-73 1039 93-87 909-13 1020 46-60 953-40 1040 93-20 906-80 The mode of using this table is exceedingly simple; for having dis- covered the density of the urine passed in 24 hours by means of the gravimeter or specific-gravity bottle, a single glance at the table will be sufficient to show the proportion of solid matter and water in 1000 grains of the urine. Then, by weighing the whole quantity of urine passed in 24 hours, the weight of solids secreted by the kidneys may be calculated by a simple rule of proportion. 57. As it is much easier to obtain the measure than the weight of urine passed in a given time, the following table becomes of use in enabling us to calculate the weight of the urine (in grains) from its bulk. A pint of distilled water weighing 8750 grains. Table 2. Specific Weight Specific Weight gravity. of one pint. gravity. of one pint. Grains. Grains. 1-010 8837 1-023 8951 1-011 8846 1-024 8960 1-012 8855 1025 8968 1-013 8863 1-026 8977 1-014 8872 1-027 8986 1-015 8881 1-028 8995 1-016 8890 i-029 9003 1-017 8898 1-030 9012 1-018 8907 1-031 9021 1019 8916 1-032 9030 1-020 8925 1-033 9038 1-021 8933 1-034 9047 1-022 8942 1-035 9056 CALCULATION OF SOLIDS. 77 58. The following example will be sufficient to point out the mode of using the preceding tables. Ex.: A patient passes in 24 hours 2J pints of urine of the specific gravity 1-020, what is the weight of solid matter thus excreted by the kidneys ? 1000 grains of urine, specific gravity 1-020, hold dissolved 46-6 grains of solids (Table 1), and a pint will weigh 8925 grains (Table 2); then, 8925 x 46-6 ---------=415-9 grains of solids in a pint; 1000 and 415-9 x 21 = 1039-72 grains, being the total quantity present in urine of 24 hours. 59. Subsequent to the publication of the first edition of this work, I calculated another table from Dr. Christison's formula (A X 2*33), which is exceedingly convenient, from its showing at a glance the number of grains of solids in, and the weight of a fluid ounce of urine, of every density from 1-010 to 1-040. Table 3. Specific Weight of Solids in one Specific Weight of Solids in one gravity. one fluid oz. fluid oz. gravity. one fluid oz. fluid oz. Grains. Grains. 1010 441-8 10-283 1025 448-4 26-119 1011 442-3 11-336 1026 448-8 27 188 1012 442-7 12-377 1027 449-3 28-265 1013 443-1 13-421 1028 449-7 29 338 1014 443-6 14-470 1029 450-1 30-413 1015 444-0 15-517 1030 450-6 31-496 1016 444-5 16-570 1031 451-0 32'575 1017 444-9 17-622 1032 451-5 33-663 1018 445 3 18-671 1033 451-9 35-746 1019 445-8 19-735 1034 452 3 36-831 1020 446-2 20-792 1035 452-8 37-925 1021 446-6 21-852 1036 453-2 38014 1022 447-1 22-918 1037 453-6 39-104 1023 447-5 23981 1038 4541 40-206 1024 448-0 24-051 1039 454-5 41-300 A glance at these figures presents us with a mode of recollecting the quantity of solids existing in urine of different specific gravities depending upon the curious coincidence existing between the figures expressing the densities and the weight of solids present; and is ex- ceedingly useful when the table is not at hand for reference. Thus, if the specific gravity of any specimen of urine be expressed in four figures, the two last will indicate the quantity of solids in a fluid ounce of the urine, within an error of little more than a grain, when the density does not exceed 1-030; above that number the error is a little greater. To illustrate this, let us suppose we are called to a I 78 PHYSIOLOGY OF URINE. patient, the integrity of the depurating functions of whose kidneys we are anxious to learn. The quantity of the urine excreted in 24 hours amounts, we will suppose, to three pints, or sixty ounces, and the density of the mixed specimens passed in the time alluded to is 1-020; now we merely have to multiply the number of ounces of urine by the last two figures of the specific gravity, to learn the quantity of solids excreted; or 60 x 20 = 1200 grains of solids. If the table were at hand, the calculation would be more rigid, for we should multiply 60 by 20-79, instead of 20; the product, 1247 grains, shows that by the former mode an error of 47 grains has been com- mitted ; an amount not sufficient to interfere materially with drawing our inductions by the bedside, and of course capable of immediate correction by referring to the table at our leisure. 60. From a large number of observations, it appears that the average amount of work performed by the kidneys in the adult, may be regarded as effecting the excretion of from 600 to 700 grains of solids in twenty-four hours. Although certain peculiarities connected with muscular exercise, regimen, and diet, as well as certain idiosyn- crasies of the patient, may influence this, yet if we regard 650 as the average expression of the number of grains of effete matter separated in twenty-four hours by the kidneys, we shall not commit any very serious error. In calculations of this kind much latitude must be allowed, and it ought at least to be assumed that the kidneys may excrete fifty grains more or less than the assumed average, without exceeding or falling short of their proper duty. Recent and very extended researches have convinced me, that the indications afforded by the characters of the quantity of solid elements of the urine excreted by the kidneys in a given time, are of the highest importance, not only as an exponent of functional lesion, but as a most important guide to the treatment of diseases. These views I developed at some length in my lectures at the Royal College of Physicians in the spring of 1848, and I hope to revert to-them in the concluding chapter of this volume.* * Dr. Bence Jones is of decided opinion that no reliance can be placed on any other mode of obtaining the amount of solids in the .urine than by careful weighing; and there is no doubt that he is correct where strict accuracy is required, as appears from the following experiments: about 500 grains of urine were in each case evaporated. Sp. gr. Solid residue. Per 1000 grs. of Urine. Before dinner,.......1028-0 found 67-03 grains; by table 65-2 grains. After dinner,........1028-5 " 65-59 Before dinner,.......1028-2 " 64-77 After dinner,........10343 " 84-65 Before dinner,.......1024-7 " 60-77 After dinner.........1024-8 " 64-61 Before dinner........1024-8 " 56-67 58-5 65-0 790 580 58-0 58-0 VARIATIONS OF COLOR. 79 61. Among the physical characters of urine, the tints not unfre- quently present in different maladies are of great importance, and worthy of being carefully studied. Whatever may be the nature of the coloring ingredients of healthy urine, it is pretty evident that they are capable of generating but a small series of tints; varying according to the degree of dilution from nearly colorless to the usual pale amber color, and up to deep brown. When much diluted, urine presents a faint greenish tint, as in the urine of early infancy, and in that of chlorosis and hysteria. If bile or blood be present, a variety of colors, varying from red to brown, blackish-green or apple-green, are produced, the latter hue being occasionally indicative of the presence of cystine (191). It is often of great importance to distinguish be- tween the substances causing some of the various colors passed by the urine, for which purpose the following table will be found of use. Color. Cause of color. Chemical and physical characters. Pathological indica-tions. Red. Purpurine. Nitric acid produces a de- Portal conges- (A.) posit of uric acid almost tion; it is gene- immediately. No change rally connected by heat. Alcohol digested with organic on the extract, acquires a mischief of the fine crimson color. Den- liver or spleen. sity moderate. (B.) Blood. Be comes turbid by heat Hemorrhage in and nitric acid, its color some part of changing to brown. The the urinary microscope discovers passages. floating blood discs. Brown. Concentration. Nitric acid precipitates uric Fever. (C.) acid readily. Density high, the addition of hydro-chloric acid to some of the urine previously warmed, produces a crimson color. (D.) Blood. See B; coagulation by heat, Obstruction to and nitric acidless marked. the escape of (E.) Bile. A drop of nitric acid, allow- bile from the ed to fall in the centre of liver or gall- a thin layer of urine on a bladder; and white plate, produces a the presence of transient play of colors, some or all of in which green and pink the elements predominate. of bile in the Greenish-brown. Blood. See B; occurring in alkaline circulation. (F.) urine. (G.) Bile. See E; occurring in very acid urine. Grass-green. Excess of sulphur. Unchanged by heat or nitric Presence of cys- (H.) acid. tine. 80 PHYSIOLOGY OF URINE. Vogel arranges the scale of colors in the three following groups: 1st. Yellowish urines. 1. Pale yellow, like a weak solution of gamboge. 2. Bright yellow, like a medium solution of gamboge. 3. Yellow, like a strong solution of gamboge. 2d. Reddish urines. 1. Reddish-yellow, like gamboge with a little carmine. 2. Yellowish-red, like gamboge with more carmine. 3. Red, like carmine with a little gamboge. 3d. Brown urines. 1. Brownish-red. 2. Reddish-brown. 3. Brownish-black (162). 62. It must not be forgotten that the coloring matter of many drugs when taken into the stomach readily and rapidly enter the urine, and from the peculiar appearance presented by it might lead to an unfounded suspicion of its being indicative of many urinary diseases. The coloring matters of the chimaphila, haematoxylum, indigo, senna, and rhubarb, will thus tint the urine very deeply, the latter more especially. I have often seen urine, colored by rhubarb, mistaken for bilious urine. The error can be at once discovered by the addition of liquor ammonias, which converts the dark orange into a crimson color. 63. Urine occasionally varies in consistence, and instead of being fluid, as is generally the case, acquires a considerable amount of vis- cidity. This is sometimes only to be detected by the readiness with which it froths on agitation, and the length of time the bubbles are retained, as in diabetes mellitus. In other cases the urine may be so viscid as to allow of being drawn into threads, from the presence of mucus (331), although the latter generally forms a dense layer at the bottom of the vessel. The same thing happens if pus occurs in rather concentrated or alkaline urine, as the alkali or saline matters present react upon the albuminous constituents of the pus, and convert it into a mucus magma, as pointed out by Dr. Babington and myself14 (328). It is occasionally, though rarely, observed that the urine is fluid whilst warm, but becomes semi-solid, like a mass of jelly, on cooling. This change depends upon the presence of self-coagulating albumen or fibrin, a state of things generally connected with severe organic mischief in the kidneys, although in some instances dependent only upon mere functional disturbance. VARIATIONS OF CONSISTENCE. 81 In the former editions of this work I stated that in a few rare instances, occurring chiefly in urine loaded with oxalate of lime, I had found it quite fluid whilst cold and gelatinizing when heated, retaining, however, its transparency; this curious change being best observed when water is poured on the warm urine, when the gelati- nous mass floats for some seconds in the water before it completely dissolves. Recent observations have led me to trace the cause of this to an abundant deposit of urate of ammonia, accompanying the oxalate, dissolving by the heat employed, and soon after separating as a gelatinous hydrate. 64. The optical properties of the urine have scarcely been applied to diagnosis, with the exception of the action saccharine urine exerts on polarized light, which has been proposed by M. Biot,15 and applied by M. Bouchardat16 to the detection of diabetes mellitus. It is quite out of place to notice here the theoretical action of diabetic urine on polarized light; for an account of which I would p;a 15 refer the reader to works especially devoted to the investigation of physical phenomena :17 and now simply content myself with pointing out the readi- est mode of applying this property to diagnosis. b Let a mirror (a), composed of half a dozen pieces of thin window glass, be fixed to an arm of a common retort stand. A brass tube (b), open at top, and closed below with a plate of glass, is fixed to a second arm. This tube should be an inch in diameter, and six or eight inches long. In a third arm, at (c), is fixed a ring of wood, supporting a doubly re- fracting rhomb of calcareous spar. Let the tube (b) be filled with water, and allow the light of a candle, or of the clouds, to be incident on the mirror (a) at an angle of 56° 45. A ray of light, polarized in a vertical plane, will consequently be reflected through the column of water in B. Then look through the crystal (c) and two images of the bottom of the tube (b) will be visible. These images are colorless, and differ merely in the intensities of their illumination. Slowly revolve the crystal (c) and one of the images will cease to be visible four times in an entire revolution. Having thus become familiar with the management of the instrument, empty the tube (b) and fill it with very clear syrup. Again revolve the eye-piece (c), and now, instead of two uncolored images only being visible, two, tinted with the most vivid colors of the spectrum, 6 Q=« 82 PHYSIOLOGY OF URINE. will be seen. These will change their hues by revolving the crystal (c). These beautiful tints are generated by a physical change pro- duced by the solution of sugar on the transmitted plane-polarized light, giving rise to the phenomena of circular polarization. 65. The quantity of sugar existing in the urine is never sufficient to present the beautiful phenomena in a satisfactory manner without taking very many precautions to insure success. For this purpose the tube (b) should be changed for one 14 inches long, as the quan- tity of sugar in urine is so much smaller than in syrup, that a larger column of fluid becomes necessary to develope the optical pheno- mena above described. As one effect of this is to oppose a greater obstacle to the passage of light, a more vivid beam becomes necessary. To attain this, a good light should be thrown into the tube from a concave mirror, which should be substituted for the reflecting plates (a) in the figure. This light should be polarized by allowing it to traverse a Nicol's single-image prism, screwed into the lower end of the tube holding the urine. If tlien diabetic urine, carefully filtered to render it as clear as possible, be placed in the tube, the utmost care being taken to exclude all extraneous light, the colored images will be visible, not, however, with the vivid tints presented by the syrup, as their hues will be modified by the color of the urine and quantity of sugar present. Whenever in this apparatus two images possessing different colors, however faint, are seen simultaneously, it is certain that the fluid in the tube possesses the power of circular polarization. And, as in the case of urine, but two bodies have been found which produce this physical change in light, viz., sugar and albumen, it is easy to dis- cover the nature of the substance which communicates this property to the urine. If, therefore, a specimen of urine, which does not coagulate by heat, produces the colored images when examined in the polariscope, it is certain that sugar is present. If the urine be tolerably free from color, as is often the case in diabetes, mere filtration through bibulous paper will render it suffi- ciently transparent to exhibit these phenomena. But, if deeper colored, a small quantity of the solution of diacetate of lead should be added, and the mixture briskly agitated; in this way almost all the urinary pigment is precipitated, and on passing the fluid through a filter it becomes fitted for the polariscope. 66. The comparative increase or decrease in the quantity of sugar in the urine during the progress of treatment may be detected by CIRCULAR POLARIZATION. 83 observing the extent of the arc through which it is necessary to rotate the eye-piece before any particular tint reappears or disap- pears. The best and most constant tint to assume as an index is a dark bluish-violet color, which precedes a yellowish-red and follows a deep blue, and has the advantage of being a distinct color easily recognized. Let us suppose the tube of the apparatus is filled with diabetic urine, and by careful examination a rotation of the eye-piece through 9° is required to develope the dark violet color. If on a subsequent examination a column of urine of the same length requires a rotation of 18° or 27° to develope the same color, we learn that the quantity of sugar present is doubled or tripled in quantity, whilst if a rotation of 3J° or 6° is sufficient, it shows that the sugar has fallen to one-half or two thirds the quantity found on the first obser- vation. There are many serious practical difficulties in the application of the polarizing power of urine to the detection of sugar, which will probably ever prevent its being generally employed, but M. Bouchar- dat having drawn the attention of the profession to it, it was neces- sary to give some explanation of it. To obtain results at all ap- proaching to accuracy, the beautiful polariscope, contrived by M. Soleil, of Paris, should be employed. Its manipulation requires, however, more tact than is likely to fall to the lot of any except those who have devoted some time to physical investigation, whilst its expense (£18 or £20) places it beyond the reach of many practi- tioners. CHAPTER III. CHEMICAL PHYSIOLOGY OF THE URINE. Acidity of Urine, 67—Composition of Urine, 68—Mean Analysis of, 69—Fixed Salts of, 70—Varieties of Composition at different Periods of the Day, 72— Urea, 73—Physiological Origin of, 74—Influenced by Food, 75—Artificial for- mation of Urea, 76—Relation of, to Salts of Ammonia, 77—Uric acid, 78— Mode in which it exists in Urine, 79—How deposited, 81—Physiological Origin, 82—Liebig's Views, 83—Objections to, 84—Boussingault's Researches, $5—Dr. B. Jones's Account, 86—Lactic Acid, 90—Creatinine, 93—Physiological forma- tion of, 94—Hippuric Acid, 96—Physiological formation of, 97—Butyric Acid, 99—Coloring Matter, 100—Purpurine, 101—An Emunctory for Carbon, 102— Sulphur-extractive, 103—Ammonia, 104—Fixed Salts, 105—Composition of the Phosphates, 106—Enderlin's Views objected to, 107—Source of the Phosphates, 108—Dependent on Food, 109—Presence of, in Faeces, 110—Source of Sulphu- ric Acid, 111—From Bile and Albumen, 112—Chloride of Sodium, 114—In Pneumonia, 115—Formation of Urinary Deposits, 116—Classification of, 117. 67. Healthy urine, uninfluenced by food, is sufficiently acid to redden litmus paper, but the intensity of the action of urine on the test-paper is subject to remarkable variations, sometimes being even replaced for a short time by an alkaline reaction without involving the necessary presence of disease. Dr. B. Jones has carefully inves- tigated this subject, and he has discovered that the urine is always most acid when the contents of the stomach possess the greatest acidity and vice versd. The urine passed the longest after food is generally the most acid, that passed during digestion is three or four times less acid, and even sometimes alkaline. Immediately before each meal, the urine always showed the greatest acidity; that passed in two or three hours after always showed the least. The decrease was greatest three hours after breakfast, and five or six hours after dinner, when it reached its minimum. In the absence of food, the acidity remained nearly the same for twelve hours, but it fell directly after taking food. With animal food only, the diminution of acidity after food was very rapid and more permanent than after mixed diet; • COMPOSITION. 85 indeed, the urine often became alkaline. With vegetable food (ex- cluding subacid fruits) the decrease of acidity after food was much less marked and the increase of acidity before food much more evi- dent. Dr. B. Jones's148 essay on the subject merits, and will well repay a careful study. 68. The chemical composition of urine has been the subject of repeated investigations during the present century, and numerous statements have from time to time been made public, respecting the elements contained in this important fluid. In a physiological point of view, the urine of health may be regarded as naturally made up of the following classes of ingredients dissolved in water: I. ORGANIC PRODUCTS. 1st. Ingredients characteristic of the secretion produced by the destructive assimilation of tissues, and sepa- rated from the blood by the kidneys. 2d. Ingredients developed principally from the food during the process of assimilation. Urea, uric acid, crea- tine, creatinine, color- ing and odorous prin- ciples. f In addition to the above, hippuric acid, lactic acid; accidental constituents. II. INORGANIC PRODUCTS. 3d. Saline combinations, separated from the blood, and derived from the food. 4th. Saline combinations chiefly generated during the pro- cess of destructive assimilation. Sulphates, phosphates, chloride of sodium and all soluble salts taken with the food and often undergoing decompo- sition in the system. Sulphates, Phosphates. III. INGREDIENTS DERIVED FROM THE URINARY PASSAGES. 5th. Mucus of the bladder. 6th. Debris of epithelium. 7th. Phosphate of lime. Of these, the first class of ingredients can alone be considered as really essential to the urine, and characteristic of it as a secretion, the kidneys being the only organs which normally eliminate these elements from the blood. The saline ingredients of the second class are met with in most secretions of the body, with the exception of the sulphates, which are rarely found except in the urine. The third 86 PHYSIOLOGY OF URINE. class of elements is met with in all fluids passing over mucous sur- faces, the phosphate of lime being derived from the mucus, of which it is a constituent. 69. As all unnecessarily minute chemical details of the analyses of urine are more interesting in their abstract bearings than in rela- tion to physiology and pathology, it would be quite out of place to insert any of the very elaborate views which have been given by some writers of the composition of the secretion under consideration. I prefer adopting the analyses of M. Becquerel,18 as the most practi- cally useful, especially as they are corroborated by the results of the researches of most recent and trustworthy observers. The following table presents a view of the normal average composition of the urine passed by healthy persons in the course of twenty-four hours; the weight of the constituents being expressed in grains: Urine of men. Urine of women. Means of both. In 24 hours. In 1000 grains. In 24 hours. In 1000 grains. In 24 hours. In 1000 grains. Weight of urine, Specific gravity, Solids, .... 19516 1-0189 610- 1000 31-1 21124 1-0151 526-8 1000 24-95 20320 1-01701 568- 1000 28- Urea, .... Uric acid, Fixed salts, . . Organic matters and} volatile saline com- V binations, . . ] 270-7-6 150-176- 12-8 -0-391 7-63 9-26 240-8-6 126-145- 10-366 0-406 6-14 8- 255-8-1 138-100-5 12-0-398 6-885 8-63 The organic matters mentioned in the above table consist of a mixture of creatine and creatinine with hippuric, and, according to some, lactic acid; a coloring pigment rich in carbon, an extractive matter containing a considerable proportion of sulphur, with a salt of ammonia, and probably of some other bodies in smaller quantities, with whose nature we are yet unacquainted. 70. The fixed salts referred to in this table consist of combinations of chlorine, phosphoric and sulphuric acid, with lime, soda, potassa, and magnesia, or their metallic bases: these substances exist nor- mally in the following average proportions: In the urine of 24 hours. In 1000 grains. Chlorine, . . . 10*15 grains, . . . 0'502 grains. Sulphuric Acid, . . 17*3 "... 0-855 " Phosphoric Acid, . . 6'4 " 0-317 " COMPOSITION. 87 In the urine of 24 hours. Soda, . Lime, . Magnesia, Potassa, 106*1 grains, In 1000 grains. 5'224 grains 139-95 6-898 The proportions in which these several ingredients exist in the urine are liable to great temporary variations from slight causes, depending upon the nature of the food, amount of exercise, and state of general health. The amount of solids in the secretion increases usually in a direct ratio with the amount of muscular exertion, and consequently metamorphosis of tissues, and inversely with the length of time elapsing after taking food. 71. The following example will be sufficient to point out the great variation existing in the composition of urine passed at different periods of the day. I collected carefully all the urine secreted by a person in good health during twenty-four hours: it amounted to only 22 ounces; he had previously drunk very little. It was passed at the following hours: at 8 a.m., eight ounces, depositing urates ; at 1 and 5 P.M., six ounces altogether; at 11 P.M., eight ounces; all these specimens were acid. The first of these was passed after having been ten hours without food, and consequently was a good specimen of urina sanguinis; the second was influenced by the morning meal and a slight lunch at noon; whilst the third, urina cibi, contained the products of the metamorphosis of food taken at dinner early in the evening. The composition of these three specimens was, in 1000 grains, as follows: When excreted. A. 8 A.M. B. 1 and 5 p.m. C. 11 P.M. D. E. Specific gravity, . % Water, ..... Solids, ..... 1016 962-72 37-28 1-020 953-40 4660 1030 930-10 69-90 1-018 958-41-94 11-0 1-1 11-2 18-0 Urea,..... Uric acid, .... Fixed salts, .... Creatine, creatinine, color-1 ing matter, and volatile V saline compounds, . j 14-3 0-28 5-1 17-6 15-3 0-9 16-5 13-9 24-4 1-33 9-9 34-27 180-4 8-0 98-0 213-0 The bulk of the urine secreted was nearly one-half the average, being but 22 ounces, and the composition of the solids existing in the 88 PHYSIOLOGY OF URINE. whole quantity is shown in the column D of the above table. In the following twenty hours, the same person having partaken more freely of fluids, secreted 36 fluid ounces of urine, and the composition of 1000 grains of which is shown in column E. 72. Urea.—Chem. comp. C2N2H4O2=60. This very important substance constitutes the form under which a large quantity of nitro- gen is expelled from the system; 270 grains of urea, or more than half an ounce, being on an average excreted by a healthy man in the course of twenty-four hours. Urea, in consequence of its combining with acids like a weak base, can be very readily discovered in urine. The nitric or oxalic acid may be used for its detection; the former being the most conve- nient for clinical observations. For this purpose let about a drachm of urine be placed in a watch-glass, and about half that quantity of colorless nitric acid be carefully added. If a normal proportion of urea exist, no change, except a darkening in tint, and the evolution of a few bubbles, will be observed, unless the weather be exceedingly cold, or the glass be placed in a freezing mixture, and then a delicate plumose crystallization of nitrate of urea will commence at the edge of the fluid. Urea may be obtained from the nitrate by pressing it be- tween folds of blotting-paper until it is nearly dry. The satin-like mass thus left, if dissolved in boiling water, and digested with a little animal charcoal, yields up most of its coloring matter, and by sepa- ration may be obtained in irregular rhomboidal plates. The nearly pure nitrate should be dissolved in as little water as possible, and carbonate of potass added until all effervescence ceases. In this way nitrate of potass is formed, and urea set free. The whole should be carefully evaporated to dryness, and digested in hot absolute alcohol, which readily dissolves the urea; and by evaporation it may be ob- tained in four-sided prisms, very soluble in both hot and cold water, and possessing the cool and saline taste of nitre.* 73. Under ordinary circumstances, no crystals of nitrate of urea will appear on the addition of nitric acid, unless the urine be concentrated by previous evaporation to one-half its bulk, or even less, before adding the acid. In some cases, indeed, an excess of urea exists, and then a rapid formation of crystals of the nitrate occurs, occa- sionally so copiously that the mixture becomes nearly solid. It is * See note, page 42, for the process of obtaining and measuring urea recom- mended by Dr. Odling and Dr. Davy. UREA. 89 important, whenever this is the case, to measure the bulk, and ascer- tain the specific gravity of the whole quantity of urine passed by the patient in twenty-four hours; for unless these exceed the average proportions of health, there is no proof that an actual excess of urea is excreted by the kidneys. A particular specimen of urine may appear richer in urea than natural, simply from the diminished amount of water present, as is well shown in the preceding table (71); in which, although the total quantity of urea present in the urine of twenty-four hours was much below the average, yet the proportion found in 1000 grains at three different periods of the day far ex- ceeded it. On this account the urine secreted shortly after a full meal, especially of animal food, as well as that voided after excessive perspiration, generally crystallizes on the addition of nitric acid. 74. Physiological Origin of Urea.—This has been already traced to the destructive assimilation of the tissues of the body (40). That urea is one of the products of this important process, and that it con- stitutes the mode in which the greatest portion of the nitrogenized elements are excreted, is unquestionable. It is probable that the ni- trogen present as a constituent of the quantity of urea excreted in twenty-four hours represents about five-sixths of that taken into the system in the food. It must not, however, be supposed that the urea is normally derived directly from the food. Its origin must be traced to the destructive assimilation of those tissues of the body which are removed to make room for new matter. Minute quantities of urea escape from the system by the skin, but this body is removed so rapidly from the blood by the kidneys that very minute traces of it only can be obtained unless these organs become diseased, and are then no longer fitted to perform their important functions of depura- tion. It is a curious fact, first noticed by MM. Bernard and Barres- wil, that, in animals from whom the kidneys have been removed, and the urea accumulates in the blood from the absence of its proper out- lets, a considerable quantity is excreted by the gastro-intestinal mu- cous membranes in the form of carbonate of ammonia, a result of the rearrangement of its elements (77). In man, and in all warm-blooded carnivorous and omnivorous mammalia, the quantity of urea far ex- ceeds that of uric acid; whilst, in carnivorous birds, serpents, and insects, the latter substance predominates, and often quite replaces the urea. Dr. Prout is inclined to believe that the urea is the pecu- liar product of the metamorphosis of the gelatinous, and uric acid of albuminous, structures.19 Liebig, on the other hand, considers that 90 PHYSIOLOGY OF URINE. uric acid is the immediate product of the change in all nitrogenized tissues, and that urea is the secondary product, arising from the action of oxygen and water in the uric acid.20 The fact that in sea-birds and many insects the uric acid remains in the state of urate of am- monia, and does not become converted into urea, notwithstanding all the conditions necessary, according to Liebig's views, for this change to exist, must cause this hypothesis to be received with great caution. The following table shows the average quantity of nitrogen and carbon evolved from the system in twenty-four hours, in the form of urea and uric acid: Quantity excreted in 24 hours. Nitrogen existing in Carbon existing in Nitrogen calculated in cubic inches. Urea, .... Uric acid, . Total, . Grains. 255-8-1 Grains. 118-95 252 Grains. 50-92 3-23 Cubic inches. 391-4 8-3 263-1 121-47 54-15 399-7 Urea is not alone eliminated from the blood by the kidneys; it has been detected in many of the fluid secretions, and among others in the humors of the eye. I have found it abundantly in the perspira- tion of persons whose kidneys are unhealthy, and in the copious eva- cuations from the intestines produced in renal dropsy by the action of elaterium. It is impossible to overlook the curious relations existing between urea and sulphocyanide of ammonium, in connection with the fact of the excretion of sulphocyanogen in the saliva. The presence of an alkaline sulphocyanide can readily be demonstrated by the pro- duction of the characteristic red color on adding a few drops of a solution of any sesquisalt of iron to the saliva. Sulphocyanide of ammonium may be regarded as urea, in which oxygen is replaced by sulphur, thus: Urea (cyanate of ammonia) = C2N2H402; ' Sulphocyanide of ammonium = C2N2H4S2. 75. - The influence of the composition of food on the quantity of urea is beautifully shown by the experiments of Dr. Lehmann,22 of Leipsic. This philosopher examined the quantity of urea secreted by his kidneys whilst living for some days on a strictly animal diet, as well as when he restricted himself to vegetable food, to a mixed diet, and to one quite free from nitrogen, consisting of starch, gum, oil, sugar, &c. The mean weight of the urea obtained from the urine UREA. 91 of twenty-four hours, under these circumstances, is expressed below in grains: Diet. Animal. Vegetable. Mixed. Non-nitro-genized. Urea in the urine of twenty ) four hours, . . . j 819-2 346-5 500-5 237-1 No one can avoid observing the great disproportion existing be- tween the quantity of urea contained in Lehmann's urine, and that generally assumed as the average; the amount secreted whilst confined to a strictly non-nitrogenized diet, nearly equalling the normal pro- portion. Still, whatever may be the idiosyncrasy of the ingenious experimenter in this matter, the result of his researches prove to a demonstration the influence of food in modifying the proportion of urea separated by the kidneys. I cannot help suspecting that the appetite of this physiologist must be rather above the average, for he alludes to his having devoured thirty-two boiled eggs in one day, which, even in the absence of other food, seems an enormous quan- tity. Lehmann has also shown that the excretion of urea is conside- rably augmented by anything which, like severe muscular exertion, increases the wear and tear of tissues. M. Lecanu23 has made some interesting observations on the con- nection between the amount of urea secreted and the age of the indi- vidual. The following presents the average results of his experi- ments on the quantity of urea and uric acid excreted in twenty-four hours at different ages : Urea. Uric acid. Adult men,.....431"9 grains, . . 13-09 grains. Adult women, .... 2"94-2 " . . 1001 " Very old men (84 to 86 years old), 124-8 " . . 6"77 " Children (under 8 years), . . 138-2 " . . 3-98 " Bischoff's observations on this subject are worthy of our careful study, and are clearly expressed in the following table from Dr. Day's "Contributions to Urology," in the "British and Foreign Medico- Chirurgical Review," July, 1855: 92 PHYSIOLOGY OF URINE. 2 OS i-H cm -** m Mr-NHO) O CO -* Tf ■* et CO CO Q0 1ON CO CO .-H CO 00 •>* CM 0C —1 CM >, t- tfd *- as »b cb -re as bi cm TO CD a ihiOhNH in t- CM as o -H l-H ^H cb o o o o CO OS CM CM a e3 u bo co *- ■■# -i> as CO *- CO CO 00 ir- cm cm oo i—i oo as oo -* i-- eg p ■*$ as co oo t-CN 00-^ OS i-h co co co co t£> as o cDHH OS ^h OS O O •S lO«5NrtH 00 »0 -c« I-H 1—1 i—1 oo *- cm cm cm cb o o o o co as CO tl / S 1—1 -H/i CM CD s a •^ O CM CO OS (H 3 i-h CO 00 i-h CO 0) *- CM cb cb as cb cb as >b i-h OlONHH l-H C5 CO CO -1 -* .t- CO —l CM CO 'V ^- o o o o cc3 •M >, -»^> bo O O OSK) t- a a! CM 00 MHiO CO J— O CO CM CD i* J3 nJJ>r- CO CO p cm as d -cf as o co co ^ 00 CO -* I—c --i S-, i'o 4h CM 4h o ,FH i^H -^< t- T* CO ■^3 lO CO CM CM CM p p O p CD ■**--* O !-H CD 00 t- CN1 ■^ ■* CO TO CM A. CO 4h CO p t- CO i-H CO TO C3 CO CO OS ~ 0) s* CD i~ 00 CO i-h CO CM CD CD t-i CD CO o o o o 1M a. i-h OS 00 ■—i CO £ o o as oo co & ifl O ^ N CO s. o CJ cp as co o CD CO Tf CM 00 CM * I—) CO CO .O ^Mi- l-H 3 CO o o o o t- as CO CM TO l-H O CO t— I-H O CO E-. o .-3 00 CM CM CM 00 O t- t— O OS u CM t- —i as j^- as o cm as oo -a CO CO O CO CM OS ■—■ 00 cb as cm O r^H 6o cb »b CD CO CO CO CM lO S>» ■>* O CM CM 3 00 ^» ^H i-H -a CM Al O O O lO as «8 CO H^> O CM • as —i lOHIO a -* co as o cm H-S faC O 00 rt ifl 00 u oi OS 00 -H CT<1 p CO CD OCIONH CO i-h CO CO ^t< »b -* OlflOO & oo cb io -^ tjh <* « c; h w s>> vo ^tf CM i-H -*^> OMlH -H OS i-H CO o o -* as d i^ CM i—i d as ■—i as t- »o i— CO 00 J-- 00 3 O Mril~-lO00 CO CO -nOOlp oo ^h as i—i as roo-* f-t- >b -^ r- bi -* 00 cb CM CM o -aiTfocy) CO CO CO as l-H i-H CM CM i-H l-H .t~ CD > CD >b o o o o CM CO as ■—i ■* i~ o CO^t-t-O !h O CO CO CD CO SO co co CC.lOf- CNl^O -HO O fa lO (N M CO CO CO CO »C CO Th 4** as cb cb cb CO CM *0 i—l O t>» CO CO f—1 i-H t-NH l-H CO i—( CO O O co as 00 CO • • . . . t ' xa ' * * " m ' u u TO a CD !- CD . "J . c3 . • 5S. • c3 . . TO* . C3 . c a = S d a CO poS ^cOPOfa UREA. 93 76. Urea is invested with peculiar interest on account of its being so readily obtained artificially, and thus enabling the chemist to closely imitate one of the most important results of the chemistry of life. A man eats an excessive meal of meat, more than he can assimilate into healthy blood, and a large proportion of it, under the influence of the water, alkali, and oxygen of arterial blood, becomes metamorphosed into urea. The chemist can take some of the same meat, and ignite it with carbonate of potass; the result is, that car- bon and nitrogen unite to form cyanogen; he adds a body which readily yields up oxygen, as the binoxide of manganese, and a cyanate of potassa is formed. This, when digested with a salt of ammonia, becomes a cyanate of that base, which requires only a rearrangement of its elements under the influence of heat to become urea. Thus: C N H 0 1 atom cyanic acid, . . . 2+1+0+1 1 " water, .... 1+1 1 " ammonia, .... 1+3 = 1 " urea,.....2+2+4+2 77. As urea consists of 2 at. carbon, 4 at. hydrogen, 2 at. nitro- gen, 2 at. oxygen, its elements are so arranged that its composition exactly resembles that of carbonate of ammonia, minus two atoms of water. C N H 0 2 atoms carbonic acid, 2 4 + 2 " ammonia, . . . 2+6 2+2+6+4 — 2 " water, .... 2+2 = 1 " urea, .... 2+2+4+2 In accordance with this view, urea is decomposed by boiling with a concentrated acid, a salt of ammonia being formed, whilst car- bonic acid is evolved; and, on the other hand, by ebullition with a solution of potass, ammonia is given off, and a carbonate of potass remains. An ingenious mode of estimating the proportion of urea existing in any fluid, founded on becoming so readily converted into an ammoniacal salt, has been proposed by M. Heintz.119 The fluid being mixed with an excess of sulphuric acid, is slowly evaporated in a retort until fumes of sulphuric acid begin to rise, a sulphate of ammonia is formed, and carbonic acid given off: the quantity of 94 PHYSIOLOGY OF URINE. ammonia in the salt, estimated by precipitation by chloride of plati- num, or the amount of carbonic acid evolved, becoming an index of the urea present, 44 grains of carbonic acid indicating 60 of urea. The mere act of boiling the urine is sufficient to convert a portion of urea into an ammoniacal salt, and by long keeping, even in close vessels, a similar change occurs. The rapidity with which this con- version is effected varies remarkably in different specimens of urine. I have known urine become alkaline within an hour of its emission, and yet, in one instance, I detected urea in a specimen of urine which had been preserved in a closely-stopped bottle upwards of ten years. The presence of a mucoid body in a state of change, acting as a ferment, certainly explains the rapid conversion of urea into carbonate of ammonia, in some urine (274). Dr. Hassall compares this passage with the following statement by Dr. B. Jones: "Pure urea maybe kept dissolved in distilled water, or it may, as you see in this test-tube, even be boiled without being changed into carbonate of ammonia; but if a few drops of ammoniacal urine, or a small quantity of mucus, is added, decompo- sition begins. By careful experiments, more may be made out on this subject than the general fact that some substance in a state of change is requisite to cause the change in the urea to begin; and the influence of the monads and vibrios, which are sometimes found in acid urine, may be determined." These two statements are not in such direct opposition as has been supposed; inasmuch as boiling urine and boiling pure urea in distilled water are not quite the same things; indeed, the urine contains probably the very substance alluded to by Dr. B. Jones as requisite to cause the change in the urea to begin. However, there is no cause for com- plaint, as the matter has led to the institution of experiments, and the establishment of the following conclusions: 1st. The simple act of boiling an aqueous solution of urea is suffi- cient to determine the gradual dissolution of that substance, and its conversion into carbonate of ammonia. 2d. The conversion of urea takes place in distilled water, even without the aid of the spirit-lamp. 3d. The decomposition of urea is effected, either with or without heat, much more readily in fluids which are alkaline, and especially in those in which the alkalinity arises from the presence of lime in any form. 4th. The conversion of urea is retarded, and sometimes altogether URIC ACID. 95 prevented, by an acid condition of the fluid in which it is present; and this is equally the case whether the solution be subjected to the heat of the spirit-lamp or not. The more acid the fluid, the greater its power of resisting the decomposition of the urea. 5th. Animal matter, in a state of decomposition, exercises a powerful influence over the transformation of urea; and this it does partly by producing an alkaline condition of the fluid in which the two substances are contained, the alkalinity being produced by the carbonate of ammonia generated during putrefaction (163). The elements of urea not only are thus related to those of carbo- nate of ammonia, but are, as we have seen, identical with those of cyanate of ammonia with water, a circumstance which explains the occasional occurrence of cyanogen compounds in urine. 78. Uric Acid.—Chem. comp. C10N4H4O6,C2H4N2O2+2C4NO2 =168. (Syn. Lithic or Urylic acid.) From the analysis of healthy urine, we learn that on an average 8*1 grains of this sub- stance is excreted from the blood by the kidneys in twenty-four hours. It has been lately suggested that uric acid always exists in the urine as a urate of soda; but it seems to me that the chemical evidence is more in favor of Dr. Prout's opinion, that the greatest proportion of the acid exists in combination with ammonia. From the accurate observations of this physician, we learn that uric acid requires 10,000 parts of water at 60° for solution, whilst there does not exist in urine quite 2500 times its weight. It is hence utterly impossible to be in a free state without supposing the existence of causes modifying its solubility, by no means justified by the present state of chemical knowledge. If, on the other hand, the acid is combined with ammonia, it must of necessity remain dissolved at ordinary temperatures. Urate of ammonia is soluble in 480 times its weight of pure water, and, in the state in which it occurs in urinary deposits, requires for solution 2789 parts of urine, according to the researches of Dr. B. Jones;24 who has also shown that the presence of a moderate quantity of saline matter increases its solu- bility. The 8-1 grains of uric acid normally secreted in twenty-four hours requires but 0-82 grains of ammonia for saturation, and the 8-92 grains of urate of ammonia thus formed will be held in solution by less than half a pint of water, or about one-fourth the quantity separated from the blood by the kidneys. If healthy urine be slowly evaporated in an air-pump vacuum, it soon becomes turbid from the formation of clouds of urate of ammonia, which ultimately subside 96 PHYSIOLOGY OF URINE. in very minute spherical masses on the sides of the Vessel. The same thing occurs when urine of rather high specific gravity is exposed to cold. These facts appear conclusive in favor of Dr. Prout's opinion. The most plausible objection to this view is the one advanced by M. Becquerel and others, viz., that a single drop of nitric acid is suffi- cient to precipitate all the uric acid naturally contained in a con- siderable quantity of urine, which, it is stated, could hardly be the case if it were combined with a base. This is an objection more apparent than real, for if it be granted that 8*92 grains of urate of ammonia are dissolved in about 40 ounces of urine, a moment's reflection will show that less than a single drop of nitric acid ought to be sufficient to precipitate all the uric acid present in half a pint of urine. ' For the quantity of ammonia combined with the uric acid in half a pint would be about 0-2 grain, which would be exactly neutralized by 0-8 grain of nitric acid, or less than a single drop. 79. Jt is, of course, quite possible that uric acid may be secreted combined with ammonia from the elements of the disorganized albu- minous tissues (82). It is, perhaps, more probable that the acid is first generated and subsequently unites with a base, which it meets, either in the nascent state, or in its progress through the structure of the kidneys. Late researches of Professor Liebig have thrown much light on this matter, in developing the reaction of alkaline basic phosphates with uric acid. It is well known that an aqueous solution of the common or tribasic phosphate of soda exerts an alka- line action on reddened litmus paper. If uric acid be heated in such a solution, it dissolves in consequence of combining with part of the soda, and setting free part of the phosphoric acid, which pro- bably forms a super-salt with some of the undecomposed phosphate.25 The fluid thus becomes acid, and reddens litmus. On cooling, the phosphoric acid reacts on the urate of soda, and about one-half the uric acid is deposited in fine prismatic crystals, resembling in shape some varieties of uric acid sand. These crystals are not pure uric acid, but contain, chemically combined, some phosphate of soda, of which they are not deprived either by boiling water or hydrochloric acid. The addition of an acid to the fluid decanted from the crystals causes a deposition of tabular crystals of uric acid. These observations are amply sufficient to explain the natural acidity of urine, and the depo- sition of crystals of impure uric acid on cooling; all that is required, being to suppose that the 0-398 grain of uric acid, the average quantity existing in 1000 grains, are dissolved in about 2-5 grains URATES. 07 of tribasic phosphate of soda, the proportion found by Simon in that quantity of healthy urine. 80. The deposits most frequently occurring in the urine on cool- ing, by evaporation in vacuo, or exposure to a freezing mixture, are however (133), neither crystalline nor composed of uric acid alone. Lehmann states that "the sediment which is deposited from acid urine in fever, and in almost all diseases accompanied with severe fever, has long been misunderstood in reference to its chemical com- position. Originally it was regarded as a precipitate of amorphous uric acid, and subsequently (and almost to the present time) it was regarded as urate of ammonia. It has, however, been fully demon- strated by Heintz and myself that this sediment consists of urate of soda, mixed with very small quantities of urate of lime and urate of ammonia." And again, further on, he remarks that "he had scarcely found any ammonia in urine," in which statement he had been confirmed by Liebig, and also by Heintz, whose direct analysis had detected but lg of ammonia in the sediment.* And again, at p. 216: "Even in alkaline urine, it is very seldom that urate of ammonia occurs as a sediment. In these cases it is found in white opaque granules, which, as has been already stated, when seen under the microscope, appear as dark globules, studded with a few acicular crystals. It scarcely ..ever occurs except in urine which, by long exposure to the air, has undergone the alkaline fer- mentation. Even in the alkaline urine of patients with paralysis of the bladder dependent on spinal disease, it is very rarely that I have found these clusters of urate of ammonia. In the alkaline urine that is sometimes passed in other conditions of the system, it is never found." Dr. Hassal, in a review of the last edition of this work, has given the analyses of five specimens of urine, in which he was ably assisted by Dr. Letheby; and as the subject is one of much importance and interest, and the experiments have been carefully made, I am happy to say that I have received Dr. Letheby's kind permission to insert them. First specimen.—Color, bright rose-red. Under the microscope it was found to consist of minute amorphous particles, which dissolved in warm water, and reappeared on cooling in their original state. Acetic acid slowly developed rhombic crystals of uric acid. The filter containing deposit was treated with half an ounce of cold water * Lehmann, vol. i, p. 221. 7 98 PHYSIOLOGY OF URINE. in three portions. This removed a quantity of urea and a little of the urate. It was then drenched with boiling water, and the filtered liquid allowed to stand for twenty-four hours. The deposit was col- lected and dried at 7° Fahr. It weighed three grains. One grain was dried at 212°, and lost thereby 0-07 of moisture; it was after- wards incinerated, and furnished 0-092 of a white ash, which was very alkaline to turmeric paper, though not permanently so; it was fusible before the blowpipe, and tinged the flame of a violet-white color. When dissolved in acetic acid, and tested with oxalate of am- monia, it gave a precipitate of oxalate of lime. One grain was distilled with two drachms of weak potash, and it gave an alkaline liquid, which contained 0-012 of ammonia. 'While boiling, the potash solution acquired a bluish-green color, showing the presence of uramile or murexide, to which the rose tint of the precipitate was doubtless due. One grain was treated with weak acetic acid, whereby 0'66 of nearly colorless uric acid was obtained; the acetic solution gave a copious precipitate with oxalate of ammonia. These results prove that the precipitate consisted of biurate of lime, with a little biurate of ammonia, and a still smaller quantity of biurate of potash, to- gether with coloring matter. The following is the percentage com- position : * Biurate of lime, . . . . . .61 " ammonia, . .... 13 " potash,......traces Moisture,.......19 Pink coloring matter (uramile or murexide), . 7 100 Second specimen.—The color was at first of a bright rose-red, becoming of a foxy or yellowish-red tint after washing with cold water. The percentage composition, obtained as in the former analysis, was— Biurate of lime,......70 " ammonia, ..... 9 Moisture,...... . 16 Coloring matter,......5 100 The solutions from which the preceding were deposited, after cool- ing, were evaporated to dryness at a temperature of 100° Fahr., and URATES. 99 were found to contain a small quantity of urea, together with biurate of lime and a little biurate of ammonia, but no urate of soda. Tliird specimen.—The urine Avas deep brown, and the diffused sediment of a pale fawn tint, and when collected on a filter of a light rose-pink, changing after some hours to a greenish hue, somewhat resembling pus. On submitting this urate to the microscope, it was seen that it had lost its usual granular form, and had become aggregated into small globular crystalline masses of a very pale color and deli- quescent appearance. The alteration of color observed was, no doubt, OAving to this change in the form of urate. The ash of the incinerated urate amounted to about 10 per cent., and gave a perma- nent stain to turmeric paper, was soluble in Avater, and tinged the flame of the bloAvpipe of a violet color, showing that it Avas chiefly composed of potash. 100 parts gave— Biurate of potash, . . . . 57-12 " lime, . . 18-37 " ammonia, . . 10-06 Moisture, ..... . 11-74 Coloring matter and loss, . . 2-71 100-00 Fourth specimen.—This was of a bright deep pink color, and was obtained from urine having a specific gravity of 1024, which, on evaporation of a few drops on a slip of glass, gave a crystalline crust of urea. It was treated with a large quantity of alcohol, by which a great deal of urea and a very little amorphous pink matter were dissolved out. Dried at 70° Fahr. its density A\*as 1100. Ten grains were treated Avith half an ounce of cold water, and set aside for tAventy-four hours; the water dissolved two. grains and became of a pale sherry-tint color. It yielded, on evaporation, a faAvn-co- lored deposit, which, being incinerated, gave 0-25 of white ash, which was found to be lime. Tavo grains were treated with two drachms of dilute acetic acid, and after tAventy-four hours, 1-2 grain of nearly Avhite uric acid Avas obtained. Two grains Avere dried for several hours over a steam bath, and lost 0-2 from escape of moisture. The remainder was then distilled Avith two drachms of weak liquor potassie, and the distillate contained 0-04 of free ammonia. Tavo grains Avere incinerated, and furnished 0-2 of white ash, which Avas found to be potash. These results give the following composition of the urate: 100 PHYSIOLOGY OF URINE. Biurate of potash, .... 42'0 " lime,......20-0 " ammonia, . . . . 19 5 Moisture,......10*0 Coloring matter and loss, ... 8'5 100-0 Fifth specimen.—Color, dull pink. The ash amounted to 12*5 per cent.; it Avas strongly and permanently alkaline, and tinged the flame of a full yellow color, from which it is manifest that it consisted in great part of soda. The acetic solution was rendered slightly turbid by oxalate of ammonia, thus proving the presence of lime; and distilled Avith potash, gave evidence of ammonia. This specimen, therefore, consisted, in great part, of urate of soda, with a small quantity of urate of lime, and probably also of urate of ammonia. In making analyses of the urates, certain precautions are neces- sary. The folloAving is the best mode of proceeding. The filtering paper should be digested in acetic acid, in order to free it from lime or other salts Avhich may be contained in it. The precipitate should be examined under the microscope, to ascertain whether it be free from oxalate of lime, uric acid, triple phosphate, or other deposits. It should be collected on the filter, well Avashed Avith proof spirit to remove urea and chlorides, and then dissolved in hot Avater, Avhich should be poured upon the precipitate on the filter, stirring gently with a feather. Of course, as the water becomes cold, the urates are thrown doAvn, Avhen they may be collected and dried for analysis. If either triple phosphate or uric acid be present the filter will retain these, while the urates pass through, but if there be any oxalate of lime, its crystals may pass through the filter, and so vitiate the analysis. It thus appears that the deposits usually considered to consist principally of urate of ammonia are, in reality, made up of urates of lime, potash, and soda, Avith very small quantities of ammonia—and even this is doubtful, as from the great difficulty of freeing these deposits entirely from urea, it is possible that the ammonia may be derived from its decomposition. *[I believe that the explanation of the proximate formation of these deposits is to be found in the action of uric acid on the microcosmic * As these views are ingenious, and are still supported by some chemists, I have hesitated to remove them, though myself persuaded of their fallacy. URIC ACID. 101 salt or double phosphate of soda and ammonia; Avhich salt, or its elements, may be regarded as a constant constituent of healthy urine. When uric acid is mixed Avith a warm solution of this triple phosphate, urate of ammonia is formed, and phosphoric acid evolved, either free or combined with a base and forming an acid salt. This urate of ammonia is not decomposed on cooling, but is simply deposited in delicate microscopic needles, readily rediss'olving on the application of heat, if sufficient water is present. On the addition of urine to a hot solution of these minute needles, they are deposited on cooling, combined with the coloring matter of urine, completely amorphous, and presenting all the characters of the commonest forms of urinary deposits.27 If, after the separation of the urate of ammonia, a fresh quantity of uric acid be heated in the supernatant fluid, more of the ammoniacal salt is formed up to a certain point; when phosphate of soda yields, and urate of soda is generated, which on cooling is de- composed in the manner already described (79). 81. I therefore ventured some time ago to propose the following as a probable explanation of the mode in which uric acid exists in healthy urine: Uric acid, at the moment of separation from the blood, comes in contact with the double phosphate of soda and am- monia, derived from the food, forms urate of ammonia, evolving phosphoric acid, which thus produces the natural acid reaction of urine. If the whole bulk of the urine be to the urate of ammonia formed, not less than about 2701 to 1, the secretion will, at the ordi- nary temperature of the air, remain clear, but if the bulk of fluid be less, an amorphous deposit of the urate will occur. On the other hand, if an excess of uric acid be separated by the kidneys, it will act on the phosphate of soda of the double salt, and hence, on cooling, the urine will deposit a crystalline sediment of acid sand, very probably mixed with amorphous urate of ammonia, the latter usually forming a layer above the crystals, which always sink to the bottom of the vessel.*'] 82. Physiological Origin of Uric Acid.—It will be sufficient to merely allude to some of the more recent opinions entertained on this subject; and the first Avhich demands attention is that of the cele- brated Liebig.28 He believes that when, in the exhausted tissues containing protein {i. e., albuminous structures), the vital force is no * The presence of the ammonio-phosphate of soda in normal urine is much doubted by many observers; Lehmann, with Liebig and others, attributes the- acidity of the urine to the presence of the acid phosphate of soda. 102 PHYSIOLOGY OF URINE. longer able to resist the chemical action of the oxygen which is con- veyed to them in the arterial blood (38), it combines Avith their elements and forms products, among Avhich uric acid is the most im- portant. Thus, the elements of one atom of the essential ingredients of all muscular and fibrous tissues (protein), Avith 91 atoms of oxygen, are equal to the elements of uric acid, carbonic acid, and water, thus— C N H 0 1 atom protein=48+6+36+ 14 f C N H 0 I 15+6+ 6 + 9=U at. uric acid. 91 " oxygen= 91 l = \ 33 66=33 " car. acid. I | 30+ 30=30 " water. 48+6+36+105 J [ 48+6+36+105 If, then, sufficient oxygen and water be conveyed in the arterial blood, the greatest part of the uric acid may be converted into urea and carbonic acid, so that the effete nitrogenized elements of the tissue reach the emunctories in a soluble form, a condition necessary for their ready excretion. C N H O 1 1 atom uric acid=10+4+4+ 6 4 " water = 4+4 6 " oxygen = 6 f C N H O 4+4+ 8 + 4=2 atoms urea. 6 12=6 " carb. acid. 10+4+8+16 ^ ^ 10+4+8+16 Dr. Garrod has shown, by a very ingenious series of experiments, that very minute traces of uric acid may be detected even in healthy blood. This is a very interesting fact, although what might have been expected, as the blood may be regarded as the main seAver into which are Avashed the results of the waste of the body prior to their final escape by their proper conduits. Professor Scherer149 has dis- covered uric acid in comparatiA^ely large quantities in the spleen, and it appears, with hypoxanthine (178), to be an important immediate result of the destructive metamorphoses of this singular organ. 83. It is, therefore, obvious, on the above hypothesis, that the larger the proportion of oxygen which circulates through a tissue in the act of destructive assimilation, the more complete will be the con- version of uric acid into urea, and in proportion as this oxygenation is perfected the former will disappear from the urine. Hence in the urine of carnivorous animals the quantity of uric acid in relation to the urea, will be in the inverse ratio of the rapidity of the circulation. URIC ACID. 103 Thus the boa-constrictor eats an enormous meal of nitrogenized food, but being a cold-blooded, sloAvly respiring animal, it takes in too little oxygen to convert the uric acid formed by the metamorphoses of its tissues into urea; and hence the semi-solid urine of this animal consists almost entirely of biurate of ammonia. On the other hand, the lion and tiger, equally carnivorous with the serpent, are rapidly respiring, warm-blooded animals, and although, from their violent muscular exertions, rapid and great destruction of tissue must occur, scarcely a trace of uric acid is found in their urine, as it is all con- verted into urea at the moment of its formation, in consequence of the abundant supply of oxygen. As combination with oxygen is the necessary condition for the metamorphosis of tissue, it folloAvs that we should be in constant danger of oxidizing to death, unless either the vital force is generated in sufficient intensity to oppose the action of oxygen, or some substance be present Avhich, opposing a less resist- ance m its influence than organized tissues, protects them from cor- rosion. The mucus covering the air-passages and the bile in the intestines, are thus supposed to be the conservative agents which protect the structures imbued with them from destruction by oxida- tion. In a like manner the non-nitrogenized elements of our food, as all fatty and amylaceous substances, interfere with the conversion of the uric acid into urea, as they monopolize great part of the oxy- gen ; hence man, being an omnivorous animal, partakes of a sufficient amount of food, rich in carbon, to prevent the complete conversion of insoluble uric acid into soluble urea, consequently the former sub- stance appears in the urine, the average proportion borne by the uric acid to urea in healthy urine being about 1 to 32. 84. If these vieAvs be correct, it Avill folloAv that, other things being equal, the proportion of uric acid in the urine will increase in the urine of a man avIio takes food rich in carbon, and decrease if he con- fines himself to a nitrogenized diet, and becomes, for a time, a car- nivorous animal. Further, the proportion of uric acid will decrease and urea increase, with the perfection of respiration and abundance of blood-discs, the reputed carriers of oxygen (35). It appears, liOAvevcr, that these vieAvs, ingenious and full of in- terest as they are, are not supported by any experience hitherto recorded,—in fact, are, in many cases, totally opposed by it. Indeed, Ave have no proof of any kind that uric acid is a necessary transition formation betAveen protein compounds and urea. The experiments of Lehmann already alluded to (75), performed upon himself, demon- 104 PHYSIOLOGY OF URINE. strate that Aregetable diet and one quite free from nitrogen decreases, and an animal diet increases, the quantity of uric acid ; the urea also increases in the same manner. The folloAving table presents the results of Lehmann's researches : Diet. Quantity excreted, in 2-1 hours, of Proportion of uric acid to urea. Uric acid. Urea. Exclusively animal, Mixed animal and vegetable, Exclusively vegetable, Food free from nitrogen, Grains. 22-64 18-17 15-7 11-24 Grains. 819 2 505-0 346-5 237-1 1 : 36-1 1 : 27 5 1 : 22-1 : 21- From this table we learn that, when living on a diet as free from nitrogen as possible, 11-24 grains of uric acid and 237*1 grains of urea Avere excreted by Lehmann's kidneys in tAventy-four hours. These quantities may be assumed as solely produced by metamor- phosis of tissue, inasmuch as there existed no other source for .them. On confining himself to a strictly animal diet, Lehmann found in his urine 22-64 uric acid, and 819*2 urea, being 11-4 more of the former and 582-1 more of the latter than can be accounted for by the disor- ganization of the tissues of his body, and, consequently, must have been derived from the ingesta. On mixing vegetable food with his meat, instead of finding an increased proportion of uric acid, as the theory of Liebig would indicate, a much smaller proportion of this substance was discovered in the urine. The statement, that in carnivorous animals the use of vegetable food' increases the amount of uric acid, is quite opposed to the fact recorded by Magendie,29 that uric acid disappears from the urine of carnivora Avhich have been fed for about three weeks on non-nitrogenized food. 85. The question, however, appears to be quite set at rest by the researches of Boussingault, performed on ducks. This very careful and laborious observer first carefully examined the quantity of uric acid excreted from the metamorphosis of tissue of the animal, by ascertaining the quantity excreted in a given time by a duck deprived of food for some hours; in another Avho had been made to SAvallow balls of clay; and a third who had been fed on gum—a body nearly free from nitrogen. He then proceeded to ascertain the increase of the acid excreted after the ingestion of various articles of food. I haA-e arranged the following table from these experiments, having re- URIC ACID. 105 duced their results to the same times—all the Aveights being calculated in English grains: Uric Acid excreted by Bucks in 24 hours. Food administered. None. Balls of clay. Gum. Casein. Gelatine. Gelatine. Fibrin. Flesh. Quantity digested, Uric acid, Nitrogen in the food, Nitrogen in the uric acid, none 4163 none none none. 4.163 none. none. 163 24 4-412 1 1 426-64 162-4 6654 53 59 14908 157 08 2711 5183 1713- 635 2 956 34 203 28 138 6 291 0 311-76 99821149136 67-08 45 7 i 96 03 This tabular view of Boussingault's researches is peculiarly in- structive, and places beyond all doubt the real office of uric acid, at least in those animals Avhich normally excrete their useless nitro- genized elements in that form. Analogous experiments of Lehmann and others, as Ave have seen, have shown that urea performs a similar function in man. The only difficulty investing the subject is simply the question, why urea is sometimes the form in Avhich nitrogen is evolved, and Avhy, at others, uric acid performs this function. That the view of Professor Liebig is untenable I have already expressed an opinion, and some serious objections are opposed to the notion of uric acid being, in man at least, the result of the metamorphosis of one set of tissues, and urea of another, since that in ducks, in Bous- singault's experiments, not a trace of urea was excreted, although carefully looked for, and yet structures physiologically identical with those of man and carnivorous animals, must have undergone meta- morphosis. The true physiological relation of urea to uric acid is still one of the disiderata of science. 86. Dr. B. Jones has more recently re-examined this subject, but chiefly in relation to the immediate influence of food, and not to the total quantity excreted in 24 hours. He found that the quantity of uric acid— After animal food in 1000 grs. of urine, sp. gr. . . 1027 was 1*022 grs. Before " " • 1*024 0*049 After vegetable food " . . 1*025 1-010 Before " " . 1*024 0-049 Exercise did not appear to materially affect the quantity of uric acid excreted. ST. The theory of the perfection of oxidation in increasing urea and diminishing the uric acid, scarcely appears to be in accordance Avith the Avcll-knoAvn fact, that in carnivorous birds, as sea-foAvl, the 106 PHYSIOLOGY OF URINE. mortar-like urine is constituted of urate of ammonia, like the urine of serpents, and yet the former class of animals are rapidly respiring, warm-blooded animals, provided Avith an abundance of oxygen, totally opposed to the serpents in their physiological characters, and appear- ing to present all the conditions required by the theory alluded to for the total conversion of uric acid into urea. This change, nevertheless, does not occur, and so large a quantity of urate of ammonia is ex- creted by sea-birds, that many islets and rocks in the tropics inhabited by them are covered to a considerable depth with this substance, which is now an important article of commerce as a manure, under the name of guano. Zimmerman30 attempted to defend Liebig's view against the objection, on the ground that the feathered skins of birds prevented contact of air to capillaries of the surface, and thus cut off one supply of oxygen. This remark, hoAvever, applies Avith equal force to the thick hides of the lion, tiger, and leopard, as Avell as to the scaly armor of serpents, and hence gives no support to either opinion. 88. From a late observation by Heller,120 it Avill appear, that of all animals, in proportion to their size, butterflies excrete the largest quantity of uric acid combined Avith ammonia. This substance appears to be a product of metamorphic changes of tissue during the pupa state, as it does not exist in the caterpillars; and the yelloAV fluid Avhich is excreted Avhen the developed insect escapes from the pupa is rich in urate of ammonia. If a butterfly be caught, and gentle pressure be applied to its abdomen, the drop or two of yellow fluid Avhich escapes contains urate of ammonia in globules, and colored by purpurine. Dr. John Davy has very recently shoAvn that all true insects he had an opportunity of examining in Barbadoes, excreted uric acid free or combined. Spiders, on the contrary, excrete uric oxide. This question will, hoAvever, again come before us. 89. What, then, is to be regarded as the physiological source of the uric acid of the urine ? There can be no question that all the phenomena of health and disease point out the probability of there being a double origin of this substance, one from the nitrogenized elements of tissues, and the other from the elements of food rich in nitrogen which escape the completion of the process of primary assimilation, or undergo the changes consequent on that function so imperfectly as not to be completely converted into the healthy con- stituents of blood. They hence yield Avith facility to the metamor- phic influences so energetically exerted in the capillary netAvork of LACTIC ACID. 107 the body, and their ultimate elements are excreted as uric acid, gene- rally combined Avith soda, lime, &c. Why they are thus excreted at one time as uric acid, or urates, and at another as urea, we are, as I have already stated, quite ignorant. 90. Lactic Acid and Lactate (?) of Ammonia.—The existence of these compounds in healthy urine, first announced by Berzelius, and admitted generally by chemists, has been called in question by Pro- fessor Liebig, who, in a careful repetition of the processes of Berze- lius, failed in detecting the slightest evidence of the presence of the lactic acid. It appears evident that'Avhat was mistaken for lactic acid is really a mixture of creatine and creatinine, discovered by Dr. Pettenkofer (93). Lehmann31 has stated that l-52 grain of free lac- tic acid, and 1-20 grain of lactate of ammonia, are contained on an average in 1000 grains of healthy urine. Since the detection of the nitrogenized bodies just alluded to, these numbers must be regarded as indicating rather the proportion of this substance, and not of lactic acid or a lactate, as Avas previously supposed. The composition of dry lactic acid (C6H505=81) bears so simple a relation to that of some of the most ordinary elements of our food, that its presence in the secretions, at least under many circumstances, might really be anticipated. Thus the elements of 1 atom of starch are equal to 2 atoms of lactic acid, 1 " cane.sugar, " +1 atom of water. 1 « gum, " " 1 " milk-sugar, *' +2 atoms of water. 1 ■' grape-sugar, " + 4 " Lactic acid can be readily formed out of the body by allowing a solution of sugar to ferment in contact Avith an animal substance in a state of change, as the mucous membrane of a calf's stomach (rennet), or a piece of Avashed cheese (casein). 91. Liebig has lately shoAvn144 that Berzelius Avas not in error when he announced lactic acid to be a constituent of the juices of the flesh; and as no appreciable quantity of it is to be detected in the urine in health, it must undergo some secondary change before its elimination from the system.* It in all probability undergoes oxidation, be- * Lehmann states that it is present in those diseases in which there is an increase in the amount of the oxalate of lime, as in pulmonary emphysema, disturbances of the nervous system, rachitis, &c. -t 108 PHYSIOLOGY OF URINE. coming converted into carbonic acid, as occurs out of the body when it is heated in contact Avith the fixed base. Thus— C H 0 1 atom lactic acid, . . . 6+5+5 +12 atoms oxygen, ... 12 6+5 + 17 — 5 atoms of water, . . . 5+ 5 = 6 atoms of carbonic acid, '. . 6+ 12 A certain, although small portion, of lactic acid is, there is some rea- son to believe, excreted in the perspiration, even in health. In some diseases, it certainly escapes freely from the skin. 92. From the late researches of M. Boussingault, it appears quite certain that lactic acid is an ingredient in the urine of herbivorous animals. He detected distinct traces of it in the urine of a pig fed upon potatoes, whilst in the urine of a coav and horse he found respectively 16-51 and 20*09 parts of an alkaline lactate in 1000 of urine. When the quantity of lactic acid is exceedingly small, the test proposed by M. Pelouze for its detection may be employed.* This is founded on the property possessed by lactic acid of prevent- ing the complete decomposition of salts of copper by alkalies. For this purpose boil the urine to be examined with milk of lime until the urea is completely decomposed, and ammonia ceases to be given off. The filtered fluid should be mixed with a solution of the sul- phate of copper, by which, if lactic acid be present, a lactate of copper is formed, and, on adding some milk of lime, oxide of copper will be precipitated. On throAving the whole on a filter, the fluid which passes through will be found free from copper, unless lactic acid be present, in which case distinct traces of the metal can be detected, by acidulating the fluid with a drop of sulphuric acid, and immersing a polished piece of iron Avire, which will become in a short time coated Avith copper. I must confess, however, that I do not feel much confidence in this test of M. Pelouze. 93. Creatine and Creatinine.—These very interesting substances, of Avhich some account has already been given (40), Avere first dis- covered in the urine by Dr. Pettenkofer, and were supposed to be peculiar to that secretion, until Professor Liebig, after some masterly * Fresh urine ought always to be used, in order to avoid the fallacy arising from the changes due to urinary fermentation, according to the views of Scherer. CREATINE — CREATININE. 109 researches, proved them to be identical Avith the crystallized body described many years ago by Chevreul in the juices of flesh. Evi- dence of their existence in the urine may be obtained in the manner already described (6), but to procure them in any quantity the process described by Liebig is by far the best. He removes the acidity of healthy urine by the addition of a little lime, and then adds chloride of calcium, until no further precipitate of phosphate of lime takes place. The filtered fluid is then evaporated to a syrupy consistence, and after the crystallization of salts from it, the super- natant fluid is decanted, and mixed Avith a saturated solution of chloride of zinc in the proportion of half an ounce to a pound of the extract of urine. In a feAV days, an abundant deposit of yelloAV granules, generally closely adhering to the vessel, will have appeared. These consist of a compound of the chloride of zinc Avith the creatine and creatinine. They should be Avashed in cold water, then dissolved in boiling Ayater, and recently precipitated oxide of lead added until the fluid becomes strongly alkaline. Chloride of lead is thus formed, and, with the separated oxide of zinc, is precipitated. The Avhole is throAvn on a filter, with a little animal charcoal, the clear solution passes through, and, on being evaporated, leaves a crystalline mass; on digesting this Avith hot alcohol, creatinine is dissolved, and creatine left. Creatine {Chem. comp. : C8N3H904+2HO=131+18=149) occurs in colorless, transparent, lustrous, rhombic crystals, is perfectly neutral, and crystallizes from its solutions in tufts, like acetate of lead. They contain about 12 per cent, of water of crystallization, are soluble in 74*4 parts of cold water, and are nearly insoluble in strong alcohol. It is of a bitter, strongly pungent taste, and irri- tating to the fauces. It loses its tAvo atoms of Avater at 110°, and is decomposed at a higher temperature. It is soluble without change in baryta water; but when boiled Avith it, it is decomposed into ammonia and carbonic acid, or urea and sarcosin. It is soluble without change in dilute acids; but Avhen heated with strong acids, it gives off its two atoms of Avater, and is converted into creatinine. Creatine contains, when dry, nearly 32 per cent, of nitrogen. Creatinine (Chem. comp. : C8N3H702=113) contains 24 per cent. of nitrogen, and differs essentially from creatine in exerting a strongly alkaline reaction. It crystallizes from its aqueous solution in small, colorless, glistening prisms; is soluble in 11-5 parts of cold water, and about 100 parts of cold alcohol. It forms a series of 110 PHYSIOLOGY OF URINE. salts Avith acids, and has a remarkable tendency to yield triple com- pounds with metallic salts, especially those of silver, mercury, zinc, and platinum. A solution of creatinine instantly throws doAvn from nitrate of silver a deposit of a triple salt in white acicular crystals. Creatine and creatinine bear a simple relation to each other, thus— C N H 0 ] atom creatine, .... 8+3+9+4 — 2 atoms water, . . . . . 2+2 1 atom creatinine, .... 8+3+7+2 Accordingly we find that creatine is converted into creatinine with great readiness by digestion with the mineral acids. During putre- faction of fluids containing it, this change in all probability occurs, for no creatine can be detected in putrid urine, the creatinine alone existing. Even in healthy urine the quantity of creatine is much smaller than that of the creatinine, and is very variable; indeed, it may be doubted whether it can be regarded as a perfectly normal ingredient. 94. Physiological Origin of Creatine and Creatinine.—It is impos- sible to doubt the really excrementitious character of these bodies; we have already seen that one of them, the creatine, is formed in considerable quantity in the infusions of muscular tissue, and as it is remoAred from the body by the kidneys, partly unchanged and partly converted (by giving up tAVO atoms of AA'ater) into creatinine, it can only be regarded as one of the forms under Avhich we find the nitrogenized elements of worn-out structures removed from the system. In this point of vieAV both these bodies are invested Avith no small interest. What at first appeared as a mere chemical curiosity, becomes in this view a physiological sub- stance, performing the important function of depurating the blood. It appears probable that creatine and its allies, creatinine and ino- sinic acid, are the direct results of the metamorphoses of certain structures, and that others tend, from some cause yet to be made out, to undergo com-ersion into other elements. Thus Liebig found creatine in the infusions of the muscles of all the mammalia he examined, as well as in foAvls, fish, and probably in the allio-ator; whilst it Avas totally absent from the brain, liver, and kidneys of animals. It would appear that the quantity of creatine bears a ratio to the Avear and tear of the muscular structures; thus, in wild and HIPPURIC ACID. Ill hunted animals the quantity was far greater than in domesticated and tame ones, even Avhen allowance Avas made for the greater quan- tity of fat existing in the latter. The heart, a never-resting muscle, yields the largest proportion of creatine. While it Avould be premature to assume as proven any vieAvs not as yet demonstrable, it may still be considered as probable that crea- tine is an early link in the stage of metamorphic changes to which muscular structures are subjected before their final elimination in the elements of the excretions. The recent discoveries of Scherer would render it probable that other organs, as the spleen, are meta- morphosed into hypoxanthine (178), a body distinct from creatine. It is hence rendered very possible that all tissues are not resolved into the same elements of excretions, and some confirmation is af- forded to the views of Dr. Prout, Avho Avas disposed to trace the origin of several of the elements of the urine to the destructive assimi- lation of distinct tissues. 95. Although Ave have seen that creatine and creatinine are both found in the urine, Ave must not conclude that they are entirely ex- creted in this manner. It is very probable Hhat a considerable pro- portion of creatine is resolved into uric acid or urea before its final elimination. We have already seen the chemical relation of creatine to uric acid, and to urea (40); its metamorphosis into the latter body, and into the peculiar substance, sarcosin (Avhich requires only the addition of the constituents of Avater to represent the elements of lactate of ammonia) is so readily effected, that a similar change oc- curring in the body is rendered very probable. 96. Hippuric Acid.—Chem. comp. C18H8N05+HO=176. (Syn. Urobenzoic acid.) This substance, long knoAA'n to exist in the urine of herbivorous animals, and, according to some, occasionally in that of man, has been shoAYn by Liebig to be a normal constituent of the latter fluid. Its presence can be demonstrated in the urine of the horse and cow with great readiness, by merely acidulating some of that fluid with hydrochloric acid, and after effervescence has ceased, filling a Avatch-glass with the mixture, and leaving it to evaporate spontaneously ; in a feAV hours delicate tufts of acicular crystals of hippuric acid will appear. The best mode of obtaining this substance from healthy urine is to evaporate a feAV ounces of urine to a very small bulk, and then add an excess of hydrochloric acid. A mix- ture of hippuric and uric acids Avith altered coloring matter will then be separated and fall to the bottom of the vessel. After a feAV hours' 112 PHYSIOLOGY OF URINE. repose the supernatant fluid should be decanted, and the deposit Avashed with a small quantity of very cold Avater. On boiling the residue with alcohol, in Avhich uric acid is insoluble, the hippuric acid will be dissolved, and by spontaneous evaporation, be left in thin, delicate needles, strongly colored from adhering impurities. Hippu- ric acid, when pure, crystallizes in long, slender, four-sided acumina- ted crystals, and requires nearly 400 times its Avcight of cold Avater for solution, and hence can be separated from even a dilute solution of any of its alkaline salts by the addition of a stronger acid. 97. When an abnormally large proportion of this acid is present, as after the administration of benzoic acid (160), or green plums, or in hippuria (201), it is easily detected by pouring about half an ounce of the urine into a capsule, and evaporating to a syrupy consistence. On adding an equal bulk of hydrochloric acid, and alloAving the Avhole to cool, a crystallization of hippuric acid in pinkish tufts of acicular crystals will occur. This is beautifully shoAvn Avith the urine of a horse or of a person Avho has taken half a scruple of benzoic acid a few hours before. If the quantity of hippuric acid is small, it frequently crystallizes on the addition of hydrochloric acid, in a very curious manner, in delicate linear branched figures, ramifying in the fluid like a sea-Aveed, or a leafless bunch of tAvigs (202). A quantity of purpurine usually falls Avith the hippuric acid, so that, Avhen drained on a filter, the paper is stained of a delicate car- mine color—a remarkable fact, Avhen Ave bear in mind the close ap- proximation existing between hippuric acid and purpurine (98). Hippuric acid must also exist in the semi-solid urine of birds, as E. Marchand detected it combined with ammonia in guano.121 98. Physiological Origin.—It is believed by its discoverer to be a derivative of some of the non-nitrogenized elements of food, and to exist nearly in the same proportion as uric acid. The quantity of hippuric acid in the urine, from the experiments of Heller, appears to be dependent in great measure on diet; for he found that a diet consisting of Avheat and rye bread, or, still better, rye bread alone, produced a urine rich in hippuric, but almost void of uric acid ; and on afterwards adopting a mixed diet, including meat, the relations of the two acids were reversed, hippuric acid disappeared, Avhile the quantity of the uric acid increased. From my OAvn researches, whilst they fully agree with the results of Liebig as to the existence of hip- puric acid, I am inclined to believe that its quantity, in health, is not constant, and always, unless after the ingestion of benzoic or cinna- BUTYRIC ACID. 113 mic acids, very much less than has been stated. It is possible that hippuric acid may constitute a means by which carbon may be evolved from the system by the kidneys, and it is probable that in cases in which the proper emunctories of this substance, the lungs and the liver, are deficient in their function, the kidneys may partially com- pensate for this by secreting a larger portion of hippuric acid. It has very recently been detected in the blood of the ox, and hence its presence in the urine of that animal is readily accounted for. It is remarkable that hippuric acid, next to the bile and purpurine, is the richest in carbon of any of the products of vital chemistry, and hence it very probably performs an office of great importance in the body. A comparison of the percentage composition of the organic material of human bile, from the analysis of Dr. Kemp, Avith that of anhydrous hippuric acid, and the coloring matter of urine from Scherer's analy- sis (102), will show the relation between them, quoad the amount of carbon.32 Urinary Bile. Hippuric acid. coloring matter Carbon, 68-40 63-93 5843 Hydrogen,. 10-13 4-64 5-16 Nitrogen, . 3-44 8-21 8-83 Oxygen, . 18-03 23-22 27-58 100- 100- 100- 99. Butyric Acid.—Occasionally present in urine, and in all pro- bability owes its origin to an imperfect assimilation of saccharine matter. It may, however, be possibly generated occasionally from the butter which forms so large a portion of our food. As a product of disease, it is met with in the white creamy deposit occasionally observed in diabetic urine. The opinion of the origin of this acid being traceable to a change in the elements of sugar, is supported by the fact that out of the body it may be generated by digesting a so- lution of sugar Avith a piece of curd of milk, which plays the part of a ferment, the sugar being converted into butyric acid with the evolution of hydrogen and carbonic acid. C H O 1 atom of sugar = 12+10+10 C H O g+ 8+ 4=1 atom butyric acid. water = 2+ 2 I _ ■ 4+ 8 = 4" carbonic acid. 4 = 4 '" hydrogen. 12+12+12 J2+12+12 114 PHYSIOLOGY OF URINE. This acid may also be derived from protein-compounds, for it has been observed that, when moist fibrin is exposed to the air for some days, it undergoes metamorphosis, becoming partly liquid, and evolves a strong odor of cheese. Carbonic, acetic, and butyric acids with ammonia are generated; and on distilling the residual mass with sulphuric acid, the two latter acids pass over into the receiver. 100. Coloring Matter of Urine.—The nature of the pigment Avhich communicates the characteristic tint to urine is quite unknoAvn. By the late Dr. Simon it was regarded as identical with hsemaphaein,33 the matter which gives to serum of blood its yellow color, and to whose presence in excess the jaundiced hue of the surface, so common in new-born infants as Avell as in cases of chlorosis and anaemia, is sup- posed to be OAving. Dr. Prout has suggested that two distinct pig- ments probably exist, one of them remarkable for its poAver of uniting with the urates and communicating to them the fawn color so charac- teristic of these salts in urinary deposits. Berzelius has indeed described such a yellow coloring matter under the name of halophyle, a term applied to it from the remarkable obstinaey with which it adheres to the urinary salts. Ether readily extracts from inspissated urine a golden-yellow aerid matter. Haller has given the name of uroxanthin to the reputed pigment, but which he has not succeeded in separating. According to him, this body is characterized by its undergoing oxidation by the action of acids, and, under the influence of disease, giving rise to uroglaucin, a blue, and urirhodin, a red pigment. These, hoAvever, are merely applied to what I have long ago described as purpurine. Heller has indeed correctly stated that these metamorphosed A'arieties of the urinary pigment may fall as insoluble deposits, but he has described as crystals of uroglaucin, uric acid merely tinted by the changed coloring matter. This error is an important one, and throws much doubt on many of his conclusions. A very characteristic reaction of this matter was pointed out by myself some years ago, founded on the action of hydrochloric acid upon previously warmed urine. When a test-tube is about one-third filled Avith healthy urine and raised to a boiling heat, the subsequent addition of a few drops of hydrochloric acid produces a tint varying, according to the proportion of coloring matter present, from a deli- cate lilac to the deepest crimson. The substance thus generated I have always regarded as identical with that excreted by the kidneys in certain diseases (especially those connected with the imperfect elimination of carbon), and which communicates the peculiar hue to the so-called pink deposits. COLORING MATTER OF URINE. 115 101. The pink pigment thus generated under the influence of disease, or by the action of hydrochloric acid, is readily soluble in weak hot alcohol, communicating to it a yellowish-pink color, and is remarkable for the facility with Avhich it unites with the urates. If some of these salts, free from all color, be dissolved in a warm solution of the pink pigment, or in urine containing it, they are deposited on cooling of a pink hue, having absorbed the coloring matter like a mordant, just as alumina carries down with it the coloring matter of cochineal. To this pigment I proposed to give the name purpu- rine, and it is, I presume, identical with what Simon afterwards called uro-erythrine, and Heller, more lately, ur-rhodin.* 102. The researches of Professor Scherer,140 of Wurtzburg, on the yellow extractive of urine, are highly important. He has supposed that this substance is the direct result of the destructive assimilation of blood-corpuscles. The folloAving is the mode he recommends for its preparation : Precipitate urine by basic acetate of lead; the deposit, consisting of a combination of the coloring matter and the acids of the urine with lead, is digested in alcohol acidulated by hydrochloric acid. The lead is thus separated from the animal » matter in question as an insoluble chloride. The alcoholic solution yields, by careful evaporation, the coloring extractive, of course more or less modified by the action of the acid, in the form of a blackish mass. By Avashing with Avater, the acid may be removed, and a scarcely soluble blackish-broAvn poAvder is left by careful desic- cation. If neutral acetate of lead be substituted for the basic salt, a much smaller quantity of animal matter is precipitated, but it appears to be richer in carbon. This, among other circumstances, leads to the conclusion that the substance termed by Scherer coloring matter of urine, is really a mixture of two or more bodies, and justifies our adopting this as a mere conventional term. Scherer found this substance, obtained from the urine of a healthy person, to consist of— Carbon,......5843 Hydrogen, . . . . . . 5*16 Nitrogen.......883 Oxygen,......27*58 * Heller alludes to uroxanthin and uroglaucin as well as ur-rhodin, but of these three uroglaucin is the only one whose existence is in any way clearly established; the experiments with regard to the other two were too incomplete to admit of any conclusion. 116 PHYSIOLOGY OF URINE. These researches invest the hitherto neglected coloring matter, or extractive of urine, with high physiological importance. It must for the future be regarded as a vehicle for the excretion of carbon from the blood by the kidneys, and these glands thus appear, in all pro- bability, to play no mean part in compensating for a deficient func- tion in those organs whose especial duty it is to secrete carbon, as the liver and lungs. To this matter we shall again return when speaking of purpurine (186). By loading the system with carbon, or by preventing its due elimi- nation, an excess of this element has been proved to escape by the kidneys. Of the former, a good illustration is met with in the urine of a healthy man who for three Aveeks daily swallowed a large quan- tity of cod-liver oil; and of the latter, the urine of a person suffering from considerable pleuritic effusion will serve as an example: Coloring matter of urine before the use of cod-liver oil. Coloring matter of urine after the use of cod-liver oil. Coloring matter of urine of the case of pleuritic effusion. Carbon, .... Hydrogen, .... Nitrogen, . . . Oxygen, .... 56-65 4-10 6-25 \ 3300 j 57*22 5-46 37-32 61-65 5-60 ( 729 \ 25-46 103. Sulphur Extractive.—It has been long known that urine con- tained sulphur in an unoxidized state, and attention was draAvn by the early chemists to urine blackening a silver vessel in which it was boiled. Professor Ronalds (noAv of Queen's College, Galway) some time ago undertook some researches on this subject, and he discovered that after the coloring extractive matter just described was precipi- tated by basic acetate of lead, the filtered fluid held in solution, besides urea, a peculiar matter, containing a large proportion of sulphur, and a small quantity of phosphorus. This matter has not been isolated, but it furnishes a medium for the elimination of at least from three to five grains of sulphur in tAventy-four hours. The physiological origin of sulphur extractive is undoubtedly to be found in the metamorphosis of part of the albuminous and fibrinous tissues; these all contain sulphur and traces of phosphorus. Whilst the greater quantities of their protein elements are converted into creatine and its allies, and urea, a small proportion containing the sulphur and phosphorus is eliminated by the kidneys in the form of this peculiar extractive matter. The taurine, a crystalline body into FIXED SALTS OF THE URINE. 117 which a part of the constituents of the bile are readily resolved, con- tains one-fourth of its weight of sulphur, and may therefore be one of the sources of the sulphur extractive of the urine. 104. Ammonia.—The presence of this alkali in the urine has been doubted by many late observers, except as a product of decomposi- tion of urea or other elements. Lehmann asserts that on treating fresh healthy urine, previously concentrated by freezing, with bichlo- ride of platinum and potassium, there is a precipitation of chloride of platinum and potassium, but no precipitation of platinum and ammo- nium ; and that, on adding caustic potash to such urine, the precipitate under the microscope does not exhibit the well-known star-like groups of laminae of basic phosphate'of ammonia and magnesia, but merely amorphous matter ; and further, that no ammonia can in this precipi- tate be chemically detected. Scherer and Liebig deny the presence of ammonia in normal urine ; and Heintz found that the ordinary urinary sediments consisted of urate of soda, Avith a little urate of lime and only traces of urate of ammonia. We have no difficulty as to the probable origin of the ammonia. If Ave carefully evaporate perfectly fresh urine in a retort, at the lowest possible temperature, the distil- late Avill contain ammonia, while the concentrated urine has an acid reaction. In this case, the acid phosphate of soda exerts a decom- posing action on the urea, or the pigment, or both, and phosphate of soda and ammonia is formed, Avhich, at a temperature of 100 degrees, evolves ammonia, and is converted into acid phosphate of soda. 105. The fixed salts of the urine are so called from their being left after the other ingredients are destroyed by a red heat; they amount on an average to upAvards of 138 grains in twenty-four hours. These consist, as has been shoAvn (70), of combinations of chlorine, sulphuric and phosphoric acids with soda, lime, magnesia, and potass. Of these the combinations of chlorine and phosphoric acid are probably en- tirely derived from the food. To show hoAv readily the supply of earthy phosphates may be thus obtained, I have calculated from the best authorities the quantities of these salts Avhich exist in an ounce of eleven different articles of food. The numbers must not be assumed as rigidly correct, as in some of the analyses the sulphates and carbonates were included with the phosphates: 118 PHYSIOLOGY OF URINE. Articles of food. Phosphates in 1 oz. Authority. Peas (Pisum sativum), . Maize (Zea mays), .... French beans (Phaseolus vulgaris), Wheat (Triticum hibernum), . Beans (Vicia faba), Potatoes (Solanum tuberosum), Rice (Oryza sativa), Milk,...... Artichoke (Helianthus tuberosus,) . Vetchling (Lathyrus tuberosus), Beef,...... Grains. 9-26 7-2 4-7 4-7 4-7 2-35 1-92 1-2 0-96 0-756 0-38 Braconnot. Gorham. Braconnot. Liebig. Einhoff. Liebig. Braconnot. Liebig. Payen and Braconnot. U 11 ii Liebig. The salts found in the urine after the use of any particular kind of food may at once be knoAvn by referring to the composition of the ashes obtained by burning the substances entering into the food—the saline elements of the ashes and of the urine being always identical. 106. It is impossible to state with certainty in what manner, and with what basis, the phosphoric acid exists in the urine. Phosphates of soda and lime are certainly present, and in all probability the former possesses the chemical constitution of the common rhombic salt, or perhaps is combined with phosphate of ammonia, forming the double, or microcosmic salt. The phosphate of magnesia is also an element of healthy urine, as on the addition of ammonia a mixture of ammonio-phosphate of magnesia and phosphate of lime is precipi- tated. The following formulae represent the atomic composition of those salts ; they are all tribasic. Phosphate of soda,* Ammonio-phosphate of soda, Phosphate of lime, Ammonio-phosphate of magnesia, (HO,2NaO,P205)+24HO (HO,NH40,NaO,P205)+8HO . (HO,2CaO,P205) (NH40,2MgO,P205)+12HO 107. The form in which the combinations of phosphoric acid with soda exist in the urine and other animal fluids has been frequently made the subject of discussion. The fact of the saline residue, ob- tained by igniting an extract of urine, being alkaline, whilst it often * Robin and Verdeil describe the two following salts as normal constituents of urine : Neutral phosphate of soda, . . (HO,2NaO,P205)+26HO Acid phosphate of soda, . . (12HO,NaO,P205)+2HO INORGANIC SALTS. 119 does not effervesce with acids, proves at once that the presence of an alkaline carbonate cannot account for its power of restoring the color of reddened litmus. Enderlin has endeavored to meet this difficulty, by assuming that phosphate of soda exists in the urine in the form of the alkaline tribasic phosphate, or 3NaO,P205. Among other serious objections that may be urged against this view, I might adduce the fact, that no evidence exists of this particular phosphate occurring, except as the artificial product of manipulations in the laboratory. There is not a particle of evidence adduced of its really existing in the urine. Its existence, however, appears very necessary for the support of Liebig's view of the non-existence in the urine of any salt of an organic acid. From a careful series of experiments, I have elsewhere shown124 that a combination of an organic acid with an alkali may exist in a fluid containing the common or rhombic phosphate of soda (HO, 2NaO,P205), and yet the residue of incineration may be free from an alkaline carbonate. This is easily explained, for during ignition, the organic acid is destroyed, and its base replaces the water in the phosphate, converting H0,2Na0,P2O5, into 3NaO,P205. I found that 9 grains of dry phosphate of soda, and 4 of dry acetate of soda, dissolved in water, evaporated to dryness and incinerated, yielded a mass of the alkaline tribasic phosphate, which did not effervesce with acids, and was free from any carbonate. Hence I consider, that until better evidence is adduced, we must be content to regard the phosphoric acid and soda as existing in the state of the common rhombic phosphate unless it is combined with the phosphate of ammonia. 108. The soluble phosphates, which far exceed in quantity the in- soluble salts, must be regarded as derived directly from the food, as well as from the albumen (111) and other elements of the blood Avhen in the act of being organized into muscle. The insoluble phosphates forming part of the structure of the body, derived originally from the blood, are conveyed to the urine in the process of metamorphoses of tissues. Some portion of the phosphoric acid of the urine is in all probability generated from the action of oxygen on many of the structures of the body, into the composition of which phosphorus largely enters, as the brain and nervous system generally. But the greatest part of the phosphoric acid is, as we have seen, derived ready formed, from without, the phosphates of lime and magnesia abounding in milk and most varieties of Aregetable food; whilst the 120 PHYSIOLOGY OF URINE. basic alkaline phosphates exist in flesh, in wheaten flour, leguminous seeds, as beans and peas, &c. 109. Dr. B. Jones has made some very laborious and interesting researches on this subject, and he has shown that the quantity of phosphates in a given quantity of urine bears some relation to the periods of taking food, as Avell as the composition of the meals. Thus, in 1000 grains of urine, the earthy phosphates ranged before taking food from 0-21 to 0-75 grain, and after taking food from 0*97 to 1-91 grain; and in the same quantity of urine, the alkaline phos- phates varied before food from 6*5 to 8-1 grains, and after food from 4*72 to 6*67 grains. The quantity of phosphatic salts is also much greater after a diet restricted to vegetable than to animal food. Thus, after a person had been limited for three days to each of these forms of nourishment, the following were the results, the urine being examined in each case on the third day. On the third day of exclu- sively vegetable diet, 1000 grains of urine, at 6 P.M., contained 0-37 grain of earthy and 8-19 of alkaline phosphates; at 11 p.m., con- tained 1-86 grain of earthy and 3-56 of alkaline phosphates. On the third day of exclusive animal diet, the same quantity of urine, at 6 p.m., contained 0-42 grain of earthy and 4-04 of alkaline phos- phates; at 11 p.m., contained 0-81 grain of earthy and 4-31 of alka- line phosphates. The quantity of phosphates of lime and magnesia in the urine is found to be considerably increased after the admini- stration of soluble salts of these two earths. The alkaline phosphates are most abundant shortly after a meal composed chiefly of bread, and do not appear to be materially affected by the circumstances which influence the excretion of the earthy salts. The ashes of blood contain the basic alkaline phosphates; and muscle, Avhen in- -cinerated, yields much phosphate of lime and some phosphate of magnesia. The alkaline and earthy phosphates, in the opinion of Liebig, are chemically combined, the former Avith albumen, the latter with fibrin. During the formation of muscular tissue, whilst blood is becoming converted into muscle, the earthy phosphates remain in the new-formed tissue in a state of chemical combination; the greater amount of the phosphates of soda and potass re-enter the circulation, are separated by the kidneys, and thus find the way into the urine. 110. A part only of the earthy phosphates contained in the food is absorbed into the circulation, the greatest proportion escaping by the intestines. Berzelius found in three ounces of human excrements six grains of earthy phosphates. INORGANIC SALTS. 121 If a tolerably fluid faecal evacuation of a person who partakes freely of farinaceous food is allowed to repose for a short time, after being mixed with a pint or two of water, and the greater part of the mixture decanted, a quantity of large crystals of triple phosphate of magnesia can be easily detected at the bottom of the vessel. These crystals are sometimes colored grass-green from the presence of bili- verdin, or of modified coloring matters of blood. The insolubility of the salts in water fully accounts for their abounding in the faeces, as the kidneys alone remove those substances not required for the reparation of tissues, which are readily soluble, according to Wohler's well-known law.125 This is well shown by con- trasting the results of Enderlin's analyses of the ashes of human blood and faeces. Ashes of blood. Ashes of fseces. Phosphates of soda (tribasic), . 22-1 . (bibasic) 2633 Chloride of sodium, . . . 54-769 A " potassium, . . . 4-416 t . . 1*367 Sulphate of soda, .... 2'461 J Earthy phosphates and oxide of iron, 5 509 . .82*462 Sulphate of lime,.........4*530 Siliceous matter,.........7-940 89255 98-932 A small quantity of phosphorus also exists in the urine in a non- oxidized form. This fact may be easily demonstrated by comparing the quantity of phosphoric acid existing in the ashes of urine obtained by simple incineration, with that found in the ashes of the same urine, after deflagrating its extract with nitre in a red-hot crucible. The excess of phosphoric acid thus found arises from the oxidation of the phosphorus of the urine. 111. The proportion of sulphuric acid present in the urine is too large to be entirely explained by its presence in the food in a state of saline combination. Indeed, an abundance of sulphuric acid may be detected in the urine, whilst food absolutely free from sulphates is taken into the stomach. The origin of this acid is rather to be traced to the oxidation of the sulphur Avhich exists with phosphorus in the elements of those tissues which contain albumen and fibrin. These two substances consisting, according to Professor Mulder, of— 122 PHYSIOLOGY OF URINE. Albumen. Fibrin. Carbon, . . 54-84 54-56 Hydrogen, . 7-09 6*90 Nitrogen, 15-83 15*72 Oxygen, • . 21-33 22*13 Phosphorus, 0-33 0-33 Sulphur, 0-68 0-36 100*1 100- Thus, during the destructive assimilation or metamorphosis of tissue, oxidation of the sulphur occurs, and explains the presence of at least a portion of the sulphuric acid met with in the urine. 112. Since the discovery made by Professor Redtenbacher of the existence of nearly twenty-five per cent, of sulphur in taurine (one of the products of the metamorphosis of bile), a portion of the sul- phuric acid of the urine may be regarded as resulting from the oxi- dation of the biliary sulphur. For it must be borne in mind that the bile is not separated from the portal blood by the liver as an entirely effete and useless product, as it certainly in some form or other re-enters the circulation, and plays an important part in the animal economy, connected in all probability with the evolution of heat, prior to the final excretion of its elements. We have already seen that a portion of sulphur is eliminated from the system in a non-oxidized form in the urine (103). Hence a part only of the sulphur not required for the purposes of the animal economy undergoes oxidation. In five specimens of urine of healthy persons, Professor Ronalds found the proportion of sulphuric acid existing in one thousand grains to bear to the non-oxidized sulphur the following proportions: 1-06:0-17—1-46:0-18—1-42:0-18—2-44:0-153—1-32:0-165. 113. We are indebted to Dr. B. Jones for some interesting obser- vations on the quantity of sulphuric acid in the urine under differ- ent circumstances. From his researches, it appears that the salts of this acid are increased in the urine by food of any kind, Avhether ani- mal or vegetable. Exercise does not appear to increase them, though from some carefully instituted experiments, Gruner concludes that extraordinary exertion and mental excitement appear to augment the excretion of the acid. The administration of sulphuric acid, except in very large quantities, has no effect on its production; but the ad- ministration of sulphur, or of sulphates of soda or magnesia, ahvays augments the quantity of sulphuric salts in the urine. INORGANIC SALTS. 123 The sulphuric acid existing in combination in the urine is best de- termined by ascertaining the quantity of sulphate of baryta precipi- tated on the addition of chloride of barium to the urine, after acidi- fying it with hydrochloric acid. Dr. B. Jones met with the following results: Urine secreted between 1 and 3 p. m. yielded from 1000 grains 7*70 *j grains of " 3 and 6 " " 7-93 I sulphate " 9 and 11 " " 11'85 j of baryta, breakfast having been taken at 9 A. M. and dinner at 6J P. M. Before food, 1000 grains of urine yielded a precipitate of sulphate of baryta, varying from 7*07 to 8*56 grains, the same quantity after food affording from 9-49 to 15-23 grains. After the administration of sulphate of magnesia, 1000 grains of urine have yielded asTnuch as 22-55 grains of sulphate of baryta. Dr. Parkes has considerably added to our knoAvledge on this sub- ject ; and his papers are well deserving of careful study. 114. The chloride of sodium of the urine is probably derived im- mediately from the common salt Avhich forms so important a consti- tuent of our food. Some of the saline combinations existing in the urine can be rea- dily recognized by the crystalline forms they present Avhen obtained by simple evaporation on a glass plate (13). 115. M. Barral, in a paper presented to the French Academy, has adduced evidence in favor of a probable function performed by the chloride of sodium; having announced that it always increased the elimination of nitrogenized compounds in the urine. His experiments were chiefly performed on sheep, and he found that the daily admi- nistration of 185 grains of chloride of sodium produced a much in- creased excretion of nitrogen, as indicated by the increase of urea and the nitrogenized compounds. Similar views had previously been announced by MM. Regnault and Reiset. It would here appear probable that common salt, for which so universal an appetite exists, besides furnishing hydrochloric acid to the stomach, and soda to the bile, also exerts an important physiological influence in aiding the metamorphosis of tissue, and consequent depuration of the blood. Hegar, whose investigations were conducted under the superinten- dence of Liebig and Vogel, found from experiments on eight men, whose ages in the instance of seven ranged from twenty to tAventy- five, Avhile the eighth was thirty-eight, that the mean quantity of 124 PHYSIOLOGY OF URINE. chlorine in the urine of twenty-four hours was 161*397 grains, the maximum being 214*78 grains, and the minimum 113-33 grains. The folloAving are the most important conclusions at which he ar- rived : 1. The amount Araried in different individuals, depending partly on the food and partly on habit of life and constitution. 2. It had no definite relation to the weight or height of the individual. 3. It attained its maximum in the afternoon, although not immedi- ately after dinner, fell to its minimum in the night, and rose again in the morning. 4. It was increased by exercise and copious draughts of water, which appeared to act by washing it out of the system, as the augmentation was only temporary. 5. Indisposition diminished the quantity. 6. In health, though no chlorides were taken with the food, they were always found, and must, therefore, have been obtained from the blood or tissues. 7. When a larger quantity was taken than usual, the whole did not escape from the system by the kidneys, nor even the boAvels. 8. The relation which the excretion of chlorine bore to urea and uric acid, and its connection with respiration, Avere not known. The quantities of the chloride can be calculated from Bischoff 's table given above. The chlorides are diminished in all cases of disease accompanied by copious exudation from the blood.* 116. Dr. Redtenbacher some time ago stated that chloride of so- dium was invariably absent from the urine passed by patients labor- ing under pneumonia. This remark Avould appear at first sight to receive a probable explanation from the altered diets of patients labor- ing under acute disease. Dr. Lionel Beale has, however, shown that this explanation is insufficient, and he has, in a very elaborate paper read before the Royal Medical and Chirurgical Society, established the following very interesting propositions : 1. That chloride of sodium is totally absent from the urine of pneumonic patients at the period of complete hepatization of the lung. 2. The chloride reappears after the resolution of the inflammation. 3. The chloride exists in the blood in the largest quantity Avhen most abundant in the urine, and vice versd. 4. The chloride'exists in very large quantity in the sputa of pneu- monic patients. 5. There is reason to believe that in pneumonia the chloride is de- termined towards the inflamed lung, and is reabsorbed and removed on the resolution of the inflammation. * Dr. Day's " Contributions to Urology." SEDIMENTS. 125 In acute rheumatism, capillary bronchitis, and typhus, as well as pneumonia, the chlorides are diminished. Dr. Hughes Bennett has furnished some useful matter on this subject. Formation of Deposits or Sediments. 117. Whenever the different constituents of the urine maintain their proper relation to each other, the fluid, as it leaves the urethra, is clear and of a pale amber color, its transparency being but slightly affected on cooling by the gradual subsidence of a slight mucous cloud, occasionally entangling in its meshes a very few microscopic crystals of uric acid. Whenever, however, one or other of the ingre- dients exist in real or comparative excess, or a new substance is superadded, the urine does not generally remain clear, but either im- mediately on being voided, or at least on cooling, becomes more or less turbid. Different names have been applied to the different de- grees and states of turbidity, viz., pellicle, cloud, eneorema, and sedi- ment, the hypostasis of the ancients. When the urine, on cooling, becomes covered with a thin mem- brane-like scum, a pellicle is said to exist; when the substance pro- ducing the opacity floats in detached portions near the surface, it is said to form a cloud, and when this falls toward the base of the vessel, it was formerly termed an eneorema, a title now forgotten; the term sediment or hypostasis being applied to a deposit collected at the bottom of the vessel. Of these, the terms pellicle, cloud, and sedi- ment, or deposit, are still retained as general terms, but are not now used for the purpose of distinguishing any real or imaginary patho- logical condition. It very frequently happens that deposits do not become visible in the urine until after it has cooled down to the tem- perature of the air; this is particularly the case with those which are soluble in warm water, as the urates, more especially those which constitute the great bulk of the red and faAvn-colored amorphous sediments. A crystalline deposit may escape detection by fixing it- self in translucent crystals on the sides of the vessel, as sometimes happens with pale uric acid and triple phosphate. It is quite pos- sible also for a crystalline substance to be present in large quantity, and yet, on account of the minuteness of the crystals and their re- fractive poAver not greatly differing from that of urine, to remain unnoticed. This is remarkably the case with oxalate of lime, and such deposits are best detected by gently Avarming the urine, and 126 PHYSIOLOGY OF URINE. after a few moments' repose, pouring off the greater part of the fluid ; on replacing this with distilled water, the previously overlooked deposit will become visible.* 118. Urinary deposits, including under this term all substances which disturb the transparency of urine by their presence, whether they subside to the bottom of the vessel or not, may be conveniently divided into the four following classes: Class 1. Deposits composed essentially of ingredients formed directly or indirectly from the metamorphosis of tissues, or from the organic elements of food, capable of assuming a crystalline form. Uric acid and urates. Uric oxide. Oxalate of lime. Oxalurate (?) of lime. Cystine. Class 2.—Deposits composed of ingredients for the most part of inorganic origin; including Phosphate of lime. Acid phosphate of lime. Ammonio-phosphate of magnesia. Carbonate of lime. Neutral phosphate of soda. Acid phosphate of soda. Silicic acid. Class 3.—^Highly colored deposits (black or blue) of doubtful origin. Cyanourine. Melanourine. Indigo. Prussian blue. Class 4. Deposits consisting of non-crystalline organic products ; including— * I have never applied heat with this view, as Dr. Owen Rees contends that by gentle heat the oxalate is formed as a result of a rearrangement of the elements of urea, especially where the urates are in excess, and not merely deposited from its greater weight in the warmed urine. The question is still sub judice, but to avoid every possibility of error, we must not be satisfied unless we find the oxalate in fresh urine, and without the aid of heat; but I shall have to consider this subject hereafter. SEDIMENTS. a. Organized. Blood. Pus. Mucus. Organic globules. Epithelium. Renal casts. Spermatozoa. Confervoid bodies. Vibriones. B. Non-organized. Milk. Patty matter. Stearolith. CHAPTER IV. CHEMICAL PATHOLOGY OF URIC ACID AND ITS COMBINATIONS. {Lithi-uria.) Color of Uric Acid Deposits, 119—Diagnosis of, 120—Characters of the Urine, 122—Microscopic Characters of the Deposits, 124—Cause of Variation, 126— Pisiform Deposits, 129—Diagnosis of Urates, 136—Character of Urine, 131— Microscopic Characters of the Deposit, 133—Urate of Soda, 135—Pathological Changes in Quantity of Uric Acid, Excess, 136—In the Blood, 137—Deficiency, 138—Influence of Perspiration, 139—Erasmus Wilson's Observations, 140—Se- guin's Experiments, 141—Liebig's Theory, 143—Becquerel's Researches, 144— Causes of Excess of Uric Acid, 146—Detection of, 147—Excess traced to Ingesta, 148—Conditions for Separation of the free Acid, 149—Uric Deposits considered as Calculous Affections, 152—Therapeutical Indications, by Diaphoretics, 153 —By Correcting the Digestive Functions, 155—By Iron, 158—By Solvents, Alkalies, 160—Vichy Water, 161—Alkaline Salts, 162—Biborate of Soda, 164 —Phosphate of Soda and Ammonia, 165—Benzoic Acids, 167—Use of Solvents, "Constitution" Water, 170. 119. When uric acid exists in a urinary deposit, uncombined with a base, it is invariably in a crystalline form, never occurring in the state of an impalpable amorphous powder. The crystals are seldom sufficiently large to allow their figure to be defined without the aid of the microscope; sometimes being so minute, that the deposit has been mistaken for urates, or even for mucus, until the microscopic exami- nation has discovered the error. Uric acid never occurs quite color- less ; indeed, excepting when mixed with the urates, which is fre- quently the case, it presents a characteristic yellow or amber color. Every shade of intensity of tint, from the palest fawn-color to the deepest amber or orange-red, may be often observed in these deposits; and hence the terms yellow or red sand are applied to them. In general, the deeper the color of the urine, the darker the sediments. 120. Diagnosis of Uric Acid Deposits.—When heated in the urine, the uric acid deposit does not dissolve; the crystals merely become opaque. They generally become more distinct from the solution of DIAGNOSIS — CHARACTERS. 129 the urates, which are frequently mixed with them, and sometimes com- pletely conceal them from view. Hence the best mode of discover- ing this deposit, is to warm the urine, when turbid from excess of urates, in a watch-glass; the acid becomes visible at the bottom of the glass, as soon as the urates dissolve. Heated with liquor potassae, the uric acid deposit dissolves, from the formation of urate of potass of ready solubility in the alkaline fluid. Hydrochloric and acetic acids are without any action, but the nitric readily dissolves it, and by careful evaporation a residue of a beautiful pink color, becoming of a rich purple on being held over the vapor of ammonia, is left. This colored residue is the murexid of Liebig, the purpurate of ammonia of Dr. Prout. Exposed to heat in a platinum spoon, the uric acid deposits readily burn, evolving an odor of bitter almond; and finally leave a small quantity of a white ash, which generally contains phosphate of soda or lime, or both. 121. Characters of Urine depositing Uric Acid.m—When urine con- tains an excess of this acid, it generally lets fall crystals on cooling, uric acid being very seldom deposited before emission. Sometimes many hours elapse before any becomes deposited, even when a com- paratively large quantity is present; this is often the case in the urine of gouty people. Occasionally, indeed, the acid is not deposited at all, but remains on the surface as a crystalline pellicle, presenting an iridescent play of colors when placed in a bright light. Urine depo- siting uric acid usually possesses a deeper amber tint than natural, sometimes being of a reddish-broAvn color. Very high-colored urine, however,-seldom deposits uric acid until after the addition of a stronger acid. Urine never lets fall spontaneously all its uric acid as a deposit, until decomposition has commenced, for after being filtered from a sediment of this substance, the addition of a drop of nitric acid generally causes the deposition of an abundance of crystals of uric acid in a few hours. Urine depositing uric acid always reddens litmus paper, and often contains an excess of urea, so as to crystallize slowly when mixed with nitric acid in a watch-glass (72). Its specific gravity is gene- rally above 1-020. An exception to the above character is presented by the pale urine of infants at the breast, among whom deposits of uric acid are common. These often appear as a yellow crystalline sand, Avhilst the supernatant urine is frequently of low specific gravity, often 1-006, as pale as water, and containing very little urea. This circumstance admits of explanation from the small proportion in 9 130 PATHOLOGY OF URIC ACID. which the alkaline phosphates, the presumed solvent for uric acid, exists in the urine of infants. 122. Microscopic Characters.—The varieties presented by uric acid in its crystalline form are very remarkable; all of them, how- ever, may be traced to some modification of the rhombic prism, which may be assumed as the normal crystalline form of this substance. But two varieties can be artificially obtained, by filtering a warm solution of urate of potass or ammonia, into dilute and warm hydro- chloric acid; either perfect rhomboids, or square tables, generally excavated at the sides into an imperfect hour-glass figure, being obtained. The latter have been erroneously described, both in this country and in America, as identical with FlS- 16- the dumb-bell deposits of oxalate of lime^ to which they have no analogy whatever, except in a distant resemblance in form. These varieties cannot always be produced at will, and appear to depend upon the strength of the solution of the urate em- ployed, and temperature of the dilute acid. Examined with polarized light, the trans- parent crystals of uric acid exhibit a beau- tiful series of colored bands, particularly with slowly precipitated specimens; their brilliancy of tint is only equalled by that of the scales of the diamond beetle. 123. The crystalline forms of urinary deposits can be examined by merely placing a drop of the turbid urine on a plate of glass, and examining it with a microscope under a good half-inch achromatic object-glass. By far the most satisfactory mode is, however, the fol- lowing—which, by rendering the crystals distinct, amply repays the trouble it requires. Allow the urine to repose for a short time in a tall vessel, decant the greater proportion, and pour a teaspoonful of the lowest turbid layer into a watch-glass, gently warming it to dis- solve the urates, and to aid the deposit. Remove the supernatant urine Avith a pipette, and replace it with a few drops of water; then place the watch-glass under the microscope, and the crystals covered "by the water will become most beautifully distinct. Dr. Venables has suggested a mode of collecting the crystalline urinary deposits for examination which is exceedingly convenient, and economizes the time required for the above process. This is founded on the ten- dency of these bodies to cohere on the cork of the bottle containing MICROSCOPIC CHARACTERS. 131 the urine. For this purpose the bottle should be inverted for a few minutes, then quickly erected, and the cork being withdrawn, the drop of fluid adhering to it should be transferred to a piece of glass. On gently coA7ering this with a piece of mica, or thin glass, the crys- talline form of the deposit can be readily recognized under the micro- scope. All crystalline deposits may be examined by transmitted or re- flected light, the latter having some advantages when the crystals are large or in masses. All that is then required is to place on the stage of the microscope, and under the watch-glass, a piece of black velvet; by means of a condensing lens, let a strong light be thrown upon the crystals ; then bring the object-glass into proper adjust- ment, and the color as well as the figure of the crystals Avill become beautifully defined on a black ground. In the folloAving microscopic views, most of the larger crystals are thus represented. 124. In Fig. 17 are represented the common rhomboidal crystals of uric acid ; these are sometimes found so thin, as to be merely pale, lozenge-shaped laminae ; more generally, however, they are thicker, and then by adjusting the light carefully their sides and true figure become well marked. Many of them appear nucleated, from the pre- sence of certain internal markings, as if one crystal included another. It seldom happens that the angles of these are sharply defined, the two obtuse corners being most generally rounded off; and sometimes the acute angles are blunted, so that the whole crystal appears elliptical. Fig. 17. Fig. 18. The most perfect specimens of these are found in deposits of yellow sand in the urine of young infants ; I have never seen them in red sand, or in deposits produced artificially by the addition of a mineral acid to urine. When the deposit has been of long continuance, especially in cases of calculous disease, the rhomboidal outline of the 132 PATHOLOGY OF URIC ACID. crystal is replaced by a square one (Fig. 18). The deposit is then generally high-colored, and the crystals much thicker than in the former variety. In these an internal marking, like a framework, is visible. Several accidental varieties of these rhomboid and square crystals exist; of these the most curious present a spindle-like figure, the obtuse edges being rounded, and the margin on either side exca- vated (Fig. 19), so as sometimes to approach a fleur-de-lis outline. Many uric deposits appear at first sight to be made up of flattened cylinders, presenting a very remarkable appearance (Fig. 20). Upon making them roll over, by adding a few drops of alcohol, or by agi- tation, the fallacy will be detected, and the supposed cylinders will be found to be really very thick lozenges lying on their sides. This variety is often found mixed Avith the urates and oxalates of lime; and is frequently observed in the deposit produced by the addition of hydrochloric acid to urine. 125/ The crystals are sometimes found to be very thin, and longer than broad, so as to represent square tables. These in general have their surfaces quite smooth, especially when they occur in pale neutral urine. When, however, they are met Avith in very acid urine, or are precipitated by the addition of nitric acid, the sides of the table are strongly defined, but the extremities are closely serrated, as if made up of a number of closely packed, irregular needles, crystallized on the body of the crystal. The Avhole surface is sometimes marked with myriads of close dark lines. When carefully examined, their bodies present a very remarkable internal marking, like two crescents placed with their convexities opposed (Fig. 21). This curious ap- pearance is only visible in the non-striated body of the crystal, and is most clearly seen after they have been dried and preserved in Canada balsam. MICROSCOPIC CHARACTERS. 133 The cause of this very remarkable appearance is not very obvious. I am, however, convinced that these crystals are compound. Dr. Burton, of Walsall, who has worked at this subject Avith great zeal, Fig. 21. Fig. 22. informs me that he regards them as being made up of two rhomboidal crystals, with their apices approximated, and then become covered up with an aggregation of acicular crystals, as shoAvn in a, b, c, Fig. 22, where these several stages of formation are represented. I have fancied that by breaking these crystals by pressure, there was evi- dence of their really being formed by a couple of acute rhombs, superposed laterally, as shown in section d, e. When such crystals are immersed in a fluid, as water, or Canada balsam, it will enter be- tween the crystals by capillary attraction, and exhibit two curved outlines where the crystals approximate most closely, as in the well- known experiment of allowing water to ascend between two glass plates slightly separated at one end. I am induced to adopt this opinion, as I have never seen these curved markings except in crystals immersed in fluid or preserved in balsam. 126. A curious question arises as to the cause of these variations ■ in the crystalline form of uric acid, for although they are all tracea- ble to recognized variations of the primary rhomboidal crystal, still there must exist some recognizable cause of these varieties. Dr. Burton has communicated to me some interesting remarks on this subject, and he seems to have a strong impression that variation in the composition of the urine modifies the form of the crystal, and hence a knowledge of the crystallized form of a deposit may possibly indicate the condition of the secretion, and consequently of the morbid state developing the lesion of function which exists. This very inge- nious idea deserves a careful examination. Dr. Schmidt, of Dorpat, has thrown much light on this subject, in 134 PATHOLOGY OF URIC ACID. a little essay on the genesis of uric acid, and he has shown that varia- tions in the rapidity and manner of the precipitation will curiously modify the results. He found that when a drop of a solution of urate of soda is placed on a plate of glass with a drop of strong acetic acid, the following results were seen: At the moment of contact, a deposit of excessively minute globules (a) appears, often presenting the mole- cular movements described by Mr. R. Brown. The globules at last cohere into oval masses (b), which ulti- Flg" 23" mately become transparent (c), and subse- quently assume the form of hexagonal tables (d), or vertical prisms. If a drop of concentrated solution of urate of soda be heated to boiling, and an excess of acetic acid added, it will remain clear at first, but soon after will begin to deposit crystals of uric acid in rectangular columns and tables (e), more rarely in pseudomorphous forms, made up of an ag- gregation of parallelopipedons. If the solution be not heated so strongly before the acetic acid is added, rhombic prisms are formed (f), and when the solution is still cooler, even these become modified in figure (g). If a drop of the mixture of solution of urate of soda and acetic acid be placed whilst boiling hot on a plate of glass, and be suddenly cooled by touching it with a glass rod, rhombic prisms are rapidly deposited, and grow up to a certain point, when on a sudden they become opaque, and split into minute rectangular paral- lelopipedons. Fig. 24. Fig. 25. 127. Coarse, and deep orange or red, sand is generally composed of cohering crystals, forming, indeed, minute calculi. Two varieties of these are frequently met with, one formed (Fig. 24) of cohering, MICROSCOPIC CHARACTERS. 135 thick, rhomboidal prisms, and the other of aggregated lozenges in spinous masses. The latter are most frequently found where a marked tendency to the formation of calculi exists (Fig. 25). It is not un- frequent to find these masses crystallized on a hair, just as sugar- candy is crystallized on a string or thread. When very hastily de- posited by the sudden cooling of the urine, or by the addition of a strong acid, uric acid is sometimes precipitated in irregular masses, resembling, on microscopic inspection, irregular fragments of yellow quartz ; this, however, is unfrequent, and is the only exception I am acquainted with to uric acid occurring in well-defined crystals. More rarely we meet-with aggregated masses of thick lozenges (124) of uric acid, presenting a very beautiful appearance, as shown (Fig. 26) from a drawing given me by Dr. Burton. All the forms of coarse uric acid gravel, on digestion in liquor potassae in the cold, dissolve nearly entirely, the insoluble residue consisting of flakes of mucus, and very frequently minute crystals of oxalate of lime. Fig. 26. Fig. 27. 128. In examining some specimens of urine, in which I had reason to suspect the presence of uric acid, I have occasionally met Avith a remarkable variety, resembling, to the naked eye, slender fibres of hairs, about the eighth of an inch in length. These, on microscopic examination, were found to consist of numerous very minute lozenges, cohering in linear masses (Fig. 27), from having crystallized oh a fibrinous cast (319) of a uriniferous tubule. 129. Another variety of uric acid deposit is exceedingly common in gouty persons; it occurs in little spherical masses of a pale yellow color, varying in size from that of small millet seeds to that of a large pea, Avhich ought indeed to be referred to the class of calculi rather than of deposits. 136 PATHOLOGY OF URIC ACID. This pisiform deposit is remarkable for its persistence often during many years ; it frequently vanishes for many months, and then re- appears. I have generally observed the patient to remain free from gout during the presence of this deposit, and often to suffer from a severe paroxysm on its sudden disappearance. It is really remark- able Avhat an enormous number of these minute calculi are frequently passed. I have met with cases in which upwards of two hundred, of the size and color of small mustard seeds, have been passed in tAvo days. These pisiform concretions, after a feAV minutes' digestion in weak nitric acid, undergo a curious change, their crystalline structure be- coming visible, presenting the appearance of numerous acute rhom- boids, diverging from a common centre. It is evident that they at their first formation, possess this form, the rounded smooth surface being subsequently produced by the deposition of minute crystals of uric acid or the urates betAveen the projecting angles. The three representations in the accompanying figure give three other forms assumed by uric acid: a is the dumb-bell crystal; b, a fusiform, and c appears to be a duplicated variety of that form of crystal which has been, in a pre- vious page (Fig. 19), compared in outline to a fleur-de-lis. 130. Diagnosis of Deposits of the Urates.—These deposits vary in color, from absolute whiteness, through almost every variety of tint, to a pale fawn-color (the most frequently met Avith), brick-red, pink, or purple. All these various-colored deposits present certain eharaeters in common; they never appear in the urine until after it has cooled, and disappear Avith the greatest readiness on the applica- tion* of heat. The purple deposits require rather a higher tempera- ture for solution than the paler A'arieties, and sometimes, on account of the concentration of the urine, the addition of a little water is necessary before they quite disappear. The addition of liquor am- moniae, or liquor potassae, immediately dissolves these deposits, but at the same time renders the urine a little turbid from the precipitate of the earthy phosphates. URATES. 137 131. Characters of Urine depositing the Urates.—The following modifications are most important: 1st. A pale urine of Ioav specific gravity (1*012), becoming opaque on cooling from the deposition of nearly white urates, which instead of readily falling, form rope-like masses in the fluid, and present, on a superficial vieAv, so much the appearance of muco-pus, as to have been mistaken for it. Their disappearance on the application of heat will at once discover their real nature. 2d. A pale amber-colored urine of moderate density (1-018), which, on cooling, lets fall a copious fawn-colored deposit, resembling a bath- brick grated into the urine, disappearing with the utmost readiness on applying a gentle heat. This deposit is of frequent occurrence, often very transient, and is so constantly an attendant on the slight- est interference with the cutaneous transpiration, that a "cold" is popularly diagnosticated whenever this state of things exists. 3d. Whenever febrile excitement prevails, the urine becomes con- centrated, rises in density (1-025), and deposits, on cooling, a reddish- brown sediment, constituting the Avell-known lateritious, or brick-dust sediment. This variety of urine generally becomes turbid on the ad- dition of a drop of nitric acid, not from the coagulation of albumen, as has been frequently but erroneously supposed, but from the pre- cipitation of uric acid in minute microscopic rhomboidal crystals, notwithstanding the amorphous appearance they present to the naked eye. 4th. In all cases Avhere there exists great obstruction to the elimi- nation of carbon, as in Avell-marked affections of the portal circula- tion, especially when connected Avith organic disease of the liver or spleen, or less frequently when suppuration, particularly of a strumous character, is going on in the body, the urine is generally found to possess, in many instances, a deep purple or copper color, often verg- ing on crimson, so as to have led to the idea of blood being present. These deep tints appear to me to depend upon the presence of an excess of purpurine (180). Whenever a deposit of the urates occurs in such urine, either spontaneously or by immersing it in a freezing mixture, it combines with the pink pigment, forming a kind of lake, and which is often so abundant as not to entirely disappear by heat, until the urine is diluted by the addition of Avater. These deposits do not exhibit their delicate tints until after being collected in a filter; they readily give up their coloring matter to alcohol, which scarcely acts on the urates they contain. 132. It has been shown by Dr. B. Jones, that the quantity of the 138 PATHOLOGY OF URIC ACID. urates really existing in the urine is not always indicated by the amount of the deposit, for if the urine is less acid than usual, it will hold dissolved much more of these salts than when of average acid- ity. On the other hand, very acid urine will cause a deposition of the urates when but a moderate proportion of this body is present. 133. Microscopic Characters of the Urates.—When a drop of urine, turbid from the presence of this substance, is placed between two pieces of glass, and examined with the microscope, a mere amor- phous precipitate is first seen. On minute examination this will be found to be com- posed of myriads of excessively minute globules adhering together, forming little linear masses (Fig. 29), often mixed with crystals of uric acid. Sometimes, especially if the urine has been long kept, the minute particles cohere and form small opaque spherical bodies, appearing black by trans- mitted light, on account of their opacity: when examined by reflected light, on a black ground, they present a buff or fawn-color. On the application of a slight heat to the drop of urine, the particles of the urates disap- pear, again becoming visible on cooling. An elegant mode of show- ing the composition of the deposit, is to place a drop of the turbid urine in a watch-glass, and gently warm it; as soon as it has become clear, add a drop of almost any acid (the hydrochloric is perhaps the best), and as soon as it has become cold examine it with the microscope. The muddiness previously produced by the urate will have become replaced by lozenges of uric acid (Fig. 13). The urate of ammonia* * These crystals are believed to be urate of soda. Fig. 31 gives other varieties Fig. 31. URATES. 139 occurs very rarely in spherules with crystals of uric acid adhering to their surface; this is occasionally observed in albuminous urine, occurring in dropsy after scarlatina (Fig. 30), and from its opacity is best observed by reflected light. Fig. 30. Fig. 32. 134. It has been stated, especially by Continental observers, that urate of ammonia occurs in deposits in delicate needles, some- times united so as to form stellae. I have never seen this variety in urine. Fig. 32 shows the minute needles and stellae of urate of ammonia, artificially prepared by dissolving uric acid in a warm solution of ammonio-phosphate of soda, and allowing the crystals to separate by repose (79). It is difficult to imagine this form ever occurring in urine, as Dr. B. Jones has shown that the presence of saline matter, or of the coloring matter of urine, interferes with the needle-like crystallization of urate of ammonia, and converts it into minute globular particles. Urate of ammo- nia is abundant in the urinary excretion of birds and reptiles, forming nearly white spongy masses. It then generally appears in the form of oval or roundish bodies, ex- hibiting something approaching to a radi- ated structure. Fig. 33 shows a specimen from the urine of the pigeon, from a draw- ing by Dr. Garrod. 135. Of the other salts of uric acid, the urate of soda is the only one I have satis- factorily recognized, forming a distinct deposit. It occurs occasion- Fig. 33. of spherical masses, either single or united, surrounded by spicules, and also of the dumb-bell form, which is not so frequently met with. 140 PATHOLOGY OF URIC ACID. ally in gout, but I have more generally met with it in the urine of persons laboring under fever, who were treated with carbonate of soda. It then occurs in round yellowish or white opaque masses, provided Avith projecting, generally curved processes, forming a very remarkable figure (Fig. 34). Varieties of this, more confusedly crys- talline, are less unfrequent. When artificially prepared, by dissolv- ing uric acid in a hot solution of carbonate or phosphate of soda, it appears in two forms, depending upon the mode of preparation. If alloAved to separate on cooling from the solution, the urate of soda crystallizes in needles and tufts (Fig. 35); but if a solution of it Fig. 34. Fig. 35. be allowed to evaporate spontaneously on a glass plate, it assumes the form of spherical masses like minute pearls. 136. Pathological Changes in the Quantity of Uric Acid and its Bases.—Independently of an alteration in the proportion of uric acid by an excess or deficiency of nitrogen in the food (84), certain patho- logical states of the system exert a most important influence on the quantity excreted. We have seen that uric acid may be traced to two great sources, viz., the disintegration of tissues, and to nitro- genized food (89). It is obvious, therefore, that whatever increases the rapidity of the former process, or interferes with the due digestion or assimilation of the latter, will materially affect the amount of uric acid contained in the urine. Experience has shown that in all dis- eases attended with great emaciation, when the wear and tear of the frame is not compensated by the supply of food, an increased quan- tity of uric acid appears in the urine, if the kidneys remain suffi- ciently healthy to perform their functions. But certain exceptions are presented to this general rule, in cases where the renal function is itself impaired, as in granular disease of the kidney (Morbus URATES. 141 Brightii). In all acute inflammatory diseases, in acute inflammation supervening upon chronic mischief, in rheumatitis, in organic, or even sometimes functional affections of organs materially influencing the circulation, as the heart, liver, and perhaps the spleen, a con- siderable increase in the quantity of uric acid will occur, and deposits of this substance, either free or combined, will appear in the urine. Taking the average of eleven cases of acute inflammatory diseases, reported by M. Becquerel, and tAvelve of continued fever (on the fifteenth day), by M. L'Heritier, we find that the quantity of uric acid was more than double the healthy average. Acute inflammation. Specific gravity of the urine, . 1-0216 Uric acid,.....1-041 In the two allied affections, gout and rheumatism, exclusive of the many neuralgic diseases properly referred to the latter, a remarkable tendency to the formation of an excess of uric acid, both pure and combined, occurs. The elements of the acid, or its combinations, are in these diseases supplied by the nitrogenized elements of the food, as well as by the changing tissues of the body. In such quantities is urate of soda often generated, that the watery portions of the blood are not sufficient for its solution; and part of it is deposited in the joints and sheaths of the tendons, producing painful swellings. 137. Dr. Garrod150 has indeed succeeded in discovering urate of soda in the blood of gouty patients, and by the following process any one may satisfy themselves of this very important fact. Collect the serum of blood of a gouty patient, evaporate it to dryness over a water-bath, and reduce the dry mass to poAvder. Digest this with water of the temperature of 100° for an hour. Urate of soda with other matters will be dissolved out, and on evaporating the solution to a small bulk, and adding a little strong acetic acid, acetate of soda will be formed, and crystals of uric acid deposited after a few hours. They are more readily obtained if a few fibres of flax or tow are placed in the fluid, as they then crystallize upon these bodies like sugar-candy on a string. Dr. Garrod found that, on first removing the fatty matter from the dried serum of blood by digestion in alco- hol,, and exhausting the insoluble residue by boiling water, the con- centrated decoction by repose became covered with a pellicle of crys- tals of urate of soda (Fig. 36). He has produced evidence to show Fever. Health. 1-0229 1-017 1-312 0-391 142 PATHOLOGY OF URIC ACID. that whilst uric acid always exists in the blood both in acute and chronic gout, it is very deficient in the urine. In the acute form of the disease, the uric acid becomes remark- ably diminished in the urine immediately before the gouty paroxysm, obviously pointing out its accumulation in the blood. 138. In all diseases attended with exces- sive debility, independently of acute dis- ease, especially where an anaemic or chlo- rotic state exists, and when the circulation is languid, or, if excited, the excitement is owing to irritation rather than inflammation, a deficiency of uric acid occurs, and no deposits ever take place in the urine, unless the quantity of water present be remarkably diminished. The diminu- tion of uric acid is well observed after losses of blood, in chlorosis, and in many neuralgic and hysteric affections. The average drawn from four cases of chlorosis, observed by Becquerel, and one of melaena, another of irritable uterus, and a third of spermatorrhoea, examined by myself, is as follows : Average density,.....1*015 Water,.......976'0 Uric acid, ......*184 The quantity of uric acid being less than one-half the normal pro- portion. 139. As a general rule, whenever the functions of the skin are impaired, where a due amount of secretion is not exhaled from the surface, an excess of nitrogen is retained in the blood, and ulti- mately separated by the kidney in the form of urates, or perhaps urea, or creatinine, which substances contain respectively 38, 46, and 37 per cent, of this element. A person in apparently good health, experiences, from exposure to a current of cold air, a slight check to perspiration, and the next time he empties his bladder he voids urine of a deeper color than is usual with him, and on cooling it becomes turbid from the precipitation of the urates. The explanation of this phenomenon, with which every one is familiar, is found in the kidneys assuming temporarily a kind of compensating function for the skin. It is true that uric acid, or the urates, are not naturally expelled from the surface of the body, but certain organic matters, rich in URATES. 143 nitrogen, certainly are ; and if their proper emunctory, the skin, has for a time its functions arrested, they are probably filtered from the circulating mass by the kidneys, in the form of urates. That nitro- genized products are exhaled from the skin is indubitable. Dr. Fara- day calcined pure river sand, and on heating it with hydrate of potass, it yielded no trace of ammonia. On merely passing this sand over his hand, and then treating it in a similar manner, ammonia was evolved. A piece of ignited asbestos, by mere pressure for a short time between the fingers, absorbed enough of some nitrogenized or- ganic matter to evolve ammonia when heated with hydrated potass. I have two or three times been consulted in the cases of patients lying bedridden from rheumatic gout, in whom one or both legs were covered with an eczematous eruption, and the parts on which the exudation from the surface had dried have been actually frosted with microscopic crystals of urate of soda. Although my observations have not been sufficiently extended to warrant its announcement as a general law, I may state that in cases of lepra, psoriasis, and ichthyosis, where the excreting functions of the skin have been much impaired, the urine has been much richer in urea than was consistent with health. 140. It is quite certain that the value and importance of the func- tions of the perspiratory system, m relation to those of the other depu- rating organs, have not been sufficiently estimated. The following observations of Mr. Erasmus Wilson126 on this subject are exceedingly striking and interesting: " I counted the perspiratory pores in the palm of the hand, and found 3528 in a square inch; now each of these pores being the aperture of a little tube of about a quarter of an inch long, it follows that in a square inch of skin on the palm of the hand, there exists a length of tube equal to 882 inches or 73*5 feet. Surely such an amount of drainage as 73 feet in every square inch of skin, assuming this to be the average of the whole body, is something won- derful, and the thought naturally intrudes itself,—What if this drain- age were obstructed?"----"The number of square inches of surface in a man of ordinary height and bulk is about 2500; the number of pores, therefore, is 8,820,000, and the number of inches of perspi- ratory tube 2,205,000, that is 183,750 feet, or 61,250 yards, or nearly 34 miles." 141. From a series of careful observations, Seguin38 ascertained that, on an average, eleven grains of matter were exhaled from the skin in a minute, equal to 15,840 grains, or 33 ounces, in 24 hours. 144 PATHOLOGY OF URIC ACID. Consequently, the amount of perspired matter very nearly equals that of the urine. The exhaled fluid was aftenvards examined by Anselmino,39 who found that it contained on an average 0-88 per cent, of solids; and 100 grains of this solid extract contained 22-9 grains of saline matter. Hence in the course of 24 hours the skin, exhales— Organic matter,.....107-47 grains. Saline matter,......81*92 " Water and volatile matter, . . . 15650-61 " 15840 •« This organic matter contains much nitrogen, and I have more than once detected it in a body resembling, if not identical with, urea, an observation confirmed by the researches of Landerer. Berzelius40 states that osmazome, another nitrogenized substance, is an ingredi- ent in the perspired fluid. It may be safely assumed, that when the skin is unable to perform its functions, the 107*47 grains of organic matter, which then lose their proper outlet, appear wholly or partly in the urine in the form of urates. 142. As already stated, the above conditions occur when the kid- neys are healthy; but if organically diseased, or even merely in a state of congestion, or when the tubular structure is in a state of inflammation, as in the dropsy after scarlet fever, they allow the exu- dation of the albuminous elements of the blood, the vital chemistry of these organs being too far deranged to allow their filtering off the proper proportions of the constituents of urine from the system. Hence, in the disease in question, the disappearance of albumen, and the increase of uric acid in the urine, become valuable indications of convalescence. Dr. Marcet41 Avas the first who suggested that inter- ference with the functions of the skin might in some way account for calculous deposits (153). 143. Professor Liebig has recognized one great cause for the ap- pearance of an excess of uric acid in the urine, founded on his theo- retical vieAvs of the conversion of this substance into urea (83). It may be thus briefly enunciated: that as normally the insoluble uric acid, presumed to be first produced by the metamorphosis of tissues, is (under the influence of oxygen, supposed to be conveyed in the red blood-discs) converted into the soluble urea, whatever increases the number of blood-discs (carriers of oxygen), or quickens the circulation, must cause the more complete conversion of uric acid LIEBIG'S HYPOTHESIS. 145 into urea ; and less of the former and more of the latter will appear in the urine. Conversely, whatever interferes Avith the perfection of oxygenation in the body, must necessarily produce an excess of uric acid. From this view,42 it folloAvs that the quantity of uric acid ought to be positively or relatively to urea, decreased in 1. Fever. 2. Acute Phlegmasiae. * 3. Phthisis. And conversely it should be increased in 1. Chlorosis. 2. Anaemia. 3. Pulmonary emphysema. The only mode of testing hypotheses of this kind, emanating from a great and respected authority, is by clinical observation; and so far as recorded facts are concerned, they fail altogether to give the slightest support to the ingenious theory of Professor Liebig.* 144. The labors of Edmund Becquerel43 in urinary pathology, furnish us with a mass of carefully recorded observations, Avhich, made with no view of supporting or disputing any preconceived notions, are peculiarly entitled to respect. The numbers in the fol- loAving table are calculated from some of the analyses alluded to, and point out the actual quantity of uric acid and urea excreted in the twenty-four hours, and the relative proportion they bear to each other in several diseases. Quantity in 24 hours of Ratio of uric acid to urea. Uric acid. Urea. Grains. Grains. Healthy urine (Becquerel's average), . 1 8-1 255* 1 : 31*48 Chlorosis, minimum of five cases, . 1*8 77-5 1:43- Chlorosis, maximum of five cases, . 6- 172- 1:29* Pulmonary emphysema, extreme dys- \ 4-9 172* 1 :35*1 pnoea, . j Phthisis, tubercles softened, 9*1 66-7 1: 7*33 Phthisis, three days before death, . 9*8 29*4 1: 3- Morbus cordis, with icterus, . 9-82 73-3 1: 76 Acute hepatitis, with icterus, . 1118 61-6 1: 5-6 Icterus, ...... 17*75 285-6 1:16-1 Milk fever,...... 19* 133* 1: 7*47 * Lehmann thus writes in reference to this theory: " The pretended oxidation of the constituents of the blood, which was supposed to explain phthisis, as well as gout and stone, is not the simple method by which alone specific disease or indi- 10 146 PATHOLOGY OF URIC ACID. From this table Ave find that in chlorosis, a disease of ansemia, in Avhich oxygenation of the blood, on the theory of Liebig, must be most imperfect, the uric acid, instead of being in excess, is positively and relatively below rather than above the healthy average (138). In pulmonary emphysema, again, the same thing is observed, although, from the want of integrity in the function of respiration, uric acid ought to abound; while in acute hepatitis, and in phthisis, diseases in which, on Liebig's own shoAving, oxidation is actively going on, the uric acid, both abstractedly and in relation to the urea, is at a minimum instead of a maximum. The curious disease, diabetes mellitus, or glucosuria, seems, moreover, to offer a serious objection to the validity of the opinion, that in phthisis, excessive oxidation is a necessary condition, and therefore the uric acid must be oxidized into urea and disappear from the urine (even if it were true that uric acid deposits did not occur in this disease). Diabetes and phthisical disease of the lungs so frequently occur together, that some patholo- gists have even gone so far as to suppose this complication to be a necessary one. Yet here, while phthisical disorganisation is pur- suing its destructive course, and excessive oxidation is supposed to be rapidly destroying the tissues of the body, an abundance of a highly carbonized, indeed, a readily oxidizable substance is generated in the body, circulates in the blood, and escapes by the kidneys. An analogous argument is afforded us by the comparative chemistry of urine of different animals. Thus, the pig is peculiarly prone to lay up enormous stores of fat in its economy, and is therefore laden with a substance whose chief function, according to the views noAV under consideration, is to appropriate oxygen, and yet in the urine of this most greasy animal no uric acid exists, but urea has been found in the proportion of 4*9 grains in 1000. I confess it seems difficult to conceive how excessive oxidation can be supposed to be going on con- temporaneously with the copious formation of inflammable bodies, sugar and fat. 145. Is it possible in any manner to reconcile these facts, the actual result of experiment and observation, with the hypothesis of Liebig ? If we admit that an amount of oxygen, requisite for the vidual well-characterized processes can be explained with scientific accuracy. For there are no acute and b%d few chronic diseases in which the oxidation of the con- stituents of the blood is not diminished or impeded." And again, " that there is no disease characterized by a too sudden or rapid oxidation of the blood." (Leh- mann's "Physiological Chemistry," by Dr. Day, vol.i, p. 219.) LIEBIG'S HYPOTHESIS. 147 destruction of tissue alone, enters the system, uric acid ought to occur in the urine; in proportion as this amount is exceeded, the acid becomes converted into urea. Therefore, by supposing that in inflammatory affections the change of tissue (or emaciation) is so rapid in its progress under the influence of disease, that all the oxygen entering the lungs in a given time is sufficient alone for the production of uric acid, an excess of this body will occur in the urine. On the other hand, if the disease does not so rapidly ema- ciate the patient, the metamorphosis of tissue will proceed suffi- ciently slow to allow oxygen to react on the uric acid, and but a minimum reaches the urine. By allowing this latitude to the theory, the general absence of uric acid deposits in chlorosis and anaemia, and their presence in inflammation, is accounted for. Still the great objection regarding phthisis remains, as this disease is espe- cially mentioned by Professor Liebig in his Avork as one in which the excess of uric acid does not occur. But even this may be reconciled to his A'ieAvs by a remark he made to me in a conversation on this very subject, that he did not mean by phthisis the disease m any stage in Avhich disorganization of lung Avas going on, for here he admitted with all, that uric acid occurred in excess, but intended his remarks to apply when only the early stage of tuberculization ex- isted, corresponding, so far as I understood him, to what is known in this country by the term tubercular cachexia. 146. Excluding all abstract theories, Avhenever an excess of uric acid, either alone or in combination with bases, occurs in the urine, a normal quantity of water being present (30 to 40 ounces in twenty- four hours), it may safely be inferred that one or other of the follow- ing states exists: „r . ~ .. ., ,, ,, , rA Fever, acute inflammation, a. Waste ot tissue more rapid than the supply oi ■ • n • , . . , . , >• rheumatic inflammation, phthi- nitrogeuized nourishment, as in . ' r J sis. ,, . „ . . ,. „ n . . Y Excessive indulgence in ani- B. Supply of nitrogen in the food greater than is . . „ , ,. . . „ , . , - , . , , » . I mal food, or the quantity of food required for the reparation and supply of tissue, r . . ,, ... . r ir J i remaining the same, with too J little bodily exercise. C. Supply of nitrogenized food not being in ex- ^ cess, but the digestive functions unable to as- I All the grades of dyspepsia. similate it. ' j d. The cutaneous outlet for nitrogenized excreta \ All, or most stages of dis- being obstructed, the kidneys are called upon I eases attended with arrest of to compensate for the deficient function. J perspiration. e. Congestion of the kidneys, produced by local i Blows and strains of the loins, causes. j disease of genital apparatus. 148 PATHOLOGY OF URIC ACID. 147. It is quite possible for an excess of uric acid to exist in the urine without forming a deposit, and vice versd, the presence of a deposit does not necessarily indicate the existence of an abnormal proportion (132). It is, hoAvever, easy to discriminate between these cases, for if a deposit of the urates be present whilst the bulk of the urine in tAventy-four hours is not below the average, it is tolerably certain that an excess of uric acid exists. But if the bulk of the urine be much beloAV the natural quantity, a deposit may occur simply from there not being sufficient Avater to hold it in solution. To de- termine whether an excess exists, let all the urine passed in twenty- four hours be collected, well shaken, and a given quantity, as about two ounces, be mixed in a conical glass vessel with about half a drachm of hydrochloric acid. In six or eight hours crystals of uric acid Avill be copiously deposited on the sides of the glass. To insure the sepa- ration of the AArhole, they should be allowed to repose for twenty-four hours, and may then be washed, dried, and Aveighed in the manner already described (19). This little operation is so easily performed, that it can scarcely be deemed troublesome; and by a simple multi- plication sum, the whole amount of uric acid secreted in twenty-four hours can thus be readily ascertained without the fear of any conside- rable error. 148. The copious deposit of the urates occurring after eating more freely of animal food than is required for the supply of the Avants of the body is a well-known phenomenon, and will occur in persons Avhose digestive organs are in perfect vigor, simply from a greater amount of matter being given them to assimilate than they are ade- quate to. In like manner, if a person's digestive powers are im- paired either partially or temporarily, as after a debauch, he will be unable to convert into healthy chyle even a small proportion of food, and hence its albuminous elements, imperfectly assimilated, enter the circulation, to be evolved by the kidneys, and perhaps other emunc- tories. Particular idiosyncrasies Avith regard to the action of the stomach on certain articles of diet also exist; thus a single cup of coffee or green tea will, in many persons, determine the formation of a de- posit in the urine, as if the caffein present in these two beverages had escaped the digestive powers of the stomach, and become converted into urates. 149. The conditions above referred to apply alike to the presence of free or combined uric acid, but certain other circumstances require consideration in connection with its occurrence in a free or crystal- CAUSES OF AN EXCESS. 149 line state only. The appearance of a deposit of urates may be caused by a mere exaggeration of a natural condition; being a simple in- crease in quantity of salts normal to the urine. When, however, the acid occurs in a free state, it shows that not only it may be in excess, but some change has occurred in the urine, which has separated it from the base with which it had been previously combined. A de- posit of free uric acid may depend on one or other of the folloAving conditions: A. An excess of this acid may exist, and be separated by the kidney in too large a quantity to be all converted into urates. B. The quantity of uric acid being normal or nearly so, certain changes occur in the urine which have induced a separation from its solvent. So long as in the pathological states above enumerated, the quan- tity of uric acid is not too great to combine with the bases simulta- neously excreted, Avhether derived, as I have supposed, from the phos- phate or not (81), the urine will be transparent upon being passed, but on cooling a more or less copious deposit of urates will take place. But if the acid exceed this quantity it is held in solution by phosphate of soda so long as the urine is warm; on cooling, being partly de- posited (79) in the form of a crystalline sand or gravel (80). If, without the amount of this substance being increased, a minute quan- tity of a stronger acid reach the urine, the uric acid is deprived of its base, and is precipitated in crystals. 150. Of the first of these conditions the urine frequently presents a good illustration in heart disease, especially in great hypertrophy of that organ, in rheumatism, and many phlegmasiae. In these, it is common to find one day a deposit of urates, and perhaps on the next a sediment of crystallized uric acid will occupy the bottom of the glass vessel, and a dense stratum of urates will rest upon it. Of the second condition, examples are furnished by cases of irrita- tive dyspepsia with pyrosis; here a large proportion of free acid is generated in the stomach, and being absorbed, finds its way to the kidneys, setting uric acid free from any soluble urate that may be present. The acid thus generated by the stomach by disease is often considerable, far exceeding the proportion poured out during healthy digestion. In one case of schirrous pylorus, in which the patient 150 PATHOLOGY OF URIC ACID. often vomited several pints of fluid in twenty-four hours, I found a quantity of free hydrochloric acid, equal in each pint to 22 grains of the pharmaceutical acid,44 in addition to a sufficient quantity of some organic acid (lactic ?) to neutralize near 7 grains of pure potass. At another time the hydrochloric acid nearly disappeared, and the quan- tity of organic acid in each pint required for saturation nearly 17 grains of the alkali. 151. If, as has been supposed, an organic acid (lactic or butyric), be an element of the perspired fluid, it is quite possible that by being retained when perspiration is obstructed, it may find its Avay to the urine, and precipitate uric acid. In this way imperfect action of the skin may cause a uric deposit without increasing the amount of nitrogenized matter conveyed to the kidney (138). Seguin, in addi- tion to the facts already stated (141), observed that perspiration Avas lessened during digestion, and considerably diminished when this function was imperfect. In this way, a bulky meal may be an indi- rect cause of a uric acid deposit, besides affording pabulum for the formation of urates (147). 152. Uric acid and urates may occur in great abundance in the urine, so as to be serious sources of irritation, and then especially become primary objects of attention as definite diseases. Still Ave must never forget that a mere deposit of urates may be the result of causes hardly amounting to disease, and may be rather regarded as an evidence of the integrity of the depurating functions of the kidneys than of their lesion. We have frequently occasion to disabuse our patients' minds of very erroneous opinions they have entertained on this point, which have added very seriously to their anxieties by apprehensions of impending disease. Uric acid or urates may be deposited in an insoluble form in the kidney or bladder, and aggre- gating, form a mass, on which, by a kind of imperfect crystallization, great quantities of the acid or its salts may be deposited, giving rise to the formation of a calculus. Uric acid is of more serious impor- tance than most other elements of calculous formations, not only from its constituting a large proportion of all urinary calculi, but even Avhen they are chiefly composed of other ingredients, the nuclei on which they are deposited are, in the great majority of cases, composed of uric acid. Of 374 calculi contained in the museum of Guy's Hos- pital, at the time I examined them, the nuclei are in 269 composed of uric acid or urate of ammonia alone.45 ■ On account of its solubility (130), urate of ammonia is not a fre- CURATIVE INDICATIONS. 151 quent component of entire calculi, although it often enters with other ingredients into their composition. Indeed, calculi wholly composed of this compound are almost peculiar to childhood; in Guy's museum there are but eight concretions entirely consisting of this substance, although it constitutes the nucleus in eighteen. It is hence very probable that if ever by medical treatment we can succeed in over- coming a calculous diathesis, or dissolving a stone in the act of groAvth, it will be by means directed to the solution of the uric acid or its combinations. 153. Regarding the medical treatment of the different forms of uric acid gravel (limiting this term to deposits occurring so persist- ently or abundantly as to have become primary sources of irritation or annoyance) much might be said. Discarding altogether the exist- ence of any specific agent for a disease which is rather symptomatic of another affection than really idiopathic, the therapeutical agents may be briefly referred to the following heads: Attention to the Function of the Skin.—The remarks already made on the effect of an arrest of perspiration in furnishing a pabulum for the formation of a deposit (138), or by retaining in the circulation a substance capable of rendering uric acid insoluble (151), show the necessity of attending to this indication. I have repeatedly seen diaphoretics, Avarm clothing, the use of a flannel, and in winter, even a chamois leather waistcoat, Avith friction by means of a flesh- glove or hair-glove, repeatedly remove a deposit of uric acid gravel; and in more than one instance, Avhere even an hereditary taint existed from gouty or calculous progenitors. The observations of Dr. Wilson Philip46 have shown that the proportion of uric acid in the urine is notably diminished by the use of active diaphoretics. It is also probable that the extreme rarity of calculous affections in the » navy might be partly explained by the kind of vapor-bath in Avhich sailors sleep, " the loAver decks being the parts allotted to repose, the ports are, for the safety of the ship, necessarily closed at night, and the temperature of the surrounding air is thereby so exalted, that the place becomes a kind of steam-bath from animal exhalations; the men being literally immersed in their own perspiration." These are the remarks of Mr. Copland Hutchinson,47 who, in allusion to the rarity of calculus among sailors, adds that from 1800 to 1815, up- Avards of 126,000 men were employed in the navy. Of these nine- tenths had been employed-at sea from a very early period of life. Only eight were affected with stone. It appears probable that three 152 PATHOLOGY OF URIC ACID. of these were affected with calculus before entering the service. So that taking all the cases in the navy in the period above mentioned, it cannot be said that more than 1 in 34,000 were the subject of calculus. 154. My own experience induces me to regard the warm or still better, the vapor-bath, as the most valuable diaphoretic. The latter is readily employed in private practice by means of the very conve- nient and portable apparatus of M. Duval, which has for a long time superseded other forms of vapor-bath at Guy's Hospital.* Actual diaphoresis is by no means necessary in the treatment of all cases of uric gravel; friction to the skin, and, when persons are suffi- ciently robust, immersion in the cold-bath, or cold sponging on rising from bed, followed by rubbing the surface of the body Avith a dry and rough towel, until reaction is produced, is often ojf great service. 155. Restoring the Tone of the Organs of Digestion.—By effecting this, a double object is attained : the perfection of the primary assimi- lation of the food by which the entrance into the blood of a crude nitro- genized matter, capable of being conArerted into uric acid, is checked (148); and the prevention of the generation of any acid, the product of unhealthy digestion (150). Avhich might be absorbed into the circulation, reach the kidneys, and act as a precipitant of uric acid. This part of the treatment of calculous affections must be modified by the peculiari- ties of the case, and, indeed, is identical Avith that of the different forms of dyspepsia. Careful attention to the bowels, avoiding exces- siAre purging, the use of minute doses of mercury, as of a grain of pil. hydrargyri or hydrarg. c. creta, Avith thrice that quantity of ext. conii, administered tAvo or three times a day, Avith moderate doses of the carbonates of potassa or soda, in the mist, gentianae comp., if constipation exist; or if not, inf. calumbae, or what is preferable, from its action on the skin, inf. serpentariae; will often effect immense relief. Where gastrodynia, Avith or Avithout pyrosis, exists, the use of half a grain of argenti nitras, or one of argenti oxidum, immedi- ately before a meal, will often check alike the gastric and renal symp- toms. But the most important element in the treatment is a rigid attention to the quality and quantity of the ingesta, taking the utmost care to select those articles of diet Avhich the patient can thoroughly digest, it being of far greater importance, in the majority of cases, to *I cannot avoid here strongly recommending a very economical and excellent vapor-bath, quite equal in its effects to the more expensive appaiatus of M. Duval, invented by Mr. Moss, of Bartholomew Square, Old Street, London. CURATIVE INDICATIONS. 153 regard this, than to choose articles of food according to their chemi- cal composition. A too bulky meal of animal or vegetable food is injurious to persons laboring under calculous dyspepsia, for whilst the former supplies too much nitrogen, both will become sources of mischief by overloading the digestive functions, and preventing the chylopoietic viscera doing their duty (148). In protracted cases, hoAvever, much good is derived by actually cutting off part of the supply of nitrogen. In this Avay, I have seen a copious deposit of uric acid gravel disappear, after other measures had failed to give relief. 156. The folloAving case is a good illustration of the latter mode of treatment: Exposure to cold. Uric, acid deposits, resisting ordinary treatment, re- lieved by diaphoretics, and cured by excluding nitrogenized food.—John Lynch, ret. 37, admitted into Guy's Hospital, on October 2d, 1839. By trade a porter in a warehouse in Spitalfields, and constantly exposed to al- ternations of temperature. When young he had lived freely, and partaken to excess of spirits and malt liquors, and had eaten meat daily. His health, up to the present illness, bad been excellent. No hereditary taint of calcu- lus or gout. On admission, be stated that nineteen months previously he had got very wet, and allowed his clothes to dry on him ■ this Avas folloAved by fever and profuse perspirations. The next day he became the subject of rheumatic pains, from which he had never since been free. He complained of constant pain in the region of the kidneys, increased by pressure and flexing the trunk, and some pain at the extremity of the penis. He passed water thrice in the day and once at night, each time discharging uric acid gravel most copiously. The latter symptom had been present a twelvemonth. The urine was not coagulable, contained some mucous flocculi, and the deposit of gravel did not disappear by boiling. The tongue Avas clean and moist, he complained of habitual heartburn, had occasional bilious vomitings, the bowels were generally relaxed, and he was griped or purged on slight causes, especially by exposure to cold. Pulse 78, natural. From October 2d to November 27th his treatment consisted of purgatives, soda and uva ursi, occasional mild mercurials, under which the deposit decidedly in- creased. He then took dec. alchemillae with potass without relief. November 27 to December 18th—A trial of diaphoretic treatment was made. The warm bath twice a week, with Pulv. Ipecacuanhas comp. gr. viij, ex. Julcpi Amnion. Acet. ^j, twice a day. Under this treatment he improved, the skin acted profusely, and the deposit gradually disappeared. January 10th, 1840.—The urine up to the present moment remained healthy • he went out of the hospital, took cold, checked the perspiration, and the uric acid deposit appeared as abundantly as before. He was again relieved by the diaphoretic treatment, but soon afterwards relapsed. It was therefore determined to confine his diet to arrowroot, sago, potatoes, bread, and butter, excluding the four ounces of cooked meat he had previously daily taken. The effect was very remarkable, the deposit almost immediately disappeared, and he remained free from it up to February 25th, when he was 154 PATHOLOGY OF URIC ACID. discharged. On one occasion the urine of this man deposited in twenty- four hours upwards of 30 grains of uric acid. 157. Moderate muscular exertion and a due amount of exercise are quite essential in the treatment of this disease; for not only do they call into play some very important functions, but often improve the general health. Besides this, Avhen the stomach is able to digest nitrogenized food imperfectly, exercise Avill often aid its assimilation by making a call upon the chylopoietic organs to supply the consequent waste of tissue. 158. Among the remedies which appear most successful when the food is not converted into healthy chyle, and an unhealthy state of the blood from the presence of imperfectly assimilated matters results, the preparations of iron deserve notice. I have repeatedly seen copious deposits of uric acid in persons of Ioav power completely dis- appear, pari passu Avith the cure of the pseudo-chlorotic symptoms, present, by the use of this important drug. The best mode of admi- nistering it, is in combination with a vegetable acid, as the stomach bears it Avell in this form, and it is probably more likely to enter the circulation. From six to nine grains of the ammonio-citrate or ammo- nio-tartrate of iron, taken thrice a day immediately after a meal in a glass of Avater, has been most successful. The solution of the sesqui- acetate of iron is also a very valuable preparation, but is often inconve- nient to prescribe, in consequence of its not being of constant strength. 159. There is one other remedy Avhich appears to exercise a marked and decided control over the formation of uric acid, although its effects are by no means so constant as might be wished. I refer to col- chicum. Wherever the general health appears to be tolerably good, and any marked irregularities of the digestive functions been cor- rected, I would recommend the careful and guarded administration of this drug in small doses, especially when there is an hereditary arthritic taint in plethoric patients. In several cases I have succeeded com- pletely in checking a long-continued secretion of uric acid by the use of the ext. colch. acet., in doses of a grain twice a day, Avith or with- out the addition of a grain of pil. hydrarg., and keeping up at the same time a moderate action in the bowels, «by some tonic aperient, as the inf. rhei or mist, gentianae co. 160. Remedies which act as Solvents of Uric Acid.—These chiefly consist of alkalies and their carbonates, biborate and phosphate of soda, benzoic and cinnamic acids. As the alkaline urates are far more soluble than the free acid, soda and potass with their carbonates CURATIVE INDICATIONS. 155 have been long popular remedies in the treatment of uric gravel. They, moreover, may exert a beneficial effect in neutralizing any free acid in the primae viae, and thus prevent a precipitant of uric acid reaching the kidneys. Liquor potassai: this drug may be employed in doses of half a drachm thrice a day ; it is best taken about an hour after a meal, and may be conveniently administered in any bland vehicle, or in a little bitter ale, Avhich conceals much of its disagreeable flavor. It is quite useless to administer this remedy in the very minute doses in which it is frequently given. The liquor potassae of the Pharmacopoeia does not contain more than about one grain of potass in ten minims, and the generally recognized greater value of Brandish's alkaline solution does not depend on any peculiar properties of this fluid, but solely on its containing more potass, and in being administered in larger doses. I have scarcely ever seen the urine rendered alkaline by the usual medicinal doses of liquor potassae ; and Dr. B. Jones has shoAvn that an ounce of this fluid administered in three days does not prevent the appearance of the acidity of the urine before food, although it much diminishes its itensity. The carbonates of potass and soda: these are far more agreeable, and far more efficient remedies,—of these the bicarbonate of potass deserves the preference. It should be given thrice a day in doses of 9j or 5ss. I think it appears to act best when taken in a glass of Avarm water. To make it more agreeable, I generally order 3ss of bicarbonate of potass and gr. v of citric acid to be stirred into a tumbler of Avarm Avater. This mixture evolves enough carbonic acid to be "sparkling," and is generally taken with readiness. To render this treatment efficacious, it is quite essential that the patient should partake very freely of diluents. Two or three pints of water drunk during the day will double the bulk of the urine, and remarkably aid the solution of uric acid. Indeed, it has been well remarked, that pure water is one of the best lithontriptics. 161. The influence of the waters of Vichy is well known, as they have acquired a really well-merited reputation in cases of uric acid gravel. These waters oavc their efficacy to the presence of carbonate of soda. The artificial Vichy Avater prepared at the German Spa, at Brighton,* and Avhich may be procured in pint bottles, possesses all * The following analysis of the artificial Vichy water prepared at the German Spa at Brighton is by Dr. Letheby, and is quoted by Dr. Hassall in his review of the previous edition of this work in the " British and Foreign Medico-Chirurgical 156 PATHOLOGY OF URIC ACID. the value of the mineral water. Indeed, I think it is preferable from its purity, being more highly charged Avith carbonic acid. I have Review :" fl The water is effervescent, from free carbonic acid. It is alkaline to test- paper, and has a specific gravity of 1005. Two thousand grains were evaporated, and yielded 9'80 grains of a very white saline residue, which consisted of— Sulphuric acid, ... ... . 0-34 Chlorine, • . 0-70 Carbonic acid, . . 3-93 Soda, . 4-19 Potassa, . . . traces Lime, . 0 34 Magnesia, . 0-18 Silica and alumina, . 0-12 9-80 These constituents may be arranged in two ways, thus Bicarbonate of soda, magnesia " lime, Sulphate of lime, ** soda, Chloride of sodium, . Silicate of alumina, . 12-84 1 2 1014 . 9 50 0*58 . 0-58 0-26 . 087 0-58 * * ' . 060 1-16 . 1-16 0-12 . 0-12 12*83 The first is the most probable arrangement of the elements ; but the second form is introduced in order to show how closely this water resembles that from the wells of Vichy, examined by Henry in 1847. The following analyses are from his paper on the subject: l 2 3 4 Nouvelle Source Source Source Source Grand Grille. Nouvelle. Pre Sale. Celestines. Bicarbonate of soda, . 9-80 . 9-68 9-10 8-27 '- . lime, . 0-21 . 0-18 0-89 0-55 " magnesia, . 0-13 . 011 . 0-81 0 42 Sulphates of soda and potash, . 0-97 . 0-82 0-52 0-38 Silicate of alumina, . 0-46 . 0*46 014 (?) " soda, .0 80 . 0-68 0-55 0-28' Alkaline chlorides, . . 1-08 . 1-00 0-60 076 1345 . 12-93 ■ 12-91 10-66 " The water also resembles the alkaline springs of Cusset and Hauterine in France. In fact, there is but little difference in the composition of the alkaline waters of Vichy, Cusset, and Hauterine; and the artificial water from the Spa at Brighton is"a very good imitation of all of them. It will be observed from these analyses that the active ingredient in all these waters is bicarbonate of soda. The dose of Vichy water is a small tumblerful two or three times a day, which amounts to about a pint, and contains 35'5 grains of bicarbonate of soda." CURATIVE INDICATIONS. 157 seen the greatest advantage gained by the use of a small tumblerful of this water on rising in the morning, and a second at dinner. To the latter dose, a glass of Madeira or pale sherry, may be sometimes added where Avine is desirable. The mixture forms a most agreeable beverage. 162. Salts of the Vegetable Acids.—A very convenient mode of impregnating the urine Avith an alkali is to administer the potass or soda in combination with a vegetable acid, especially with the acetic, citric, or tartaric. The mode in Avhich these act is easily explained: when acetate, citrate, or tartrate of potass is ignited, the acid absorbs oxygen, and is converted into carbonic acid and water, part of the former uniting with the alkali. In a similar manner are these salts decomposed during the process of healthy digestion: a carbonate (389) finds its Avay into the circulation, and, reaching the kidneys, renders the urine alkaline. If, hoAvever, the digestive poAvers are impaired, the vegetable acid is only partly decomposed, and in some feAV persons it escapes the influence of digestion altogether. 114 grains of tartrate of potass, 106 of citrate, 99 of the acetate, absorb respectively 40, 48, and 64 grains of oxygen, to be converted into carbonate of potass and Avater. These salts may be administered by directing the use of the common saline poAvders made Avith carbonates of potass or soda and the citric or tartaric acid in effervescence. Tartrate of potass readily renders the urine alkaline, half an hour being sufficient to render its effects on the urine apparent; in doses of thirty grains, dissolved in at least tAvo ounces of Avater, it may be conveniently given three times a day. During its administration, the uric acid deposits disappear, and the urine rises in specific gravity. There is one great objection to this salt in its tendency to irritate the bowels. On this account, as well for the sake of its more grate- ful flavor, I am accustomed to prefer the acetate of potass. Thirty grains of this salt, with a drachm of syrup of orange-peel, and a drop or tAvo of oil of lemon, constitute a most agreeable draught, to Avhich the most fastidious patient seldom objects. In this Avay, the urine may be kept in a moderately alkaline state for any length of time, Avithout interfering, as the free and carbonated alkalies are apt to do, with the function of digestion. We thus preserve the patient from the probability of the formation of a calculus, and gain time for the employment of remedies calculated to remove the exciting cause of the uric acid diathesis. 163. It is a remarkable fact that in the Rhenish provinces, Avhere the common beverage of the inhabitants consists of poor Avines con- * 158 PATHOLOGY OF URIC ACID. taining a considerable quantity of bitartrate of potass, calculous af- fections are unknown,—a circumstance admitting of explanation by the decomposition of the bitartrate into carbonate of potass, Avhich thus prevents the urine becoming sufficiently acid to alloAV the de- posit of uric acid. When not contraindicated, the use of roasted apples, strawberries, currants, and some other fruits containing alka- line citrates and malates, are capable of making the urine alkaline, and may be occasionally employed with advantage. Some persons cannot bear the use of free or carbonated alkalies without suffering severely in their general health, nor is their pro- tracted use altogether without some ill effect. A flabby state of the muscles and an anaemiated condition of the system are frequently produced by the persistent use of alkaline remedies. Their injudi- cious employment may, indeed, possibly induce the formation of oxalic acid. It must not be forgotten that the urine cannot be rendered alka- line for any length of time without risk of precipitating the phosphates of lime and magnesia, thus giving the patient a change of evils in- stead of removing them. In reading the accounts recorded of the treatment of real or imaginary calculous affections a century ago, by the celebrated alkaline remedy of Miss Stevens, it is impossible to avoid noticing how very much of the sabulous and fetid state of the urine of her patients was obviously engendered, not by the disease, but by the remedy. 164. Biborate of Soda.—Uric acid is soluble in a solution of borax, the biborate of soda,—more so, indeed, than in alkaline carbonates; and this salt may be taken for some time, at least by male patients, Avithout producing any very injurious constitutional effects, and readily finds its way into the urine. On this account its administration has been suggested in cases of uric acid gravel, but it has not been much employed in this country. In women, this drug cannot be employed with impunity, as it certainly exerts a stimulant action on the uterus, and I have seen it in tAvo instances produce abortion. The borate of potass has been strongly recommended as a substi- tute for ordinary borax, on account of its greater efficacy as a sol- vent for uric acid. M. Bouchardat recommends the folloAving re- medy as very efficacious in uric gravel; it should be mixed Avith as large a quantity of water as can be conveniently drunk, and taken several times in the day whilst effervescing. If it purges, it of course must be taken less frequently, or in smaller quantities. CURATIVE INDICATIONS. 159 R Potassas bitartratis, 3j, gr. xv ; '■ boratis, .** bicarbon. aa, gr. xv. M. Fiat pulvis. 165. Phosphates of Soda and Ammonia.—The remarkable solvent action of phosphate of soda on uric acid, to which Liebig directed attention (79), inspires a hope that its administration may be of use in cases of calculous disease, by impregnating the urine with an active solvent. All that is required to insure this drug reaching the urine is to administer it in solution sufficiently diluted; 9j to Jss might be administered in any vehicle, as in broth or gruel, for Avhen diluted the phosphate tastes like common salt, and few persons ob- ject to its flavor. I have administered this drug in several chronic cases of uric acid gravel, and in some with the effect of rapidly causing a disappearance of the deposit. The triple salt, ammonio- phosphate of soda, Avould, perhaps, be a more active remedy than the simple phosphate, but its disagreeable flavor constitutes an ob- jection to its employment. 166. Dr. Buckler, of Baltimore, has proposed the use of phosphate of ammonia in the treatment of the uric acid diathesis, whether this body be deposited in the urine as a calculous formation, or in the joints combined with soda, as in rheumatic gout. The practice has also been sanctioned by subsequent Avriters. This salt may be given in doses of ten grains thrice a day, dissolved in any bland vehicle. I have given it a fair trial in hospital practice, and have no hesitation in saying that it has ahvays succeeded in keeping uric acid in solu- tion in the urine, and in this respect it has appeared to be at least equal, if not superior, to borax and phosphate of soda, but I certainly haAre never seen it diminish the tophaceous deposits in chronic gout. In more recent effusion into the joints of subacute forms of rheumatic gout it has certainly been of service. 167. Benzoic Acid.—Much attention has been drawn to the effects of benzoic acid in preventing the formation of uric acid, by the ob- servations of Mr. Alexander Ure.49 When this acid or its salts are administered, they are acted upon by the stomach in a very different manner from the other vegetable acids. Instead of becoming oxi- dized, and converted into carbonic acid, benzoic acid combines Avith those nitrogenized elements which would othenvise have formed urea or uric acid, and is converted into hippuric acid (96). It has been stated that the quantity of uric acid falls, when the benzoic acid is 160 PATHOLOGY OF URIC ACID. administered, beloAV the average quantity, or even disappears from the urine. This has been, however, shoAvn to be an error by Dr. Garrod,50 Avho has observed that the urea alone diminishes in quantity. Be this as it may, it is certain that the acid does appropriate to itself some body rich in nitrogen to form hippuric acid; and experience has shoAvn that, in cases Avhere an excess of uric acid is secreted, the administration of this drug appears to limit it to about the normal quantity. The body with Avhich benzoic acid combines, has the same composition as glycocoll or sugar of gelatine, and is, in all proba- bility, identical Avith it. C H N 0 1 atom benzoic acid, . . . 14+5+0+3 + 1 " glycocoll, .... 4+4+1+3 = Hippuric acid, .... 18+9+1+6 168. If ten or fifteen grains of benzoic acid be swallowed on retiring to rest, and the urine passed on rising from bed the folloAving morning be examined, it will be found to contain abundance of hip- purate of ammonia. A couple of drachms of it evaporated in a watch-glass to a feAV drops, and mixed with hydrochloric acid, generally becomes nearly solid in a short time from the deposition of delicate interlacing needles of hippuric acid. This transformation of benzoic into hippuric acid seems to be very rapid, for the latter can be detected in the urine withim half an hour after a dose of the former has been SAvalloAved, the Aveight exceeding that of the benzoic acid employed, by about one-third. Benzoic acid may be administered, in doses of eight or ten grains, in syrup, or dissolved in a weak solution of carbonate or phosphate of soda, thrice a day. Cinnamon-Avater forms a good vehicle, as cinnamic acid exerts a similar action to the benzoic, becoming con- verted into hippuric acid. I have found the following formula of great service in several cases of chronic uric acid gravel: K Sodas Carbonatis, ^iss • v Acidi Benzoici, Qij ; Sodas Phosphatis, 3iij ; Aquas Ferventis, f^iv, solve et adde Aquas Cinnamomi, fjviiss; Tincturas Hyoscyami, f.^iv. Fiat mistura cujus sumat asger, coch. ij, amp. ter in die. CURATIVE INDICATIONS. 161 Perhaps a more efficient remedy is found in the benzoate of ammonia, a salt indeed to which Dr. Holland has directed the attention of the profession. This may be extemporaneously prepared by dissolving five or six grains of benzoic acid and as much sesquicarbonate of am- monia in an ounce of boiling water. A very nearly neutral solution is thus obtained, which may be given thrice a day Avith the addition of a little syrup, and twenty or thirty minims of tincture of henbane. Benzoic acid is one of the very few acids which decidedly increase the acidity of the urine, and (in addition to its chemical action) it acts beneficially by exciting diaphoresis, and thus fulfils an impor- tant general indication in the treatment of calculous affections (153). 169. It is important to bear in mind that by the employment of remedies capable of dissolving a deposit in the urine, we are merely palliating, not curing the disease. And we must never lose sight of the great importance of endeavoring to remove that pathological state of the Avhole system, or of any particular organ, AAdiich may be the exciting cause of the calculous formation. Nothing but a careful investigation of symptoms can put us in possession of the knoAvledge necessary for this purpose. Still, solvent remedies are not to be despised; for when the disease is chronic, and does not readily yield to treatment, it is of the utmost importance to prevent the formation of a calculus, or lessen the irritation produced by the presence of gravel, whilst endeavoring to remove the primary affection which led to the formation of the deposit; and hence these indications should be carefully attended to. We are rarely called upon to treat deposits of urates as special diseases, as they are generally not persistent and are readily traced to their exciting cause. Sometimes, hoAvever, patients become fear- fully depressed and nervous from the constantly muddy character of the urine, and in spite of an assurance that there is no fear of a cal- culus, we are compelled to treat the affection. In such cases, any saline diuretic, as the nitrate of potass in doses of ten grains, or, still better, the acetate in doses of a scruple, pretty largely diluted, and taken three times a day, will soon cause the deposit to vanish. 170. I cannot avoid alluding here to an empirical remedy sold under the absurd name of " constitution-water;" this is prepared by a person residing at Henley-in-Arden, who has, I believe, an enor- mous sale for it. This remedy owes its virtues to the presence of impure carbonate of potass, probably obtained directly from the ashes of some vegetable matter. On examining a specimen of this 11 162 • PATHOLOGY OF URIC ACID. preparation I have found it to have a specific gravity of 1*023. It effervesced with acids, and exerted an alkaline action on turmeric paper. Saturated with nitric acid, it copiously precipitated nitrate of barytes, nitrate of silver, and oxalate of ammonia. It hence con- tained sulphates, chlorides, and a salt of lime. A fluid-ounce super- saturated with sulphuric acid and evaporated, left 10*8 gr. of sul- phate of potass after ignition, equivalent to very nearly 5*9 grains of potass existing in the fluid combined with carbonic acid. There can be no question of the advantage that has resulted in some cases from the use of this remedy, nor on the other hand, can there be any doubt of the injury it has inflicted when improperly administered. The secret of its success in uric acid gravel (the only class of cases in which it should be employed) depends upon the large quantity of the alkaline salt administered in twenty-four hours. Our doses are gene- rally too small when alkalies are administered in such cases, and I certainly owe the knowledge of this fact to some successful results of the so-called constitution-water. I now constantly prescribe, with very great advantage, especially in the cases of pisiform uric acid gravel (in which patients will pass scores of calculi, the size and appearance of mustard seeds, at a time), in imitation of this prepara- tion, from two to four drachms of bicarbonate of potass dissolved in 30 or 40 ounces of water, in the course of twenty-four hours. CHAPTER, V. CHEMICAL PATHOLOGY OF URIC OXIDE. [Xanthi-uria.) History, 171—Diagnosis of Uric Oxide, 174, 175—Characters of Urine depositing, 175—Microscopic Character of, 176—Pathological Indications, 177—Excreted by Spiders, 179. Uric Oxide. Syn. Xanthic oxide—Xanthine—Urous acid. 171. This substance has not been discovered among the constitu- ents of healthy urine, although it is probable that it bears some rela- tion to the yellow coloring matter; and hence it may possibly exist in minute quantities, and have escaped the investigations of chemists. But little is known either of the chemical or pathological history of this very rare ingredient of calculous concretions. It was first met with by Dr. Marcet,51 constituting the whole of a small calculus weighing but eight grains; the history of the case being unknown. Some years aftenvards, some minute pisiform concretions passed by a gentleman with diseased bladder were found by M. Laugier25 to consist of uric oxide. More recently this substance was discovered in a stone removed by Professor Langenbeck, of Hanover,53 from a boy eight years of age. It weighed 338 grains, and after examina- tion by Professor Stromeyer, was submitted to minute chemical in- vestigation by Professors Wohler and Liebig. A fragment of this calculus has been, by the kindness of* my friend, Dr. Willis, placed in the museum of Guy's Hospital. A fourth specimen, Aveighing but seven grains, Avas lately removed from the urethra of a boy by Pro- fessor Dulk, of Konigsberg.54 Uric oxide has been met with in de- posits by Berzelius,55 M. Morin, of Geneva,56 and one or two other observers. 164 PATHOLOGY OF URIC OXIDE. 172. A substance closely allied to uric oxide, and termed guanine, has been observed by Dr. Unger in the Peruvian guano, the dried excrementitious matter of sea-birds. To obtain it, he directs guano to be digested in milk of lime until the solution assumes a yelloAvish- green tint, the mixture is then filtered, and hydrochloric acid added ; a mixed precipitate of uric acid and guanine falls. On boiling this with hydrochloric acid guanine dissolves, and on cooling, a compound of it with the acid crystallizes. This, on being digested with ammo- nia leaves guanine pure in the form of a Avhite poAvder.122 Guanine is a white pulverulent body, quite insoluble in water, without any alkaline action on test-paper, but yet is a tolerably active base, form- ing salts with several acids. The sulphate crystallizes in long brilliant needles. It contains 46-62 per cent, of nitrogen, and its atomic composition is C10N5H5O2. 173. Very recently, another body allied to uric oxide has been discovered by Professor Scherer in the spleen and heart both in man and the ox (39). This substance he has termed hypoxanthine, and it is scarcely soluble in cold Avater, requiring 1090 parts for solution ; but dissolves in 180 parts of boiling water. It contains 40*8 per cent, of nitrogen, and its atomic composition is C^H^. It is often found in such large quantities in the spleen, that it is deposited from a boiling decoction by mere cooling. 174. Diagnosis of Uric Oxide.—Concretions composed of this substance closely resemble and are generally mistaken for uric acid. They present externally a similar appearance, but their sections are of a well-marked salmon, or rather cinnamon tint, which, to a prac- tised eye, will distinguish such concretions from uric acid. Accord- ing to Berzelius, when uric oxide forms a urinary deposit, it appears as a gray powder. In the only case in Avhich I ever met with a de- posit composed of a substance approaching uric oxide in chemical characters, it presented a honey-yellow color. A wax-like lustre is readily assumed by submitting fragments of uric oxide to friction. If a deposit be suspected to consist of, or to contain this substance it should be digested in a weak solution of carbonate of potass, Avhich removes uric acid, and leaves the oxide undissolved. So closely do these two bodies resemble each other, that their diagnostic distinc- tions Avill be best observed by contrasting their action towards re- agents. MICROSCOPIC CHARACTERS. 165 Uric oxide. Uric acid. 1. Dissolves slowly in nitric acid, al- 1. Dissolves readily in nitric acid with most without the evolution of bubbles copious effervescence. of gas. 2. The nitric solution leaves by evapo- 2. The nitric solution leaves by evapo- ration a yellow residue. ration a pink residue. 3. Soluble in strong sulphuric acid, 3. Is precipitated by water from its not precipitated on the addition of solution in concentrated sulphuric acid. water. 4. Its solution in liquor potassas is 4. Hydrochlorate of ammonia pre- not disturbed by hydrochlorate of am- cipitates it combined with ammonia monia. from its solution in liquor potassas. 5. Precipitated uncombined, when a 5. A current of carbonic acid gas current of carbonic acid traverses its throws down from the alkaline solution solution in potass. an acid urate of potass. 6. Insoluble in solution of carbonate 6. Readily soluble in dilute solution of potass. . of carbonate of potass. 7. Ignited in a tube, does not yield 7. When ignited, yields urea as one of urea. its products. This substance might also be confounded with cystine, but may be distinguished from it by its insolubility in hydrochloric and oxalic acids, and by its want of crystalline form as vieAved by the micro- scope. Uric oxide has constituted the whole mass of the calculus in all, except in that examined by Professor Dulk, in which the nucleus consisted of uric acid. According to him, uric oxide furnishes, Avith nitric acid, some of the same products Avhich uric acid yields, espe- cially alloxantin. 175. Characters of Urine depositing Uric Oxide.—Unknown, no observations of the urine of the persons from whom calculi of this substance Avere removed having been recorded. 176. Microscopic Characters of Uric Oxide.—This substance does not appear to assume a crystalline form. A careful microscopic ex- amination of the fragment of the calculus removed by Langenbeck, and now in the museum of Guy's Hospital, failed in detecting any appearance of crystalline arrangement. I dissolved a portion of this concretion in liquor potassae, and precipitated the oxide very slowly by the cautious addition of acetic acid. Uric oxide fell in a perfectly amorphous state, presenting none of the Avell-defined crystalline forms which uric acid assumes Avhen similarly treated. The only instance (174) in Avhich I had reason to believe a deposit was made up of this substance was in the urine of a child, which let 166 PATHOLOGY OF URIC OXIDE. fall by cooling a honey-yellow sediment. - This, on microscopic ex- amination, by reflected light, was found to be composed of rather large yellow masses, having much the appearance of yellow wax, and presented no trace of crystalline structure. This substance was re- placed in the next specimen I examined, by uric acid. 177. Pathological and Therapeutical Indications. — Unknown, although from the remarkable similarity of their composition it is highly probable that the majority of the remarks already made on the pathology of uric acid apply to that of the oxide. Uric oxide consists of C5]Sr2H202; if,, therefore, we suppose tAvo atoms to be oxidized by combining with tAvo of oxygen, one atom of uric acid will be found. C N H 0 2 atoms uric oxide, .... 10+4+4+4 +2 " oxygen, .... 2 =1 " uric acid, .... 10+4+4+6 178. The relation of the hypoxanthine recently discovered in the spleen and heart (in which organs it seems to constitute the transi- tion stage, assumed wholly or partly by the old and exhausted tis- sues before their transformation into the elements of urine) to uric oxide, and consequently uric acid, is peculiarly interesting. C H N 0 1 atom uric oxide, .... 5+2+2+2 —1 " oxygen, .... 1 =1 " hypoxanthine, . . . 5+2+2+1 179. Dr. John Davy has announced his belief that the urinary ex- cretions of scorpions and spiders consists chiefly of uric oxide. He obtained a body presenting all the properties of this substance from the excrements of all the different spiders he examined; whilst in those of true insects he found uric acid exclusively. It is remarkable that in most of the recorded cases, the uric oxide has occurred only in children. One observer stated that he had met with it as a deposit in diabetic urine.57 Very recently two German chemists, MM. Strahl and Lieber- kiihn,152 have announced the existence of traces of uric oxide in human urine. But if the body they have described is to be regarded as a normal ingredient of urine, it, as Lehmann has suggested, is more likely to be identical with guanine, on account of its solubility in hydrochloric acid. CHAPTER, VI. CHEMICAL PATHOLOGY OF PURPURINE. {Porphy-uria.) Diagnosis, 180—Chemical Composition, 182—Microscopic Characters, 183—Cha- racters of Urine containing Purpurine, 184—Pathological Indications, 185— Means of Vicarious Excretion of Carbon, 186—Relation to Bile-pigment, 187. 180. The chemical characters of this remarkable coloring matter have been already pointed out, but it merits some notice as a patho- logical product, from the serious lesions its presence frequently in- dicates. On account of its solubility in water, purpurine never oc- curs as a deposit, unless the urates are present, which have the property of removing a considerable proportion of purpurine from: urine, and assuming thereby a more or less deep carmine tint. 181. Diagnosis.—When a deposit of urates is colored by this sub>- stance, it presents a tint varying from the palest flesh-color to the deepest carmine. To appreciate the beauty of these- tints, the de- posit should be collected on a filter, and allowed-to dry. The pre- sence of purpurine favors the deposit of urates and interferes with their ready solubility on the application of heat; the- free dilution with Avater is often required to aid their solution. I have never seen purpurine coloring any other deposits except those of urate of soda, and hippuric acid when precipitated from concentrated urine by hy- drochloric acid. Uric acid scarcely appears to have- any affinity for it. It is by no means uncommon for a very highly colored de- posit of pink urates to be by a careless observer mistaken for blood, and I .have seen this error committed when it occurred in albuminous urine. The appearance of the deposit when collected on a filter, and its giving up the purpurine to alcohol, will at once remove any doubt on the subject, and the absence of blood-discs on microscopic exa- mination will aid in demonstrating the real nature of the deposit. 168 PATHOLOGY OF PURPURINE. 182. The chemical composition of purpurine, occurring as a pro- duct of disease, is unknoAvn. This body bears no analogy whatever to murexid or purpurate of ammonia, substances with which it Avas long confounded, owing to the countenance afforded to this opinion by the high authority of Dr. Prout. This want of identity is so clearly made out that I have deemed it unnecessary to adduce the evidence brought forward in the first edition of this work on the subject. According to Scherer, the purpurine generated by the action of hydrochloric acid on urine consists of— Carbon,.......62*51 Hydrogen,.......5*79 Nitrogen,.......j 31.Y0 Oxygen,.......) There are several calculi in Guy's museum, with layers of urate of ammonia deeply stained with purpurine. Similar calculi have been described by Mr. Taylor,58 as occurring in the museum of St. Bar- tholomew's Hospital, and Brugnatelli*59 has recorded many instances of the same kind. 183. Microscopic Characters.—Ahvays those of the deposit with which the purpurine is combined. All the sediments I have met Avith were amorphous. I possesss one specimen, however, of a rich pink color, given me by Dr. Percy, in which the deep crimson urate is composed of minute ovoid particles acuminated at both extremities, and posssessing a crystalline lustre. 184. Characters of the Urine containing Purpurine.—It invaria- bly happens that when an excess of the urates is present, they, on the urine cooling, fall to the bottom of the vessel, carrying doAvn a great part of the purpurine. If this excess be not present, the urine simply presents a pink or purple color, and on dissolving white and pure urate of ammonia in it by heat, it is precipitated on cooling deeply colored by the purpurine. The presence of the yellow ex- tractive which yields purpurine, can be readily discovered by the action of the hydrochloric acid as already described (102). On evaporating urine containing purpurine to the consistence of an extract, and digesting it in alcohol, a fine purple tincture is obtained, the intensity of the tint being rather heightened by acids and dimi- nished by alkalies. The specific gravity of this highly colored urine is subject to great variation; when the color is as deep as brandy, its density varies from PATHOLOGICAL INDICATIONS. 169 about 1*022 to 1*030. The addition of nitric acid generally produces an immediate muddy deposit of uric acid, made up of microscopic rhomboids, which has been more than once mistaken for albumen. 185. Pathological Indications.—The presence of an excess of pur- purine appears to be intimately and invariably dependent upon some imperfection in the excretion of carbon by those organs whose special function it is to eliminate this element from the blood, as the liver and lungs, but especially the former. It hence is almost always con- nected with some functional or organic mischief of the liver, spleen, or some other organ connected with the portal circulation. The appear- ance of a flesh-colored deposit in the urine is the commonest accom- paniment of even slight derangement of the hepatic function, as every case of dyspepsia occurring in gin-drinkers points out. The intensity of color of the deposit appears to be nearly in relation with the mag- nitude of the existing disease. In the malignantly diseased, in the contracted, hobnail, or cirrhosed liver, the pink deposits are almost constantly present in the urine. They are also of frequent occur- rence in the hypertrophy of the spleen following,ague. The most beautifully colored deposits I have seen have occurred in ascites con- nected with organic disease of the liver ; and I think I have received some assistance in the diagnosis between dropsy depending upon he- patic and peritoneal disease, in the presence of the pink deposits in the former, and their general absence in the latter. I have occasionally seen the deposits in question occur in phthisis, when large quantities of pus were poured out from vomicae, as well as in deep-seated suppura- tion, as in psoas abscess. But even in these cases, the excretion of carbon and the integrity of the portal circulation are always more or less influenced. My experience, indeed, leads me to express a firm belief that an excess of purpurine is almost pathognomonic of disease in the organs in which portal blood circulates, and consequently must be essentially connected with the non-elimination of the carbonized elements existing in that fluid. Indeed, from very careful observations especially directed to the pathological indications of these pink de- posits, I doubt their ever occurring even in phthisis or other affections of a strumous character, unless' the liver present obvious evidence of derangement either in its structure or functions. I am anxious to direct attention to this fact, for instances have occurred to me in which the presence or absence of pink deposits have enabled me to distinguish, in cases of abdominal tumors, their connection or Avant of relation to the liver or spleen. 170 PATHOLOGY OF PURPURINE. 186. This opinion of the pathological indications of purpurine, which I have noAV for some years supported and taught in my lectures at Guy's Hospital, received important confirmation from the re- searches of Professor Scherer,140 of which mention has already been made (102). This excellent chemist* observed that when a person in good health is confined to a diet nearly free from nitrogen, active exercise being avoided, the quantity of carbon and hydrogen excreted in the urine is ahvays at a maximum. In fever, or where metamor- phosis of tissue (31) is actively going on, in addition to the abundance of nitrogenized products eliminated in the urine by the kidneys, a pink pigment, very rich in carbon, communicating the well-knoAvn tint to the secretion, also exists. This state of things ahvays occurs, and affords a ready explanation of the characteristic high color of febrile urine, unless a great diminution of water or some other cause exist to explain it. Scherer found the following proportions of carbon and hydrogen in the pigment of urine of a case of hectic, and two cases of typhus fever: Hectic Fever. Typhus Fever. Typhus Fever. Carbon,.....65*25 . . 64-43 . . 62-80 Hydrogen,.....6*59 . . 6*30 . . 6*39 Oxygen and nitrogen, . . 28*16 . . 29*27 . . 30*81 Indeed, in every case the presence of an excess of a highly car- bonized pigment, independently of any deposit, as shown by the test of hydrochloric acid and heat, may be regarded as a satisfactory in- dication of a lesion of function of one of the great normal emuncto- ries of carbon, especially the lungs and liver. The presence of this matter in the urine is, therefore, to be regarded as an evidence of the kidneys performing a compensating function for the lungs or liver. 187. It is a curious fact, and one Avhich strongly substantiates the accuracy of this opinion, that the coloring matter of bile often coexists * I trust I may not be considered too egotistic in remarking that the opinions above expressed of the function of the pink pigment, as well as the use of the hy- drochloric acid test for its detection, are original with myself. They were the result of careful clinical observation, and were announced in my lectures, delivered at Guy's Hospital in 1841-2, afterwards reported in the "Medical Gazette." A long review of these lectures was given by Professor Scherer himself, in Canstatt's " Jahresbericht," for 1843, in which he translated the account I had given of the hydrochloric acid test, and of the supposed function of purpurine. So that he must ■have been well acquainted with my own observations, made four years before the announcement of his own much more elaborate researches. PATHOLOGICAL INDICATIONS. 171 Avith this carbonized coloring matter or purpurine. This may, often where scarcely suspected, be detected by collecting the precipitate produced, by adding diacetate of lead to the urine, on a filter, and boiling it in alcohol acidulated by hydrochloric acid. The bile-pig- ment Avill dissolve, forming a green solution. Another remarkable corroboration of this opinion is afforded by the analogy in composi- tion existing between the carbonized coloring matter of urine (purpu- rine) and the bile-pigment (biliphoein) so frequently met Avith in urine in cases of jaundice, and easily recognized by proper tests (61). This pigment may be obtained by precipitating it from urine by chloride of barium, and digesting the precipitate in alcohol, acidulated by sul- phuric acid. The following is a view of the chemical composition of the coloring matters under consideration: Carbon,.... Hydrogen, . . Nitrogen,. . . Oxygen, . . . Normal co-loring matter of urine. Urinary color-ing matter in jaundice. Urinary color-ing matter in or-ganic disease of the liver. Bile-pigment from urine. 58-43 5-16 8-83 27-58 60-19 6-66 J 34-25 65-76 6-01 J 28*23 68-182 7-437 7-074 17-261 CHAPTER VII. CHEMICAL PATHOLOGY OF CYSTINE. {Cystin-uria.) History, 188—Diagnosis of Cystine, 189—Liebig's Test, 190—Characters of Urine depositing it, 191—Spontaneous Changes in Cystine, 193—Microscopical Cha- acter of, 194—Simulated by Chloride of Sodium, 196—Pathological Origin, 197 —Probable connection with Struma and Imperfect State of Hepatic Functions, 199—Therapeutical Indications, 200. 188. This substance was first discovered by Dr. Wollaston in a calculus given him by Dr. Reeve, of NorAvich. It does not exist as an ingredient of healthy urine, and rarely occurs as an element in the diseased secretion, although it is probable that the sulphur- extractive (103) of urine may bear some relation to this substance, pos- sibly, indeed, being the source from Avhich it is derived. Its chemical composition is extremely remarkable, as it contains no less than 26 per cent, of sulphur. Cystine has been found in urinary sediments by very feAV observers, and it was not recognized in this form until a long period after its discovery in calculi. 189. Diagnosis of Cystine.—This substance, when present in the urine, forms a nearly white or pale fawn-colored pulverulent deposit, much resembling the pale variety of the urates (130.) The greatest proportion of it appears to be merely diffused through the urine Avhilst in the bladder, as at the moment of emission the secretion is always turbid, and very soon deposits a very copious sediment. I have seen a six-ounce bottle full of urine let fall by repose a sedi- ment of cystine of the height of half an inch. On applying heat to the urine, the deposit undergoes no change, and very sloAvly dissolves on the subsequent addition of hydrochloric or nitric acid. Pure cys- tine is soluble in the mineral and insoluble in the vegetable acids; t DIAGNOSIS. 173 with the former it forms imperfect saline combinations, which gene- rally leave by evaporation gummy masses or acicular crystals. It is readily soluble in ammonia and the fixed alkalies and their carbo- nates, but insoluble in carbonate of ammonia. Heated on platina foil it burns, evolving a peculiar and disagreeable odor. A deposit of cystine may be distinguished from one of white urates, by not disappearing on Avarming the urine, and from the earthy phos- phates, by being insoluble in very dilute hydrochloric or strong acetic acid. The best character of cystine is its ready solubility in ammo- nia, mere agitation of some of the deposit with liquor ammoniae being sufficient to dissolve it, and a few drops of the fluid, when allowed to evaporate spontaneously on a slip of glass, leaves six-sided tables of cystine (194). The ammoniacal solution, when kept for some time in a Avhite glass bottle, stains it black, from the combination of the sulphur of the cystine with the lead in the glass. 190. Another test has been proposed by^Liebig,60 founded on the presence of sulphur; he directs the deposit suspected to contain cys- tine to be dissolved in an alkaline solution of lead, made by adding liquor potassae to a Aveak solution of acetate of lead until the oxide at first thrown doAvn is redissolved. On heating the mixture, a black precipitate of sulphuret of lead appears if cystine be present. All sulphuretted animal matters similarly treated yield black precipitates, and hence this test is useless if any portion of albuminous or mucous substances, or of bile, is mixed with the deposit to be examined. If cystine exist, mixed with urates or phosphates, in a deposit, it is easily discoArered by a few minutes' digestion with ammonia; and the evaporation of a few drops of the fluid, as already mentioned, leaves the characteristic crystals. This process is not liable to the fallacy of Liebig's test. Cystine has never been artificially formed; some fruitless attempts have been made to effect this by treating albumen Avith the sulphuret of potassium. The internal administration of sul- phur does not appear to induce its formation, for I have repeatedly examined the urine of patients who were taking sulphur in large quantities, without detecting it. ^ 191. Character of Urine depositing Cystine.—Most of the speci- mens of this variety of urine that I have met with, Avere pale yellow, presenting more of the honey-yelloAV than the usual amber tint of urine, not unfrequently possessing a somewhat oily appearance, like diabetic urine. The specific gravity of cystic urine is generally below the average, and is sometimes passed in larger quantity than natural. 174 PATHOLOGY OF CYSTINE. In one case (a child), in which Dr. Willis61 met Avith cystine, the urine Avas of a specific gravity of 1*030 ; but this is certainly unusual. It is often neutral, less frequently acid to litmus paper, but soon becomes alkaline by keeping. The odor of this form of urine is very peculiar, bearing in general a close resemblance to that of sweetbrier, and is sometimes rather poAverful; less frequently the odor is fetid, like putrid cabbage, owing, I suspect, to partial decomposition and evolution of sulphuretted hy- drogen. In such specimens the color has usually changed from pale yellow to green. In one case that occurred to me, the urine was actually of a bright apple-green; it presented this tint for a few days, and the specimens subsequently voided were yelloAv. Cystic urine, on being kept for a short time, has its surface covered with a greasy-looking pellicle, consisting of a mixture of crystals of cystine and ammonio-phosphate of magnesia. I have frequently observed it to undergo a kind of imperfect viscous fermen- tation in warm weather, bubbles of gas being evolved, and the Avhole becoming ropy and rather viscid (349). A certain portion of cystine exists in solution in the urine, as the addition of acetic acid ahvays precipitates a small quantity. When a case of this disease is carefully Avatched, and the urine repeatedly examined, the deposit Avill often be found to vanish for days together; but crystals of cystine are even then generally precipitated by acetic acid. The urea and uric acid are present in very small quantities, and in some specimens the latter is nearly absent. I found a speci- men of urine passed by a boy from whom a cystine calculus had been removed a short time previously by my late colleague, Mr. Aston Key, to consist of— i Water,.......974*444 Solids,.......25-556 Urea (impure),..... 5*7 Uric acid,...... -016 Cystine,....... '340 Extract containing the fixed-salts, . . 19*5 192. In another case of a patient under the care of Dr. Shear- man, of Rotherham, who has entered with great zeal and success into these inquiries, I found a fluid-ounce of the urine to yield, on evapora- tion, fifteen grains of solid matter, consisting of— MICROSCOPIC CHARACTERS. 175 rJric acid,........0*2 Urea,........3-7 Cystine, A Creatinine, > ...... 8*1 Extractives, J Earthy phosphates,.....0*2 Alkaline phosphates and sulphates and chloride of sodium,......2-8 15- This urine deposited a tolerably copious sediment of crystallized cystine, but did not possess the peculiar SAveetbrier odor. It was passed by a delicate strumous child, who was the subject of seArere pneumonia. 193. Calculi composed of cystine are generally pale yellow or fawn colored, but by long keeping they undergo some change, and assume a greenish-gray, and sometimes a fine greenish-blue tint. The speci- mens described by Dr. Marcet in 1817, and existing in the museum of Guy's Hospital, were at that time pale brown; they noAv possess a color resembling that of green sulphate of iron, which hue they have, to my knoAvledge, presented for the last twenty years. A similar change of color has been observed by Dr. Peter in tAvo cys- tine calculi preserved in the medical museum of Transylvania Uni- versity. He observed that the change commenced on that side of the concretion which was exposed to the light. This change of color in the concretions, as Avell as in the urine, before alluded to, is pro- bably OAving to some change in which the evolution of sulphur is an element. 194. Microscopic Characters of Cystine.—These are so well marked and easily recognized, that the microscopic examination of a sedirnent composed of cystine, renders the application of tests almost unnecessary. When an ammoniacal solution of cystine is alloAved to evaporate spontaneously on a piece of glass, it leaves crystals in the form of six-sided laminae (Fig. 37). These are probably exceedingly short hexagonal prisms. When the evaporation is slowly and carefully performed, these laminae are transparent; but in general they are crystallized in a confused and irregular manner in the centre, the margins only being perfectly transparent. When examined by polarized light, these crystals, Avhen sufficiently thin, present a beau- 176 PATHOLOGY OF CYSTINE. tiful series of tints, which are not observed AArhen thick, on account of the high refracting power of cystine. Fig. 37. Fig. 38. 195. When cystine occurs as a sediment, it is always crystallized, never under any circumstances being amorphous. Among the crystals a few regular six-sided laminae are often seen, but the great mass is composed of a large number of superposed plates, so that the com- pound crystals thus produced appear multangular, as if sharply crenate at the margin; and the whole surface is traversed by lines, which are really the edges of separate crystals (Fig. 38). They thus resemble little white rosettes when vieAved by reflected light. These compound crystals always appear darker in the centre than at the circumference, which is sometimes quite transparent. Prisms of the triple phosphate (264) are often mixed with the cystine, but on the addition of a few drops of acetic acid, they readily dissolve, leaving the rosettes of cystine unaffected. 196. A fallacy may possibly arise in the detection of cystine under the microscope, by the evaporation of the urine, and crystallization Fig. 39. Fig. 40. of the chloride of sodium or common salt. The salt naturally crys- tallizes in cubes, but assumes an octohedral figure if urea be present. PATHOLOGICAL ORIGIN. 177 If, however, a small quantity be allowed to crystallize spontaneously from its solution in urine, it forms minute transparent crystals, which present generally a three, four, or six-sided outline (Fig. 39), ac- cording to the position in which they happen to lie on the glass, and might at first be mistaken for plates of cystine. Their solubility in water, and absence of all color when examined by polarized light, will prevent these crystals from being mistaken for cystine. If urine con- taining common salt be hastily evaporated on a slip of glass, the regular transparent octohedrons are not met with, being replaced by a series of elegant crystals, shaped like crosslets and daggers (Fig. 40). The appearance of these, on the evaporation of a fluid containing a little common salt, is a tolerably safe indication of the presence of urea. Uric acid also occasionally assumes the form of hexagonal tablets, but may be distinguished by the absence of the superficial marking. 197. Pathological Origin and Indications of Cystine.—This curious substance is, in all probability, a derivative of albumen, or of structures into Avhich it enters, and appears to be the result of de- rangement of the secondary assimilative processes (39), essentially connected with the excessive elimination of sulphur; every ounce of cystine containing more than two drachms of this element. A ques- tion may be entertained whether cystine may not be a metamorphic form of the normal sulphur-extractive of the urine, or the condition assumed by this extractive when an excess of sulphur is eliminated. From an examination of its chemical composition, their appears no difficulty in explaining the origin of cystine, by supposing that it is formed by those elements of our tissues which Avould normally have been converted into urea and uric acid (38), in consequence of the presence of an excess of sulphur; probably connected essentially with a scrofulous diathesis. Cystine consists of C6NH604S2. CNHOS") f CNHOS 1 atom urea, . 2+2+ 4+2+0 12+2+12+8+4=2 at. cystine. 1 " uric acid, 10+4+ 4+6+0 4 =4 at. nitrog. 1 " sulphu- j •"""""' retted hydrog. 4 4 12+6+12+8+4J [12+6+12+8+4 198. Although but little is knowc. of the pathological condition of the system which induces the formation of cystine, there is sufficient evidence before us to justify our expressing a strong opinion of its essentially scrofulous and remarkably hereditary character. In one 12 178 PATHOLOGY OF CYSTINE. family alone several members were nearly at the same time affected with cystin-uria; and one instance exists in which it can be traced, with tolerable certainty, through three generations. In one well- marked case, which fell under the care of Mr. Luke, at the London Hospital, extensive disorganization of the kidneys coexisted with a cystine calculus. There is, probably, a remarkable deficiency of the process of oxidation in these cases; Dr. Prout has even seen fatty matter mixed with the urine, and suggests the probability of its con- nection with fatty liver. And this opinion seems to be by no means improbable, especially Avhen Ave regard the close approximation that exists between the elementary composition of cystine and taurine, the crystallized substance into AA'hich bile is partly converted by digestion Avith hydrochloric acid. The following is a comparative view of the percentage compositions of cystine and taurine: Cystine. Taurine Carbon, 30000 19-2 Hydrogen, 5*000 5*6 Nitrogen, 11*000 11*2 Oxygen, 26*667 38*4 Sulphur, 26-667 25*6 So that it appears by no means unlikely that the excretion of cystine may be a means, under certain circumstances, of compensating for deficient action of the liver quoad the excretion of sulphur. It appears that the sulphur discovered by Redtenbacher in taurine, was by former chemists confounded Avith oxygen, as was the case in the earlier analyses of cystine. 199. Dr. Shearman has been kind enough to send to me specimens of the cystine he discovered in the urine of chlorotic females,— a very interesting circumstance in connection with the probable general deficiency of oxidation existing in this affection. In a com- munication from the zealous and excellent physician alluded to, he mentioned the following particulars: Some urine passed by a chlorotic girl, after being mixed with am- monia, and set aside in a white phial, evolved in a few days sufficient sulphuretted hydrogen to stain the glass black. When fresh, the urine had a very peculiar odor, and deposited a white sediment un- affected by acetic or hydrochloric acid, but soluble in ammonia. The solution left, by evaporation, six-sided laminae, which, in all their microscopical and optical properties, resembled cystine. Tavo specimens of urine exhibiting these characters were passed by CURATIVE INDICATIONS. 179 tAvo sisters ; a third Avas obtained from a girl belonging to another family. I am convinced that the urine in many cases of depressed health, in strumous patients especially, not very unfrequently contains crystals of cystine, not sufficiently abundant to form a distinct de- posit, but still obvious enough on microscopic examination. 200. Therapeutical Indications.—These are unfortunately in the present state of our knowledge not very well understood. The cases in which a moderately large quantity of cystine exists, have been observed too seldom to allow of any accumulation of experience, and most of them having occurred in private practice, have precluded that minute and persistent watching which is so necessary for satis- factory information. The most important indications are to correct the unhealthy condition of the assimilative functions, and if possible to render the cystine, so long as it continues to be formed, soluble in the urine. To effect the latter, the persistent use of nitro-hydro- chloric acid has been recommended by Dr. Prout, and in some cases with success. In my hands, I must confess, it failed in either dis- solving the deposit, or preventing its formation. The general health should be most carefully attended to, and everything interfering with it removed as completely as possible. Sea-bathing, exercise, nutri- tious and digestible diet, with attention to the functions of the skin, promise to do much. I feel inclined to place great confidence in the use of iron, especially of the syrup of iodide of iron, in doses of 3ss to 3j immediately after each meal. Unfortunately, as in all ailments demonstrably hereditary, we have an obstinate disease to treat, and the prognosis must be extremely guarded, as in the majority of cases the generation of cystine goes on to the formation of a calculus. CHAPTER VIII. CHEMICAL PATHOLOGY OF HIPPURIC ACID. {Hippuria.) History, 201—Diagnosis of Hippuric Urine, 202—Process for the Detection of the Acid, 203—Microscopic Characters, 204—Pathological Origin of Hippuric Acid, 205—M. Bouchardat's Case of Hippuria, 206—Dr. Garrod's Case, 207—Dr. Pet- tenkofer's Case, 208—Hippuria traceable to Imperfect Assimilation of Carbon, 209. 201. Hippuric acid is very generally present in the urine of her- bivorous animals, and is indebted for its present appellation to its constant occurrence in the urine of the horse. Rouille, as long as seventy years ago, described it as occurring in the urine of gramini- vorous mammals, but mistook it for benzoic acid. Scheele, and sub- sequently Fourcroy, Reynard, and Proust, demonstrated its existence in the urine of young infants. Lehmann and Ambrosiani announced its presence in diabetic urine, and still more recently it has been proved by Professor Liebig to be a constant element in the healthy secretion, although in so small quantity as to escape detection (8) ex- cept by a very careful and tedious chemical analysis. 202. Diagnosis of Urine containing an Excess of Hippuric Acid.— As this substance never, so far as is yet known, appears in the form of a sediment until after the addition of a stronger acid, our diagnosis must entirely depend upon the characters of the urine containing it. Urine containing an excess of hippuric acid is generally either very slightly acid or neutral, often alkaline. Its characters can be best studied in the urine of a cow or calf, as the copious deposit of carbonate of lime, as well as its viscidity, makes the horse's urine a more difficult object for examination. When the presence of hip- puric acid is directly traceable to the ingestion of benzoic acid, an exception to the above characters is met with, the urine then being diagnosis. 181 acid, often remarkably so, which, I believe, is never the case when hippuric acid occurs independently of the administration of cinnamic or benzoic acids. The odor is generally like that of Avhey, and the specific gravity, so far as has been yet observed, below rather than above the healthy average, varying in M. Bouchardat's case (206) from 1*006 to 1*008. Deposits of the triple phosphate of magnesia are by no means unfrequent in such urine. A drop of neutral or alkaline hippuric urine, as that of the calf, when allowed to evaporate spontaneously on a glass plate, leaves delicate feathers of hippurate of ammonia, very distinct in appearance from any crystals I have seen from any other variety of urine. 203. To detect the presence of an abnormal proportion of hippuric acid, fill a large watch-glass with the urine, and evaporate it over a lamp to a few drops, then add about half the bulk of hydrochloric acid and set the mixture aside. On the addition of the acid, the mixture becomes bright pink, and a pungent odor, not unlike that of new hay, is evolved. After a few hours, examine the contents of the watch-glass, and if an excess of hippuric acid be present, its charac- teristic linear crystals will be observed. These almost always assume a very remarkable form, like a bunch of leafless twigs, cohering with sufficient firmness to allow of their being washed and dried in this position (Fig. 41a). The Avatch-glass should not be emptied for tAventy-four hours after the first addi- tion of the acid, for sometimes the crystals form very slowly, owing to their solubility in the precipitant. The glass should be examined under the microscope, and deli- cate, slender, often branched, crystalline needles of hippuric acid, which may escape the naked eye, may thus be detected (Fig. 41 b). Sometimes so much hippuric acid is present, that, if sufficient time be allowed, crystals of it appear without any previous evapora- tion. This is well seen in the urine of the horse, especially when ob- tained after being well fed, and rested all day in the stable. It is quite certain, hoAvever, that a considerable quantity of hippuric acid may be present and yet escape detection by this process, in conse- quence of the urea interfering Avith its crystallization. From very careful experiments, I find that when the acid exists in less quantity than one grain in the fluid-ounce of urine, it cannot be thus detected. 182 PATHOLOGY OF HIPPURIC ACID. In this case we must haAre recourse to the process before described for the preparation of the acid from the healthy urine (96). 204. Microscopic Characters of Hippuric Acid.—If crystals are obtained by the modes just described, all possible doubt of their real nature may be removed by dissolving a portion in alcohol and another portion in hot water. On placing a drop of these solutions, Avhen cold, on plates of glass, beautiful crystals, some possessing a dendritic and plumose outline, others arranged like zeolites, will be left by the spontaneous evaporation of the alcoholic solution (Fig. 42), and minute Fig. 42. Fig. 43. needles, mixed with four-sided prisms acuminated at their ends, will be formed from the watery solution (Fig. 43). On heating some of the crystals in a glass tube until they begin to char, they evolve a very characteristic odor of the Tonquin bean. All these characters may be observed, and the crystals readily ob- tained from the urine passed by a person an hour or two after swal- lowing 10 grains of benzoic acid. Both the hippuric and benzoic acids will disappear from the urine of over-driven animals. I could not detect a trace of either in the urine of an ox Avhich had been driven up from the country to Smith- field and killed a few hours after. Neither of these acids Avas found by Boussingault in the urine of pigs, even when their food was varied. The large amount of carbon appropriated by these animals in their enormous accumulation of fat, probably interferes with any conside- rable excretion of this element by the kidneys. 205. Pathological Origin and Indications of Hippuric Acid.— This part of our subject is enveloped in much obscurity. All that is known with certainty of the matter may be thus stated: A. Hippuric acid appears to be peculiar to vegetable feeders, and PATHOLOGICAL ORIGIN. 183 to be most constant in those which take little or no exercise. Thus it abounds in stall-fed cattle, and disappears, being replaced by benzoic acid, in those that are worked; a fact explained by the larger proportion of carbon and hydrogen existing in hippuric as compared to benzoic acid. The former contains 18, and the latter 14 atoms of carbon in each equi- valent. B. When in excess in human urine, it has been generally traceable to peculiarities of food. In one case connected evidently with a long confinement to a milk diet (206); in another, to the almost exclusive use of apples (208). Its occasional (but by no means constant) occurrence in the urine of infants at the breast is, in all probability, traceable to their mal-assimilat- ing the large quantity of carbon contained in the food. C. It does not necessarily interfere, at least in man, with the pro- / duction of uric acid ; for although the latter is occasionally absent, yet not so constantly as to lead to a belief that hip- puric and uric acids do not replace each other.* D. In general a deficiency of urea occurs in hippuric urine. It appears nearly proved that the elements of glycocoll or sugar of gelatine (C4NH403), by the presence of which hippuric differs from benzoic acid, are derived either from urea or from nitrogenized matter, which would, under ordinary circum- stances, have formed this substance. 206. The following case, in Avhich albumen coexisted with hippuric acid, is recorded by M. Bouchardat: Madame G—, aet. 53, the mother of one child, residing in the country, possessing good general health, and in easy circumstances, ceased to men- struate at the age of 45. After this period she became frequently the sub- ject of a severe obscure hepatic and intestinal affection, which, as her con- valescence was protracted, led to her being placed on a milk diet. She kept to this for nine years, and her health became re-established. Her general diet consisted of coffee, with a pint of milk, and five ounces of bread, for breakfast. For dinner, soup-maigre or graisse, with two ounces of meat, and about five of vegetables, and as much of bread, taking wine and water for drink. In the evening she took merely a pint of milk. This lady's health again gave way • there was great lassitude and much indisposition to exertion, with,absence of all perspiration, which, for the preceding nine years, had been profuse. Skin harsh and almost scaly. Vague pains in the region of the liver, with a jaundiced tint of the surface. Faeces black. Mouth dry, with a disagreeable taste. Headache and tinnitus aurium * vision imperfect. * Vide (98) note. 184 PATHOLOGY OF HIPPURIC ACID. The night passed in broken slumbers. Palpitation of heart, accompanied with an ansemic murmur in the carotids, and a rapid pulse. Slight oedema of the lower extremities towards evening. For months previously she had become the subject of partial paralysis of the right side, which disappeared on deple- tion. Lungs healthy, although the subject of occasional dyspnoea. The most prominent symptoms of all were, however, increased bulk of the urine, and thirst, often drinking six to ten pints of water in the day. Character of the Urine.—Limpid, with a whey-like odor. Sp. gr. 1006-8, acid, slightly coagulable by heat. On evaporating the urine to a small bulk, and adding hydrochloric acid, the hippuric acid crystallized on cooling. Uric acid was absent. The urine consisted of— Water,.....985*46 Solids,.....14-54 Urea,........1*56 Hippuric acid, ...... 2*23 Albumen, ....... 1*47 Fixed salts,.......5-28 Organic and volatile combinations, . . 4- 1454 This patient ultimately sank exhausted. 207. The second case occurred to Dr. Garrod, to whom I am in- debted for the following brief account of it: The subject of this affection was a young man, get. 23, who in September, 1842, became a patient of Dr. Garrod's for general malaise, accompanied by the excretion of an excess of urea in his urine, and the deposition of amnio- niaco-magnesian phosphate, from which, under the use of opiates with nitric acid, he recovered. A few months subsequently he suffered from an attack of atonic dyspepsia, with pain in the loins. On adding some hydrochloric acid to the urine for the purpose of precipitating uric acid, long crystals of hippuric acid were formed, and on these the uric acid was slowly deposited. This condition of urine continued for several days, half a pint yielding as much as 40 grains of hippuric acid. The uric acid and urea existed in nor- mal proportion. After a few days the hippuric acid decreased in quantity, so that the urine did not afford crystals on the addition of hydrochloric acid until concentrated by evaporation. In a short time the urine became nor- mal. No information as to the source of the hippuric acid could be obtained from the history of the patient. He had lived on a mixed diet, and never used any excess of vegetable food, nor had he ever taken any benzoic acid. 208. The third, and perhaps most interesting case, is the folloAV- ing, and was published by Dr. Pettenkofer, who examined the urine: A girl, 83t. 13, admitted in January, 1844, with chorea, into the Julius Hospital of Wurzburg, under the care of Dr. De Marcus. She had been long the subject of chorea, complicated with anomalous hysteric symptoms. Prior to her admission she refused to take any other food than apples, with bread and water, upon which she had for some time entirely subsisted. The urine was yellow, limpid, and faintly acid when first passed, soon hecom- PATHOLOGICAL ORIGIN. 185 ing alkaline, and depositing crystals of triple phosphate of magnesia. The addition of hydrochloric acid to it after moderate concentration, produced a copious formation of crystals of hippuric acid. The addition of nitric acid, by its oxidizing influence, caused the deposit of hippuric to be replaced by ie of benzoic acid. In 1000 parts of the urine there were— Water,.....959*332 Solids,..... 40-668 1000* Solids soluble in alcohol, . . . 18*451 -' insoluble in alcohol, . . . 9417 Anhydrous hippuric acid, . . . 12*800 40*668 Fixed salts containing much carbonate of soda, 10*599. The characters of the urine in this case approached those of an herbivorous animal in the presence of hippuric acid and of carbonate of soda in the ash, as well as in the absence of uric acid. The hippuric acid disappeared, and the urine assumed its normal propor- tions on inducing the girl to return to a mixed diet. 209. From what little experience we possess regarding hippuria, it appears pretty certain that the existence of this condition of the urine is generally connected with the use of a diet deficient in nitrogen, or in the mal-assimilation of the carbon of the food. Its following tem- porarily the use of benzoic acid, its occurring after the use of nearly exclusively vegetable food (208), or of a milk diet, as shown in Bou- chardat's case (206), as well as in infants at the breast, all help to prove the former proposition. I do not know enough of Dr. Garrod's case (207) to be able to state hoAv far this might be regarded as an exam- ple of the second condition. If the functions of the liver quoad the depurating influence of the gland, were imperfectly performed, we should possess a probable solution of the cause of the presence of hippuric acid in urine. When Ave regard the composition of hippuric acid (98), and call to mind the fact of its occurring in stall-fed cattle, and its being replaced by an acid less rich in carbon in ani- mals taking much exercise, we cannot avoid arriving at the conclu- sion that hippuric acid may be one of the agents by which the kid- neys perform a vicarious function for the liver in removing an excess of carbon from the system. In this respect, hippuric acid probably performs an analogous func- tion to purpurine and bile-pigment (187), each being respectively competent to the removal from the system of 63-93, 62-0, and 186 PATHOLOGY OF HIPPURIC ACID. 68*182 per cent, of carbon, and 4*6, 6*2, and 7*437 per cent, of hydrogen. 210. My own experience in these cases has been too limited to justify my offering any opinion on the pathological complications at- tending them. From what little I have observed, I feel inclined to believe that Avhen an excess of hippuric acid exists, it may ahvays be regarded as traceable to, and pathognomonic of, the deficient func- tion of the liver, lungs, or skin, the great emunctories of carbon ; or to the use of food deficient in nitrogen. It hence follows, that our treatment will consist in appealing to the function at fault, and care- fully regulating the diet. I would suggest the propriety of seeking for the presence of hip- puric acid in the urine, where it is copious, of low specific gravity, but slightly acid or neutral, and occurring in persons who have a dry and inactive state of surface with anaemia. In many pseudo-chlo- rotic cases in both sexes, I am inclined to believe an abnormal pro- portion of this acid will often be met Avith. CHAPTER IX. CHEMICAL PATHOLOGY OF OXALATE AND OXALURATE (?) OF LIME.* {Oxaluria.) History, 211—Long Overlooked, 213—Diagnosis of Oxalate of Lime, 214—Micro- scopic Forms of, 215—Oxalurate of Lime, 219—Relation of Oxalic to Oxaluric Acid, 221—Uric Acid erroneously Described as Oxalate of Lime, 222—Dr. Ba- con's Researches, 223, 225—Characters of Urine depositing the Oxalate, 227— Presence of Epithelium and Excess of Urea, 228—Complication with other De- posits, 229—Pathological Origin of the Oxalate of Lime, 232—Absence of Sugar in Oxaluria, 233—Oxalate of Lime in the Blood, 235—Formation of Oxalic Acid from Urea and Uric Acid, 237—Derivation of Oxalic Acid from Vegetable In- gesta, 240—Oxalate in Mucous Secretions, 241—Symptoms of Oxaluria with Excess of Urea, 243—Without Excess of Urea, 245—Exciting Causes of, 248— Therapeutical Indications, 249—Illustrative Cases, 252. History. 211. Oxalate of lime is so frequently present in the urine, is so often a constituent of one of the most annoying forms of calculous * The subject of this chapter has been so well handled by the author, and the objections raised against it have been either so completely answered or anticipated, that I should have considered further discussion unnecessary, were it not that its principal opponents, among whom we must class Lehmann, Scherer, Dr. Bence Jones, and Dr. Owen Rees, were men of distinguished ability and scientific acquire- ments. We must, however, be guided by reason, not led by authority. Lehmann observes: "With reference to the occurrence of oxalate of lime in certain morbid conditions, Prout, Bird, and others make very different statements, none of which are yet fully established : numerous examinations have convinced me that in this country, at least, the sediments of oxalate of lime are much rarer than they are re- presented to be by English writers. These observations have led to the following result: when the respiratory process is in any way disturbed we most frequently observe a copious excretion of oxalate of lime......In the dyspeptic conditions in which Prout and Bird have found sediments of oxalate of lime, I have failed in discovering anything of the sort; on the contrary, I have found the sediments in 188 PATHOLOGY OF OXALATE OF LIME. concretions, and is so generally important in its pathological bear- ings, that it merits especial attention, and I am now particularly the urine of such patients to be free from these crystals. The reason why the Eng- lish have so often found this salt in the urine, may be that in England the urine is generally in a more concentrated state than in Germany, and, as Bird very cor- rectly remarks, oxalate of lime is more rapidly separated from a concentrated than an aqueous urine: moreover, experience at the bedside teaches every unprejudiced observer that the appearance of oxalate of lime in the urine is by no means accom- panied by the groups of symptoms which certain English physicians describe as pertaining to what they call the oxalic diathesis......It seems, moreover, un- reasonable to set up such a diathesis• since the establishment of a special disease from a single symptom—that symptom being only the occurrence of oxalate of lime —is entirely opposed to the spirit of rational medicine. From Wohler and Liebig's discovery that uric acid is decomposed by peroxide of lead into urea, allantoin, and oxalic acid, it has been pretty generally assumed that the oxalic acid of the urine is due to an oxidation of the uric acid; the oxalic acid in this case not being con- verted into carbonic acid, as usually occurs in the healthy organism." Scherer accounts for the oxalate of lime in the urine by considering it due to de- composition during the acid fermentation, and explains the process on the supposi- tion that the mucus of the bladder is a fermenting body, and that the extractive pigment is the substance metamorphosed into lactic acid. Dr. Owen Rees, in his lectures before the College of Physicians, depends mainly on Scherer's views in his argument in opposition to the existence of the oxalic diathesis, and ingeniously rejects many of the author's cases, for the reason that the heat which was applied to the urine might itself have been the cause of the formation of oxalate of lime from decomposition. Dr. Bence Jones observes : *' Oxalate of lime is so frequently found in the urine of those who are in perfect health, that I do not consider it as in- dicating any disease, but only a disorder of no serious importance. It scarcely in- dicates a more serious derangement of the general health than a deposit of urate of ammonia does. It may be found in the urine of all who lead sedentary lives, taking insufficient air and exercise, and more food than is requisite for the daily wants of the system." This constitutes the case of the opponents of the existence of such a disease as oxaluria, or such a diathesis as the oxalic acid diathesis. The arguments on the other side may, for the most part, be found in or gleaned from the previous edi- tions of this work. 1st. It is not denied that oxalate of lime may, and frequently does occur, in the urine of persons enjoying good health; and Lehmann himself correctly says the same of sugar: viz , that it is the quantity of sugar which is pre- sent which constitutes the characteristic symptoms of diabetes mellitus.* Yet he does not deny the existence of diabetes. 2d. Oxalate of lime may be formed in the urine after removal from the body, and its formation may be favored by the ap- plication of heat; but the crystals of oxalate of lime are, nevertheless, found in fresh urine, and do not necessarily require the application of heat for their detec- tion ; indeed, I never myself use heat for this purpose, and yet I have seldom failed to detect the octohedral crystals in cases where the symptoms have led me to look * Vol. ii, p. 427. HISTORY. 189 anxious to allude to the importance of carefully studying the relations of this form of deposit to certain states of health, because it seems now to run some risk of being tossed aside as a thing of no conse- quence. A curious revulsion of feeling seems to have taken place, among some, at least, on this subject. When I first discovered oxa- late of lime as a crystalline deposit, and announced its frequency, my observations were doubted by many, and whenever they were favored with any attention, they were always distinctly stated to rest exclusively on my authority. Now that more extended observations have demonstrated the truth of my statements, we are told, both in this country and abroad, that oxalate of lime is of constant occur- rence, and of no importance. A remark to which too many sufferers from this diathesis can give a melancholy denial. 212. The supposed extreme rarity of crystalline deposits of oxalate of lime in the urine had often attracted the notice of writers on cal- culous affections, and many had expressed their surprise that, although they had repeatedly examined the urine in cases where calculi of oxalate of lime exist, they had not succeeded in detecting a deposit of this substance. To the generally admitted accuracy of this state- ment all investigators had borne witness; thus, in the third edition of the elegant and elaborate work of Dr. Prout, AAThich must be re- garded as giving the most complete account of the state of our know- ledge on these matters at the time it was published (1840), the deposit of oxalate of lime was scarcely described. The remarks there made on the oxalic diathesis applied to the cases in which the oxalate of for them. 3. That the oxalate of lime may be held in solution in the urine, and afterwards deposited, as the causes determining its solution cease to exist • there- fore its non-detection in the freshly passed urine is no proof of its absence, but only of its non-deposition. The case of those opposing the existence of oxaluria is argued from the occurrence of the crystals in the urine up to the supposed constitu- tional derangement, instead of from the constitutional derangement to the urinary deposit; and this step in the argument takes the following form: A certain group of symptoms, distinctly marked, and consequently easily recognized, constituting a form of dyspepsia, but differing in many respects from that of gout, is almost uni- versally accompanied by the passing of urine containing oxalate of lime ; and this position has never as yet been shaken. It is a matter of indifference whether the disease be named oxaluria or dyspepsia, with a tendency to the formation of oxalic acid, i. c, oxalic dyspepsia. It may by some be considered improper to name a disease from a single symptom, but if that symptom be constant, constituting the differentia of the disease, it matters little, as far as science is concerned, whether the differentia be taken alone, or in connection with its subject, in the name, as long as the definition of the disease be full and accurate. 190 PATHOLOGY OF OXALATE OF LIME. lime has existed in a truly calculous form, or to those in Avhich the presence of oxalic acid is rather suspected than proved ;62 the whole series of observations inclining to the generally received notion of the almost necessary connection between the presence of saccharine matter and development of oxalic acid. M. Raver alludes, on the authority of M. Donne", only to the artificial production of crystals of oxalate of lime, effected by administering to patients alkaline oxa- lates ;63 and figures, among his very accurate delineations of urinary deposits, the precipitate produced by the addition of oxalate of ammo- nia to urine. The only case of the occurrence of oxalate of lime in the urine that he cites is one which occurred to myself several years ago, the details of which appeared in the " Medical Gazette,"64 in a laborious paper on urinary deposits, by Dr. Brett. And this is also the only instance alluded to by Dr. Willis, in his interesting work on Urinary Diseases. I was first led to question the accuracy of the generally received opinion of the extreme rarity of the presence of oxalate of lime in a crystalline form, during my examination of urinary deposits pre- paratory to the publication of an essay in the seventh volume of the Guy's Hospital Reports. Subsequently, in the extensive field of experience at my command, I pursued these researches on a large scale, and examined microscopically the urine in an immense number of cases of various diseases.65 The result of this investigation led to the discovery of the comparative frequency of oxalate of lime in the urine in fine and well-defined octohedral crystals, and of the connec- tion between the occurrence of this substance and the existence of a certain series of ailments, generally characterized by nervous irrita- bility. The accounts of my researches were published in the London Medical Gazette for 1842. 213. The reason of the oxalate having been overlooked so long is explained with great readiness, for without the aid of the microscope it is utterly impossible to demonstrate its presence, so long as it is diffused through the urine in separate crystals. In the less frequent form of minute concretions or hemp-seed calculi, of course it is readily recognized, but such cases are as rare as the occurrence of the oxalate in separate crystals is common. It will be a matter of great interest to investigate the comparative frequency of the oxalate of lime in the urine in different localities, for the purpose of ascertaining how far the formation of this salt is connected with the depressing influences always more or less active MICROSCOPIC CHARACTERS. 191 in large and densely populated cities; for, in the cases of disease oc- curring in the metropolis, I have no hesitation in declaring, as the result of my own experience, that the oxalate is of far more frequent occurrence in the urine than the deposits of earthy phosphates. And since the publication of the first edition of this work I have received repeated communications from provincial practitioners confirming this statement. Indeed I am convinced that traces of this salt in the minutest microscopic crystals can be detected in the urine of persons who are free from any apparent disease. Hence oxalate of lime must be regarded as one of the common results of metamorphosis of tissue, but the existence of the traces of the substance (which indeed may be regarded as a physiological condition), is a very different thing from its presence in large crystals and considerable quantities, and which can be only deemed as existing under a state of system strictly pathological. Diagnosis and Microscopic Characters of Oxalate and Oxalurate (?) of Lime. 214. To examine urine for the purpose of detecting the existence of the salt under consideration, alloAV a portion passed a few hours after a meal to repose in a glass vessel: if this be done in winter, or during the prevalence of frequent and rapid alternations of tempera- ture, a more or less dense deposit of urates will generally make its appearance, arising either from the sudden cooling of the urine, or from interference with the functions of the skin prior to its excretion. In warm Aveather, however, or when the functions of the skin are tolerably perfect, the urine, albeit it may be really loaded with oxa- late of lime, may still appear limpid, or, at furthest, its lower layers only be rendered opaque by the deposition of a cloud of vesical mucus. Decant the upper 6-7ths of the urine, pour a portion of the remainder into a watch-glass, and gently warm it over a lamp; in a few seconds the heat will have rendered the fluid specifically lighter, and induced the deposition of the crystals of oxalate, if any be pre- sent : this may be hastened by gently moving the glass, so as to give the fluid a rotatory motion, which will collect the oxalate at the bottom of the capsule. The application of warmth serves also to remove the obscurity arising from the presence of urates, Avhich is readily dis- solved on exposing urine containing it to a gentle heat (130). Having allowed the urine to repose for a minute or two, remove the greater portion of the fluid with a pipette, and replace it by distilled 192 PATHOLOGY OF OXALATE OF LIME. water.* A white powder, often of a glistening appearance, like diamond-dust, will now become visible, and this (under a low magni- fying power, as by placing the capsule under a microscope furnished with a half-inch object-glass), will be found to consist of crystals of oxalate of lime in beautifully formed transparent octohedra, with sharply defined edges and angles (Fig. 44). 215. If the light is very bright, these crystals generally resemble cubes marked with a cross, the point of intersection of the two arms corresponding to one of the apices of the octohedron (Fig. 45). Fig. 44. Fig. 45. Fig. 46. It sometimes happens that the oxalate is present in the form of exceedingly minute crystals: it then resembles a series of minute cubes, often adhering together like blood-discs: these, however, are readily and distinctly resolved into octohedra under a higher magnifying power. More rarely oxalate of lime assumes a someAvhat different form, apparently being made up of a square prism, with a four-sided pyramid at each end (Fig. 46), forming a dodecahedron. If the crystals be collected and ignited on platinum foil, oxalic acid is decomposed, and carbonate of lime left; the subsequent addi- tion of dilute nitric acid dissolves the residue with effervescence. * It has been stated that the crystals of oxalate of lime, thus obtained, may be formed by the process of heating, and may not have existed, as such, previously, in the urine; but even were this the case, it is ascertained that the process does not, in all instances, in which uric acid or urates are present, produce a similar result; hence in certain instances a modifying cause is present, which may be taken as evidence in favor of the existence of a distinct diathesis. It is, however, never necessary to have recourse to this process, the crystals are sufficiently clear without it; though it certainly offers to those unacquainted with the microscopical appear- ance, a ready means of obtaining good specimens. MICROSCOPIC CHARACTERS. 193 This is by far the most satisfactory process for the detection of oxalate of lime, and although it requires a little tact, still, after some trials, it can readily be performed in a very few minutes. But even this little Avastc of time may be avoided, by placing a drop of the lowermost stratum of the urine on a plate of glass, placing over it a fragment of thin glass or mica, and then submitting it to the micro- scope : the crystals diffused through the fluid becoming very beauti- fully distinct (123). In this way, however, it is obvious that a very much smaller quantity is submitted to examination than by the former process. 216. It is a very remarkable and interesting circumstance, that this salt, although I have now examined a very large number of speci- mens of urine containing it, has scarcely ever occurred to me in the form of a distinct deposit; remaining for days diffused through the fluid, even when present in so large a quantity that each drop of the urine, when placed under the microscope, was found loaded with the crystals. If, however, any substance, capable of constituting a nucleus be present, the oxalate will be deposited around it, although scarcely in cohering masses, and invariably colorless and beautifully transparent. The only exception to this is met with in the large and fine octohedral crystals of the oxalate which I discovered in the urine of the horse.130 These are slightly opaque, and possess a fine amber hue, constituting most beautiful microscopic objeets. If, as occasion- ally occurs, a specimen of oxalic urine happen to contain an excess of triple phosphate, the crystals of this salt are found mixed with those of the oxalate. I have also found the octohedra beautifully crystallized on a hair accidentally present in the urine, like sugar- candy on a string. 217. The fact of a large quantity of the oxalate, when present, escaping the eye, is explained, I suspect, from its refractive power approaching that of the urine ; for whenever we meet with the speci- men in which the salt has partially subsided, and replace the decanted urine by distilled Avater, the crystals often become readily perceptible to the unaided eye, resembling so many glistening points in the fluid. The oxalate of lime although absolutely insoluble in water must be soluble in urine, for its lustrous crystalline form sufficiently indicates the fact of its previous solution. Indeed, not unfrequently, even on the most careful examination, no traces of oxalate can be discovered in a specimen of urine recently voided, and yet after twelve hours' 13 194 PATHOLOGY OF OXALATE OF LIME. repose an abundance of this salt in even large crystals can be readily detected. Lehmann has observed, when discussing Scherer's ingenious views on the acid fermentation of urine, that " oxalate of lime may possibly be formed or separated during this process, and that the close con- nection between the separation of uric acid and the formation of this salt is supported by the fact that most samples of urine, Avhether sedi- mentary or non-sedimentary, exhibit no trace of the presence of oxa- late of lime, when examined under the microscope, as long as they are fresh, although some of the known crystals of oxalate of lime may be detected as soon as the uric acid crystals are formed; and, indeed, that the abundance of such crystals in morbid urine is proportioned to the rapidity with which acid fermentation is induced, and the con- sequent early deposition of free uric acid." Dr. OAven Rees—indors- ing these views, and stating in addition that the process of warming the urine facilitates the formation of oxalate of lime—has questioned the existence of any special diathesis. These views I have in another place endeavored to answer. 218. The crystals of the oxalate, when collected in the manner above directed in a watch-glass, are unaltered by boiling either in acetic acid (223-5) or solution of potass. In nitric acid they readily dissolve without effervescence. The solution may be very readily watched under the microscope. When the oxalate is allowed to dry on a plate of glass, and then examined, each crystal presents a very curious appearance, resembling two con- centric cubes, with their angles and sides opposed, the inner one transparent, and the outer black, so that each resembles a translucent cube set in a black frame (Fig. 47). This is best observed, unless the crystals are very large, under a half-inch object-glass ; as with a higher power this appearance is lost. Oxalate of lime when ar- tificially prepared by precipitation appears as an amorphous powder, but which under a high magnifying power can be resolved into myriads of minute crys- tals with a rectangular outline. Lehmann has stated, however, that a close imitation may be obtained of the urinary crystals in flattish octohedra by precipitating a very dilute solution of a lime salt at a boiling heat with oxalate of ammonia. DUMB-BELL CRYSTALS. 195 219. Occasionally some very remarkable crystals are met with, shaped like dumb-bells, or rather like two kidneys with their conca- vities opposed, and sometimes so closely approximating as to appear circular, the surfaces being finely striated. These crystals are pro- duced, in all probability, by a zeolitic arrangement of minute acicu- lar crystals (Fig. 48), presenting a physical structure resembling that of spherical crystals of carbonate of lime.* We meet with many Fig. 48. Fig. 49. modifications of these elegant crystals : sometimes they are oval lami- nae, in which no striae or evidence of structure can be detected until * In the dumb-bell and oval crystals of oxalate of lime the markings are gene- rally concentric; and there is some reason for supposing that crystals having radiating lines may consist of uric acid. Dr. Hassall has noticed ('* Lancet," 1850) certain modifications of the octohedron, and also of the dumb-bell formation, of Fig. 50. which Fig. 50, taken from his paper in the twenty-third number of the " British and Foreign Medico-Chirurgical Review," offers a fair illustration. He remarks that soluble dumb-bells in the uriue frequently consist of sulphuric acid in combina- tion with soda or potash. 196 PATHOLOGY OF OXALATE OF LIME. they are examined by polarized light. In some of these a sort of nucleus can be detected. Some of the most frequent varieties of these crystals are shown in Fig. 49. I have noAv met Avith many cases in which these various crystals have been present. Some of these have been under my care for months ; and I have had repeated opportunities of examining the urine. The remarkable crystals now referred to, became in all mixed with, and ultimately replaced by, the ordinary octohedral variety. 220. These dumb-bells and oval crystals, although I have always described them as oxalate of lime, have always presented a very seri- ous difficulty to their being thus regarded, in consequence of the pecu- liarity of their optical characters. It is well knoAvn that all crystals referable to the cube or regular octohedron never possess double refraction, and hence scarcely exert any influence upon a plain polar- ized ray of light. In accordance with this law, the ordinary crystals of oxalate of lime do not in the slightest degree exhibit the pheno- mena of color when examined in the polarizing microscope ; merely in the slightest degree, if lying in a favorable position, appearing illuminated, when the polarizing prisms are crossed. On the other hand, the dumb-bell crystals, as I long ago stated, exhibit a beauti- ful series of colored rings traversed by a black cross. Recently I had an opportunity of carefully examining the chemical reaction of these crystals. A gentleman* who had been under the care of the la-te Dr. Prout, consulted me shortly after his lamented death, and on drawing my attention to his urine, I observed the most copious deposit of the crystals in question I ever witnessed. Without much difficulty I obtained a sufficient quantity for the following experi- ments : a. They slowly dissolved in boiling dilute hydrochloric acid; from this solution ammonia threw down a white precipitate. The whole Avas left in a watch-glass to spontaneous evapora- tion. Very large and fine cubes of hydrochlorate of ammonia, unmixed with any of the ordinary plumose crystals, were left. Mixed with these was a white amorphous powder of oxalate of lime. b. Kept under water in a warm greenhouse for ten days, the mix- * This gentleman, whom I have frequently seen, has told me that, at the time when these crystals were observed, he had, by Dr. Prout's direction, been living mainly on meat, taking it thrice a day; he had also been using the Doctor's acid mixture. DUMB-BELL CRYSTALS. 197 ture evolved a fetid ammoniacal odor, and some of the dumb- . bells had become replaced by ordinary octohedral crystals of oxalate of lime. C. Boiled in strong hydrochloric acid, they readily dissolved, and were totally changed. For on spontaneous evaporation a series of tufts of beautiful crystalline needles were left exactly like oxalate of ammonia; but differed from it in being totally insoluble in water and readily soluble in a drop of hydro- chloric acid. D. Boiled in strong nitric acid they readily dissolved without change, for a drop of the solution allowed to evaporate spon- taneously on a plate of glass, left a crystallized mass of dumb- bells, generally more elegant and regularly crystallized than they are met with in the urine. Hastily evaporated, the crystals became nearly circular. E. Ignited in a platinum spoon they blackened, evolved an odor of burnt horn, and readily became white, without appearing to diminish in bulk. Under the microscope, the crystals ap- peared to be unaffected in shape, but were opaque. They reddened moistened turmeric paper, were insoluble in water, and dissolved in dilute sulphuric acid with violent efferves- cence, leaving, by evaporation, crystals of sulphate of lime. 221. I was unable to proceed further in these investigations, for the deposit, on the patient's marriage, became suddenly replaced by the ordinary octohedral crystals, and I could not procure any more of the dumb-bell form.* We may, however, safely conclude that they do not consist of mere oxalate of lime, for their powerful action on polarized light is quite incompatible Avith their being composed exclu- sively of this salt. The action of heat (e) shows that they are readily coiiArerted into carbonate of lime without change of form. The experiment with hydrochloric acid and ammonia (c) would seem to render it probable that urea was in some way evolved as the result- ing hydrochlorate crystallized in cubes. The different influence of nitric and hydrochloric acid is exceedingly interesting, and merits a careful study whenever an opportunity presents itself for their inves- * Although I have examined several specimens of this gentleman's urine, I have never since recognized the dumb-bell crystals. The octohedral ones, however, are at present in great numbers and various sizes on the recurrence of a common catarrh or attack of dyspepsia. 198 PATHOLOGY OF OXALATE OF LIME. tigation. Most microscopic observers are familiar with the optical properties of oxalurate of ammonia, and coupling the complete resem- blance of crystalline form and double refracting power of this salt Avith the dumb-bell deposits, I think we may venture to assume the high probability of the latter consisting of oxalurate of lime, a salt which differs from oxalate of lime in ultimate constitution only in the pre- sence of the elements of urea and absence of the constituents of water; for C N H 0 2 atoms oxalic acid, ... 4 6 1 " urea, .... 2+2+4+2 6+2+4+8 —1 " water, .... 1+1 = " oxaluric acid, . . . 6+2+3+7 222. Dr. Frick, of Baltimore,154 has stated that the dumb-bell crys- tals do not contain lime, and that they consist of uric acid. This extraordinary assertion was not founded on any analysis of the crys- tals I have described, and rests on no better foundation than that uric acid, when kept under water for some time, as well as when pre- cipitated under certain circumstances, presents an approach to the dumb-bell form.* It has long been known that uric acid will some- times assume the form of plates excavated at the sides (122), but really remaining so utterly unlike the crystals I described, that it is difficult to conceive any one committing so remarkable an error. For crystals which dissohre in boiling nitric acid without change, and at a red heat are converted into carbonate of lime, can hardly be mistaken for uric acid. 223. Dr. Bacon,153 another American physician, in a most ela- borate paper, displaying great power of research, read before the Boston Society for Medical Observations, has completely refuted Dr. Frick's hypothesis, and has added very largely to our knowledge of the chemistry of the dumb-bell crystals. Dr. Bacon is inclined to believe that the oval crystals I have described are dumb-bells seen endwise; they show, with polarized light, one or two circular, colored rings near the centre, and an oval band near the outside. On sub- mitting the crystals to heat and the action of acids, he obtained the same results as myself. He, however, ascertained that strong acetic acid (containing 39 per cent, of glacial acid) slowly dissolved them, * Vide Fig. 28 a, where true dumb-bells of uric acid are represented. DUMB-BELL CRYSTALS. 199 forming a transparent solution, which, on spontaneous evaporation, left an abunda-nce of zeolitic crystals, varying in figure from circular striated plates to dumb-bells. Mixed with these are a few long, four- sided prisms, which exhibited, like the zeolitic crystals, beautiful colored bands, Avhen examined with polarized light. 224. When digested in a cold solution of carbonate of soda, Dr. Bacon found that the dumb-bells became opaque and were disin- tegrated ; a white deposit of carbonate of lime in a few hours formed at the bottom of the vessel. This dissolved with effervescence in acetic acid, and the solution was rendered opaque on the addition of oxalate of ammonia. The fluid decanted from the carbonate of lime of course contained a soda salt, of the acid of the dumb-bell. On neutralizing this with nitric acid, the solution gave a precipitate with nitrate of silver, soluble in nitric acid as well as in ammonia. The silver precipitate did not fulminate with heat, like oxalate of silver. 225. Dr. Bacon examined the effect of the different acids on artifi- cially prepared oxalate of lime. He ascertained that when dissolved in hydrochloric acid, an abundance of zeolitic forms Avere obtained by hasty evaporation. But when allowed to evaporate spontaneously, a mixture of transparent rhomboidal plates, minute octohedra, and four-sided prisms, often arranged in rosettes, with the zeolitic crys- tals, were obtained. The rhomboids and zeolite groups acted power- fully on polarized light, the prisms less strongly, and the octohedra not at all. On submitting these crystals to analysis, the rhomboids were found to contain hydrochloric acid, but the prisms and octohedra were pure oxalate of lime. Oxalate of lime sloAvly dissolved in very strong acetic acid, and, on rapidly evaporating the solution, circular radiated crystals were left; they were frequently fissured in one or tAvo places, and exhibit the cross and rings by polarized light. Dr. Griffith had previously ascertained that artificial oxalate of lime, dissolved in nitric acid and evaporated, left a deposit of radiated crystals very like the dumb-bell crystals. From the result of all his experiments, Dr. Bacon expresses his opinion that the dumb-bell crystals I have described consist of a " salt of lime containing either oxalic, oxaluric, or, perhaps, some other organic acid easily converted into oxalic acid; but the exact nature of the acid remains to be determined by future investigation." 226. The greatest possible variation in the size of these crystals is often observed, not only in different specimens of urine, but often in the very same portion. I have often met with small octohedra of 200 PATHOLOGY OF OXALATE OF LIME. oxalate mixed with others four or six times larger in a single drop of urine. The following measurements were made from some speci- mens preserved between plates of glass ; by means of the beautiful micrometer of Powell, belonging to the large microscope constructed by him for Guy's Hospital: Inch. Length of a side of the largest octohedra, .... t^it " " smaller ditto,.....jt'ts " " smallest ditto,.....s^W " " octohedra in the urine of a horse, . T£g Long diameter of large'■dumb-bell" crystals, . . . jfa Short diameter of ditto,.......T£^ Diameter of some nearly circular, . . . . . j^s Long diameter of the smallest " dumb-bells," . . . T4?5 Short diameter of ditto,...... . 23*5 5 Characters of Urine containing the Oxalate and Oxalurate (?) of Lime. 227. In the great majority of cases the urine is of a fine amber hue, often darker than in health, but never presenting to my view any approach*to the greenish tint which has been described as charac- teristic of this secretion during the presence of the oxalic diathesis, unless the coloring matter of blood be present. In a few cases the urine was paler than natural; and then was always of lower specific gravity. This, hoAvever, was in most instances but a transient al- teration, depending upon accidental causes; the odor was generally natural, rarely aromatic like mignonette. In many instances a de- posit of urates, occasionally tinted pink by purpurine, fell during cooling. I have observed this to be infinitely more* frequent during the spring than summer: hence it in all probability depended upon the influence of cold upon the cutaneous functions, causing a large amount of nitrogen and carbon, under the form of urates and purpu- rine, to be excreted by the kidney (138). The specific gravity of oxalic urine varies extremely; in rather more than half the speci- mens being, however, between 1*015 and 1*025. In eighty-five different specimens of which I preserved notes, the ratio of the den- sities was as follows: In 9 specimens the specific gravity ranged from . 1*000 : 1*015 In 27 " " . 1-016 : 1-020 In 23 " " . 1-021 : 1-025 In 26 " " . 1*025 : 1-030 CHARACTERS OF THE URINE. 201 The densities of the specimen of urine passed before going to bed at night, and immediately on rising in the morning, were frequently very different; thus, in twenty-six cases in which the night and morning urine were separately examined— The night specimen was heaviest in . . . 12 The morning specimen heaviest in ... 5 Both alike in........9 And, as a general rule, the heaviest specimens contained most of the oxalate. It seldom happened that the total quantity of urine passed in these cases very much exceeded the average proportion ; in a very few only positive diuresis could be said to exist. Fre- quently the patients have, from occasional irritability of bladder, mistaken the frequent desire to pass urine for an increased quantity; but the absence of any very considerable increase was proved by positive measurement of the quantity of urine passed in twenty-four hours. 228. Some of the specimens of oxalic urine gave a precipitate with salts of lime, insoluble in acetic acid, and consisting of oxa- late of lime. This, in some instances at least, depended on the pre- sence of oxalate of ammonia, or of some other soluble salt of this acid. The acidity of these specimens was always well marked, often far more so than in health, and never being absent. I have not yet met with a single case in which an alkaline, or even positive neutral, state existed, unless complicated with calculus or diseased bladder. A greater increase in the quantity of urea than the density of the urine would have led us to suspect, was frequently found; indeed, I have scarcely met with a specimen in which, when the density was above 1-015, distinct indications of an excess of urea were not met with. In twenty-four of the eighty-five specimens above referred to, so large a quantity was present, that very rapid, and in some almost immediate crystallization ensued on the addition of nitric acid. In general, in cases Avhere the greatest excess of urea was present, the largest and most abundant crystals of the oxalate were detected. Mr. J. H. Stallard, of Leicester, who has contributed some impor- tant information on this subject, has discovered that in oxalic urine the indeterminate organic matters (57) are greatly increased, often reaching nearly double the average proportion excreted in twenty- four hours. I can fully confirm the accuracy of this observation, and indeed believe that it explains the emaciation so frequent in this 202 PATHOLOGY OF OXALATE OF LIME. affection. Dr. Maclagan* has observed on this subject, that the mean density of the urine Avas 1024-4 ; that the observed difference of density between the morning and evening urine Avas confirmed, and had reference to the fact that the presence of oxalate in the urine was commonly connected with a disorder, more or less impor- tant, of the digestive and assimilative processes; that the color Avas paler than that of healthy urine ; that the sweetbrier odor Avas fre- quently present; that in some instances the urine was more or less fetid, but never ammoniacal, and but seldom ever resinous; that the reaction was in general strongly acid. Complication of the Oxalate of Lime with other Deposits. 229. In more than half the cases, the oxalate of lime was found unmixed with any other saline deposit; in a very few, crystals of uric acid were found from the first, mixed with the octohedra of oxa- late of lime; and in nearly all the successful cases, this acid appeared in the course of the treatment, and ultimately replaced the oxalate altogether, at a period generally contemporary with the convalescence of the patient. Much more rarely, prisms and stellae of the ammo- niaco-magnesian phosphate Avere found mixed with the oxalate, and occasionally replacing it in the course of the treatment; and still less frequently the phosphate was observed in the urine some time before the appearance of the oxalate. In several specimens a copious troubling was produced on the ap- plication of heat; this generally depended upon the precipitation of the earthy phosphates, as a drop of dilute acid immediately restored the limpidity of the fluid. This troubling, in very few cases, has been found to depend upon the presence of albumen, and then it was usually transient, and generally traceable to the presence of some secretions from an irritable vesical mucous membrane. I have met with but few well-marked instances of a complication of this oxalic affection with granular degeneration of the kidneys. Out of the eighty-five cases before referred to (227), Oxalate was present unmixed in Mixed with urates, Mixed with uric acid, . Mixed with triple phosphate, Phosphate deposited by heat, 43 cases. 15 " 15 " 4 « 85 ♦"Edinburgh Monthly Journal," Dec. 1853, and Jan. 1854. COMPLICATIONS. 203 In one of the specimens containing the triple phosphate, the appli- cation of heat produced a deposit of the earthy salts.* 230. Much oxalate of lime often crystallizes from urine after suf- ficient repose, and even if, in cases of oxaluria, the fresh urine be filtered through paper so as to separate every trace of deposit, and then set aside for twenty-four hours, a fresh formation of crystals will be detected. One very constant phenomenon is observed in the microscopic ex- amination of oxalic urine, viz.: the presence of a very large quantity of epitheliarcells (341); it is, indeed, the exception to the general rule to meet with this form of urine free from such an admixture. So constantly has it been found, that a white deposit of epithelium has repeatedly attracted my attention, and led to the suspicion of the probable presence of oxalate of lime. Sometimes the cells of epithe- lium are found unaltered in form, being more or less oval and dis- tended with fluid; more frequently they are empty, and then resemble flat oval scales, marked with a circular spot in the centre. Some- times irregular lacerated fragments of epithelial structure are met with; and frequently, if the light is not too intense, a portion of the urine can, under the microscope, be seen to be full of them. 231. Although the oxalate of lime is generally found diffused through the urine, yet, if much mucus is present, so as to form a tolera- bly dense cloud, the salt may often be seen entangled in its meshes like Morning Evening Urine. Urine. * Dr. Maclagan found that the oxalates were unmixed in . 16 . . 14 " " with other saline de- posits, . . . 16 . . 20 " ** not examined, . . 5 . . 3 37 Of the saline constituents the urates alone occurred frequently; next in order, but comparatively rarely, were found uric acid, oxalurates, and amorphous phos- phates; and then, in almost solitary instances, triple phosphate, cystine, xanthine, pus, sugar, blood, and in six instances a more or less marked reaction of purpurine. The epithelium in 37 specimens Morning Urine. Evening Urine. was copious, ... 12 .. 10 " trifling, ... 20 .. 24 " not examined, . 5 3 37 As a general rule, the oxalate was more abundant in the evening than in the morning urine. 204 PATHOLOGY OF OXALATE OF LIME. glistening points; and whenever any other matter is present, Avhich becomes deposited by repose, a greater portion of the oxalate will almost invariably fall with it. This is particularly the case when triple phosphate of magnesia and ammonia, or uric acid, exists under the form of a crystalline deposit; for, on submitting a portion of this to the microscope, the octohedra of oxalate may be readily detected mixed with the prisms or stellae of the former, or with the tables or lozenges of the latter. Pathological Origin of Oxalate of Lime. 232. This question is one of great interest, and becomes the more important since the discovery of the very frequent existence of this salt in the urine; so that, instead of being very rare, it really is con- siderably more frequent than many other deposits (213). It is scarcely possible to avoid being impressed with the very probable physiological relation between oxalic acid and sugar: we know that the latter sub- stance forms a considerable item in our list of aliments; we know that the great majority of farinaceous matters are partially converted into this element during the act of digestion.66 It is indisputable that, under certain circumstances, it finds its way into the blood, and is eliminated by the kidneys; even when artificially introduced it is thus thrown out of the system. I have in my possession fine crystals of sugar, prepared by Dr. Percy from the urine of a dog, into whose veins he had previously injected a solution of that substance. Lastly, we know that, under certain morbid influences, the great proportion of our food may, whilst in the stomach, be converted into sugar, which, becoming absorbed, rapidly passes through the circulation, and is thrown out of the system by the kidneys as an effete matter, with the effect of producing more or less rapid emaciation, and in most cases leading to fatal marasmus. Dr. Aldridge,141 of Dublin, has even suggested the probability of a substance analogous to sugar, capable of undergoing acetous fermentation, being a normal element of the urine. Then, recollecting the facility with which sugar and its chemical allies, as starch, gum, and wood fibres are, under the in- fluence of oxidizing agents, converted into oxalic acid, and having sufficient amount of evidence to prove that when oxalic acid is really found in the urine, symptoms bearing no distant relation to those of a diabetic character are met with, Ave are almost inevitably led to draw ORIGIN. * 205 the induction that the oxalate of lime found in the secretion owes its origin to sugar, and to locate the fons et origo mali in the digestive organs. It was only after extended observation that I convinced myself that the connection between oxalate of lime and sugar is by no means a necessary one (234). 233. That some very slight disturbing causes influencing the assimi- lative functions will give rise to the presence of oxalate in the urine is perfectly true, even when the food taken does not contain oxalic acid ready formed, but this is generally a temporary change, and soon disappears on the removal of the exciting cause., Far different are the results and character of those cases in which a deposit of oxalate steadily continues for some time. A disease of great consequence, of often serious importance, is then set up, one which demands very great attention on the part of the physician. From a careful examination of the urine in a large number of these cases, I have arrived at the following conclusions regarding the cir- cumstances under which the oxalate of lime occurs in the urine. 1. That in the urine under examination oxalate of lime is present partly dissolved in, and partly diffused through the fluid, from whence it is deposited in a crystalline form. 2. That in rather more than one-third of the cases uric acid or urates existedin large excess, forming the greater bulk of the existing deposit. 3. That in all, there exists a greater proportion of urea than in natural and healthy urine of the same density; and in nearly 30 per cent, of the cases, so large a quantity of urea was present, that the fluid crystallized into a solid mass on the addition of nitric acid. 4. That the urates found in the deposits of oxalic urine are occa- sionally tinted of a pink hue. 5. That an excess of phosphate frequently accompanies the oxalate. 6. Tljat the existence of sugar in the specimens I have examined is the exception to the rule. 234. Every one is now familiar with the composition of the urine in diabetes, and it has been determined, from extended observation, that, as a general rule, diabetic urine very seldom contains in a given quantity any excess of urea, uric acid, or urates, especially the pink variety ; and that this secretion is remarkably free from saline de- posits ; the increased specific gravity depending upon the presence of large proportions of sugar. In the oxalic urine under consideration, the density increases with the quantity of urea, which is often pre- 206 *PATHOLOGY OF OXALATE OF LIME. sent in large excess. Indeed, I regard the presence of a greater or less excess of urea almost as characteristic of the morbid state of urine for which I am contending, as the oxalate of lime itself. De- posits of uric acid and urates are also frequent; and, further, no analogy whatever with saccharine urine exists, save in density, which we have already learned depends upon a totally different cause. Thus, so far as the abstract examination of the urine is concerned, not the slightest countenance is given to the idea of there being any relation between oxalic and saccharine urine, however much our pre- conceived and hypothetical views may have led us to expect the ex- istence of such. In but few instances have I yet found sugar present in oxalic urine; and although these investigations were commenced with a strong bias in favor of the almost* necessary connection be- tween the presence of saccharine matter and oxalic acid, yet, in pro- portion as I have extended my researches, this idea became less and less supported by experience. In fact, I have very rarely met with oxalate of lime in diabetic urine. What, then, is the source of the oxalate of lime ? and how can its continued production be explained consistently with the phenomena presented by the urine ? From the symptoms presented in cases of this disease, there is no difficulty in proving to a demonstration the positive and constant existence of serious functional derangement of the digestive organs, especially the stomach, duodenum, and liver; and, further, that the quantity of oxalic acid generated is, to a very considerable extent, under the con- trol of diet; some articles of food quite free from oxalic acid at once causing the excretion of this substance in very large quantities, whilst others appear to have the effect of nearly totally checking it. These circumstances alone, together with the emaciation so generally pre- sent in the disease under consideration, at once prove, that whatever be the immediate agent which causes the kidneys to secrete the oxalic acid from the blood, the primary cause must, as Dr. Prout has Avell and satisfactorily shown, be referred to an unhealthy condition of the digestive and assimilative functions. 235. That the oxalic acid really does find its way into the blood, has been proved beyond all doubt by Dr. Garrod. This gentleman, who so successfully demonstrated the presence of urate of soda in the circulating fluid, was kind enough to place in my hands some octohedral crystals he obtained from the serum of blood of a patient laboring under albuminuria. From all the observations I was able to make on these crystals, I can fully confirm the accuracy of Dr. . EXCESS OF UREA. 207 Garrod's opinion of their consisting of oxalate of lime. They were obtained in the following manner. The serum of blood was eva- porated to dryness and digested in alcohol, the insoluble residue Avas treated with boiling water, evaporated and mixed with acetic acid, with the vieAV of detecting uric acid. Instead of crystals of this substance, a white deposit of octohedral oxalate of lime fell. It is difficult to explain the presence of so insoluble a salt in solution in the blood, but it is very probable that the opinion of Br. Schmidt,155 of Dorpat, may be correct. He has assumed that there exists in the animal economy a tendency to the formation of a soluble triple com- pound of oxalic acid, lime, and albumen (oxalsaures albumin-kalk), which, by its decomposition, allows oxalate of lime to crystallize. Probably such a compound exists in the blood in disease, and when the acetic acid is added, as in Dr. Garrod's process, the albumen is separated and the oxalate set free. A compound of this sort exists in yeast-cells, for when recent, minute microscopic examination fails to detect any crystals, but when kept long enough to undergo de- composition, octohedral crystals of oxalate were found by Dr. Schmidt to be abundantly evolved. Very recently Mr. Simons has given an account of a membranous cyst which he found on the olfactory nerve of a horse, containing a large crystal of oxalate of lime.157 236. As an excess of urea, and often of uric acid, in most in- stances coexists Avith deposits of oxalate of lime, it is highly probable that both these unnatural states of the secretion are produced by the same morbid influence. Further, when the very remarkable chemical relation existing between uric acid, urea, and oxalic acid, is borne in mind, as well as the readiness with which the former of these bodies is convertible into the latter, is it not legitimate to suppose that the disease under consideration may be regarded as a form of what has been aptly termed by Dr. Willis azoturia (of which an ex- cess of urea is the prevalent indication), in which the vital chemistry of the kidney has converted part of the urea, or of the elements which would in health have formed this substance, into oxalic acid ? This vieAV appear#to me to be supported by what I have observed of the history, symptoms, and progress of the cases, as contrasted with the changes presented by the urine during treatment. It may, how- ever, be asked, from whence are the nitrogenized matters derived, Avhose metamorphic changes (31) give rise to the formation of oxalic acid ? are they derived from the tissues of the body, like healthy urea and uric acid ?(38) Of course it is quite possible that 208 PATHOLOGY OF OXALATE OF LIME. such may be their origin, but as the quantity of oxalate of lime de- posited from the urine is ahvays the greatest after a full meal, and often absent in the urina sanguinis, or that passed on rising in the morning, frequently disappearing under the influence of a carefully regulated diet, and reappearing on returning to the use of unwhole- some food, it is highly probable that this salt is, in the majority of cases, primarily derived from the mal-assimilated elements of food, and not, like uric acid generally, a product of metamorphosed struc- tures.* 237. The ready conversion of uric into oxalic acid, under the in- fluence of oxidizing agents, has been satisfactorily demonstrated by Professors Liebig and Wohler; for when uric acid is heated in water and peroxide of lead, the latter gives up part of its oxygen, and oxalic acid, with allantoin, the peculiar ingredient of the allantoic fluid of the foetal calf, are generated. The ultimate constitution of this substance differs from that of oxalate of ammonia only in the absence of the elements of water. In the following equation this decomposition of the allantoin is assumed to have occurred— C N H 0 1 atom uric acid = 10+4+ 4+ 6 +2 " oxygen = 2 +6 " water = 6+6 10+4+10+14 C N H 0 2+2+ 4+2 = 1 atom urea. 4 6 = 2" oxalic acid. 4+2+ 6+6 = 2 " oxalate of ammonia. 10+4+10+14 The readiness with which, under certain circumstances, uric acid is converted into the oxalate, may be well illustrated by a fact Avhich has been observed in connection with the guano of South America (87), a substance now so largely employed as a manure. This con- tains, when recent, a considerable proportion of urate of ammonia, which salt, after a certain length of time, often during the voyage to this country, nearly wholly disappears, and is replaced by oxalate of * I am inclined to the opinion, though not as yet furnished with sufficient facts to assert it confidently, that whenever the crystals of oxalate of lime are not to be found in the morning urine, i. e., in the urina sanguinis, the case is more one of ordinary dyspepsia, the deposit being the result of changes in the nitrogenized food, and may generally be relieved by the usual treatment; but that if not so relieved, it passes on to the stage of confirmed oxaluria,—when the deposit is due to the abnormal destructive assimilation of effete tissues,—Liebig's metamorphoses of tissue. ITS RELATION TO UREA. 209 ammonia. The urinary excretion of caterpillars, consisting chiefly of urate of ammonia, is also frequently found to contain fine crystals of oxalate of lime. The theoretical relation between urea and oxalic- acid is readily shown; for if we conceive urea to exist in the blood, and it be the duty of the kidney to separate it, we have only to assrme that its elements undergo a rearrangement in the act of elimi- nation from the circulating mass, the result of which is the appropri- ation of the elements of water and evolution of oxygen, to insure the conversion of urea into oxalate of ammonia. We know that under a depressing influence exerted on the nervous system at large, or upon a portion of it connected with the functions of the kidney, as during typhus adynamic fever on the one hand (271), and blows over, or a fracture of the spine on the other (274), such decomposing influence is unquestionable, and the urine becomes loaded with carbonate of ammonia from a rearrangement of the component elements of the urea; one atom of urea and two of water being resolved into two atoms of carbonate of ammonia. If, then, this depressing influence be modified so as to interfere with the formation of an alkaline salt, we may suppose it probable that urea may undergo a different metamor- phosis, and become converted into oxalic acid, ammonia, and oxygen. 1 atom urea C NHO] = 2+2+4+2 water = 2+2 2+2+6+4, fCNHO 2 3 = 1 atom oxalic acid. 2+6 =2 " ammonia. 1 = 1 " oxygen. 2+2+6+4 238. Since the first publication of this formula, Professor Liebig has suggested that oxalic acid is a derivative of uric acid, and not of urea, thus: CNHO] fCNHO 1 atom of uric acid = 10+4+4+ 6 4+4+8+ 4 = 2 atoms urea. 4 " water = 4+ 4 3 " oxygen = 3 f 6 9 = 3" oxalic acid. ■ 10+4+8+13 J [ 10+4+8+13 It is, however, a matter of very secondary importance whether the oxalic acid be a derivative of uric acid or urea, considering the close relation Avhich exists between these two bodies (82). From whatever source it may arise, the presence of oxalic acid in the urine must necessarily lead to the formation of oxalate of lime, as this acid readily precipitates lime from all its combinations with acids. 14 210 PATHOLOGY OF OXALATE OF LIME. 239. Having traced the origin of oxalate of lime deposits to changes in nitrogenized food, or to an abnormal destructive assimila- tion of effete tissues, it becomes next of importance to direct atten- tion to the fact that this salt may often be a direct derivative from vegetable food, for it is quite certain, from the researches of Schleiden and others, that oxalic acid is of all acids that which is most exten- sively diffused through the vegetable kingdom. In the polygonaceae, it particularly abounds, and after the- ingestion of preparations of rhubarb and sorrel, crystals of oxalate of lime can always be detected in the urine. Oxalate of lime constitutes a large proportion of the acicular crystals or raphides so common in the intercellular lacunae of many plants, and in the liber of trees it is of very frequent occur- rence. These crystals of oxalate of lime are developed in the cells of the vegetable structure, and it is impossible to avoid being struck with the curious analogy presented in the Fig- 51. formations of cells in both animal and vegetable life. In Fig. 51, at a, b, are shown cells from the outer layer of the bulb of an onion, containing crystals of oxalate of lime in octohedra and prisms, figured by Mr. Quekett, and at c in an epithelial cell filled Avith octohedral crys- tals of the same salt which was detected in the urine by Dr. G. Johnson. The physio- logical origin of oxalic acid in vegetables is referable to a process of deoxidation, and admits of ready ex- planation. It is well known that under the influence of light the leaves of plants possess the power of decomposing the carbonic acid of the air, and evolving its oxygen ; the carbon becomes fixed in their tissue. The generation of oxalic acid becomes a nearly necessary result of the first stage of this deoxygenizing action, and most of the other vegetable acids may be regarded as the results of ulterior changes. Thus: C H 0 12+ 24 = 12 atoms of carbonic acid. — 6 12+ 18 = 6 atoms of anhydrous oxalic acid. + 6+ 6 = 6 atoms of water. 12+6+24 = 6 atoms of hydrated oxalic acid. CONNECTION WITH FOOD. 211 9 12+6+15 = 1^ atom of tartaric acid. 3 1£ atom malic acid. 1 atom of water. 1 atom of citric acid. 2 atoms of wafer. 12+3+ 9 = lichenic acid. Thus we are authorized in assuming that animals and vegetables generate oxalic acid by two very distinct processes, the former by oxidation, the latter by deoxidation. These facts show the vast importance of carefully ascertaining the peculiarities of the patient's diet, before giving too confident an opinion as to the morbid state of the urine. 240. The use of rhubarb and sorrel is, as I have already stated, a common source of oxalate of lime in the urine. Tomatoes also contain enough of a soluble salt of oxalic acid to cause a deposition of oxalate of lime in the urine. The abundance of the oxalate of lime which I have shown to exist in the urine of the horse is probably owing to the quantity of sorrel always present in hay. Some careful re- searches into the influence of food in causing the appearance of oxa- late of lime in the urine have been made by Mr. Rose of Swaffham. He has shown that many articles of ordinary diet are sufficient to produce a temporary oxaluria, under certain states of health; turnips and onions have thus appeared to determine its presence. It seems that oxalate of lime taken into the stomach does not, on account of its insolubility, enter the blood, nor reach the urine. In good states of health, onions, although containing an abundance of crystallized oxalate of lime, do not generally cause this substance to appear in urine. 241. It hence becomes a very important matter to diagnose between deposits of oxalate of lime which acquire their acid directly from the food in which it existed ready formed, and those in which its origin is strictly pathological. The nature of the patient's food will soon enable us to resolve this question satisfactorily. It may, however, often assist in our diagnosis to recollect that the great acidity, the high specific gravity, and excess of urea generally present in true oxaluria, will often at once distinguish between a deposit the result of diseased action and one of accidental origin. 12+6+12 = - 1+1 = 12+5+11 = — 2+2 = 212 PATHOLOGY OF OXALATE OF LIME. 242. It is a curious circumstance, that oxalate of lime exists in many mucous secretions, and may hence be occasionally found on the surface of mucous structures in a crystallized form. In this state it has been detected in the mucous membrane of the gall-bladder and of the uterus during pregnancy. ■ Symptoms accompanying the Secretion of Oxalic Acid. A. Oxaluria, with Excess of Urea and Extractive Matter in the Urine. 243. It is impossible to connect any definite set of symptoms with all cases in which the oxalate of lime appears in the urine, indeed persons will often go about their ordinary duties in apparently fair health for a long time, and yet be constantly excreting the oxalate of lime. In consequence of this, some persons have actually affirmed that oxalate of lime has no relation with any pathological state of the system, and its appearance in the urine is of no consequence. This opinion can result from very limited experience alone; indeed I am not sure that Lehmann, valuable as is his opinion as a chemist, has any claim on our confidence as a practical physician ; and he is chiefly referred to as advocating the erroneous view I have alluded to. If this kind of reasoning be admitted, the existence of albumen or blood in the urine might be regarded as of no importance, because we often meet with patients affected with this very condition, and yet are so free from apparent indisposition, that we are often unable to persuade them to take care of their health, until the disease indicated by the state of urine in question has proceeded to an incurable condition. 244. Persons affected Avith the form of disease referable to this class are generally remarkably depressed in spirits, and their melan- choly aspect has often enabled me to suspect the presence of oxalic acid in the urine. Sometimes a peculiar lurid greenish hue of the surface has been observed, but more generally the face has the dark and dingy aspect so common in some forms of dyspepsia in which the functions of the liver are deranged. They are generally much ema- ciated, excepting in slight cases, extremely nervous, and painfully susceptible to external impressions, often hypochondriacal to an ex- treme degree, and in very many cases labor under the impression that they are about to fall victims to consumption. They complain bitterly of incapability of exerting themselves, the slightest exertion SYMPTOMS. 213 bringing on fatigue. Some feverish excitement, with the palms of the hands and soles of the feet dry and parched, especially in the evening, is often present in severe cases. In temper they are irrita- ble and excitable; in men the sexual power is generally deficient, and often absent, an effect probably owing to the exhaustion pro- duced by the excessive secretion of urea so common in this affection (220). A severe and constant pain or sense of weight across the loins, is generally a prominent symptom, with often some amount of irritability of bladder. The mental faculties are generally but slightly affected, loss of memory being sometimes more or less present. Well- marked dyspeptic feelings are always complained of. Indeed, in most of the cases in which I have been consulted, I have been gene- rally told that the patient was ailing, losing flesh, health and spirits, daily ; or remaining persistently ill and weak without any definite or demonstrable cause. The urine is always of high specific gravity, often being within the diabetic range, and seldom below 1*025 or 1*030. This increase of specific gravity depends not only upon an excess of urea (for the urine generally crystallizes readily with nitric acid), but upon the existence of an abnormally large proportion of the extractive matters of the secretion (54). It is invariably acid, often excessively so. The tendency to eruptions of minute furunculi, and even sometimes of large boils, is an exceedingly frequent con- comitant of the state of the urine under consideration, and becomes a striking indication of the depressed state of the general health. In some instances the patients have been suspected to be phthisical. It is, however, remarkable, that I have yet met with very few cases in which phthisis was present. In very few instances only have I seen the cases terminate in the formation of a calculus. As to the source of the oxalate of lime, it can, I think, only be referred to the same origin as the accompanying urea (237) and extractive matters, Adz., an exaggerated activity of the second stage of the secondary or destructive assimilation, the metamorphosis of tissue of Liebig. It is only in this way that the attending emaciation can be satisfactorily accounted for. B. Oxaluria, unattended by Excess of Urea or Extractive Matter. 245. In these cases the oxalate of lime is generally merely one of a series of symptoms developed under the influence of diseases which interfere with the assimilative functions ; perhaps of those which affect 214 PATHOLOGY OF OXALATE OF LIME. most prominently the integrity of function of the ganglionic nerves. Hence, in many acute diseases, a deposit of oxalate of lime is not uncommon, especially in acute rheumatism. The deposits of urate so frequent in this painful disease being rarely free from the crystals of the oxalate. When it thus occurs, it is not to be regarded as involving the ne- cessity of special treatment, and generally disappears pari passu with the cure of the accompanying malady. 246. Among chronic diseases (especially in certain forms of chronic dyspepsia), attended by gastralgia, oxalate of lime often abounds in the urine, and seems to act as a local irritant. This is exceedingly frequent among persons whose nervous systems become much excited by anxiety, and the pressure of important business. It has occurred to me repeatedly to notice this state of things in barristers and solici- tors, especially when hard worked. The irritability of bladder, so common an ailment among many members of the legal profession, has been, in so many'cases which have fallen under my notice, accom- panied by the abundant excretion of crystals of oxalate of lime, and has disappeared on the removal of this deposit, that I cannot avoid regarding this substance as playing the part of a local irritant.* 247. In some chronic affections of the air-passages, oxalate of lime has been abundantly met with in the urine, and perhaps more fre- quently in old bronchitis with emphysematous lungs than in other affections. Lehmann has offered a very ingenious explanation of this, by supposing that in the deficient state of the pulmonary func- tions, oxygenation of carbon is partly performed vicariously in the capillary structure of the kidneys, oxalic acid (C203) being formed instead of carbonic acid (C02). 248. The immediate exciting causes of the secretion of oxalic acid are, in the majority of cases at least, generally well marked; and in nearly all the predisposing cause is the same, viz., a chronic and per- sistent derangement of the general health, or the result of previous acute disease, dyspepsia, injury to the constitution by syphilis and mercury (Case I), by childbearing and overlactation, by venereal excesses or intemperance (Cases III, VII). The accession of the disease has generally been traced to some circumstance which has determined the irritation to the urinary organs. Among the most * I have observed in several cases, a burning sensation over the iliac region, and the parts supplied by the superficial branches of the first division of the lumbar plexus. TREATMENT. 215 frequent of these causes, I have observed exposure of the lower part of the spine to cold (Case II), mechanical violence inflicted over the kidneys (Case VI), severe irritation following the introduction of a bougie or catheter, or unnatural excitement of the genital organs, as shown by the frequent occurrence of involuntary seminal emissions (Case V). The most inveterate case of this kind I ever met with was in the person of a gentleman, who committed the worse than foolish act of testing his sexual powers, previous to his marriage, by sleeping with two women. The result was an epileptic fit, and for three years after he paid a heavy penalty for his folly in the persis- tence of the symptoms above described in an aggravated form, so that he dragged on a miserable existence, although surrounded with everything which ought to render life happy. Dr. Rigby has lately shown that deposits of oxalate of lime occur often during the existence of functional and organic disease of the uterus. In many cases, however, no other obvious cause existed than great mental anxiety (Case IV), produced by excessive devotion to business or study. Therapeutical Indications. 249. The treatment, in the majority of cases, is very successful; a few only resisting all the plans Avhich were adopted. As a gene- ral rule the functions of the body, where obviously imperfect, should be corrected, the general health attended to by the removal of all unnaturally exciting or depressing influences, the skin should be pro- tected from the sudden alternations of temperature by a flannel or woollen covering, and the diet carefully regulated. This has gene- rally consisted of Avell-cooked digestible food, obtained in about equal proportions from the animal and vegetable kingdoms, all things which tend to produce flatulence being carefully avoided. The drink should consist of water, or some bland fluid, beer and wine being generally excluded, especially the former, unless the patient's depression render such positively necessary. A very small quantity of brandy in a glass of Avater has generally appeared to be the most congenial beve- rage at the meals. The administration of nitric acid,* as suggested * The exhibition of acids in some forms of dyspepsia has received, of late, most interesting explanation from the researches of Jolly and Graham, as considered by Lehmann. Jolly found by experiments the endosmotic qualities of acid are in pro- 216 PATHOLOGY OF OXALATE OF LIME. by Dr. Prout, or what appeared to be preferable, the nitro-hydro- chloric acid, in small doses, in some bitter infusion; or, laxative mixture, as the mistura gentianae comp., is, with minute doses of mercury, generally successful, if continued a sufficient length of time. There is an important fact connected with the adminis- tration of the nitro-hydrochloric acid, upon which I feel quite sure its success materially depends. The really active agent is not a mere mixture of the two acids (such as may be obtained by ordering a combination of the diluted acids), but is the peculiar compound, the so-called aqua regia arising from the mutual decomposition of the two acids. Hence they should always be prescribed in the propor- tion of one part nitric and tAvo or three of hydrochloric acid, with a direction for them to remain together for at least a few minutes before being diluted to the proper extent for administration in medicine. Where great nervous irritability exists, the sulphate of zinc is often of great service. It should be given in graduated doses, beginning with one grain, thrice a day, increasing the dose every third or fourth day until 18 or 20 grains are taken daily. The addition of a grain or two of ext. of hyoscyami or camphor often enables it to be better borne. The shower-bath, by acting in a similar manner, has been also of great service. Where the patient is anaemiated or chlorotic, the salts of iron in large doses appear to be of great use, not only by subduing the irritable state of the nervous system, but by increasing a healthier condition of the blood. No preparation of this important drug succeeds better than the ammonio-citrate or ammonio-tartrate, in doses of seven or eight grains thrice a day, dissolved in a glass of water. The headache occasionally following the use of iron is readily prevented, and the success of the remedy insured by taking it di- rectly after a meal, so that it may be assimilated with the food. 250. In a few obstinate cases, resisting all other treatment, I have prescribed colchicum with advantage. The influence of this remedy in often checking a long-continued formation of uric acid has been already alluded to (159). And in some cases, where copious deposits of oxalate of lime existed, they have, under the influence of this drug, portion to those of alkalies as 0-350 to 215-725, and according to Graham, the dif- fusibility of acids was extremely great, that of alkalies very small. We know that free acid is commonly found as far as the middle of the ileum, notwithstanding the excess of the pancreatic juice and the bile; and its use evidently appears to be to promote the endosmotic current from the cavity of the intestine, and consequently resorption of the soluble constituents of the chyme. TREATMENT. 217 become replaced by uric acid or urates, thus inducing a condition of urine much more amenable to treatment. The rationale of the action of colchicum is probably traceable, not to any specific power it exer- cises over any form of urinary deposit in particular, but rather in the influence it exerts over the secreting functions, controlling the action of the heart (on which it appears to act as a direct sedative), and consequently the capillary circulation, the very seat of secretion. The circumstance of the replacement of oxalate of lime by uric acid or urates, under the influence of the colchicum, may be regarded as evidence of its influence on the capillary system in inducing the for- mation of normal products from the disintegration of effete and ex- hausted tissues during the process of secondary assimilation. 251. Occasionally some very painful cases present themselves, in which all the symptoms above enumerated are present in an almost exaggerated form, the nervous system being excessively irritable. The patient often then presents the sallow aspect, the occasionally flushed face, and the emaciation so generally indicative of organic disease, yet on the most careful examination none can be elicited. I have repeatedly seen cases of this kind which gave me great anxiety, fearing that some serious lesion had escaped attention; and yet, with the exception of the copious elimination of oxalate of lime with uri- nary extraction, no indication of disease could be elicited. The sub- sequent recovery of the patient (often indeed very tedious and protracted), has, however, proved the absence of the dreaded organic mischief. Within these few days, I saw a gentleman from York- shire, who consulted me three years ago, with all these symptoms; his emaciation increased at one time to such an extent he could hardly walk. He appeared to be almost poisoned by the oxalic acid circu- lating in his blood, and, although now quite well, the disease did not completely yield for nearly two years. 252. I have selected the following cases merely on account of their illustrating the chief varieties of ailments in which I have met with the oxalate, more than for the sake of pointing out the treatment. They may be regarded as illustrations of the set of symptoms most generally occurring in the cases in which large quantities of oxalate and oxalurate of lime appear in the system. It would be easy to fill a volume Avith accounts of cases of this kind ; but they would be quite out of place in a work of this character. I only trust that they will appear of sufficient importance to draAv attention to the subject gene- rally, and to impress the profession with the fact of the very frequent, 218 PATHOLOGY OF OXALATE OF LIME. and very generally overlooked, production of oxalic acid in the animal economy. I would beg to refer to a very excellent paper on the various symptoms associated with oxaluria by Dr. Begbie, in the "Edinburgh Monthly Journal" for August, 1849. A paper of peculiar value, not less from the care evidenced in it in the observance of facts, than in the sphere of observation being so different from that from which my own experience has been drawn. ILLUSTRATIVE CASES. Case I.—Intense hypochondriasis ; emaciation ; copious discharge of crystals of oxalate of lime, with excess of urea. On Feb. 15th, 1842,1 was consulted by Mr. W. Stone, in the case of a gentleman residing in a densely populated district in this metropolis. He was a remarkably fine man, about thirty years of age, of dark complexion, and whole expression strongly characteristic of deep melancholy; he was highly educated, and appeared to have painfully susceptible feelings. It appeared from his history that, until within the last four years his health had been excellent * at that time he contracted a sore, which was regarded as syphilitic, and so treated with, inter alia, abundance of mercury and iodine, which appeared to have aided in bringing on an extremely cachectic condi- tion. Partially recovering from this, he left England on an Eastern tour. During his wanderings he underwent treatment for what he regarded as a return of venereal symptoms, apparently only manifested by relaxation of the throat, producing a hacking cough. At the latter place he fell under the care of Dr. MacGuffog, who evidently took a very correct view of the case, and he received decided benefit from his treatment. At last, wearied and dispirited, with an irritable throat, bearing about with him what he regarded as a venereal taint, and tired with wandering, he returned to England, a prey to the most abject hypochondriasis. When I saw him, his naturally expres- sive countenance indicated despair; he complained bitterly of the inefficacy of medicine, and seemed only in doubt whether he were doomed to die of syphilis or phthisis. The pulse was quick and irritable; tongue morbidly red at the tip and edges, and covered in the centre with a creamy fur. He had lately lost much flesh • he was troubled with a constant hacking cough, which evidently depended on an enlarged uvula; for on examining the chest I could not succeed in detecting any evidence of disease. There was extreme palpitation, increased by eating and by exercise, much flatulent distension of the colon, with pain between the shoulders, across the loins, and over the region of the stomach; extreme restlessness and nervous excitement, accom- panied every action. The bowels were inclined to be constipated; urine co- pious ; appetite rather voracious, but unsatisfying * skin acted imperfectly. Feb. 15th.—The urine passed last night was acid, pale, of specific gravity 1-0295, contained much mucus, with abundance of flesh-colored urates in suspension. On warming a portion, so as to dissolve the latter, a very copi- ous crystalline deposit of oxalate of lime, in cuboid crystals, was rendered beautifully visible by the microscope. A large excess of urea was present, the addition of an equal bulk of nitric acid rendering some of the urine placed 220 PATHOLOGY OF OXALATE OF LIME. on a watch-glass nearly solid in ten minutes. The urine passed this morn- ing was precisely similar. R. Acid. Nitrici dil., Acid. Hydrochlor. dil., fui Jss; Inf. Serpentaria?, ,^xj ; Syr. Zingib., ^j. M. capt. £j, ter die. R. Ext. Aloes Pur., gr. ij ; Conf. Opii, gr. iij. M. ft. pil. o. n. s. Allowed a bland nutritious diet, with three glasses of old sherry daily: no vegetables, butter, or sugar. 27th.—Continued the treatment up to this date with very marked improve- ment; his expression was now cheerful; bowels acted freely and healthily; pain much less; skin active; throat not so troublesome.—Pcrgat. The night urine was now of lower specific gravity, being 1-020, scarcely containing an excess of urea; a slight deposit of urates was present, mixed with but a small quantity of oxalate of lime in crystals. The morning urine contained less of the oxalate. He continued this treatment patiently and persistently until March 20th, when he was so much better that he desired to take a country trip. I dis- continued his medicines, and ordered him a mild tonic aperient occasionally. May 1st.—I again saw this gentleman. He had gained strength, flesh, and spirits; he only complained of occasional headache, and a dread of a re- turn of his ailment, and was anxious to break through his restrictions of diet. The urine now contained no excess of urea, and was nearly free from oxalate of lime. An occasional aperient was ordered for him. June 4th.—He again called upon me; he was free from disease, and his most pressing evil seemed rather to arise from a lurking dread of phthisis than aught else. The urine was natural. Case II.—Intense lumbar pain following exposure to cold ; diuresis; great hypochondriasis; copious discharge of oxalate of lime following, and succeeded by uric acid gravel; excess of urea. Mr. F----, set. 53, a gentleman residing in the suburbs, came under my care, May 1st, 1842, complaining of intense pain across the loins, so severe as to interfere materially with his comfort. From his history it appeared that the general health had been good ; always had an excellent, indeed often a voracious appetite, and been " a heavy feeder," eating and drinking abun- dantly, but scarcely ever had been intoxicated. His life had been one of great activity, being daily, for several hours, out on horseback, or in his gig. Ten years ago he became the subject of severe irritative dyspepsia, lasting about six months; from this he recovered, and remained tolerably well for four years, when he suffered a relapse, attended with severe pain in the left hypochondrium, referred, by the late Mr. Vance, under whose care he then was, to flatulent distension of the colon, consequent on constipation. This pain had since been more or less constantly present, and was generally re- lieved by an escape of flatus. About five years ago he went to Cheltenham on the outside of a coach, and got chilled. He soon became the subject of severe lumbar pain, which, although frequently varying much in severity, had now left him. It was greatly increased by all indiscretions in diet, and when absent, a hearty meal would at any time bring it on ; when present, it completely crippled him. By making a powerful effort he could sometimes manage to walk; and this generally gave some amount of relief, although too ILLUSTRATIVE CASES. 221 much exercise would always bring it on. He felt no increase of pain when riding on horseback, but a short drive on a coach would bring on a paroxysm of lumbar pain. Neither headache nor sickness had been present during the whole illness. The urine was generally turbid, and occasionally passed in larger quantities than natural. This gentleman had of late become subject to .the most distressing hypochondriasis, looking at all occurrences as tinted with a coloring of melancholy or misfortune. So far as I could learn, the sexual powers had not become materially impaired. He had never had pains along the ureters, and inherited no tendency to calculus or gout. The tongue was tolerably clean, having in its centre a mere creamy layer. The bowels acted well. May 1st.—The urine passed last night was pale amber-colored; it con- tained much mucus, was acid, did not coagulate by heat; it contained in diffusion a large quantity of urates, which, on the application of heat, dis- solved, and left a copious deposit of lozenges of uric acid, mixed with coher- ing crystals of that substance in the form of crystalline gravel; its specific gravity was 1-026; it did not coagulate by heat, but contained an excess of urea; on the addition of nitric acid, it in a few seconds became filled with fine crystals of nitrate of urea. The urine passed this morning was of specific gravity 1*024, and in other respects resembled the night urine. R. Hyd. c. Creta, gr. iss; Ipecac. Pulv., gr. j. Ft. pilula o. n. s. Omit all beer and spirits, as well as fatty and indigestible articles of food. Plain diet, with animal food once daily. 8th.—Much the same; the bowels had acted with copious bilious dis- charges ; pain still intense; depression very great. The urine passed last night was of specific gravity 1030; it was acid, pale, contained abundance of urates, which, by heat, disappeared, leaving, distinctly visible under the microscope, a copious deposit df oxalate of lime in minute octohedra, mixed with an abundance of nucleated epithelium : no uric acid. On the addition of nitric acid, the urine almost immediately solidified from the copious crys- tallization of nitrate of urea. The morning urine was of specific gravity 1-027. It contained a great excess of urea, and resembled the night urine in every particular, except that the urates were tinted with pink, and the crystals of oxalate of lime were much larger, being fine octohedra. R. Acidi Nitrici, ^Kiij; Acidi Hydrochlorici, ™Kvj, ter in die ex cyatho Inf. lupuli, sumend. 9th.—The urine was sent to me; that passed last night was healthy in color; quite limpid ; sp. gr. 1027. Under the microscope it appeared full , of fine octohedra of oxalate of lime. That passed this morning resembled it in everything, save in its lower specific gravity, being 1-021. Both contained excess of urea. 16th.—Very much improved. He had been quite free from pain for several days; was in excellent spirits. He had taken more exercise, having been out rook-shooting the whole week, and been " living well." Last night's urine was of specific gravity 1*022. No visible deposit. Under the microscope a few small octohedra of oxalate of lime, mixed with •• cylinders" of uric acid, were visible. The specimen passed this morning was of sp. gr. 1017, and contained still fewer crystals of the oxalate. 222 PATHOLOGY OF OXALATE OF LIME. 23d.—Appeared completely well in health and spirits; he was now cheerful and free from pain. The urine passed this morning contained no oxalate ; had a slight deposit of uric acid in lozenges, but was still rather too high in specific gravity, being 1-024. • Oct. 2d, 1845.—This gentleman again came under my care, having en- joyed excellent health since I had last seen him. He had become the sub- ject of a "fit of gravel," ending in the passage of several very minute uric acid calculi. Aug. 8th, 1850.—I again saw this patient laboring under irregular gout, from which he quickly recovered. Case III.—Irritative dyspepsia, gastrorrhcea, great emaciation and depres- sion, voracious appetite, copious deposit of oxalate of lime in large and well-defined crystals, M. W., vet. 35, came under my care April 26th, 1842; a pallid nervous woman; had one child nineteen months ago; suckled it during nine months; previous to this had suffered from four miscarriages, losing at each a large quantity of blood ; had no leucorrhoea. Previous to her first pregnancy her health had been excellent. During the last year she had been rapidly losing flesh, and her energies were almost prostrate, the spirits being intensely de- pressed. She had, for a long period, suffered from pain at the scrobiculus cordis and gastrorrhcea. For several months her most serious evil had been a fixed persistent pain across the loins; became much more intense by exer- tion. No evidence of uterine disease; bowels constipated; appetite craving, and distressing, never being satisfied; thirst great; flatus considerable. 26th.—Shortly after each meal a gush of limpid fluid "rose from the sto- mach, which, in about an hour after, was followed by the vomiting of the meal in a semi-digested state, mixed with a considerable quantity of black grumous matter; bowels confined. Pil. Col. c. Hyd., 9ss, o. n. s. 30th.—Bowels freely open; vomiting considerable and distressing, accom- panied with great pain at the epigastrium. Pil. Cal. c. Opii, j; ante prandium quotidie; M.M. c. M.S., ^ss, c. Acid. Hy- drocyan. dil., Trjjv, t. d. May 5th.—Bowels freely open ; vomiting not so frequent; complained of severe pain, referred to the right side of the chest. Rep. Mist. R. Bismuth. Trisnitratis, Conii fob, Sodas Carbon, sic, aa, g. iv, t. d. 10th.—Was suddenly seized last night with fainting, and severe pain in epigastrium. This was relieved by a little brandy and water. After a short time sleep came on, and she awoke somewhat relieved. The emaciation had rapidly increased during the fortnight. I now requested her to send me a specimen of the urine passed in the evening. It was pale, of sp. gr. 1-030, acid, and turbid from the presence of flesh-colored urates. On exposing a portion to heat, the latter dissolved, and a white opaque deposit was left; this, under the jnicroscope, was found to consist of oval epithelial scales, mixed with very fine and large octohedra of oxalate of lime. ILLUSTRATIVE CASES. 223 Perstet in usu pulverum ; Ammonia? Sesquicarbonatis, gr. iv; ex Inf. Ser- pent., :|j; et Sp. Eth. Sulph. co., *5ss, ter in die. 11th.—Passed a good night; no pain either in back or epigastrium; much headache; bowels thrice open from a dose of rhubarb she had taken this morning; motions offensive; no sickness since yesterday; felt comfortable, but weak; urine clear; oxalate of lime not so abundant. Mis. Effervescens c. Syr. Papav., "5j, 4tis horis. 12th.—Vomited yesterday after dinner; passed a good night; complained this morning of pain all over the abdomen, and between the scapulae; bowels acting freely. Pergat. Fotus Papaveris abdomini. 16th.—Decidedly improving; could now bear on the stomach a light meal of animal food; complained bitterly of pain across the abdomen, compared to a cord tightly drawn round it. R. Sp. Ammon. Arom., '"J'xx; Inf. Serpent., §j; Syr. Papav., *5j. M. ter in die. 21st.—Improving; was gaining flesh and spirits; complained of gastro- dynia daily after dinner. Pergat. Pil. Cal. c. Opii, j, bis die. 27th.—Had gained strength enough to walk from Hoxton, where she resided, to my house; was very much better, but still had great lumbar pain. The urine was still of rather too high a density, contained an excess of urea, and tolerably copious deposit of crystals of oxalate of lime. R. Inf. Serpent., §j ; Acid. Nitrici dil., Acid. Hydrochlor. dil., aa ™j"v. M: ter die. Allowed to take some porter. 29th.—Much improved; urine copious, pale, sp. gr. 1-009. June 7th.—Convalescing; urine 1019, free from oxalate. 13th.—Had suffered a slight relapse, attended with returns of lumbar pain, following her taking a glass of hard porter. This lasted but a few hours; and she intended leaving town to recruit her strength in the country. Case IV.—Emaciation; extreme melancholy, following great mental dis- tress; severe lumbar pain; great excess of urea, and discharge of oxalate of lime ; remarkable gelatinization of the urine by heat. C. O, set. 39, a tall, thin woman, of fair complexion, presenting the appearance of great emaciation, came under my care on May 3d, 1842. She had been a widow four years; had had two husbands, and lost both by phthisis; this, with her depressed circumstances, had caused her to expe- rience great mental and bodily distress. She had had eight children, of which she had lost six. Menstruation still regular, but, to use her own expression, almost djowned in leucorrhoea; bowels habitually constipated. She stated that she had for two years been gradually losing flesh; but lately this had so increased as to amount to rapid emaciation. Her depression and 224 PATHOLOGY OF OXALATE OF LIME. melancholy were intense, probably, however, partly arising from her being dependent on dress-making as the only means of support. For some months past she had been the subject of almost constant "wearing" pain across the loins, increasing by exercise, and so severe at night as to prevent her lying in the recumbent position. The pain was always increased by exercise. Her nights were usually sleepless; and if she did get a little rest, she started from it with the most frightful dreams. She had frequent palpitations, and pain about the epigastrium after taking food; no great amount of flatulence; tongue red at the tip and edges, white fur in the centre. Pil. Col. c. Hyd., ii, o. n. s.; Emp. Belladonna? regioni cordis. May 6th.—The urine passed last night was of sp. gr. 1-027, acid, and turbid from holding urates in diffusion. On decanting the clear portion, and gently heating the opaque part, the urates dissolved, and left a copious deposit of microscopic octohedra of oxalate of lime, and numerous scales of nucleated epithelium. No change was produced in this urine by heat. The specimen passed this morning was of sp. gr. 1-011, very pale and limpid. It became opaque on the application of heat; the troubling not being re- moved by nitric acid. It scarcely contained a trace of oxalate of lime. I ordered all medicines to be omitted, for the purpose of watching the state of the urine for a few days. 8th.—Bowels for three days had been confined. She complained of a sense of distension in the abdomen, and had for two days been confined to bed with intense headache, giddiness, and feverish excitement. Morning urine clear, 1-028, acid ; no oxalate. Night urine contained a mucous cloud, 1-022, abundance of oxalate of lime in octohedral crystals. Pil. Col. c. Hyd., ij, 6tishoris ad catharsin. 9th.—Last night's urine turbid from the presence of urates; felt very weak. Mist. Gent. Co., §j ; c. SprvAmnion. Arom., '"J'xx, ter in die. 13th.—Much the same; constipation continued. Pulv. Jalapse Co., jj, o. n. s. 15th.—No change for the better; bowels had acted well; she still felt wretchedly ill and depressed. The urine passed last night was of a density of 1-028, acid, pale, and con- tained in suspension the fawn-colored urates. On warming a portion, the urates dissolved, and the clear fluid soon let fall a white deposit, which, on decanting the still warm liquor, and examination under the microscope, was found to consist of various sized octohedra of oxalate of lime, mixed with myriads of oval nucleated epithelial scales. During the application of heat, the urine underwent a remarkable change. It did not become opaque, or coagulate, but assumed a gelatinous consistence, retaining its transparency. It then required violent agitation to diffuse it through water. This effect, at the time new to me, I have since repeatedly observed, and it seems to chiefly arise from the urates combining; with the water, thus forming a gelatinous hydrate. The morning urine was of sp. gr. 1030, contained an abundance of epithe- ILLUSTRATIVE CASES. 225 Hum, but no oxalate. Both specimens were loaded with urea, and were con- verted into nearly semi-solid crystalline masses on the addition of nitric acid. Rep. medicamenta. 17th.—Improving; bowels acted well, and leucorrhoea decreasing; gene- ral health better; the symptoms of uterine irritation had decreased with the leucorrhoea, but the want of strength, emaciation, depression, and severe lumbar pain, continued; the oxalate of lime still abundant in the night urine. Acid. Nitric. Dil. 1?t*xv; ex Dec. Cinch., 3j, bis die. Ordered nutritious diet, avoiding vegetables and beer, weak gin-and-water at dinner. June 1st.—Had been, during the last week, completely free from lumbar pain ; this morning, apparently owing to an indiscretion in diet last even- ing, had a slight return. The urine passed last night just before going to bed was pale, of specific gravity, 1*015, contained abundance of epithelial scales, and no visible oxalate. Rep. omnia. 5th.—The return of lumbar pain had been quite evanescent; she was now quite free; complained of debility and occasional headache; still suf- fered from constipation; skin acted well; occasional feverish flushes, espe- cially in the evening. The urine passed last night had increased in specific gravity to 1029; it was loaded with pale urates; contained no oxalate of lime, and, by heat, underwent the remarkable gelatinization before referred to. Rep. Mistura—Sumat. Pil. Col. c. Hyd., ^ss, p. r. n. 12th.—By taking the pills on alternate nights, a tolerably healthy action of the bowels had been kept up; she was much improved; the flushes were less frequent; no return of lumbar pain; merely complained now of not feel- ing quite strong. Inf. Serpentariae, gj, t. d. Allowed a little porter. 13th.—The urine passed last night was of a density of 1028, healthy in color, contained no visible deposit, save a mucous cloud. The microscope, however, detected a considerable deposit of octohedral crystals of oxalate of lime, with an immense quantity of oval nucleated epithelial scales. Ordered to omit the porter. 26th.—Felt quite well. The oxalate had again disappeared. Case V.—Rapid emaciation and depression; nervous palpitations ; lumbar pain; excess of urea, and discharge of oxalate of lime. J. B., set. 31, came under my care June 3d, 1842. A tall and remarkably fine man, extremely emaciated, his cheeks hollow, and his whole appearance resembling that of a diabetic patient. He was a currier, and was exposed to extreme alternations of temperature, working in a half-bent position, without a coat or waistcoat, in a shop through which were constant currents of air. He was unmarried, and had been very irregular with regard 15 226 PATHOLOGY OF OXALATE OF LIME. to women; for two years he had been gradually losing flesh, strength, and spirits; his sexual powers had also rapidly declined, and now scarcely existed; he had frequent seminal emissions in his sleep, which left him weak, ex- hausted, and melancholy, during the ensuing day. Regarding his previous habits, he considered he had been temperate, rarely getting intoxicated more than twice a week, and then on porter or ale. During two months his decline had been rapid,—afaci/is descensus. He had now an almost constant headache, a constant aching pain across the loins, a sense of sinking at the stomach, as if, to use his own expression, he had no inside, frequent chills, with cold clammy sweats, succeeded by feverish flushes; tongue red at the tip and edges, with a white central fur; frequent giddiness; his memory had been for some time failing. His nights were wretchedly restless, gene- rally tossing all night from side to side, in vain endeavoring to sleep, and if he slumbered, he awoke as fatigued as when he retired to rest; appetite bad; no thirst; frequent palpitation and flatulence; pulse small and irritable; no chest disease. Sumat. Pulv. Rhsei Salin., gj, eras mane; 5th.—Bowels acted once yesterday from the powder; hands tremulous. The urine passed last night was deep amber-color, acid, of a density of 1030, no visible deposit; by microscopic examination, however, myriads of splendid octohedral crystals of oxalate of lime became visible. On the addition of nitric acid to the urine, a copious formation of crystals of nitrate of urea occurred. The urine passed this morning was paler, acid, of a density of 1-025, and contained less oxalate and urea. Pil. Col. c. Hyd., ij, o. n. s.; Acid. Nitric, dilut., **5!xv, ter die, ex. Dec. Cinchonas, ^j. Nutritious diet, light pudding daily, no beer, weak brandy-and-water at dinner. 15th.—Bowels acted thrice daily; motions offensive and dark-colored; complained greatly of palpitation of the heaigt. Rep. Mist. c. Inf. Serpentariae, vice Dec. Cinchona?. The urine passed last night was deep amber-colored, of specific gravity 1-028 : the microscope detected myriads of smaller octohedra than before. The morning urine was of a density of 1-018. 28th.—Very much improved; rested better at night; no lumbar pain; great sense of sinking at the scrobiculus cordis. Night urine, 1026, de- posited phosphates by heat, and contained numerous minute crystals of oxa- late of lime. Morning urine, 1*026, like the night specimen, but did not be- come opaque by heat. M. Ferri Co., gj; c. Tr. Lytta?, *Kx, b. d. July 2d.—Improving; seminal emissions ceased. Still copious octohedra in the night urine, which was of the density of 1025. Sumat. Vin. Colch., ^x, ex. Mist. Gent. Co., §j, b. d. 10th.—So much better that he was anxious to leave London on a long journey; the urine was now free from oxalate. ILLUSTRATIVE CASES. 227 Case VI.—Discharge of oxalurate {?) of lime, apparently succeeding to mechanical injury. B. M----, get. 48, came under my care May 25, 1842 : a pallid-looking man, with a face, although not remarkably attenuated, presenting a gaunt, hollow aspect, with a slight hectic flush over each cheek bone; engaged up to the age of 32 as a ship's carpenter, in vessels chiefly in the Mediterranean, and once in a priA'ateer on the American coast; during this time his life was one of great intemperance, drinking rum abundantly. Since he had left the navy he had worked as a cabinet-maker. In 1851, whilst lifting a heavy weight he experienced a "wrench" across the loins, the effects of which in- jury, although apparently not severe at the time, had eA-er since, more or less, annoyed him ; although his general health, up to the last year, had been tolerably perfect. His chief ailment now consisted in a gradual, but persistent loss of strength and health during the last twelve months, during which period he had lived more regularly than previously. He was very low-spirited ; his memory had of late become defective ; perspired freely on the slightest exertion; had frequent nausea at the sight of food; appetite bad ; no pain in the stomach after the meals; no acid or bitter eructations; great and frequent flatulent distension. His nights were wretched and restless. During the last year, a fixed and constant pain across the loins had distressed him; this he could succeed in walking off for a time, but fatigue would eventually increase it; the bowels had, of late, been relaxed, acting three or four times a day, the motions being dark and fluid; his sexual appetite and powers had of late rapidly declined; frequent involuntary seminal emissions appeared at night; the tongue was clean, vividly red, and polished at the tip and edges; pulse full and hard, but jerking. The urine passed on the night of May 25th was clear, amber-colored, acid, of specific gravity 1-017, and contained no visible deposit; a drop of the lower stratum of the urine, after repose, was full of dumb-bell crystals, which were hard and somewhat gritty, unaltered by boil- ing acetic acid, but readily soluble in nitric and hydrochloric acids. The specimen passed in the morning resembled the last; was of the density of 1-012; it let fall a slightly cloudy deposit by repose, which, under the microscope, was found to be made up of myriads of minute cuboid crystals of oxalate, mixed with a very few dumb-bells. R. Acidi Hydrochlorici, ^iij ; Acidi Nitrici, *5j ; Mist. Camphorae, giiiss ; M. capl. cochl. j, min. ; ex. Inf. Anthemidis, 3iss, ter die ; Sumat. Pil. Hydr. Chlor. Co., gr. v. o. n. He was ordered to wear a flannel bandage round the loins, to keep to a bland nutritious diet, omitting all fermented liquors. 27th.—Night urine clear, amber-colored, no visible deposit, 1016, very acid, no opacity by heat; some white pearly granules became visible by re- pose, which consisted of cohering dumb-bell crystals. Morning specimen pale, contained mucous clouds, with some flakes of uric acid mixed with cohering dumb-bells. June 2d.—Notwithstanding the warm weather, he had not perspired so much as usual; bowels acted once daily; motions dark and tolerably healthy; urine in less quantity; that passed at night, 1019, pale, and had a copious deposit of " cylinders" of uric acid, mixed with lozenges and rosettes, nearly free from oxalate of lime. The morning specimen was 1-018 in density, and 228 PATHOLOGY OF OXALATE OF LIME. perfectly resembled that passed at night. He got better nights' rest; lumbar pain still severe, but altogether felt stronger. 9th.—Tongue not so vividly red; gums slightly affected. Has been drink- ing cider, which not appearing to disagree, I have permitted him to continue. The night urine is of density 1-024, and contained a curious deposit of uric acid. Rep. Mist; omitte pil. 23d.—Improving manifestly in general health; no sickness; bowels acted well. Night urine 1-018; morning 1-015; no visible deposit; felt only weak and nervous. Zinci Sulph., gr. ss., c. Conf. Opii gr. iij, forma pilul., ter die. 30th.—Convalescing; had now only a pain in the back, chiefly confined to the spine, from the first lumbar vertebra to the sacrum; this was not constant, but came on after fatigue in the evening; still complained of frequent in- voluntary seminal emissions at night. He was ordered to continue his zinc, and to have cold water copiously applied in a stream from a kettle over the genitals and loins twice a week. Case VII.— Copious secretion ofoxalate oflime ; over-lactation ; probable existence of calculus in the right kidney. M. R., aet. 37, came under my care, December 14, 1843; a pallid, thin woman, the mother of two children; had been for years ailing from vague pains connected with irritable uterus. Eighteen years ago, whilst in service, she received a violent blow in the right hypochondrium, and had never since been free from more or less persistent pain in that region, extending to the right kidney. From the period when she received the blow, she had, at each return of the catamenia, been jaundiced, and was generally relieved by spon- taneous bilious vomiting. Every two or three months she suffered severe paroxysms of pain in the region of the right kidney, lasting three or four days, and relieved by a copious discharge of very turbid urine, attended with great irritability of the stomach, no haematuria. After one of these attacks she brought me the urine. Night urine—pale, acid, specific gravity 1*025, with a copious deposit of urates, which vanished on the application of heat, and left undissolved an immense number of the largest dumb-bell crystals I ever saw. Morning urine—clear; by heat a scanty deposit of phosphates fell; much epithelial debris; no oxalate. Ordered her a generous diet, and to wean her infant, who was thirteen months old; no medicine. December 18th.—Had suffered much from sickness; pains over the right kidney less defined; bowels acted well; felt extremely weak and depressed; probably owing to over-lactation. R. Acidi Nitrici, *5j. , ----Hydrochlorici, Jiss. Irif. Gentianae co., ^iss. M. Ft. gutta?. Capt. coch., j, parv. ter die ex aquae cyatho. She continued this treatment persistently until February 20th; the oxalate of lime gradually disappeared, and she appeared tolerably well. I again saw this patient in June; she had still frequent returns of renal suffering, with occasional discharge of oxalate of lime; her general health remained good. There was but little doubt of the existence of a calculus of oxalate of lime in the right kidney. CHAPTER X. CHEMICAL PATHOLOGY OF THE EARTHY SALTS. {Phosphuria.) (Phosphate of Lime, Ammonio-phosphate of Magnesia, and Carbonate of Lime.) Phosphatic Salts in Urine, 253—Earthy and Alkaline Phosphates, 254—Diagnosis of, 255—Chemical Constitution of, 257—Phosphate of Lime, 258—Appearance of Deposits, 259—Deposition of Phosphates by Heat, 261—Appearances of Phos- phatic Urine, 263—Microscopic Character of Deposits, 264—Pathological Indi- cations of Phosphates generally, 265—Of Triple Salt, 266—Occurrence of, with- out Organic Disease, 268—In Extreme Old Age, 269—Deposition of Phosphates during Convalescence from Acute Disease, 270—During Fever, 271—During Insanity, 272—Mixed Phosphates, 273—-With Alkaline Urine, 274—State of Urine in Paraplegia, 275—Mr. Curling's Explanation, 276—Dr. Snow's, 277— Occurrence of Phosphates in Diseased Bladder, 279—Formation of Calculi, 281 —General Indications of Phosphatic Deposits, 282—Secretion of Phosphates of Lime by Mucous Surfaces, 284—Therapeutic Indications of Phosphates, 285— When Complicated with Acute Dyspepsia, 286—With Irritable Stomach and Emaciation, 288—With Oxaluria, 289—With Marasmus, 290—Uncertain Action of Acids, 292—Case Ending in Calculus, 294—With Diseased Mucous Mem- brane of Bladder, 295—Deposit of Carbonate of Lime, 298—In the Horse, 299— Of Silicic Acid, 300. 253. We have already seen that a considerable quantity of phos- phoric acid is excreted from the blood by the kidneys in the course of twenty-four hours, divided between four bases, soda, ammonia, lime, and magnesia, forming, in all probability, the three following salts, whose composition has been already pointed out: Ammonio-phosphate of soda. Phosphate of magnesia. Phosphate of lime.* * To these salts must be added the neutral acid phosphates of soda, the pre- sence of which is asserted by Robin and Verdeil, and confirmed by Dr. Hassall. Lehmann states, on the subject of the presence of ammoniacal salts in the urine, 230 PATHOLOGY OF EARTHY SALTS. The first of these is readily soluble in Avater, and on the hypothesis I have ventured to suggest (81), is of importance as the solvent of uric acid, and probably is indirectly the source of the acidity of urine. The other two salts are nearly totally insoluble, although the presence of a very minute portion of almost any acid, even the carbonic, ena- bles water to dissolve a considerable quantity. They are besides soluble, to a' certain extent, in hydrochlorate of ammonia, and possi- bly may sometimes exist in the urine thus dissolved. In healthy urine, the earthy phosphates are held in solution by the acid of the superphosphates, produced by the action of uric (or hippuric) acid on the tribasic alkaline salts (79); and these are also, according to Enderlin,69 capable of dissolving a certain quantity of phosphate of lime. The physiological source of the phosphates has been already pointed out. 254. It has been already stated that the earthy phosphates are always abundant after a meal, and that the reverse applies to the alkaline salts (109). Phosphoric acid, it must be recollected, may be excreted in large excess Avithout forming a deposit, in consequence of its being combined with an alkaline base, and hence when the secre- tion of an excess of phosphoric acid is to be looked for, it can by no means be indicated by the amount of earthy salts deposited. There is always three or four times more phosphoric acid in a given speci- men of urine in the form of a soluble alkaline salt, than is precipitated as an insoluble earthy compound. Indeed, the presence of an excess of lime and magnesia has more to do with determining a deposition of insoluble phosphate than an excess of phosphoric acid. Still, a large amount of valuable information can be obtained by observa- tions founded on the deposits of earthy phosphates, and as in very many cases the circumstances under which these salts are deposited often constitute the elements of various diseases, the quantity of phosphatic deposits becomes of very great importance. Diagnosis of the Earthy Phosphates. 255. Deposits of these salts are always white, unless colored with blood; soluble in dilute hydrochloric acid, and insoluble in ammonia thatr the hydrochlorate of ammonia, phosphate of soda and ammonia, and phosphate of magnesia and ammonia, do not occur in fresh urine. The experiments upon which this opinion is founded I have previously given. DIAGNOSIS. 231 or liquor potassae. On heating the urine, the deposit undergoes no further change, except agglomerating into little masses. Mucus, pus, and blood, are often present in the urine, and mask the chemical characters of the deposit. 256. If a very small quantity of a solution of sesquicarbonate of ammonia be added to a large quantity of healthy urine, the mixture becomes turbid from a deposit of the triple phosphate, mixed with some phosphate of lime. On placing a drop of this turbid urine under the microscope, myriads of minute prisms of the triple salt (264), mixed with amorphous granules of the phosphate of lime, will be seen floating in the fluid; these readily disappear on the addition of a drop of almost any acid. As these earthy salts are insoluble in water, it is evident tha,t they must be held in solution in the urine by the free acid Avhich generally exists. If from any cause the quan- tity of solvent acid falls beloAV the necessary proportion, the earthy phosphates appear diffused through the urine, disturbing its transpa- rency and subside, forming a deposit. Hence, Avhenever the urine is alkaline, phosphatic deposits are necessary consequences. If urine be secreted Avith so small a proportion of acid as barely to redden litmus paper, a deposit of triple phosphate often occurs Avithin a few hours after emission; a phenomenon probably depending partly on the influence of the mucous matter present, which, readily undergoing change, acts like a ferment, induces decomposition of urea, and the formation of carbonate of ammonia (274), which, by neutralizing the solvent acid, throAvs down the phosphates. The precipitation of the phosphates thus takes place in a manner analogous to that in which carbonate of lime is thrown down, the action being, hoAvever, here limited to a neutralization of the free acid ; indeed, Avhere phosphate of lime forms the great bulk of a deposit, a certain portion of carbo- nate is generally present. The triple phosphate which is precipitated artificially from urine by means of a very small quantity of sesquicarbonate of ammonia, and Avhich occurs spontaneously in prismatic crystals (264 A), is a neutral salt, and may coexist as a deposit with a very sensible acidity of the supernatant urine. It by no means follows that the existence of a deposit of this salt involves the necessarily alkaline state of the urine. 257. There is, however, another triple phosphate produced artifi- cially by the addition of an excess of ammonia to urine, and which is of frequent occurrence in the fluid when in an alkaline or putres- 232 PATHOLOGY OF EARTHY SALTS. cent condition. This differs from the former salt in containing an excess of base, and cannot possibly be present in urine which exerts the slightest acid reaction on litmus paper. The crystals are quite characteristic, being invariably stellar or foliaceous (264 D). This salt is termed the basic phosphate, but the chemical distinctions be- tween this and the prismatic salt are very unsatisfactory. I am aAvare of but one chemist who has given formulae for the two salts, but in a manner so opposed to the known habitudes of phosphoric acid as to authorize their rejection. The composition of the ammonio-phosphate of magnesia previously given (106) applies to stellar salt. The pro- bable constitution of the two salts is^- In the neutral or prismatic salt (dry) = (HO,NH40,MgO)+P205. In the basic or stellar salt (dry) = (NH40^Mg0)+P205. 258. The phosphate of lime, which is often precipitated Avith the neutral, and always with the basic triple salt, is not quite so readily soluble in very dilute acids as the two latter, and hence, when a mixed deposit of the calcareous and magnesian phosphates exist, the phos- phate of lime is but sloAvly acted upon when digested in very dilute acetic acid, which readily dissolves the magnesian salt. When the triple or calcareous phosphates are separately exposed to the heat of a blowpipe flame, they fuse with great difficulty, and not until the heat has been urged to the utmost. If, however, the phosphate of lime is mixed with a triple phosphate in about equal proportions, they readily melt into a Avhite enamel. These mixed salts constitute what is hence termed the fusible calculus, and they can be readily detected by this property in concretions ; a character very available in the examination of gravel and calculi, as the two phosphates gene- rally occur together. 259. The physical appearance presented by deposits of the earthy phosphates varies extremely ; sometimes, especially Avhen. the triple salt forms the chief portion of the deposit, it falls to the bottom of the vessel as a white crystalline gravel. If but a small quantity of this substance be present, it may readily escape detection by remain- ing for a long time diffused through the urine; after a few hours' repose some of the crystals collect on the surface, forming an irides- cent pellicle, reflecting colored bands, like a soap-bubble, or a thin layer of oil. If, then, the lower layers of the urine be placed in a watch-glass, and held obliquely over the flame of a candle or any APPEARANCE OF THE URINE. 233 strong light, a series of glittering points will become visible from the reflection of light from the facets of the minute prisms of the salt. The phosphates will often subside towards the bottom of the con- taining vessel like a dense cloud of mucus, for which they are fre- quently mistaken. Not unfrequently they will, in very alkaline urine, form dense masses in the urine, hanging in ropes like the thickest puriform mucus, from which it is utterly impossible to distinguish them by the naked eye. Their disappearance on the addition of hydrochloric acid will at once detect their true nature. Where, as frequently occurs, a large quantity of ropy mucus, pus, or blood, coexists with the phosphates, no mode of investigation can be so satis- factory as the examination of a few drops of the urine between two plates of glass, by the microscope, when the characteristic crystals of the phosphates are readily recognized (264). 260. The phosphates are occasionally found mixed in a deposit with urates; in this case the latter is always of a pale variety, and nearly white. It has, indeed, been stated that when urine deposits pale urates, it indicates a tendency to the deposition of the phos- phates. This remark is so far true, that as phosphatic urine is usu- ally very pale, it would follow, as a necessary consequence, that any urate deposited from it would be nearly white, from the absence of coloring matter to tint it of any other hue. Beyond the fact, then, that white urates are deposited by pale urine, and that phosphatic urine is often scarcely colored, I am not aware of any 'circumstance authorizing the belief of any necessary connection between them. State of Urine depositing Earthy Phosphates. 261. It is, as we have seen, by no means necessary for urine to be alkaline for a deposit of phosphates to exist (256); indeed, in the majority of cases, urine which deposits the triple phosphate is acid at the time of emission. This may appear rather paradoxical, when we recollect the ready solubility of triple phosphate in a very weak acid; but admits of a ready explanation, when the fact that a fluid may redden litmus, and still contain no uncombined acid, is borne in mind. Thus, some neutral salts redden litmus paper, and yet contain no free acid. And this fact may in some cases explain the occasional acid reaction of urine, where deposits of phosphates exist. It has been rendered very probable, by the interesting experiments of my 234 PATHOLOGY OF EARTHY SALTS. colleague, Dr. Rees,48 that hydrochlorate of ammonia* may in some instances be really the solvent of the earthy phosphates Avhen in excess, as they are to a certain extent soluble in solutions of this salt. These solutions possess the very remarkable property of be- coming opaque by ebullition, from a deposition of a portion of the earthy salt. The very same phenomenon often occurs in urine Avhich contains an excess of phosphates. Indeed, it is not unfrequent to meet with urine which does not contain any visible deposit, and yet on the application of heat appears to coagulate, not from the presence of albumen, but from the deposition of earthy phosphates. The ad- dition of a drop of nitric acid immediately dissolves this deposit, and distinguishes it from albumen (315). A different explanation to this phenomenon has been offered by Dr. Hargrave Brett,117 and undoubt- edly is perfectly true in some cases. Dr. Brett's explanation is founded on the solubility of phosphates in water impregnated with carbonic acid. It has been long known that carbonic acid frequently exists in a free state in the urine, and in a large number of specimens examined by Dr. Brett and myself we succeeded in readily isolating it. These experiments were made several years ago, in consequence of our having noticed some curious phenomena presented by the urine of a student at Guy's Hospital (since dead), a pupil of the late Mr. Bryant, of Kennington. This gentleman, in endeavoring to raise a heavy sack of Epsom salts, strained his back, and soon after fell into a state of marasmus, with occasional hectic, which ultimately ex- hausted him. During the last six months of his life he passed a very large quantity of pale acid urine, which, by keeping, soon became alkaline. This urine was limpid when first passed, but became opaque as soon as it had cooled, still, however, retaining its acidity, so that the deposition of the phosphates did not necessarily depend upon the development of an alkali. On warming the fresh urine an evolution of carbonic acid gas took place, accompanied by a deposi- tion of phosphates. When two portions of the fresh urine were placed, - as soon as passed, in separate bottles, one being left open, the other closely corked, the urine contained in the latter remained transparent, and that in the former became opaque. 262. Another explanation of the precipitation of the earthy salts by heat has been proposed by Dr. B. Jones.139 He has shown, that if to any urine rich in phosphates, as that passed shortly after a full * The presence of this salt in fresh urine, as previously stated, is doubted by Lehmann. APPEARANCE OF THE URINE. 235 meal, a minute portion of an alkali, or of common phosphate of soda (tribasic) be added so as to neutralize any great excess of acid, the subsequent application of heat produces a precipitation of the earthy salts. If, therefore, a more than average proportion of the latter exists in a barely acid urine, their precipitation by heat would appear to be a necessary consequence. 263. The urine, in cases where an excess of phosphates of either kind exists, varies very materially in its physical character. Certainly no general rule can be assigned for the color, density, or quantity of the urine secreted in these cases, taking.them in a mass; although I think there* are certain facts connected with the presence of the phosphatic deposits Avhich serve to connect the color and quantity of the urine with the pathological conditions producing, or at least co- existing with them. As a general rule, where phosphatic deposits, whether magnesian, calcareous, or both, exist for a considerable time, the urine is pale, often whey-like, generally secreted in very large quantities, and of low specific gravity (1-005—1-014). This is especially the case where organic lesion of the kidneys exists. On the other hand, when the de- posits are of occasional occurrence, often disappearing and recurring in the course of a few days, the urine generally presents a deep- amber-color, and is not only of high specific gravity (1-020—1-030), but often contains an excess of urea, and presents an iridescent pel- licle on its surface by repose. This is especially the character of the phosphatic urine secreted under the influence of some forms of irrita- tive dyspepsia, and where the phosphates themselves may be traced to mal-assimilation. A considerable quantity of prisms of triple phosphate are often found in the urine entangled in the meshes of a mucous cloud. This frequently occurs in the urine passed after an indigestible meal, especially after eating a large quantity of bread, and will often be observed for a day or two and then disappear. Again, phosphatic urine may be met with, varying from a pale whey-like hue to deep brown or greenish-brown, exceedingly fetid, generally but not constantly alkaline, and loaded with dense ropy mucus, often tinged with blood, and in which large crystals of the triple phosphate and amorphous masses of phosphate of lime are entangled. This variety is almost always met Avith, either under the irritation of a calculus, or even of a catheter worn in the bladder (277), or where actual disease of its mucous lining exists. 236 PATHOLOGY OF EARTHY SALTS. Microscopic Characters of Earthy Phosphates. 264. A. Prisms of Neutral Triple Phosphates.—These are always exceedingly well defined, the angles and edges of the crystals being remarkably sharp and perfect (Fig. 51). The triangular prism is the form most frequently met with, but it presents every variety in its terminations. These are sometimes merely truncated, often bevelled off, and not unfrequently the terminal edges are replaced by facets. I scarcely know a more beautiful microscopic object than is afforded by a well-marked deposit of this salt. The different degrees of trans- parency presented by these crystals are very remarkable; generally they are so transparent as to resemble prisms of glass or crystal; sometimes presenting an enamel-like opacity, so that they can only be viewed as opaque objects. This change may be artificially effected by exposing the transparent prisms to a boiling heat. When pre- served in balsam, they depolarize light, exhibiting a beautiful series of tints, when the axes of the tourmalines or calc-spars are crossed in the polarizing microscope. B. Simple Stellas of the Neutral Salt.—These are in fact minute calculous concretions, and are generally composed of acicular prisms Fig. 51. Fig. 52. cohering at one end, so as to represent simple stellae (Fig. 52). Not unfrequently they adhere so closely and are so crowded as to resemble rosettes. I have repeatedly seen small prisms crystallized*like uric acid on one of the fine transparent hair-like bodies which are of fre- quent occurrence in urine (fibrinous casts of tubules). The crystals of the phosphatic magnesian salts are invariably colorless, never presenting the yellow or orange hue of uric acid. MICROSCOPIC CHARACTERS. 237 C. Penniform Crystals of Neutral Salt*—This very elegant variety of the neutral magnesian phosphate has occasionally fallen under my notice, and has occurred in a very few cases. It presents the appearance of striated feather-like crystals, two being generally connected so as to cause them to resemble a pair of wings (Fig. 53). I cannot give any satisfactory explanation of the cause of this curious and elegant variety, nor whether these crystals differ in any way chemically from the prismatic form. The few specimens I have met with occurred in acid urine. D. Stellar and Foliaceous Crystals of Basic Salt.—This variety, as I have already stated, cannot generally be regarded in any other light than as a secondary formation taking place out of the body. Fig. 53. Fig. 54. When rapidly formed, this salt generally appears in the form of six- rayed stars, each ray being serrated, or irregularly crenate, often runcinate, like the leaf of the taraxacum (Fig. 54). This, however, presents several subordinate varieties, depending in all probability, upon accidental circumstances. When this salt is more slowly formed, as on the surface of the urine in pregnancy, it presents large and broad foliaceous laminae, often so thin and transparent as to escape notice altogether, especially if viewed in too strong a light. I have, indeed often overlooked them until I illuminated the specimen under the microscope with polarized light, when they start into view elegantly tinted Avith colors, in which pink and green are the most prominent. E. Phosphate of Lime.—I have never seen this salt in a crystal- line form, but it has been said to occur in irregularly crystallized masses.67 In all the specimens I have examined, no appearance of * Dr. Hassall states, in the April number of the "Lancet," for 1853, that the penniform crystals are composed of phosphate of lime, and do not occur in fresh urine. 238 PATHOLOGY OF EARTHY SALTS. structure could be detected; the phosphate either resembling an amorphous powder, or collected in roundish particles often adhering to prisms of triple phosphate. The sediments of this substance are remarkably opaque, so that when even a minute portion is examined between plates of glass, the layer, however thin, and Avhite by reflected, ahvays appears yellow or brownish by transmitted light. Robin and Verdeil, in the twenty-ninth chapter of the second volume of their valuable work, state that the neutral phosphate of soda (2NaO,HO,Ph05,26HO) is met with, without exception, in all the solids and fluids of the system, and that human urine contains both the neutral and acid phosphate of soda. Having remarked that the chemical study of the phosphates had not attained the same degree of precision as the study of other inorganic substances, and that the mode of proving their presence from their ash was subject to doubt, give directions for crystallizing the phosphates, for which purpose the non-crystallizable substances must be eliminated. When once the phosphatic crystals have been obtained, it is easy, from their size, to study their form and determine their chemical relation. "When we decant the fluid from highly concentrated urine to sepa- rate the saline deposit, and add to it absolute alcohol, crystals of the neutral phosphate of soda are slowly deposited upon the sides of the vessel. These are tables derived from the rectangular, or right rhom- boidal prism, with truncation of their edges. Sometimes these tables are irregular, and variously striated upon their surfaces. They polar- Fig. 55. Fig. 56. ize light, and the last forms, especially, give colors the most remark- able for their tint and intensity. It is easy, with a little practice, to MICROSCOPIC CHARACTERS. 239 distinguish these from all other urinary crystals, and, above all from the acid phosphate." In the following chapter they treat of the acid phosphate of soda (NaO,12HO,Ph05,2HO) which, as yet, has only been found in the urine. The modes of transformation of the three phosphates are noticed, and the probability that the acidity, alkalinity, or neutrality of urine may be due to the presence of one of them. They give the following directions for its preparation. Acid Phosphate of Soda.—" Extraction. This salt may be ob- tained crystallized in the urine by following the same method as indi- cated in the treatment of the neutral phosphate of soda. Three or four days after the crystallization of this latter salt, there are depo- sited crystals which are much more soluble in Avater; and their depo- sition may be hastened by adding either to the liquor already treated with absolute alcohol. These crystals, from the mode of truncation of their angles, or the sides of the base, appear to be derived from the rectangular, or right rhomboidal prism. The truncation usually makes almost the whole of the base. The forms of these crystals vary but little: they are either prisms or tables. They are very trans- parent, and their faces can only be well discovered as they turn upon themselves under the microscope. They generally adhere to the side of the vessel, and are rarely well formed. They are flattened and incompletely formed on the side adhering to the vessel." (Robin and Verdeil, ii, 340.)* * The accompanying plate (Fig. 57), represents the long, slender crystals of the phosphate of magnesia, observed in the urine of a man who was taking the hypo- 240 PATHOLOGY OF EARTHY SALTS. Pathological Indications of the Phosphates. • 265. The persistent occurrence of deposits of the earthy phos- phates in the urine, must be regarded as of serious importance, ahvays indicating the existence of important functional, and, too frequently, even of organic mischief. One general law appears to govern the pathological development of these deposits, viz., that they always exist simultaneously with a depressed state of nervous energy, often general, rarely more local, in its seat. Of the former, the result of wear and tear of body and mind in old people, and of the latter the effects of local injury to the spine, will senre as examples. It is true, that in the majority of these cases there is much irritability present; there is often an excited pulse, a tongue white on the surface and red at the margin and tip, with a dry, often imperspirable, occasionally hot skin. Still it is irritability with depression, a kind of erethism of the nervous system, if the expression be permitted, like that ob- served after considerable losses of blood. The pathological state of sulphite of soda for sarcinae ventriculi. The urine was clear, alkaline, turning turmeric paper brown, and contained the crystals in large quantities. They were very similar to those mentioned by Dr. Hassall in the " Lancet."* In Dr. Has- sall's case the patient was also the subject of sarcinae ventriculi, and was treated by the hyposulphite, but I do not know whether he was taking it at the time when the urine was examined. " In this case, the deposit of earthy phosphates, usually so abundant in the night excretion, examined by the microscope, was found in one sample to consist chiefly of a great number of long and slender crystals, stretching right across the field. of vision, pointed at either extremity, frequently split or divided into smaller secondary crystals, and more or less aggregated into bundles. The deposit procured from another sample consisted principally of the same crys- tals, although they were very much larger, and of somewhat a different shape. Their form, as nearly as could be ascertained, was that of a six-sided prism, the extremities being usually pointed, and furnished with two unequal facettes, not unfrequently the ends were truncated, and occasionally oblique. The deposit was examined chemically more than once, both by Dr. Hassall and Dr. Letheby, and was found to consist chiefly of phosphate of magnesia with some ammonia, and a little phosphate of lime ; the latter substances being present as impurities, and forming, in all probability, no part in the composition of the crystals."! At the time I first noticed these crystals, I was not aware of Dr. HassalPs observations ; but on referring to different sources to see whether the subject had been previously brought forward, I found the above, which I have much pleasure, as well from the interest I myself take in the subject, the causes being so similar, as in j ustice to the original observer, to transfer to these pages. * Jan. 29,1853. t Ranking's " Abstract," vol. xvii, p. 81. > TRIPLE PHOSPHATE. 241 the system accompanying the appearance of deposits of phosphate of lime, are analogous to those occurring with the triple salt; indeed, as has been already observed (263), they often, and in alkaline urine always, occur simultaneously. So far as my own experience has ex- tended, when the deposit has consisted chiefly of the calcareous salt, the patients have appeared to present more marked evidence of ex- haustion, and of the previous existence of some drain on the nervous system, than Avhen the triple salt alone existed: unless its source is strictly local (284). 266. When the triple salt occurs in small quantities, nearly or entirely free from phosphate of lime (the urine being acidulous or neutral at the moment of emission, and not restoring the color of reddened litmus paper until some time after), we have the simplest cases, or those in Avhich the amount of organic or functional lesion is at a minimum. These patients are generally regarded as laboring under severe dyspepsia. The most prominent symptoms they present, are great irritability of temper, extreme restlessness, mal-performance of the digestive functions, with such imperfect assimilation of the in- gesta, that a certain and often extreme amount of emaciation is a constant attendant. The appetite is uncertain, occasionally being voracious ; vomiting, or at least irritability of stomach, frequent; fatigue is induced by the slightest exercise ; there is a remarkable inaptitude to any mental or bodily exertion, and the patient is often, from the exhaustion thus produced, unfitted for his ordinary duties. In severe cases these symptoms become aggravated by an excessive elimination of urea, Avhich aids considerably in depressing the patient's strength. The urine is generally of a rich amber color, generally depositing phosphates on the application of heat, and of high specific gravity 1*025—1*030. Where the presence of triple phosphate is only occasional, its connection may be traced to some cause which has rendered the system morbidly irritable, at the same time that its tone or vigor has become depressed. The simplest examples of this kind that have occurred to me, have been in the cases of individuals of nervous temperament, who have periodical duties to perform re- quiring extreme mental tension and bodily exertion. I have wit- nessed this state of things several times in clergymen, especially in those AA*ho, from the nature of some secular engagements, have been # compelled to lead sedentary lives during the Aveek, and to perform full duties on Sundays. The best illustration of this I ever met Avith Avas in the person of a Avell-knoAvn and deservedly popular clergyman, 16 242 PATHOLOGY OF EARTHY SALTS. who, from his connection with a public school, scarcely used any ex- ercise during the week, whilst on Sunday he performed duty thrice in his church. This g'entleman was a tall, thin person, of dark com- plexion, lustrous eyes, and almost phthisical aspect. He Avas the subject of constant dyspepsia. The urine passed on Saturday evening, as Avell as on Sunday morning, although repeatedly examined, was healthy, except in depositing urates, and being of high specific gravity. Before his Sunday duties Avere completed, he almost inva- riably became the subject of extreme fatigue, Avith a painful aching sensation across the loins, in addition to the flatulence and epigastric uneasiness under which he ahvays labored. The urine voided before retiring to rest, after the severe exertions of the day, Avas almost con- stantly of a deep amber hue, high specific gravity, and deposited the triple phosphate in abundance. The urine of Monday would contain less of this salt, Avhich generally disappeared on the following day, and once more reappeared on the following Sunday evening. I had an opportunity of observing this state of things for several weeks, and it ultimately disappeared by the patient relaxing from his duties and enjoying the amusement of travelling for a feAV Aveeks. 267. Another most severe case of this disease Avas lately under my care in the person of a West Indian proprietor Avith a naturally highly susceptible nervous system, rendered still more so by the refinements of education. He had suffered sad reverses, and become the subject of the train of symptoms just described; his irritability was most dis-' tressing, and rendered more intolerable by the severe efforts he made to restrain it. He had a hot dry skin, a quick and irritable pulse, mind much depressed, and, in spite of a large share of good sense, was always under the influence of apprehension of some im- pending peril. The urine was always acid, and remained so for a day after emission, even in hot weather; its specific gravity was 1*028; by heat it became opaque from the deposition of phosphate of lime, and soon after passing, even before it was perfectly cold, a copious deposit of prismatic crystals of the triple phosphate appeared. I have seen an ounce bottle of his urine let fall a deposit reaching to one-tenth of the height of the fluid. This deposit lessened rapidly on the partial alleviation of the mental depression and anxiety of the patient, almost without medicine. 268. In mild cases of indigestion, especially in gouty dyspepsia, it is not uncommon to find the iridescent pellicle of triple salt, the urine being rich in urea. T^is condition must be regarded as an TRIPLE PHOSPHATE. 243 attempt made to get rid of an excess of a salt derived either directly from the food or by a freer disorganization of tissues by secondary assimilation than exists in health. This peculiar state of the urine is characterized, it must be recollected, as well by its being acid, or at least neutral, and rich in urea, as by the phosphatic pellicle. This is an important distinction between the urine in question and that se- creted by many persons after breakfast, where fluids have been freely drank, and bread rather copiously partaken of. In many persons, even in good health, the urine voided shortly after breakfast is alka- line, pale, soon becoming covered with a pellicle of phosphates, but of low specific gravity, and containing but a small quantity of animal matter. I have repeatedly observed the occurrence of this phos- phatic urine, rich in urea, in the dyspepsia attended with a sense of weight and tightness after food, with flatulent distension of the sto- mach so frequent in women at the period of their great climacteric. This state does not generally terminate in decided gravel or the forma- tion of a stone ; it is rather to be regarded as an index of the state of the assimilative functions than as leading to the ulterior deposit of calculous matter. The most valuable diagnostic mark of these cases, in contradistinction to those where organic mischief is to be appre- hended, is founded on the fact that the phosphates are chiefly confined to the urine passed at night. The following table, gives the result of some observations on this kind of urine. URINE DEPOSITING PHOSPHATES INDEPENDENTLY OF ORGANIC DISEASE. Evening urine. Morning urine. Case. Color. Density. Action on litmus. Deposit. Color. Density. Action on litmus. Deposit. Pale amber. 1-029 Neutral. Prisms of triple phosphates. Dark Amber. 1*031 Neutral. Red urates. Gouty dyspepsia. Normal. 1*028 Alkaline. Ditto. Normal. 1-025 Acid. Urates. Ditto. Pale. 1*020 Neutral. Ditto with phos-phate of lime. Pale. 1*025 Acid. Uric acid. Ditto. Pale. 1*022 Neutral. Nearly all phos-phate of lime. Normal. 1*025 Acid. Uric acid. Ditto. Normal. 1-028 Barely alka-line. Prisms and stellae of phosphates. Normal. 1*031 Neutral. Uric acid and scanty prisms of phosphate. Dyspepsia of in-temperance. Amber. 1-025 Acid. Prisms of phos-phate. Normal. 1*020 Acid. None. Dyspepsia follow-ing fatigue. Amber. 1*025 Acid. Fine stellae of triple salt. Normal. 1*020 Acid. None. Dysmenorrhcea. Normal. 1*030 Acid. Do. abundant. Amber. 1*025 Acid. None. Dyspepsia and ner-vous excitement. ALKALINE URINE. 245 269. Deposits of the triple salt frequently occur in very old people, in whom the state of decrepitude depending on senility has either become extreme, or been aggravated by low living and a want of the ordinary comforts of life. In several cases of this kind occurring in octogenarian dependents on parochial relief, the urine has been very pale, of low specific gravity (1*008—1*012), subacid or neutral, and extremely fetid. This fcetor, not unlike that of stale fish, did not appear to depend so much upon the presence of free ammonia, as from the occurrence of a slow decomposition of the organic consti- tuents of the urine. 270. Crystals of triple phosphate have been observed by Professor Schonlein and Dr. Simon in the urine of a person convalescing from pleurisy and pneumonia. I have met Avith them very generally in the slightly acid urine of patients who were just emerging from an attack of acute disease, especially of rheumatic fever. During one summer the urine of all the patients under my care at Guy's Hospital was almost daily examined by two of my then most indefatigable and intelligent pupils, Dr. R. Finch and Dr. H. F. Johnson, acting at that time as clinical reporters. The results of their investigation was the discovery of the fact above stated. In these cases, also, the pre- sence of the salt must be regarded as indicative of irritability with exhaustion, and it disappears spontaneously on the recovery of health and vigor. 271. It has been frequently stated, that in the course of continued fever, the urine at a certain period becomes alkaline, and deposits phosphates. It is well known that early in fever the urine is high- colored, acid, and loaded with uric acid or urates (140); and it is distinctly stated by Dr. Simon,72 from observations made under the sanction of Professor Schonlein, of Berlin, that the acidity vanishes, and is replaced by an alkaline state, at a period of the disease vary- ing with the powers of the patient, but generally about the end of the second Aveek. Simon states that in cases of severe typhoid fever, in which the urine is acid and deep-colored, it, just at the period when comatose symptoms set in, becomes alkalin,e and pale. On examina- tion, he found carbonate of ammonia in solution, resulting, of course, from the rearrangement of the elements of urea (77). That this altera- tion of acid to alkaline urine may and does occasionally occur in the course of a case of fever, is certain, but that it is the general rule, as assumed by Schonlein and Simon, is certainly opposed to all the ex- perience I have had in the disease in question. M. Becquerel73 has 246 PATHOLOGY OF EARTHY SALTS. made a similar remark, and adds, that out of thirty-eight cases of typhus, where urine Avas constantly examined, he found it alkaline in one case only, and in this, pus was present. Dr. Graves,74 of Dublin, some time ago, drew attention to the fact that the urine in fever was occasionally ammoniacal, and deposited the earthy phosphates ; in the two cases related by him extreme exhaustion existed, in one anasarca, and in the other petechiae accompanied the fever. In the epidemic of maculated fever, which occurred in London some years ago, I often found the urine alkaline in the second week; but this appeared to me almost peculiar to that epidemic. On submitting the urine to analysis, a marked deficiency, and after a time, a total absence of urea was detected. Hence it appeared, that owing to the state of enervation Avhich existed, the kidneys in separating C2N2 H604 from the blood, instead of excreting these elements, as C2N2 H402,=urea and 2HO=water, allowed them to become obedient to ordinary chemical laws, and they then arranged themselves into 2C02+2 NH3=two atoms of carbonate of ammonia. In all cases in Avhich alkaline urine occurs, care must be taken to ascertain the possibility of its having been produced by the ingestion of salts of the vegetable acids, or by subacid fruits, as Prof. Wohler131 has shown that a meal of apples or baked plums soon renders the secretion alka- line (163). 272. The researches of Drs. Sutherland and Rigby135 on the urine of insane patients, appear to authorize the assumption, that cerebral lesion, independent of any obvious implications of spinal mischief, may induce the conversion of urea into carbonate of ammonia. They found the urine capable of effervescing on the addition of acetic acid in 34 per cent, of cases of dementia, 30 per cent, of melancholy, and 16 per cent, of mania. 273. When the deposit is copious, either readily falling to the bottom of the vessel, or remaining suspended in the urine like mucus, the two phosphates are generally found mixed. In these cases, an alkaline condition of the urine almost invariably occurs, a piece of turmeric paper being readily stained brown on being immersed in it. The odor also is very disagreeable, and is generally said to be am- moniacal, although in very many instances the term fetid would be more appropriate, as ammonia is by no means necessarily evolved. This kind of urine, if not depending upon organic disease of the urinary apparatus, is always connected with some serious affection of the spinal marrow. - In a mild form, this is observed after slight vio- ALKALINE URINE. 247 lence inflicted on the spine or over the region of the kidneys, and generally disappears in a few days. I have seen a copious deposit of phosphates Avith alkaline urine occur for a feAV days in the case of a young gentleman Avho had exerted himself too much in a riding school. The fact of alkaline urine resulting from strains or blows on the back was first noticed by Dr. Prout,68 and injuries to the loins have been long enumerated among the existing causes of renal calculi. This alkaline state of the urine and deposition of phosphates, is a pretty constant result of anything which depresses the nervous energy of the spinal marroAV, whether the result of insidious disease of the spine, or the effect of sudden mechanical violence. Further, as observed by Sir B. Brodie, this condition of the urine, Avhenever it follows spinal injuries, appears not to be connected with the particular locality of the injury, but to occur equally in accidents to the lumbar, dorsal, or cervical regions. 274. It is well known that all the hollow organs of the body are endued with a sufficient amount of nervous energy, or vital power, to preserve the fluids they contain from change for a long time. Thus the blood in an artery, even Avhen its motion is prevented by a liga- ture, does not change in a space of time sufficient to convert it, if removed from the vessel, into a putrescent mass. The bile in the gall-bladder, the urine in the kidneys and bladder, the faeces in the intestines, are examples of the same fact. This laAv even obtains in disease ; for a serous or purulent effusion, the result of morbid action, will be preserved in the living cavities of the body unchanged, while a few hours would be sufficient to render it fetid and putrid, if ex- posed, out of the body, to the influence of a similar temperature. It is therefore evident that in so complex a fluid as the urine, the vital endowments of #the living cavities containing it, alone preserves it from undergoing the change which so readily occurs out of the body. The poAver thus possessed by the bladder of preserving its contents unchanged is indisputably dependent upon the integrity of the spinal nerves, and branches from the organic system supplying it. If, there- fore, any injury, even of an indirect character, be inflicted upon them, the result must of necessity be the diminution, to a certain extent, of the vital power of the organ, and the fluid it contains will become susceptible of changes analogous to those which occur in it when re- moved from the body. One of these changes is the union of the urea Avith the elements of water, and the formation of the carbonate of ammonia (77). The base of this salt, by uniting with the normal 243 PATHOLOGY OF EARTHY SALTS. acid of the urine, will precipitate the earthy phosphates with some carbonate of lime; the latter being the result of the decomposing in- fluence of the carbonate of ammonia on the phosphate of lime. Whe- ther the decomposition of urea be the primary chemical change, or is the result of some antecedent one, is unknown. Professor Dumas118 has ingeniously suggested that the vesical mucus may undergo a putrescent change; and this, acting as a ferment, may induce the metamorphosis of urea into carbonate of ammonia, just as yeast aids the conversion of sugar into alcohol. 275. The urine thus rendered ammoniacal, acts as an irritant on the mucous membrane of the bladder, exciting a form of inflamma- tory action ; and the result of this is the secretion of a large quan- tity of mucus of a more viscid character than usual. By persistence of the irritation, puriform mucus is at length poured out, and this, from the chemical influence of the carbonate of ammonia, becomes changed into a viscid, almost gelatinous mass; sometimes so tenacious as to form long viscid tough ropes of mucus, capable of being draAvn out to the length of several inches without breaking. The formation of this matter greatly adds to the patient's sufferings, by preventing the ready escape of the urine even when the contractile power of the bladder is not quite paralyzed. I thus regard the depressed vitality of the bladder to be the initiative in these series of changes ; the next step is the decomposition of the urine and formation of carbonate of ammonia, which acts as the exciting cause of the ex- cessive secretion of unhealthy mucus, the urine being supposed to be acid at the time of secretion by the kidneys. In the case of a woman in Guy's Hospital, laboring under complete paraplegia, and passing, with the aid of a catheter, fetid, alkaline, and phosphatic urine, I washed out the bladder with warm water, and allowing the secretion of urine to go on for half an hour, the catheter was again introduced, and an ounce of pale acid urine escaped; proving that the alkaline condition of the urine previously removed was owing to the changes it undenvent subsequent to secretion. 276. A somewhat different vieAV of the cause of alkaline urine has been published by Mr. Blizard Curling;71 this gentleman believes that the immediate result of spinal lesion, is the loss of the natural sensibility of the bladder; the effect of this is the secretion of un- healthy alkalescent mucus, which acting chemically upon the urine, renders it alkaline, and leads to the deposition of the earthy phos- phates. Subsequently the urine may be actually secreted in an ALKALINE URINE. 249 alkaline state by the extension of irritation from the bladder to the kidneys, or by the latter sympathizing with the debilitated yet irri- table state of the system. The opinion that alkaline urine may eventually be secreted by an extension of irritation to the kidney, receives considerable support from an interesting case which occurred some time ago in Guy's Hospital. A man Avas admitted under the care of my colleague, Mr. Bransby Cooper, for injury to the spine, resulting from accident. He Avas paraplegic; the urine soon became alkaline, and he died. On a post-mortem examination, the contents of the bladder restored the color of reddened litmus paper, and on making a section of the kidneys, the papillae were found incrusted with prismatic crystals of the triple phosphate. 277. Mr. Curling considers that the mere continuance of urine in the bladder is not sufficient to allow it to become alkaline, but that a diseased condition of the mucous lining is a necessary condi- tion in effecting this change. Hence in enlarged prostate, when the bladder is often distended for a long time, the urine is generally acid, even when only emptied by the catheter twice in the day. But when, on the other hand, a catheter is worn in the bladder, so that no accumulation can take place, the urine is often alkaline; a cir- cumstance admitting only of explanation by the secretion of un- healthy mucus, excited by the irritation of the instrument.* 278. Dr. Snow has made some ingenious experiments on the con- ditions for the development of alkalescence in the urine whilst in the bladder, and he has produced much evidence to prove that whenever this cannot contract so as to get rid of all its contents, the small quantity thus retained will become alkaline, and be sufficient to in- duce a similar state in the freshly secreted urine soon after its drop- ping from the mouth of the ureter upon it. Newly voided acid urine Avas kept at a temperature of 100°, dropping from one vessel into another, about the rate at which it enters the bladder. The upper glass vessel used was emptied completely, and washed with water every six or eight hours before putting in fresh urine, but the lower one had ahvays a feAV drops of stale urine left in. The result was * Dr. Owen Rees's views on this subject are well known. They are clearly enunciated, and supported by some strong facts ; I fully concur with him in the benefit of alkaline treatment in those cases in which the alkalinity of the urine is decidedly due to irritation or inflammation of the mucous membrane. His remarks, also, on the use, or rather the abuse of the catheter, are most important. 250 PATHOLOGY OF EARTHY SALTS. that the urine in the lower vessel Avas ahvays alkaline, whilst that in the upper was constantly acid. These researches afford a strong argument in favor of the practice of frequently washing out the bladder, in cases of alkaline urine. 279. The urine may be alkaline, and loaded with phosphates, simply from disease limited to the bladder. In all cases in which disease of the mucous membrane, especially of a chronic character, exists, more particularly where retention of urine occifrs, the urine is almost always phosphatic, and abounds in viscid mucus. This is seen in cases of old stricture of the urethra, chronic cystitis, and many of the affections included under the generic term of Irritable bladder. I have witnessed more than one instance in which the state of urine alluded to has resulted, in women, from secretion of unhealthy mucus, by the propagation of irritation from an irritable uterus, or ev^n inflamed Angina. In all these cases the patient's suffering is much increased by the formation of soft pseudo-calculous masses of mucus and phosphates, blocking up the urethra. 280. This condition ought to be regarded as quite distinct from the cases already alluded to, in which the presence of the phosphatic deposit is indicative of, and produced by, great irritability and de- pression, or spinal lesion. It is hence very important to be able to diagnose correctly between cases of alkaline urine depending upon causes strictly local {i. e. bladder affection), and those of a more general character. Dr. B. Jones139 has suggested for this purpose the action on litmus paper, as it would appear that urine is alkaline from ammonia when the cause is local, and from a fixed alkali when the ailment is more general. He has certainly succeeded in esta- blishing the fact that urine may be frequently alkaline and not am- moniacal, although of course when ammoniacal it is always alkaline. The urine which, as already stated, is sometimes alkaline after breakfast, generally owes this to a fixed alkaline carbonate being present. In such urine a piece of red litmus paper is always turned blue, and remains so after being dried even by artificial heat. Whereas, if the urine is alkaline from the presence of carbonate of ammonia, although red litmus paper is rendered blue when immersed in it, yet by drying, especially if held near a fire to warm it, the ammonia evaporates, and the paper resumes its red tint. There is another important distinction between these two forms of alkaline urine. When alkaline from ammonia, abundant crystals of triple phosphate are always found; whilst, when ammonia Avas absent, Dr. DIAGNOSIS. 251 Jones states that these crystals are rarely present, and are replaced by a copious and dense deposit of phosphate of lime. 281. Cases occasionally present themselves in which the urine is very copious, pale, and freely deposits the phosphates, independent of any local disease in the genito-urinary organs, and in which the general symptoms are those of marasmus; the appearance of the patient, and his most prominent ailments, much resembling a case of diabetes. It is in these that the formation of a calculus is more espe- cially to be dreaded ; and even if these evils be arrested, the patient too generally goes on from bad to worse, and dies worn out with irri- tation. An instance of this kind has been alluded to (267), and I shall have occasion to refer to another when speaking of the treatment (294) of the disease. Even in these, a careful investigation of the case will generally lead to a detection of some antecedent causes of spinal mischief; and in many, abuse of the sexual organs have con- stituted the most prominent exciting cause. I have seen some in which no other antecedent morbid influence could be discovered than the cachexia produced by the abuse of mercury. 282. The deposits of phosphates, where no organic disease exists, are often absent, not only for hours (266), but for days together; and this fact will often enable us to predict, with tolerable confidence, the happy termination of the case. From all the experience which I have had of phosphatic deposits, I feel confidence in offering the following as a safe induction from clinical observation, and one of great service in practice. That, where the presence of a deposit of phosphates is independent of the irritation of a calculus, or of organic disease, it is most abun- dant in the urine passed in the evening {urine of digestion), and absent or replaced by uric acid, or urates, in the morning {urine of the blood), the urine being always of a tolerably natural color, never below, and often above the mean density. Where the presence of phosphatic salts depends on the irritation of a calculus, or of organic mischief in the urinary passages, the urine is pale and whey-like, of a density below the average, often considerably so, and the earthy deposit is nearly equally abundant in the night and morning urine. 283. I cannot close this part of my subject without drawing atten- tion to the conclusions arrived at by Dr. B. Jones on the relation borne by phosphatic salts to certain pathological conditions. Their importance is too great to permit them to be overlooked. He has shoAvn: 1. That no determination of an excessive secretion of phos- 252 PATHOLOGY OF EARTHY SALTS. phoric acid can be afforded by the deposit of earthy salts, unless the quantity of lime and magnesia in the food be taken into account. 2. That no real increase of phosphatic salts occurs in spinal diseases, notwithstanding the existence of deposits. 3. That in fever, and in most acute inflammations, the phosphatic salts are not increased. 4. That in old cases of mania, melancholy, paralysis of the insane, or in chronic cases of disease in which nervous tissues are uninfluenced, no conclusions can be drawn. 5. In fractures of the skull the phosphatic salts increase only when any inflammatory action occurs in the brain, and in acute phrenitis an excessive increase takes place. 6. In de- lirium tremens there is a marked deficiency of phosphates, unless they are introduced Avith the ingesta; an excess is, hoAvever, met Avith in some functional affections of the brain. 284. Some curious cases are occasionally met with, in which enor- mous quantities of phosphate of lime have come away for a long time in the urine without apparently doing much mischief. A very re- markable instance of this kind occurred some years ago among the out-patients of Guy's Hospital, in the person of John Jenkins, an old man under the care of my colleague, Dr. Hughes. This patient was an habitual dyspeptic, and had labored under pyrosis from boyhood. He had during many years been in the habit of passing almost milky urine, Avhich by repose deposited such an extraordinary quantity of phosphate of lime, that he brought to me at one time more than an ounce of the salt. He had been for this disease under the treatment of half the hospital physicians and surgeons in London. He had stated that fifty years previously he had been a patient at Guy's Hospital, under Dr. Saunders, and subsequently under Dr. Fordyce at St. Thomas's; but his urine had never at any time exhibited any signs of improvement. Indeed, all the remedies tried appeared quite use- less ; at the same time, this man's general health Avas-so good that there Avas scarcely an excuse for submitting him to any course of treatment beyond the apprehension of the possible formation of a calculus. In cases of this kind it is very possible that the phosphate of lime is secreted from the mucous membrane of the bladder, and not derived from the urine. All mucous secretions contain phosphoric acid, combined with earthy bases; and hence, if an excess of the latter is secreted with the vesical mucus, it may be washed away with the urine and form a deposit. This is by no means unfrequent in the irritable bladder, depending on the existence of prostatic diseases, &c.; we have a perfect analogy to this in the calculous concre.tions IRRITATIVE DYSPEPSIA. 253 found in the ducts and glands furnishing mucous secretions. These are all prone to secrete phosphates in too great an excess to be washed away with the secretion; they are therefore retained, and form a calculus. These, from whatever part of the body they are obtained, present nearly the same composition. Composition of Phosphatic Concretions. Species. Prostatic. Seminal. Salivary (horse). Salivary (human). 75* 2* 23* Pancreatic. BO-S' 7- Phosphate of lime, . Carbonate of lime, . Animal matter and water, 84-5 •5 150 90-2* 10* 3* 84* 12- Authority, Lassaigne Peschier Lassaigne G. B. G. B. 285. Therapeutical Indications.—In considering the indications for treatment in cases where the phosphates appear in the urine in the form of deposits, whether their quantity be in excess or not, it will be necessary to regard practically at least four pathological con- ditions, the existence of one or other of which must be deduced from the symptoms presented by the patient. A. Cases in which dyspepsia, often to an aggravated extent, with some febrile and nervous irritation, exists independently of any evidence of antecedent injury to the spine (266). B. Cases characterized by high nervous irritability, with a varying amount of marasmus, following a blow or other violence in- flicted on the spine, but without paralysis (273). c. Cases in Avhich the phosphatic urine coexists with paraplegia, the results of spinal lesion (275). D. Cases of diseased mucous membrane of the bladder (279). Of these it will be only neeessary to direct attention to the first, second, and fourth series of cases, as the third includes cases in which the deposition of phosphates constitutes a mere symptom of a grave and serious lesion, which, whether the result of accidental violence or insidious disease, must be treated according-to the particular dis- ease existing. Phosphatic Deposits connected with Irritative Dyspepsia. 286. Examples of this class of cases, or those in which a particular form of irritative dyspepsia is the characteristic feature, are by no 254 PATHOLOGY OF EARTHY SALTS. means uncommon. Every now and then patients present themselves, in whom the most prominent symptoms are a capricious appetite, sense of weight and fulness at the praecordia, especially after meals, irregular bowels, severe lancinating pains darting between the scapulae from the pit of the stomach; much flatulence, tongue white, often with injected marginal papillae, sometimes morbidly red over its Avhole surface ; pulse quick and irritable, dull heavy aching pain across the loins, excessive depression of spirits, despondency so intense as often to excite the most painful ideas. In a merchant surrounded by affluence, apprehensions of impending beggary often embitter the moments that are free from the excitement of business; in the me- chanic, unfounded ideas of immediate loss of employment, and visions of the interior of a workhouse, are generally present. On examining the urine', its specific gravity is often above the average ; the depo- sition of crystalline or amorphous phosphates, and often excess of urea, will refer the case to its proper class, as one of irritative dys- pepsia, in which the excess of phosphates indicates the "drain" on the nervous energies. 287. The treatment of these cases must be rather directed by general principles, than limited to effecting the mere solution of phosphatic deposits. It is true,' that by the persistent administration of acids the deposits may disappear for a time, but the ailment goes on; all that is effected by such treatment is to mask a symptom, and an important one, of the progress of the malady. After having at- tended to the morale of the case, as far as possible removing from the patient any morbid influence existing in his mind, whether real or imaginary, the next thing is to attend to the general health. The bowels should be freed from any unhealthy accumulation by a mild mercurial laxative, as a few grains of pil. hydrarg., followed by a dose of rhubarb or castor oil; but all active purging should be avoided, as it generally aggravates the distress of the patient, and decidedly interferes with the success of the treatment. A combina- tion of a tonic laxative with a sedative may then be administered, as tinct. hyoscyami et sp. ammon. aromatici, aa, ituxx—3ss, ex. mist. gentianae co., §j, ter in die. If the bowels be irritable, the inf. cas- carillae, or inf. serpentariae, may be substituted for the mist, gen- tianae comp. Should gastrodynia exist, great relief will be obtained by the administration of half a grain of oxide of silver, made into a pill with confection of opium, before a meal. The diet should be very carefully regulated, all bland nutritious articles of food being IRRITATIVE DYSPEPSIA. 255 preferred; vegetables should be avoided, and in general a small quantity of good sherry may be allowed. By a plan of treatment of this kind, the patients generally do well, and the phosphates and ex- cess of urea vanish from the urine. As the patient approaches con- valescence, much good is often effected by the use of sulphate of zinc in gradually increasing doses, beginning with a grain thrice a day, made into a pill with a little ext. hyoscyami, or ext. gentianae, and increasing the quantity every three or four days, until five grains or more are taken at a dose. Under the use of the zinc, I have seen many cases do Avell, in which the irritable state of the nervous sys- tem, and accompanying mental excitement, almost approached in severity and character that observed in delirium tremens. I need hardly say that change of scene and occupation are important adju- vants to our medical treatment. 288. Much less frequently these cases will become chronic, the* secretion of phosphates being continued for years, and the irritability of stomach being so severe and persistent as to lead to the emaciation of the patient and presence of all the symptoms of scirrhous pylorus. These cases are sometimes relieved by the administration of strychnia. This drug has a remarkable influence over a simply irritable stomach, and is indeed superior to any other anti-emetic remedy, providing there be no acute or inflammatory action in the affected organ; and under its use I have seen the urine assume a remarkably healthy character. It may, indeed, be hazarded as a probable opinion, that strychnia may prevent the decomposition of urine in the bladder and consequent deposition of earthy salts, from its influence on the spinal nerves. The following case is a remarkable illustration of the fore- going remarks. It is abridged from the account of Dr. Robert Finch, who reported it: Irritative dyspepsia simulating scirrhous pylorus, with copious secretion of triple phosphates. G----L----, set. 18, admitted into Luke's Ward, under Dr. Golding Bird, April 9, 1845, a native of Bristol, and employed at an iron factory; had always lived temperately, and his health, previous to the present illness, had been good, being merely the subject of occasional attacks of indigestion, with flatulent eructations. Four years before, vomiting had come on sud- denly, after an ordinary meal, accompanied by severe pains at the pit of the stomach, to which, in a less severe form, he had been subject during the previous year. With occasional, but rare intermissions, this vomiting recur- red daily after every meal for six months, being preceded by intense pain, 256 PATHOLOGY OF EARTHY SALTS. relieved on emptying the stomach. It became less frequent for the following eight months, occurring but once or twice a day, but never losing it for twenty-four hours at a time. He then became a patient at the Bristol In- firmary, and underwent a great variety of treatment, with the general result of obtaining partial Relief, but never losing his daily paroxysms of pain and vomiting. On admission into Guy's Hospital, the lad's complexion was pale and bloodless, with a slight icteric tint; emaciation most extreme, his bones were barely covered, and his face was so extraordinarily emaciated, that it rather resembled a skull, over which parchment had been drawn, than anything else. His general appearance was that of a person in the last stage of scir- rhous pylorus. He complained of burning heat at the scrobiculus cordis, and heavy pain across the loins; tongue clear and red; pulse quick and sharp; skin dry and imperspirable. He always vomited a short time after every meal, and declared that he had not passed a single day during four years without being sick three or four times. There was great thirst; bowels acted daily, with frequent eructations possessing an odor of stale fish. Urine loaded with triple phosphate, and alkaline, with a disgusting fishy odor, even *when first passed; sp. gr. 1020, not albuminous. No tumor could be felt at the scrobiculus cordis, where there was some tenderness on pressure; the abdomen distended with flatus. April 9th.—Vomited nearly four pints of thin acid yeast-like matter. Misturae Magnesias, ^j, ter in die. Milk diet. 11th.—Vomited daily after dinner. The vomited matter presented the same yeast-like appearance. Urine had an ammoniacal odor, and deposited phosphates copiously. R. Strychnia?, gr. j. Acidi Nitrici dil., *"jj. Aquae, ,?xij.—Solve et capiat aeger, §j, ter in die. He was strictly confined to milk diet; the medicine to be taken fifteen minutes before each meal. 14th.—Vomited yesterday before dinner, and again after tea, and after breakfast this morning.—P. 15th.—Vomited last night, but not since ; has passed 30 ounces of urine in the preceding twen.ty-four hours, copiously depositing phosphates; appe- tite good; begged for a continuance of the medicine, stating that it kept his food down ; abdomen not so flatulent. 16th.—In no pain; vomited last night at seven o'clock, with rather more than usual pain; urine alkaline; 40 ounces in twenty-four hours, and full of prismatic triple phosphates. . R. Olei Tiglii, 3j. Lin. Saponis, ^vij. ' M. ft. Linimentum scrobiculo cordis bis die illinendum et Pergat. Fish diet. 19th.—Not vomited since the morning of the 17th ; the liniment brought out a crop of pustules; felt no pain since the vomiting ceased; urine neutral, containing but little deposit; complained of great thirst.—P. 22d.—For the last two nights his skin has acted freely; urine free from deposit, sp. gr. 1014; troublesome flatulent eructations.—P. IRRITATIVE DYSPEPSIA. 257 From this report the same treatment being continued, the patient im- proved, the vomiting ceased, and the urine became acid. He had recovered his good looks, and became decidedly fat in his face. On May 19th, he suffered a slight relapse after paroxysms of pain in the region of the left kidney, followed by vomiting and the discharge of urine loaded with phos- phates, and becoming alkaline soon after emission. This was but a transient attack; he soon recovered, and left the hospital apparently quite well. May 31st.—This patient appeared among the out-patients apparently pretty well; he had suffered one relapse since leaving the hospital after a copious meal of tripe. The urine was, however, not quite healthy, and con- tained some phosphates. 289. Sometimes, although rarely, the phosphates will disappear from the urine, and be replaced by the oxalate of lime; a change that should excite serious apprehensions for the patient's ultimate welfare. This generally occurs in persons who by imprudence have draAvn some time previously a heaAry bill upon their health. The fol- lowing is one of the feAV cases of this kind I have witnessed. Irritable bladder following repeated gonorrhoea; dyspepsia; severe lumbar pain ; triple phosphates followed by crystals of oxalate of lime. I was requested by my friend, Mr. Complin, of Charterhouse Square, to see a patient in whom he suspected the presence of renal disease. He was a fine, florid person, aet. 25, who, from his own confession, had been most irregular in his habits; he owned to having labored under twenty-five dif- ferent attacks of gonorrhoea. Eight years ago he had cystitis, following the injection of some fluid into the urethra for the cure of gonorrhoea; he at the same time drinking a bottle of port daily. During this attack he passed a large quantity of bloody mucus, which continued pretty constantly for five months; nor did it entirely cease for fifteen months. He was then treated by Dr. Budd, of Plymouth. He spent the year 1837, and part of the succeeding one, in yachting to the West Indies and Southern Africa. He then returned to England, and got married. His habits became more regular, occasionally only indulging in wine. His appetite, however, continued to be, as it ever was, most vora- cious, often eating, as he at least declared, three pounds of meat and bread for dinner. In January, 1842, he fancied he had some obstruction in the urethra, and passed a bougie; this produced much irritation, and was followed by intense pain over the left kidney, darting to the sacro-sciatic notch; this continued up to the time I saw him (April the 23d), occasionally only being absent for a day or two, always being reproduced after partaking of a hearty or in- digestible meal. Walking did not appear to increase the pain; on the con- trary, although its severity often crippled him, yet if he could succeed in walking a few yards, he was generally relieved. When the severe pain was absent, there was always a considerable amount of tenderness on pressure over the left kidney. To add to his annoyances, he suffered considerably from irritability of the sexual organs, attributed to 17 258 PATHOLOGY OF EARTHY SALTS. his rarely being able to indulge in sexual intercourse, in consequence of his wife suffering from profuse monorrhagia. April 23d.—The urine passed last evening was faintly alkaline, of specific gravity 1 028, of natural color, and appeared to contain a dense mucous de- posit, which, under the microscope, was found to consist of large prisms of triple phosphate, mixed with stellae, formed by a number of finer prisms co- hering together. By repose an iridescent film of crystals of the triple salt formed on the surface of the urine; and on the application of heat, an amor- phous deposit of the phosphate of lime fell. On the addition of acetic acid to the turbid urine under the microscope, the whole deposit dissolved, the prisms vanishing much more rapidly than the stellae. 24th —The urine passed this morning was neutral, of a deep amber color; its specific gravity was 1-031; it coutained a mucous cloud, entangling a few prisms; on the application of heat a thick deposit of phosphate fell. A large excess of urea was present; the addition of nitric acid producing a rapid growth of crystals of the nitrate of urea in a few seconds. 25th.—His symptoms continued the same. The urine was again examined; that passed last night was acid, of a deep amber color, and of a density of 1030; it contained merely a delicate mucous cloud in suspension, there being no distinct deposit; on the application of heat, a deposit of phosphates, soluble in acetic acid, occurred. A large excess of urea was present. On placing a drop of the urine under the microscope, it was found abundantly loaded with very large octohedral crystals of oxalate of lime, unmixed with phosphates or urates. *2'jth.—The urine passed this morning much resembled the night speci- mens, save that it was quite free from oxalate; its specific gravity was 1-030, and was loaded with urea; it did not become turbid by heat. May 2d.—I again saw my patient; up to this time he had taken no medicine, except a brisk purgative, as I was anxious to watch the urine. He now stated that since its action the lumbar pain had become diminished. He boasted to me that two evenings previous he had drank a bottle and a half of port at dinner, and felt better for it. He begged to be allowed to avoid physic, unless he became worse; and it was with some difficulty that I procured af specimen o urine. 3d.—The urine passed last evening was acid, of a deep amber, specific gravity 1-030, contained no visible deposit, but the microscope detected an abundant deposit of octohedral crystals of oxalate of lime diffused through it; it deposited phosphates by heat, and contained a large excess of urea. 4th.—The urine passed this morning resembled the last-described speci- men; both were remarkable for the oily appearance they presented when poured from one vessel to another—a circumstance probably depending upon the great excess of urea they contained. Phosphatic Deposits connected with Functional {?) Spinal Lesions. 290. Cases of the second class, characterized by a much higher amount of nervous irritability, and of a rapidly progressing emacia- tion, traceable to some shock to the spine, are not so frequent as those just alluded to, and are far less amenable to treatment. FUNCTIONAL SPINAL LESIONS. 259 In these, the phosphatic deposit is often copious, and sometimes consists nearly exclusively of phosphate of lime; the lumbar pain and Aveight are considerable, the skin often dry and scarcely perspi- rable ; in some cases, indeed, I have seen it look as if varnished; the tongue sometimes white, is often red; the thirst often great ; indeed, the general appearance of the case closely resembles one of diabetes. The urine is generally more copious than natural, almost always pale, and of a specific gravity below the average. On investigating the patient's history, some evidence of a previous strain or wrench of the back, or a blow over the spine, is ahvays elicited. These patients are seldom hypochondriacal; but intense irritability of temper, and a painfully anxious expression of countenance and manner, are almost invariably present. 291. In the treatment of these cases it is important to bear in mind the fact, that although the first exciting cause of the malady is to be found in some shock in the spinal cord, involving the integrity of function of some of its nerves, more especially of those Avhich are con- nected Avith the great sympathetic (and supply the Avhole of the chylo- poietic viscera), yet the irritation has beeome reflected to the brain, and hence the excitability and the depressed health such cases always present. The great end and aim must be to subdue the morbidly irritable state of the brain and nervous system ; to remove any cause, if such exist, interfering with the healthy state of the spinal struc- ture ; and subsequently, by a generous diet and persistent use of those tonics which appear especially to exert their influence on the organic nerves, as silver, bismuth, zinc, &c, to endeavor to restore the assimilative functions to their due vigor. Besides the general indications to be fulfilled by regulated diet, amusement, exercise, &c, the use of narcotics, especially of opium, or the preparations of mor- phia, should be regarded as of the highest value ; and we are indebted to Dr. Prout for first directing the attention of the profession to their use. 292. The case of this affection recorded by Dr. Prout75 was one of peculiar severity, and I have had but few cases before me in practice which at all equalled it. I can, however, add my testimony to the efficacy of narcotics in the cases I have seen. Morphia appears to me to be someAvhat preferable to crude opium, and under the persistent use for several weeks of one-third, or even one-half of a grain of the acetate, three or four times in the twenty-four hours, the deposit has vanished from the urine, and the patient done well. In these as in 260 PATHOLOGY OF EARTHY SALTS. the preceding class of cases, the shower-bath, and cold douche over the loins, followed by friction Avith horse-hair gloves, have been of essential service. To succeed in the cases, the treatment must be persistent, for they are essentially chronic in their character; and if remedies be intermitted too soon, may end in fatal marasmus, and in some, the formation of a calculus. 293. Cases occasionally occur in which the symptoms are of a much milder character, but Avhich insidiously go on to the formation of a calculus. It is in these in particular that the use of acids is called for, to hold the phosphatic salts in solution, and prevent their being moulded into a concretion in the pelvis of a kidney. Unfortunately there is a great uncertainty attending their use ; indeed, I felt almost inclined to question whether any of the mineral acids, except the phosphoric, really do reach the urine, and thus destroy its alkaline character; certainly, in the majority of cases, even their'continued employment appears to be utterly ineffectual in rendering the urine acid. Dr. B. Jones has shown, that the continued administration of dilute sulphuric acid in doses far above those ordinarily employed, or indeed safely administered, in medicine, hardly added in the slightest degree to the acidity of the urine. So far as I have Avatched cases of this kind, the nitric acid seems to produce the smallest amount of gastric derangement, and appears sometimes to render the urine acid, or at least diminish its alkaline reaction. Although I do not feel in- clined to believe that the acid itself really reaches the urine, and acts as a solvent for the deposit, I am disposed to explain its influence by a reference, to its tonic and alterative action, so that Avhen it acts at all, it does so by improving the general health. From some late ob- servations, it appears probable that bodies which coagulate albumen are by no means readily if ever absorbed, and cannot consequently be discovered in the urine; thus gallic acid, which scarcely acts on albumen, is absorbed, and soon reaches the urine ;132 while its close ally, tannin or tannic acid (324), readily coagulates albumen, and I believe has not been discovered in the urine after its administration. Is it possible, by this view, to explain the facts recorded in the first edition of this Avork, that phosphoric acid had appeared in many cases to lessen the alkalescence of the urine when other acids Avere useless ? Mr. Ure76 has recommended the employment of benzoic acid, under the idea of its destroying the alkaline state of the urine in conse- quence of its metamorphosis into hippuric acid; and he has recorded the history of a case thus treated. I confess that in my hands this PHOSPHATIC CYSTITIS. 261 drug has not been very successful, and when it is recollected that hippuric acid requires about four hundred parts of water for solution, and that it reaches the urine combined with ammonia (168), and not in a free state, Ave can, I think, hardly place much confidence in it as a solvent for the earthy phosphates.* 294. The following case will illustrate the general progress of an excess of phosphates, ending in the formation of a calculus : Phosphatic urine and formation of calculi, following injury to the kidney; gradually increasing diuresis ; persistence of the deposit of phosphates. George W-------, set. 39, came under my care February 24th, 1843 ; he had been engaged at the distillery of Messrs. Booth, during the preceding five years, during which period he had partaken pretty freely of gin. Four years before he fell down a trap-door, and fractured two ribs on the left side. From that time he had almost constant pains in the region of the right kidney, with occasional, although slight haematuria, to which, as he states, he had been more or less subject from childhood. About six months after his ac- cident he suffered from intense pain in the course of the right ureter, fol- lowed by retention of urine, which was relieved by the passage of an oval calculus. He remained tolerably well until a year ago, when after another similar attack, a second calculus escaped. From this time he remained free from complaint, except the occasional discharge of white sand in his urine, until Sunday, February 19th. On the evening of that day he was attacked with what he regarded as colic, attended with excessive vomiting; this con- tinued until February 21st, when he was relieved by the bowels acting. For six months before the man came under my care he had been subject to profuse nocturnal perspiration, and his skin acted copiously on slight ex- ertion during the day. The desire to pass urine, which had been very fre- quent since the passage of the first calculus, had of. late much increased, so that he was called upon to empty the bladder a dozen times a day. He was much emaciated, his countenance pale and haggard, his mariner anxious; pulse 100, soft; tongue clean ; complained of heavy aching pains across the loins. The calculi were brought to me, and on analysis I found them to con- sist of the triple phosphate, with a small quantity of phosphate of lime. Urine 35 ounces in twenty-four hours. February 25th.— Urine passed, at night.—Specific gravity 1-020, neutral to litmus paper, deep brandy-colored, with a copious white crystalline sedi- ment of the triple phosphate mixed with mucus. A deposit of phosphate of lime occurred on the application of heat. Morning urine.—Same as the night specimen, but the sediment more copious. February 26th.— Urine of twenty-four hours only 22$ ounces, faintly alka- line and brandy-colored. Specific gravity 1022, no deposition by heat. Sediment copious, and as before consisted of triple salts. The small bulk and high color of the urine of* the last two days was attributable to rather copious purging from an aloetic aperient he had been taking. * The acidity of the urine may, in certain morbid states, be referred to the pre- sence of hippuric or lactic acid. 262 PATHOLOGY OF EARTHY SALTS. A nutritious diet was ordered, and a flannel bandage to the loins. R. Acidi Nitrici diluti, i*£xx ter die ex. dec. sarsae. co. cyatho. February 28. Urine 35 oz. ~) Faint,y a,ka]ine to ]itmuSj « I' ---In °Z' r and loaded with PhosPha- o fi °Z' i m k I ^c deposits. " 3. ----57 oz. sp. gr. 1015 J * March 3d.—The dose of acid had been gradually increased to half a drachm. The urine in increasing in quantity, had become paler and whey-like; the morning and evening specimens exactly corresponded, and both contained a copious sediment, which to the naked eye resembled pus. It, however, con- sisted of large prisms of phosphate mixed with very little mucus. The night specimen only deposited phosphate of lime on applying heat. All the urine contained a small quantity of albumen. The patient felt better, and was nearly free from a severe lumbar pain, which had been distressing a week before. Rep. omnia. March 5th. Perspiration at night less intense. March 4th. Urine 47 ounces) 0 ,nin , i -, •. « 5th. ____45 ounces \ SP- gr- 1019 neutral, deposit copious. " 6th. ----60 ounces) 0 -, A1e L i j -L ru u 7th.____70 ounces j Sp< gr' 1>016 neutral* deP0Slt stl11 copious. " 10th. Sufficiently relieved to enter business ; he thought the urine continued increasing, but he had not measured it. Sp. gr. 1-015 neutral. April 7th.—Improving slowly in health, urine still profuse and pale, still copiously depositing phosphates. Complained of return of lumbar pain. Applic. emp. opii regioni renum. Acidi benzoici, gr. vj bis die. 14th.—Urine certainly improved; a mere mucous cloud in the morning specimen, 1014; night specimen, 1014: both slightly acid for the first time, and containing hippurate of ammonia. He passes 80 ounces in twenty- four hours.—P. 21st.—Much the same in health ; urine the same in quantity and density, but rather a copious deposition of phosphates has occurred. He looked as emaciated as ever, but declared he felt fit for all his duties. He wished to leave off his medical treatment. October 29th.—I again saw him ; his general health was improved, and he was stouter; had had but one attack of pain in the kidney since I saw him. He still passed a very large quantity of urine containing a small quantity of phosphates in diffusion, quite neutral to test-paper. Specific gravity 1-015. His only complaint now was a want of power on contracting the bladder, being often obliged to use powerful efforts to expel the urine. There was no stric- ture, but he had found great relief to his symptoms by emptying the bladder with an elastic catheter every night. He effected this himself, and was then enabled to get a good night's rest. November 5th.—Much the same; urine 50 ounces in twenty-four hours. August 2d, 1844.—Tolerably comfortable in health; urine still pale, copious, and neutral, without sediment, but soon by heat let fall a deposit of phosphate of lime. PHOSPHATIC CYSTITIS. 263 Phosphatic Deposits connected with some Local Lesion of the Urinary Organs. v 295. The third class of cases, or those in which the phosphates are probably entirely secreted Avith unhealthy mucus from a diseased lining membrane of the bladder, are familiar to every practitioner. Chronic cystitis or cystorrhoea, and retention of urine, from stricture of the urethra or enlarged prostate, may and often do, lead to this state of things. Here, of course, the primary affection, rather than its effect, the deposit of phosphates, must be the great object of treat- ment. The urine is often very fetid and pale, sometimes green, and almost viscid from the abundance of mucus. On placing some of the latter between plates of glass under the microscope, abundant crystals of the triple phosphate are seen entangled in it. One point of great practical consequence must be borne in mind in forming a prognosis from the state of the urine, viz., not to regard it as ammoniacal, because the odor is offensive; and not to consider the deposit as purulent because it looks so. A piece of litmus paper will often show the urine to be neutral, and sometimes even acid, whilst microscopic inspection often proves the puriform appearance of the urine to be OAving to an admixture of phosphates with mucus. For want of these precautions, I have seen some cases regarded as almost hopeless, Avhich afterAvards yielded to judicious treatment. It is quite certain that the mucous membrane of the bladder may, under the influence of chronic inflammation, secrete so much of the earthy phosphates and unhealthy mucus as to render the urine puriform and offensive, Avithout having necessarily undergone any structural change. 296. Several cases have occurred to me in practice, in Avhich the kind of urine just referred to Avas secreted for a long time, and yet yielded readily to treatment. In these, the greatest good has arisen from freeing the bladder from the phosphates which appear almost to incrust it, by acid injections. In this Avay, cases have occasionally yielded Avhich have quite defied all other treatment. The following case is a good illustration of this, and I record it in the hope of draAving particular attention to this form of phosphatic cystitis, if a name be required for the disease. Phosphatic cystitis coexisting with pregnancy and vaginitis?—Discharge of phosphatic calculi—Cure by injection. Mrs. K—, a fair and delicate-looking lady, 34 years of age, residing in 264 PATHOLOGY OF EARTHY SALTS. Essex, was married in 1832, and had nine children in the succeeding ten years, being pregnant of a tenth when she came under my notice in May, 1842. She appeared to have enjoyed good health up to December, 1841, when without any assignable cause, she had severe scalding in micturition, with considerable irritability of bladder. These symptoms rapidly increased in severity, and soon afterwards the urine became loaded with mucus, occa- sionally streaked with blood. She continued getting worse until March, 1842, when her sufferings became intense; she had frequent desire to pass water every few minutes, with most distressing straining, especially after each attempt at emptying the bladder; this almost entirely deprived her of *leep. The urine was thick, fetid, and let fall a copious deposit, which was con- sidered as purulent; although acid when first passed, it soon became ammo- niacal. About this time, as a calculus was suspected, a sound Avas passed; this gave rise to the most excruciating pain, but no stone was detected. She suffered severely from haemorrhoids, and sexual intercourse was attended with positive torture, so that from her own account her life became a miser- able bunU1.. of woes. From the report of the very experienced surgeon under whose care this lady was (Dr. May, of Maldon), it appears that the bladder was decidedly thickened. In May, 1842, I was consulted by letter, the patient being then three months pregnant, and two specimens of urine, which were described s being purulent and bloody, were sent up. On examination I found the specific gravity of the urine to be only 1-009; it was opaque and rather green; odor extremely fetid, although faintly acid to litmus paper. A thick creamy deposit equal in volume to one-fourth of the whole, occupied the bottom of the bottle. The deposit, which bore the closest resemblance to pus I ever saw, was examined by placing a portion between two slips of glass under the microscope. It consisted of mucous particles, with a few blood-discs, and myriads of large prismatic crystals of the triple phosphate, mixed with amorphous phosphate of lime. On pouring the lower layers of the urine containing the deposit from one vessel to another, it formed a nearly continuous rope, and entangled some small coagula of blood. But mere traces of albumen were found in the urine. I suggested a nutri- tious diet, and Pil. Saponis comp gr v, pro. suppositorio omni nocte. Acidi Hydrochlorici diluti nr,x, dosi ad ttj*xxx gradatim adaucta, ter die ex. Dec. Sarsae co. In a fortnight (May 20th) I received a report from Dr. May, with another specimen of the urine, and some irregular calculous masses the size of peas, consisting of crystals of triple phosphate with mucus. " The poor lady tells me that manual aid was required to remove them from the orifice of the meatus, some hemorrhage followed, and continued for a few days. The deposit bears a less proportion to the urine than it did, and the intervals between the attempts made to empty the bladder are longer. The recumbent position increases her uneasiness, and renders micturition more frequent (about twice in an hour). An aggravated condition of habitual haemorrhoids has rendered it necessary to substitute an anodyne draught for the supposi- tories. She has continued the use of the acid, and she has certainly not lost ground: on the contrary, she appears stronger. Within the last few days the legs had become cedematous; this has been the case in previous pregnancies, but not at so early a period." I then suggested the daily careful injection into the bladder of acidi hydrochlorici, ttjjx, vini opii, iijjxx, in barley-water, CARBONATE OF LIME. 265 in the hope of dissolving and bringing away some of the phosphatic masses which I suspected to be in the bladder, and thus remove one source of irri- tation. A poultice of conium leaves was directed to be placed over the pubes, and the recumbent position enjoined. In a few weeks, I received a letter from my friend, Dr. Baker, of Maldon, who had seen the patient in consultation with Dr. May; he states, " I am happy to say that Mrs. K— has derived infinite benefit from the use of the injection into the bladder. She could nbt, previously to her injection, retain her urine for twenty minutes, and then the pain and straining was most distressing; she can now retain it for hours without pain, and there is no appearance of deposit." I had an opportunity of seeing this patient with Dr. Baker, on June 19th, on being called to Maldon to see another case; she was well, and progressing comfortably with her pregnancy. It is rather a curious circumstance that I was consulted in the spring of the following year, by the son of this lady, for a calculous affection, the urine being loaded with triple phosphate. 297. I cannot speak too highly of the extreme advantage obtained, in almost every case where phosphatic alkaline urine exists, by Avash- ing out the bladder by means of injections of warm Avater. Even when the urine is loaded with alkaline mucus mixed with basic phos- phates, so often the case when the bladder is unable to expel its contents from enlarged prostate, or from spinal paralysis, the injec- tion of Avarm water so as to wash out the bladder effectually two or three times a Aveek is of the utmost value. It is quite remarkable how suddenly the secretion of mucus and phosphates will decrease by this mode of treatment; after two or three repetitions of the injection, the urine, which a few days before was thick and ropy, becomes transparent and healthy. It sometimes happens that the distension of the bladder by a sufficiently copious injection excites pain, and hence is ill borne by the patient. This inconvenience may be prevented by using the double canula catheter, by which the water entering the bladder from an opening at the end of the cathe- ter, after washing the walls of the viscus, escapes by the second aperture, and hence all distension is prevented.* Deposits of Carbonate of Lime. 298. It has been already stated that carbonate of lime often occurs in small proportions in deposits of earthy phosphates, Avhen the urine is decidedly alkaline. Its origin may then be explained by a decom- * An excellent double canula elastic catheter has been constructed for this purpose by Mr. Weedon, of Hart Street. 266 PATHOLOGY OF EARTHY SALTS. position of phosphate of lime by the carbonate of ammonia Avhich replaces the urea. In this state the carbonate of lime simply ap- pears as an amorphous powder, and its presence may easily be re- cognized by the addition of any dilute acid, Avhich dissolves it with effervescence. Care must, hoAvever, be taken to wash the deposit Avith water before adding the acid, for unless all traces of adherent carbonate of ammonia are remoAred, an effervescence will be excited by the acid, whether the calcareous salt be present or not. Very rarely, the carbonate is found crystallized in dense stellae, affecting the circular form, and apparently composed of excessively slender prisms (rhomboids ?) cohering at the centre (Fig. 58). The feAV instances of this kind I have met Avith occurred in neutral or faintly acid urine, a condition probably necessary to insure the regu- lar structure of the little crystalline masses. Polarized light shows that the structure of the mass is regular, its density decreasing with the Fig. 58. Fig. 59. distance from the centre, for a black cross becomes visible in each, on properly arranging the calc-spar prisms of the polarizing microscope. 299. Deposits of carbonate of lime are of constant occurrence in the urine of herbivora. These may be readily collected for examina- tion from the urine of the horse, in which they occur spontaneously. When examined by the microscope, after being washed Avith Avater, the particles of the carbonate are observed to be small transparent spheres, like globules of glass, and strongly refracting light. Al- lowed to dry, and examined after immersion in Canada balsam, their structure is beautifully distinct. Each sphere being made up of myriads of minute needles radiating from a common centre (Fig. 59); the Avhole having a circular and well-defined outline, in wbich respect they differ greatly from the carbonate deposited from human urine. With polarized light, these interesting objects present a series of concentric colored rings traversed by a black SILICIOUS DEPOSITS. 267 cross. These beautiful little bodies present a remarkable resem- blance to pearls, the well-known concretions of the pearl-oyster. Indeed, they may almost be regarded as urinary pearls. I have some in my possession from the bladder of an ox, presented to me by my friend Mr. Rose, of Swaffham, larger than mustard-seeds, and forming really good pearls. Some of the same kind have been described by my colleague, Dr. Alfred Taylor. In the urine of the horse, large crystals of oxalate of lime occur mixed with these spheres of carbonate of lime, and probably origi- nating from the presence of sorrel {Rumex Acetosa) in the hay on which the animal had been fed. The oxalate is generally in the octohedral form and amber-colored, but my friend Mr. Havers has shown me specimens in which the dumb-bell crystals coexisted Avith the ordinary oxalate and carbonate.* Some few cases are recorded, in Avhich little concretions and gravel of carbonate of lime have been passed in the urine, as if an excess of lime had been eliminated without its usual adjunct, phosphoric acid. I haAre, hoAvever, never met Avith any examples of this kind, although I have detected carbonate of lime in phosphatic calculi, both mixed with the mass of the concretion, or more rarely forming a distinct stratum. Carbonate of magnesia is said to occur occasionally in phosphatic deposits, its presence being in all probability due to the decomposi- tion of phosphate of magnesia by carbonate of ammonia (metamor- phosed urea). Deposits of Silicic Acid. 300. Silicic acid exists in infinitesimaily small quantities in some of the animal fluids, and therefore may possibly be met with as a urinary deposit. It was found in crystals, forming part of a calcu- lous concretion, by Dr. Yellowley,77 and some other instances of its occurrence have been recorded. Lassaigne78 found a calculus con- sisting of pure silicic acid in the urethra of a lamb, and Wurzer79 has given the analysis of one removed from an ox, in which silicic acid existed to the amount of thirty-eight per cent. It is, however, very necessary to be on one's guard respecting sili- cious concretions ; for as there is a popular notion that calculous mat- ter is bond fide gravel, whenever an imposition is intended, a silicious * The carbonate of lime occurs occasionally in the form of dumb-bells, of which a representation is given in atlas accompanying Lehmann's work, Pfcite I, fig. 2, by Dr. Otto Funke. 268 PATHOLOGY OF EARTHY SALTS. pebble is usuilly chosen to deceive the medical attendant. I have met Avith repeated instances of this, in which common rolled pebbles of quartz have been placed in my hands, Avith the assertion that they were actually passed from the bladder. This has usually occurred in hysterical girls, who labored under that most unintelligibly morbid desire of deceiving the doctor, by representing themselves as afflicted with some disease of the genito-urinary organs. I haA'e heard of in- stances in Avhich such pebbles have actually been thrust by a girl into her OAvn urethra, and thus have reached the bladder. In a case men- tioned to me by Dr. Christison, a piece of chlorite slate was found forming part of the supposed calculus, thus attesting its true origin. Within the last feAV days a young lady was brought to me for the pur- pose of being treated for a calculous affection, for which she had been under the care of her family attendant in the country. She had de- ceived him by exhibiting to him considerable masses of common pearl- spar, and she brought me a large quantity of the same substance in a bottle. She appeared to be excessively indignant on my telling her that this mineral could not be derived from the bladder. A case occurred many years ago in St. Thomas's Hospital, in which the late Mr. Cline operated, and removed a quantity of common coals from the bladder of a patient. Not long ago a gentleman had a calculus crushed by my colleague, Mr. Bransby B. Cooper. The case made a great impression on several members of his family, and none more so than a delicate susceptible nephew. He soon after complained of difficulty of micturition, passed an abundance of supposed gravel, and at last his urethra was blocked up by a calculus, which, however, with a little aid from his uncle was removed. This calculus, as well as the gravel he declared he had passed, although in quantity large enough to fill a small Avine-glass, was placed in my hands. All these presumed calculi were angular fragments of silicious pebbles, and owed their origin to a neighboring garden, and not to the bladder of this young gentleman. The reason for this imposition was quite un- intelligible. 301. As silicic acid has been found in calculi by such excellent observers as the late Dr. YelloAvley, and Dr. Venables, and as the ox and lamb mentioned by Wurzer and Lassaigne could hardly have been supposed to have put the silicious matter into their OAvn bladders, the occasional possible occurrence of silicic acid in urinary deposits and concretions must be conceded. Still, that it is extremely rare, all experience h-as proved, as indeed might be anticipated from the chemi- cal relations of this very refractory substance. CHAPTER XI. DEPOSITS OF ABNORMAL BLUE OR BLACK COLORING MATTERS. Blue and Black Deposits, 302—Braconnot's Cyanourine, 303—Diagnosis of, 304— Schmidt's Blue Pigment, 305—Indigo, 306—Diagnosis of, 307—Prussian Blue, 308—Alleged Presence of Cyanate of Ammonia, 309—Diagnosis of Prussian Blue. 310—Black Deposits described by Braconnot, Marcet, Dulk, and Dr. Hughes, 311. 302. In addition to the various tints communicated to urine by bile and blood (61, 314), certain peculiar coloring matters, strictly the products of diseased action, are occasionally, although very rarely, met with. These generally communicate to the urine a blue or black color. Three different blue pigments, at least, have been met Avith, viz., cyanourine, indigo, and percyanide of iron, and probably two black ones, melanourine and melanic acid. Blue, green, and black urine has been described by the ancients, but it is probable that the variety of tints so often mentioned by all physicians since Hippocrates, were produced by blood or bile modified by the state of the urine. 303. Cyanourine was first discovered by Braconnot,80 and has since been observed by Spangenberg, Gamier, Delens, and others. Urine containing it possesses a deep blue color, and by repose lets it fall as a blue deposit capable of being readily separated by the filter. It maybe freed from adhering mucus, uric acid, phosphates, &c, by Avashing with Avater, and digesting it in hot diluted sulphuric acid. The cyanourine may be precipitated from the acid solution by the careful addition of magnesia. It may also be obtained by boiling the blue deposit from the urine in alcohol, and evaporating the solution to dryness. 304. Diagnostic Characters.—Cyanourine is a tasteless and in- odorous dark blue powder, scarcely soluble in water, merely at a boil- ing heat communicating to it a brown color, which on the addition of an acid, becomes red; moderately soluble in boiling alcohol, being 270 PATHOLOGY OF ABNORMAL PIGMENTS. partly deposited on cooling. Diluted acids dissolve it, the solution being brown or red, according to the proportion of acid present. The solution in sulphuric acid leaves, by evaporation, a carmine-red ex- tract, Avhich dissolves in water, forming a brown fluid. Ammonia, lime-water, and magnesia, precipitate it unchanged from its acid solu- tion. Hot solutions of alkaline carbonates dissolve cyanourine, form- ing a red, Avhilst the pure alkalies yield a brown solution. Nitric acid converts this substance, like indigo, into nitro-picric acid. Heated in a glass tube, it forms an oily fluid which burns to a bulky ash. Cyanourine is distinguished from indigo by not subliming when heated in a tube, and from percyanide of iron by not yielding sesqui- oxide of iron when digested Avith carbonate of potass. 305. Another modification of blue coloring matter has been de- scribed by Dr. Schmidt as occasionally occurring in the urine of patients under hydropathic treatment at Grafenberg.113 The deposit consisted of ovoid globules about one-third the size of a blood-cor- puscle, and of a fine blue color. It was partially soluble in hot ether and alcohol forming blue solutions. Neither dilute sulphuric acid nor ammonia acted on it. Oxalic acid dissolved it, forming a blue solution. Potass, aided by heat, destroyed its color. No uric acid could be detected. The origin of this pigment is quite obscure; it is probably trace- able to some metamorphic change in a protein compound; for we know that albumen, when boiled with hydrochloric acid, forms a bluish solution. Also, when vegetable gluten, a body closely allied to albu- men spontaneously decomposes in the air, it becomes partly con- verted into a blue substance. Dr. Heller has lately stated that these curious deposits are merely metamorphosed uroxanthine or yelloAV coloring matter of urine, and has applied the name of uroglaucine to the blue pigment. He assumes, therefore, that it is identical with what I have described as purpurine, produced by the action of hydro- chloric acid on previously warmed urine. The statements of Heller, however, are mixed up with certain inaccuracies, and can hardly be admitted without more minute investigation. The pathological indications of these substances are quite unknoAvn. 306. Indigo.—This pigment, when taken into the stomach, as is occasionally done in the empirical treatment of epilepsy, finds its way into the urine, forming a blue deposit. It, however, appears proba- ble that indigo has occasionally been generated in the animal economy, and instances of this kind have occurred to Drs. Prout81 and Simon.82 INDIGO. 271 When this substance is present, the urine acquires a dark blue color, and by repose a deposit of the same hue falls. This, when collected on a filter, presents all the well-knoAvn chemical characters of indigo. The composition of this substance (C16NH502) approaches suffi- ciently close to that of some animal products to render its occasional development in the organism a matter of high probability.* 307. Diagnostic Characters of Indigo.—This substance dissolves in strong sulphuric acid, forming a purple solution. Nitric acid con- verts it into nitro-picric acid. Carefully heated in a tube, it sublimes in purplish-red crystals. By deoxidizing agents it is bleached, and white indigo produced; this, by exposure to the air, loses an atom of hydrogen by oxidation, and becomes blue. Simon83 gives the folloAA*ing as the best mode of detecting indigo in a blue deposit. Heat the deposit with a little grape-sugar in a mixture of alcohol and liquor potassae, the blue color disappears and yellow solution . is obtained. By agitation and exposure to the air the fluid assumes * Dr. Hassall, in the "Philosophical Transactions" (vol. cxliv), has a paper on this subject, in which he forms the following conclusions. That blue indigo is frequently formed in human urine, and, according to its quantity, imparts to the urine a deep green or bluish-green color; sometimes even forms a pellicle of nearly pure indigo over the whole surface of the liquid, at other times the quantity is so small as only to be detected by the microscope. That exposure to the air for some days, or some cause facilitating oxygenation, is necessary for the development of the indigo. That it is often accompanied by a brown extractive in considerable quantities, closely resembling, in its composition and chemical reactions, haematin. That the source of the indigo probably is altered haematin, a modified urine pig- ment (cyanourine and uroglaucine). That the urines in which the indigo occurred in largest-quantities are of a pale-straw color, readily becoming turbid and alkaline, and of low specific gravity. That it does not occur in healthy-urine, but frequently, though not exclusively, in the urines of patients the subjects of Bright's disease, or pulmonary affections. That it appears to be associated rather with a general morbid condition than with affection of any particalar organs. The relation between indigo and haematin appears, by comparing one atom of haematin with three of indigo. 1 atom of hasmatin == C44 H22 N3 O6 3 " indigo = C48H18N306 Or, according to the suggestion of Dr. Letheby, the relation stands thus: CHNO^c CHNO 1 atom of haematin = 44+22+3 6 2 atoms of indigo = 32+12+2+4 2 " water = 2 2 |= 1 " leucine = 12+12+1+4 44+24+3+8 J I 44+24+3+8 272 PATHOLOGY OF ABNORMAL PIGMENTS. a red, and eventually a green color, from the reproduction of blue indigo. The pathological indications of deposit of indigo are unknown. Whenever they are met with, care should be taken to investigate the patient's history, so as to discover whether this substance had been previously medicinally administered. 308. Sesqui-ferrocyanide yof Iron, or Prussian Blue.—This sub- stance was first found by M. Julia Fontanelle8* in the urine of a boy residing at Mont-Louis in the Pyrenees. He was laboring under severe colic, attributed to his having SAvallowed a quantity of ink. The blue deposit continued for a day or two after the attack, leaving the urine of its natural color, but containing some soluble cyanide, as a blue precipitate was produced on the addition of a salt of iron. Several other instances of Prussian blue deposits have occurred, and it is remarkable that in most of them iron has been accidentally or intentionally taken. These deposits are said to be artificially pro- duced by giving to a patient who has been taking some preparations of iron, a few doses of ferrocyanide of potassium. The origin of the cyanogen of the blue deposit can be readily ex- plained from the known composition of urea. We have seen that this substance may be regarded as a carbonate of ammonia (30), but it may also be considered as a cyanate of that base, thus— C N H 0 1 atom cyanic acid = Il atom cyanogen = 2+1 (1 -■ oxygen, = 1 1 " ammonia = 1+3 1 " water = 1+1 Composition of an atom of urea = 2+2+4+2 As Prussian blue consists of a combination of iron with cyanogen, if any cause determines the resolution of urea into the above proxi- mate elements, and iron be present, a precipitate of the sesqui-ferro- cyanide must be the necessary result. 309. It has been asserted by Professor Pietro Piretti of Rome,134 that when persons labor under the influence of malarious poison, the urea normally present in the urine is really replaced by cyanate of ammonia, and which can be obtained by careful evaporation. He adds, that during the successful treatment of ague by valerianate of quina, the cyanate gradually disappears, and is replaced by true urea. 310. Diagnostic Characters of Prussian Blue.—A blue powder MELANOURINE. 273 insoluble in water and alcohol. By digestion with liquor potassae its color is destroyed, sesquioxide of iron being set free, and a yelloAv solution of ferrocyanide of potassium formed. This solution is pre- cipitated blue by sesquisalts of iron, and hair-brown by sulphate of copper. The pathological indications of these deposits are unknown. 311. Melanourine and Melanic Acid.—Under these names have been described some black pigments which have been met with in urine. Their chemical properties are very ill-defined, and their origin and pathology alike obscure. It is more than probable that, in some instances at least, these pigments ought to be regarded rather as altered coloring matter of blood than anything else. a. Braconnot85 has described a black matter which he regarded as a weak salifiable base; it occurred in the blue urine (286), and re- mained in solution after the cyanourine fell. It was obtained after the latter had fallen, by merely boiling the clear urine, when the black matter coagulated and became insoluble. It in all probability was merely modified haematosine. b. The late Dr. Marcet86 met with a black matter in the urine of a child, unaccompanied by the ordinary constituents of the secretion. To this substance the name of melanic acid was applied by Dr. Prout. The urine in Avhich it occurred was like ink; it sloAvly deposited black flocculi after the addition of an acid. The black matter was insoluble in Avater and alcohol; nitric and sulphuric acids dissolved it, forming a black solution, which by dilution deposited the pigment unchanged. Alkalies and their carbonates dissolved it, and acids precipitated it from its solution. Its alkaline solution produced brown precipitates on the addition of metallic salts. c. Professor Dulk, of Konigsberg, has described a curious kind of urine of a blackish-gray color, passed by a patient affected with hepatic disease. On filtering it, a yellow fluid, which was merely diluted urine, passed through, and a black matter was collected on the paper. This Avas slightly soluble in nitric and hydrochloric acids; the solution being precipitated by tincture of galls. Professor Dulk suggests that this pigment was merely a highly carbonized haematosine, arising from the imperfect performance of the hepatic functions. d. Dr. Hughes, in the "Guy's Hospital Reports" (vol. ii, p. 52, 3d series), has narrated a few cases of black urine. In the first case, which was under his own oare, the urine, after the administration of 18 # 274 PATHOLOGY OF ABNORMAL PIGMENTS. creasote to allay vomiting, was of a dirty or brownish-black color, clear, unaltered by heat, nitric acid, or liquor potassae, even on boil- ing, without sediment, and remained unchanged in appearance after being kept in an open vessel for several days. There Avere no traces of blood-globules, or of any other solid substance, under the micro- scope. After death, miliary tubercles, and some recent pneumonic deposit, were found in the lungs. The cavity of the peritoneum ay as obliterated by strumous peritonitis. The structure of the liver was fatty. The common iliac, external iliac, and the commencement of the femoral vein of the left side, were filled with a clot of fibrin ad- herent to the coats of the vessel, and soft and whitish in the centre. The condition of bladder and kidneys is not mentioned. The second case was one of fever; the urine was of a bright blue color, but was throAvn away by the nurse before any analysis could be made. The third was a case of strumous peritonitis, in Avhich a black deposit occurred upon boiling the urine Avith nitric acid. These two cases were furnished by Dr. Wilks. Dr. Hughes in all alludes to nine cases, but excludes two, inasmuch as one of them was not Avatched, so that the coloring matter might have been improperly introduced, and in the other the urine was not examined. Of the remaining seven, creasote had been taken internally in three cases; in two, tar had been applied externally for psoriasis ; in six cases the urine was black and clear, and was but slightly, if at all, affected by chemical re- agents. In the seventh, a dense, black precipitate was thrown down by heat and nitric acid. Dr. Odling states, concerning this urine, that the black precipitate, on subsequent exposure, became an indigo- blue deposit. He considers that creasote and indigo belonging to two closely allied chemical families throws light upon its nature. CHAPTER XII. NON-CRYSTALLINE ORGANIC DEPOSITS. Use of the Microscope, 312—Elements of Blood in Urine, 313—Diagnosis, 314— Albumen, 315—Tests for, 317—Casts of Tubuli, 318—Haematosine, 320— Microscopic Characters of Blood-discs, 321—Pathological Indications, 322— Therapeutical Indications, 323—Of Albumen, 325—Purulent Urine, 327— Diagnosis, 328—Microscopic Characters, 329—Pathological Indications, 330— Mucous Urine, 331—Tests for, 332—Microscopic Characters, 333—Pathological Indications, 334—Therapeutical Indications, 335—Value of Injections, 337— Large Organic Globules, 338—Small Globules, 340—Epithelial Debris, 341— Spermatic Urine, 342—Microscopic Characters, 343—Connection with Oxalate of Lime, 344—Pathological Indications, 345—Treatment, 346—Growth of Torula in Urine, 348—Microscopic Characters, 349—Presence of Sugar in Urine, 350— Tests for, and Pathological and Therapeutical Indications of, 351—Fungoid Growths, 352—Development of Vibrio Lineola, 354—Milky Urine, 356—Kies- tein, 357—Diagnosis, 358—Connection with Pregnancy, 359—Fatty and Oily Urine, 367—Fat in Cells, 368—Chemical Characters of Chylous Urine, 370— Microscopic Characters, 371—Pathological Indications, 372—Case of, 373— Cases in the Mauritius, 375—Dr. Jones's Researches, 376—Uro-stealith, 378— Diagnosis of, 379—Characters of Urine, 380—Pathological Indications, 381. 312. The elements of the urinary deposits already examined, are capable of being easily recognized by their trystalline form or chemi- cal properties. Those which we have now to investigate are organic substances, often possessing organization, and sometimes enjoying an independent vitality. In the detection of these in deposits, micro- scopical examination is in almost every instance quite indispensable, and in many furnishes the only means for discovering their true nature. The best mode of examining these deposits microscopically, is to alloAv the urine to repose in a glass cylindrical vessel for a short time, decant the upper nine-tenths of the fluid, and then place a drop of the residue on a plate of glass. Carefully cover it with a piece of very thin glass, and submit it to the microscope. A good achromatic 276 NON-CRYSTALLINE ORGANIC DEPOSITS. objective of a quarter of an inch focus is generally sufficient for all these investigations, but it is sometimes necessary to use one of one- seventh or one-eighth of an inch, Avhen the object is very minute ; but to a person familiar with these observations a good half-inch glass is sufficient for almost.all cases. ELEMENTS OF BLOOD. 313. The blood may be regarded as made up of red corpuscles, floating in a fluid holding in solution the soluble elements of the blood, and possessing the poAver of spontaneous coagulation in consequence of the presence of fibrin. To this fluid the name of liquor sanguinis v is conventionally applied; a term first, I believe, used by my col- league, Dr. Babington, with whose ingenious and important researches on the blood most are well acquainted. All, or any of the elements of the blood may find their way into the urine, either as the result of mechanical violence to the kidney or any part of the genito-urinary track, of the irritation of a calculus, of organic disease, or any breach of surface of the mucous membrane of the kidneys or bladder ; or of sufficient pressure upon the renal veins to prevent the return of blood from the kidneys to the cavae (322). We may find in the urine serum of blood, alone or accompanied by red particles ; sometimes the liquor sanguinis is alone effused, and containing but a small proportion of coloring matter; or more frequently, all the elements of blood may be poured out together. Of the first of these, the urine of morbus Brightii, and of cases of anasarca resulting from scarlatina, are good examples; in these the urine is characterized by the presence of albumen, and in acute cases presents the dingy or smoky aspect cha- racteristic of the presence of coloring matter of blood, or of entire blood-corpuscles. Of the second condition, the urine in fungus haematodes of the kidney furnishes a good example; this is often ob- served to be of the color of infusion of roses whilst warm, and on cooling solidifies into a pink transparent mass, like red-currant jelly, retaining the figure of the vessel. Every case of idiopathic or symp- tomatic haematura affords examples of the presence of all the ele- ments of blood in the secretion. 314. Diagnosis of Urine containing Blood.—When blood is effused in any considerable quantity in the urine, it coagulates into blackish masses like pieces of black-currant jelly; and when it partly coagu- ALBUMINOUS URINE. 277 lates in the bladder, linear masses of clot of nearly the shape of leeches are passed from the urethra, often to the great distress of the patient by producing temporary suppression of urine. Even after this coagulation, the urine retains a port-wine color, and the micro- scope detects an abundance of entire blood-corpuscles ; although in a great proportion of them, the investing membranes have given way, and the colored contents become diffused through the urine. If too small a quantity of blood has been effused to give a decided red color to the urine, it will be frequently found possessing merely a dirty, dingy hue ; less frequently being of a pink color like the washings of flesh. In either case a sufficient number of blood-corpuscles will sub- side by repose to allow of their being readily identified by the micro- scope (321). The coagulation of urine by repose will readily indicate the pre- sence of the liquor sanguinis, as the fibrin it contains is the only spontaneously coagulating substance in the body. This element is very rarely effused by itself, being generally mixed with blood-cor- puscles, giving the coagulum a red color; or with a fatty matter, which causes the coagulum to assume the appearance of blanc-mange (370). Fibrin is, however, sometimes found deposited in the form of minute linear tubular masses, each being probably the cast of one of the uriniferous tubules (319). The red coloring matter, or haemato- sine, and the albumen of serum, do not present characters always sufficiently satisfactory to alloAV of their being identified without the application of reagents. 315. Albumen may readily be detected in urine containing it, by the production of an opacity by the application of heat. This ex- periment, where any amount of accuracy is required, should ahvays be performed in a clean test-tube, heated over a spirit-lamp. The common mode of heating it in a metallic spoon over a candle, although answering the purpose very tolerably when a glass tube cannot be procured, is infinitely inferior in the delicacy of its indica- tions. But if a spoon is used, it should be half-filled with the urine, and the extreme end of the bowl be placed over the flame of a candle. In this Avay the thin layer of urine near the end of the spoon soon boils, and the Avhite striae of this coagulated albumen which gradually diffuse themselves through the cooler parts of the fluid, enable a very small quantity of this substance to be detected. If a large quantity of albumen be present, the urine will become quite solid on the application of heat, and will vary from this state to the production of a mere 278 NON-CRYSTALLINE ORGANIC DEPOSITS. opalescence, according to the quantity existing in the urine. It is a curious fact, that the greatest amount of coagulation by heat, is often found in urine either free from or containing but a small quantity of the coloring matter of blood. The dingy-red urine in gra- nular disease of the kidneys, generally deposits less albumen by heat than when it is straw-colored, and nearly free from haematosine. 316. Albumen does not require actual ebullition for its coagulation by heat; if any be present in urine, the latter becomes opaque before a bubble of vapor is evolved. The addition of a drop of nitric acid to albuminous urine immedi- ately produces a copious coagulation of the albumen, but if only mere traces of the latter be present, the opacity first produced will disap- pear by agitation, and will reappear by the addition of a second drop of the acid. A drop of mixture of one part of nitric acid and three of hydrochloric acid, is much more decided in its effects, and more delicate in its indications than pure nitric acid. This admits of ready explanation in the evolution of chlorine by the abstraction of hydrogen from the hydrochloric acid, and thus one of the most delicate precipi- i tants of the protein compounds is set free. Another delicate test consists in the addition of a solution of ferro- cyanide of potassiun previously acidulated with acetic acid. This, like the last test, has the inconvenient property of precipitating other protein compounds besides albumen, as mucus, &c. 317. As a general rule, if urine becomes opaque by heat and on the addition of nitric acid, albumen is present. It is important to bear in mind that certain sources of fallacy exist Avhen only one of these tests is used. A. Heat will produce a Avhite precipitate in urine containing an excess of earthy phosphates (261). Distinguished from albu- men by disappearing on the addition of a drop of any acid. B. Heat being applied to urine containing deposits of urates, will sometimes, if actual ebullition be prolonged, produce a deposit of an animal matter (tritoxide of protein ?) insoluble in nitric acid. This is rare, but is distinguished from albumen by being deposited only after protracted ebullition. c. Nitric acid will often produce white deposits in the urine of patients under the influence of copaiba, cubebs,83 and perhaps some other resinous diuretics. Distinguished from albumen in not being produced by heat. D. Nitric acid will, in some concentrated urine, as in the scanty ALBUMINOUS URINE. 279 secretion of fever, often produce a dense buff-colored amor- phous precipitate of uric acid. Distinguished from albumen in not being produced by heat. E. Albumen may be present in urine and not be precipitated by heat, providing the secretion be alkaline. If, therefore, urine suspected to be albuminous, is capable of restoring the blue color of reddened litmus paper, nitric acid must be used as a test, as albumen, when combined with alkalies, does not coa- gulate by heat. F. Albumen may be present and yet escape detection from using dirty test-tubes ; a small quantity of an acid, or a little solu- tion of potass or soda, left in the tube, will prevent the pre- cipitation of albumen by heat from urine boiled in such a tube. G. It may occasionally happen that albumen may be present in the same incipient or hydrated state in which, according to Dr. Prout, it occurs in chyle.84 Heat scarcely affects this variety of albumen, except by ebullition ; but nitric acid immediately coagulates it. Where but small quantities of albumen are present in urine containing rather more than an average pro- portion of phosphate of soda, the application of heat scarcely produces any visible opacity until after the addition of an acid, and hence it is possible for the albumen to be errone- ously regarded as existing in the hydrated state; a condition Avhich has never occurred to me. In the later stages of dia- betes mellitus, I have occasionally found the urine previously warmed rendered opaque on the addition of nitric acid ; the precipitated matter appeared to me to resemble some of the oxygenized compounds of protein described by Mulder. 318. A remarkable substance allied to albumen has been detected in the urine by Dr. B. Jones in cases of rickets; it differs from albu- men in not being precipitated by heat or nitric acid. But on boiling the urine and allowing it to cool, a precipitate fell, which redissolved on the application of heat. Alcohol added to the urine readily coa- gulated this substance. Dr. Jones considers this substance to be allied to the albuminous matters (oxides of protein ?) found in the buffy coat of inflamed blood and in pus.* * In certain forms or stages of albuminuria or Bright's disease, or the desqua- mative nephritis of Dr. Johnson, the urine deposits a sediment, which consists of the altered epithelium, with its exudations, of the urinary passages ; it is of a dirty- white hue, easily diffused by agitation, and not unlike mucus, though at once dis- 280 NON-CRYSTALLINE ORGANIC DEPOSITS. 319. Albumen is occasionally found in the urine in a coagulated state, and presenting a tubular vermicular appearance. In this form tinguished from it by being dissolved and gelatinized by a solution of potash. I speak of certain forms, as now it is clear that under the head of albuminuria, or Bright's disease, are not only to be enumerated merely various stages of the same disease, but really and essentially distinct forms, constituting different diseases, varying in their origin, the rapidity of their course, their pathological indications, and in the microscopical appearances of the urinary sediments. Closely connected with this subject are the names of Bright, Barlow, and John- son, and I refer with much confidence to their writings, principally contained in the different numbers of the " Guy's Hospital Reports," for a full detail of the symptoms and treatment; I also have much satisfaction in alluding to a paper by Dr. Wilks,* in which he sums up clearly, but fully, the opinions held in the Medical School of Guy's, regarding the distinct forms assumed by this disease, as shown by the symptoms during life, and the microscopic appearances after death. I now proceed to notice the microscopic appearances of the sediments. 1. The renal cells (Fig. 60), when in situ, are polygonalf bodies, but become spheroidal or subspheroidal on detachment; they measure from about jsVo" to 5^5 Par'' of an inch in diameter, and contain nuclei, but are occasionally filled with granules or fat. They seldom occur alone, but are generally Fig. 60. found associated with epithelial casts or blood-discs, and mark the acute stages of desquamative nephritis, though any tempo- rary irritation of the lining of the renal tubes may cause their detachment and subsequent removal in the urine. 2. True epithelial casts are represented in Fig. 61,1, magnified about 200. They show the earliest deviation from the healthy condition. There may be some difference of opinion as to their structure. Some pathologists represent them as arising from the moulding of fibrin which has exuded from the Malpighian bodies, and entan- gled, in its passage through the tubes, blood corpuscles and the epithelial cells, previously shed by a process of desquamation. Such bodies are certainly found, but I shall refer to them afterwards as rather belonging to what have been called hyaline, or structureless casts. The true epithelial casts are about 7Jjj of an inch in diameter. They are elongated pieces of the epithelial lining of the convoluted renal tubes. The cells which stud their surfaces contain nuclei and granular mat- ter, and are rather more opaque than natural, and in parts detached. These casts, as well as the renal cells, are indicative of the acute stage of morbus Brightii, or desquamative nephritis. 3. Granular casts, are represented in Fig. 61,2, and Fig. 62, 3, and are of several kinds. The first are similar to the true epithelial casts, and differ from them only in that the cells are more decidedly filled with granular matter, and in points detached, leaving the basement membrane bare. Fig. 61, 2, mao-nified about 250. These may be called granular epithelial casts. In the next sta°-e the cells appear to have been disintegrated, and the granular matter is thickly sprinkled over the surface (Fig. 62, 3). In the next form the surface of the * "Guy's Hospital Reports," 2d series, vol. vii. f Kolliker, translation by Sydenham Society. ALBUMINOUS URINE. 281 it has been mistaken for minute hairs (Fig. 64). It is of common occur- rence in Bright's disease, even in the earlier stages, and the deposit appears to be made up of fibrinous (albumi- nous) casts of the uriniferous tubules of the kidney. Portions of epithe- lium are often found adhering to them, generally, according to Dr. G. John- son, loaded with fat (369). Urine con- taining these bodies lets them fall by cast is equally sprinkled with granules, but the origin is different; in the former the granules are developed within the cells, even before their separation; but in the latter they are formed from protein compounds secreted within the cavity Fig. 61. Fig. 62. of the tube. They are found, more especially the latter, in the chronic stage of desquamative nephritis, and are considered by Dr. Todd to have a close relation to chronic gout, and indicate a small contracted kidney with irregular surface, which he calls the gouty kidney. In cases of the gouty kidney, the urine in the first stage is in appearance healthy, only occasionally albuminous, and the sediment consists mostly of disintegrated epithelium; as the disease advances to the second and third stages the urine becomes paler, and permanently albu- minous ; and in the last stage contains large waxy or hyaline casts, jfa of an inch in diameter. 4. Fatty casts are represented in Fig. 62, 4, and are of various kinds. The earliest change is a deposition of fatty matter within the renal cells before their detachment. To the eye they resemble the epithelial casts, except that many of the cells contain fatty matter in the form of granules. In the course of the disease the deposition of fat increases, the cells lose their character, and there appear globules of fat studding a structureless membrane. Dr. Johnson states Fig. 64. 282 NON-CRYSTALLINE ORGANIC DEPOSITS. repose in the form of a dirty-white sediment, easily diffused by agitation, and not unlike mucus. A solution of potash dissolves that the oily or fatty casts, though occasionally occurring as a consequence of acute desquamative nephritis, belong more especially to the non-desquamative form of the disease. The urine in the early stage is albuminous, but contains neither epithelium nor casts. As the disease progresses, a light cloudy sediment is deposited, which is found to contain small waxy casts of about jgVo" 0I" an mcb in diameter, with oil globules or oval cells with more or less oily contents. Some of the oil may be the product of the metamorphosis of fibrinous or albuminous exudations. 5. Hyaline, structureless, or waxy casts, are of different sizes, and consist of fibri- nous exudations, whether from the Malpighian bodies or from the walls of the tubes, either before or after epithelial desquamation, and moulded in the tubu- lar form during their passage down the tubes. 1. The smaller size measures about -f ffVo" 0I" an mca iQ diameter, and are the product of the fibrinous exuda- tion from the Malpighian bodies while the epithelial surface is unbroken. Their presence marks the acute stage of the non-desquamative form of the disease. 2. The large size measures about T^jj of an inch, and appears to originate from fibrinous exudation within the tubes after the detachment of the epithelial cells. Fig. 63. 6 Fig. 63, 5 and 6, representing the two sizes, are taken from Dr. Johnson's work. They are rather too coarse ; occasionally they appear in the field as mere tubular shades, with perhaps one or two altered renal cells, or granular matter attached. 6 and 7. Pus- and blood-casts are generally formed by the entangling of the pus or blood-corpuscles in the moulded fibrin; in fact are hyaline casts studded with pus-cells or blood-corpuscles. But occasionally they appear as epithelial casts, having the cells either replaced by, or studded with pus or blood corpuscles. The latter indicate the existence of acute disease, calculous irritation, or malig- ALBUMINOUS URINE. 283 and gelatinizes the deposit, which will at once distinguish it from mucus. The tubular masses of albumen are seldom larger than 51 or totj inch, generally much shorter, and in diameter correspond closely Avith that of the tubuli uriniferi, never exceeding T0^ inch. This deposit may be regarded as almost pathognomonic of Bright's disease. 320. Hcematosine (C44H22N306Fe) is regarded as the coloring mat- ter of the blood, normally contained Avithin the delicate sac of the corpuscles, particles, discs, or globules of blood; all these terms being synonymous. It is not knoAvn whether it is the product of the metamorphosis of the true coloring matter of the blood, or whether it only bears the same kind of relation to that substance as does coagu- lated albumen to that principle in its fluid state. It cannot be sepa- rated in a soluble condition from the globulin. When pure, it occurs as a dark-brown, slightly lustrous mass, which on trituration adheres to the pestle. It has neither taste nor smell; is insoluble in water, alcohol, ether, acetate of the oxide of ethyl, and fatty and volatile oils. Mulder, hoAvever, regards it as slightly soluble in fatty and ethereal oils. It dissolves readily in weak alcohol, to which sulphuric or hydrochloric acid has been added, forming a brown solution, which being saturated with an alkali, assumes a blood-red color. After trituration with sulphate of potash it dissolves for the most part in water. Even very dilute solutions of the caustic alkalies and their carbonates in water or alcohol dissolve it in almost every proportion. Chlorine dissolves the perchloride of iron and throws down white flocculi, soluble in alcohol and ether but not in water, which, dried at 100°, appear as a light-colored powder, unaffected by hydrochloric acid, but soluble in alkalies, forming a reddish solution, consisting of nant disease. In acute disease, the epithelial casts are also present; in cases of calculus, the other diagnostic signs will throw light on the nature of the case; and in the third, or malignant disease, carcinomatous cells will probably be pre- sent, and aid the diagnosis. Though in these three instances the investigation of the general symptoms would probably be sufficient, yet when the mind is bent on elucidating a nice point in diagnosis, the microscopic examination is of the utmost value. Pus-casts indicate pyelitis, or suppurative disease of the epithelial lining of the pelvis and tubes of the kidney. This may originate in,—1, morbid conditions of the blood ; 2, the application of external violence; 3, from changes consequent on retention of urine; and 4, from the inflammation caused by cal- culous irritation.* * Dr. Johnson, " On the Diseases of the Kidney." 284 NON-CRYSTALLINE ORGANIC DEPOSITS. chlorous acid and haematosine freed from iron, according to Mulder, who gives the following as the composition of the latter : Carbon, 44 atoms, 65*347 Hydrogen, 22 " . . 5-445 Nitrogen, 3 " . . 10*396 Oxygen, 6 " . 11-881 Iron, 1 " . . 6*931 100000* When haematosine is present, the urine is always more or less colored by it, and a few entire corpuscles are almost always found floating in the fluid. It never occurs unaccompanied by albumen, and being acted upon by tests in a similar manner, the remarks already made on the latter substance (317) apply equally to haematosine, ex- cepting that the deposits produced by heat or nitric acid are always brown instead of white. M. Pariset105 has proposed the following process for the detection of blood in urine, as least liable to fallacy. Boil the urine and filter it. Brown coagula of haematosine and albu- men will be left on the filter; pour on these some liquor potassae, and if haematosine be present, a greenish solution will pass through, from which hydrochloric acid will precipitate white coagula of protein. The following, in addition to those mentioned as affecting albumen, are the most serious sources of fallacy in the detection of haematosine. 1. Purpurine, when present in the urine (184), will often com- municate to it so intense a color as to cause the patient to report his urine to be bloody. Distinguished by not being affected in color or transparency at a boiling heat. 2. Uric acid, when present in concentrated urine, as in the first week of fever, is often immediately precipitated by nitric acid, brown coagula, much resembling those of haematosine, falling; but really composed of extremely minute crystals of uric acid. Distinguished by not being affected by heat, and by the microscopic character of the deposit (124). 3. Bile, or at least its coloring ingredient, often tints the urine of a deep brown color, and may lead to an unfounded suspicion of the presence of blood. One or other of the following tests will at once detect bile or its coloring matter in a fluid. a. Pour on a white plate, or sheet of writing-paper, a small quan- * Lehmann. ALBUMINOUS URINE. 285 tity of the urine, so as to form an exceedingly thin layer, and care- fully alloAv a drop or tAvo of nitric acid to fall upon it. An immediate play of colors, in which green and pink predominate, will, if the color- ing matter of bile be present, appear around the spot where the acid falls. b. (Pcttenkofer's Test.)—To a small quantity of the suspected urine in a test-tube, two-thirds of its volume of sulphuric acid are to be carefully added, taking care that the mixture, which soon becomes hot, never exceeds a temperature of 144°. Three or four drops of a solution of one part of sugar to four of water are then added, and the mixture shaken. A violet-red color becomes developed if bile be present. My own experience of this test has not led me to regard it as either a generally useful or trustworthy one, and in applying it there are numerous sources of fallacy to be guarded against, arising chiefly from the action of sulphuric acid on sugar, which develops a red color in the absence of bile. A mixture of albumen or oil with sugar Avill, even in very minute quantities, produce a purple or scarlet color, with sulphuric acid, as Raspail long ago stated. c. (Heller's Test.)—Add to the urine any albuminous fluid, as serum of blood or white of egg; then pour in sufficient nitric acid to produce a considerable albuminous coagulum. On examining this after a short repose, it will be found to possess a bluish or green color if bile-pigment existed in the urine, whilst, if none were present, the deposited mass will be Avhite or merely slightly yellow. d. It may occasionally happen that bile may exist in the urine so modified (oxidized ?) as not to exhibit the characteristic reaction with acids. This has been observed in cases of cholera; the urine, although containing modified bile, became merely imperfectly reddened by it. Ammonia then becomes a valuable test, as it produces an immediate deep-red color.106 The fallacies of this test are the accidental pre- sence of A'egetable coloring matters, especially rhubarb, and the newly observed fatty body, stearolith (378). 4. Hosmatoxylon, administered as a medicine, "will often, by the red color it communicates to the urine, lead to an unfounded suspicion of the existence of haematosine. Distinguished by the dark precipi- tate produced by sulphate of iron, and by absence of coagulation by heat. 5. Pareira, Chimaphila, and even Senna, will sometimes commu- nicate a dark-broAvn tint to the urine; but the absence of all the cha- racteristics of albumen and haematosine will distinguish it from the color produced by blood. 286 NON-CRYSTALLINE ORGANIC DEPOSITS. 321. Microscopic Characters of Blood-Corpuscles.—These furnish the readiest and most infallible mode of detecting blood in the urine. To discover them, if the urine possess a red or broAvn color, a drop taken from it after agitation will be sufficient to allow their ready de- tection. But if the urine be barely colored, it is better to alloAv it to repose for some hours, and examine a drop from the bottom of the vessel, to which the corpuscles generally sink Avith readiness. If blood be recently effused into the bladder from some mechanical injury, the components are observed not only unaltered in figure, but even adhering in rouleaux (Fig. 65), as when a drop of fresh blood unmixed with urine is examined. If the blood is present in smaller quantity, or even if copious, but more slowly effused, all traces of the linear arrangement of the cor- puscles is lost, and they are found separate and floating in the fluid (Fig. 66). On first examining the object, the corpuscles resemble little rings; an optical illusion arising from their being nearly emptied of their contents by exosmosis. The corpuscle thus becoming a doubly concave disc, a change which receives a ready explanation by the very interesting demonstration of the real structures of the cor- puscles by Dr. Rees.90 Sometimes an appearance of a spiral fibre, like that described by Dr. Martin Barry,91 is observed. This ap- Fig. 65. Fig. 66. pearance of the supposed fibre has always appeared to me to be an optical illusion arising from the delicate investing membrane of the nearly empty corpuscle collapsing in circular folds round the nucleus, as a centre. By longer repose in urine, the corpuscles alter still further in figure, becoming irregular at their margins, as is shown in part of Fig. 66.* * The blood-casts which in many cases of haematuria are found in the urine have been already noticed, in connection with the subject of renal casts. They are gene- rally hyaline or structureless casts, entangling in their passage downwards the cor- puscles of the blood. THERAPEUTICAL INDICATIONS. 287 Whatever are the modifications presented by the blood-corpuscles in urine, their non-granular surface, uniform size, and yellow color under the microscope, will always be sufficient to identify them. 322. Pathological Indications.—Whenever the elements of blood appear in the urine, there is ample proof of the existence of active or passive hemorrhage. If, however, the quantity of haematosine be so minute as barely to tint the urine, it is probable that the albumen present may be readily secreted {i. e., without breach of surface) by the kidney assuming an abnormal function. This is probably the case in the peculiar disease of the kidney so laboriously and successfully elucidated by Dr. Bright, the effusion of albumen being, in the first stage of the disease, an attempt to relieve a congested condition of the kidney, and must be regarded as an effort of diseased function; whilst the structural changes which afterwards occur unfit the kid- ney for eliminating the normal nitrogenized elements of urine, and the chief relic of its secreting power is found in the separation of water and albumen from the blood. On the recession of some affec- tions, in which the cutaneous function is temporarily impaired or suspended, especially in scarlatina, a congested kidney occurs as an almost necessary result, and albuminous urine results as in the first stage of morbus Brightii. During the existence of pregnancy, and perhaps of some pelvic tumors, the urine is occasionally and tempo- rarily albuminous ; a fact first noticed by my colleague, Dr. Lever,92 and meeting with a probable explanation from the possible existence of pressure on the emulgent veins, a condition which the researches of Dr. Robinson92 have shown to be capable of producing congestion of the kidney and serous urine. Where blood is present in large quantity, or coagula are mixed with the urine, hemorrhage from some breach of surface is indicated ; and the immediate cause of this, whether a ruptured vessel from excessive congestion in any part of the urinary organs, the irritation of a cal- culus, mechanical violence, or malignant disease, as fungoid degene- ration,* can alone be made out by a careful examination of the exist- ing symptoms. 323. Therapeutical Indications.—These will vary according to the immediate cause producing the sanguineous or albuminous effusion. Of course, Avhere active hemorrhage exists, the treatment Avill be di- rected by the view taken by the practitioner of its immediate exciting * The source may mostly, in these cases, be determined by the appearance of compound cells when the urine is placed under the microscope. 288 NON-CRYSTALLINE ORGANIC DEPOSITS. causes. Absolute rest, the local application of cold to the hips and loins, the relief of congestion of the kidneys by local or general blood- letting, free action on the bowels by saline (sedative) purgatives, with dilute acids, will constitute the essential part of the therapeutic agents. The administration of the acetate of lead is frequently of great service, but it should be administered boldly, and in tolerably large doses, for a short time; a plan far more effectual than that generally followed, of giving small doses for a longer period. In doses of three or four grains, with one-fourth of a grain of opium in a pill, repeated evTery two hours until six or eight doses are taken, this remedy is very successful. I, however, prefer administering the lead in solution; in this form it is readily taken by the patient, and seems to act most efficiently, as in the following formula: R. Plumbi acetatis, gr. xxiv ; Aceti destillati, fgj ; Syrupi papaveris, ffj ; Aquae rosae, f*§iij • Aquae destillatae, f§iv. M. fiat mistura. Cujus sumat aeger coch. ij magna omni secunda, hora. If care be taken to keep the bowels acting by a saline purgative, no fear of any unpleasant consequences from the lead need be appre- hended during the period required" to give it a fair trial. The gums should, however, be watched, and if the blue edge described by the late Dr. Burton94 be seen, the medicine must be at once given up. 324. No remedy has, howeA^er, appeared to me to be of such extra- ordinary value in the treatment of haematuria, as gallic acid. I have seen this drug arrest for many weeks bleeding from an enlarged and (fungoid ?) kidney, after all other remedies had failed. It should be given in doses of at least five grains in a draught, with mucilage, and a little tinct. hyoscyami, and repeated at short intervals. This drug really acts as a direct astringent, reaching the capillaries of the kid- ney, and finding its way into the urine, which soon becomes so im- pregnated with it as to be changed into ink on the addition of a few drops of tinctura ferri sesquichloridi. I believe it to be very important to take every precaution that tannic acid or tannin is not substituted for gallic acid. Closely allied as these bodies are, and readily as the former is converted into the latter, merely by a few hours' exposure of its solution to the air, still there is great reason to believe that tannin is never absorbed as such into the circulation. Professor Miilder182 has explained this on the HEMATURIA. 289 power it possesses of coagulating albumen, and hence, unless it under- goes some previous change, it cannot possibly circulate in the blood, as it Avould immediately coagulate it. Mulder has declared his belief that if the astringent matter present in two ounces of cinchona bark could, by any possibility, be absorbed into the blood, it would, in this manner, produce instant death. 325. When the only constituent of blood present in the urine is albumen, the treatment will vary according to Avhether the kidney is merely congested or structurally affected. The treatment of the latter class of cases has been fully detailed elsewhere,95 so that it is unnecessary for me to give any account of it. The treatment of the acute stage of congested kidney, occurring in children in the dropsy after scarlet fever, when the urine is albuminous, and dingy from the presence of red particles, is, in the great majority of cases, so suc- cessful and uncomplicated, that it is important to allude to it.* I may remark, as a prophylactic remedy, that the warm bath is invaluable ; I scarcely recollect, even in a large experience, a case of dropsy after scarlet fever occurring when the Avarm bath was daily used as soon as the skin began to exfoliate, and continued until a perspiring healthy surface was obtained. When anasarca has occur- * In the chronic stages of the various phases of disease known as Bright's disease, as in the acute stages, the point of first importance is attention to the skin and the secretions generally, avoiding, if possible, mercurials and diuretics. The accumulated experience of many years has shown that patients cannot bear the operation of mercury; in some cases, indeed, the smallest quantity, even a couple of grains of blue pill, has produced violent and dangerous salivation. And I think that I may also state that general experience is equally against the use of diuretics. In the early stages the tubes are blocked up by disintegrated epithelium, and the blood is already overcharged with a diuretic in the shape of the retained urea, which in the latter stages, on the removal of the obstruction, renders the use of any other diuretic unnecessary. I am not unaware that the treatment by diuretics has been advocated by Dr. Burrows ; but the pathology of the disease, as at present under- stood, certainly contraindicates their use, and the more rational course of treat- ment is attended with such a degree of success as to disincline me to run the risk of recommending remedies which may be either dangerous or unnecessary. The measures best adopted to restore and preserve the functions of the skin are—warm baths, flannel clothing, and antimony ; while the compound jalap powder, with or without elaterium, in doses for the adult of two scruples of the powder, with one-sixth of a grain of elaterium, is the most effectual remedy for relieving the bowels. When the kidneys begin to act, as shown by the increased secretion of the urine, and the skin is perspirable, chalybeates are indicated ; and I have myself found the tincture of the sesquichloride of iron, in doses of fifteen minims, with or without an equal quantity of tincture of henbane, the best mode of prescribing them. 19 290 NON-CRYSTALLINE ORGANIC DEPOSITS. red, strict confinement to bed, or at least to a Avarm room, must be enjoined, the warm bath used tAvice a Aveek, and a free action on the skin encouraged. The bowels should be kept acting by the pulvis jalapae compositus, and the antimonii potassio-tartras administered in doses varying from one-tAvelfth to one-eighth of a grain, four or five times in the twenty-four hours, according to the age and strength of the patient. A bland and nearly fluid but moderately nutritious diet should be enjoined. This plan must be continued until all anasarca has vanished, a supple and perspiring surface obtained, and urine free from albumen. The remedies may then be gradually left off, a more nutritious diet alloAved, and the ammonio-citrate of iron administered thrice daily, in doses of three to five grains, to remove the anaemiated state of the patient. On leaving the bedroom, a flannel Avaistcoat, extending to the loins, should be worn for some time. This treat- ment has been almost invariably successful in every case I have employed it, and I may remark that I have never in these cases wit- nessed the excessive prostration said by some to be the almost neces- sary result of the employment of antimony in the diseases of children. 326. I cannot too anxiously caution the practitioner against the employment of the still too generally used diuretics in these cases. A more mischievous practice can hardly be employed, for on the recession of scarlatina the lining membrane of the tubuli is often left inflamed, the tubules themselves being obstructed by an abundance of desquamatory epithelium. The necessary effect of stimulating diu- retics is to determine blood towards already oppressed kidneys; to injure organs, moreover, Avhose important depurating offices are so necessary to the continuance of life, and the integrity of which dimi- nishes as congestion increases. Bloody urine, the non-eliminatioh of effete nitrogenized elements from the blood, and death by convul- sions, have repeatedly resulted from this most serious error.* PURULENT DEPOSITS. 327. Pus is not unfrequently met with in the urine, as the result of suppuration of the kidney, or of some portion of the genito-urinary mucous membrane, or of abscesses from adjoining viscera or ab- normal growths, bursting into the urinary cavities. There is said also to be occasionally another source of purulent matter in the urine See note, p. 289. PURULENT DEPOSITS. 291 viz., when a vicarious discharge of pus occurs from the kidneys. Many pathologists, especially in Germany, have declared their belief in the frequent occurrence of this phenomenon, and cases have been recorded of empyema disappearing contemporaneously with the dis- charge of purulent urine. The subject is, however, still obscure, and any opinion must in the present state of our knoAvledgelbe given with caution (330). At present, however, there does not exist a single satisfactory proof that bodies, the size of pus-particles, can ever enter or escape through the walls of capillary vessels without breach of structure. In all cases Avhere a purulent deposit is really absorbed into the circula- tion, independently of breach of surface, it is, in all probability, first metamorphosed into soluble products. 328. Characters of Urine containing Pus.—Generally acid or neutral, unless long kept, and sIoav to assume putrefactive change. By repose, pus falls to the bottom, forming a dense homogeneous layer of a pale greenish cream color, never hanging in ropes in the fluid like mucus (unless the urine is alkaline), and becoming by agi- tation uniformly diffused through it. The addition of acetic acid neither prevents this diffusion, nor dissolves the deposit. If a portion of the deposited pus be agitated with an equal quantity of liquor potassae, it forms a dense translucent gelatinous or mucous mass, often so solid that the tube can be inverted Avithout any escaping. On decanting some urine from the deposited pus, the presence of albumen can be detected by heat and nitric acid (317). When pus is agitated Avith ether, a quantity of fat is dissolved, Avhich is left in the form of yellow butter-like globules, when the ether is allowed to evaporate in a watch-glass. The peculiar action of liquor potassae, coupled with the albuminous state of the urine, constitute the best test for the detection of pus. If the urine containing pus happen to be alkaline and to contain free ammonia, the character of the deposit is completely altered, becoming viscid, not readily diffused by agitation through the fluid, and resembles in appearance some varieties of mucous deposits. The detection of albumen in the supernatant fluid by the addition of nitric acid, and the conversion of the deposit into a white granular mass, destitute of its previous viscidity by the addition of acetic acid, will generally enable a safe opinion as to the nature of the deposit to be arrived at. A source of fallacy may occur in the urine of women, which may be supposed to contain pus, merely from an admixture of 292 NON-CRYSTALLINE ORGANIC DEPOSITS. leucorrhoeal or other vaginal discharges. In such specimens, traces of albumen can generally be detected in the urine, whilst the deposit, instead of presenting the dense homogeneous layer so characteristic of pus, is flocculent and granular, although often extremely copious, and readily gelatinizing with liquor potassae. 329. Microscopic Characters of Pus.—This substance consists essentially of round granules, or particles rather larger than blood- corpuscles, floating in an albuminous fluid, or liquor puris, differing essentially from liquor sanguinis, in the absence of a spontaneously coagulating power. When a drop of a purulent fluid is placed under the microscope, the particles become visible ; they are white, roughly granular exteriorly, and are much more opaque than blood-corpuscles (Fig. 67, a). On the addition of a drop of acetic acid, the interior of the particle becomes visible, and is found to be filled Avith several transparent bodies or nuclei, as shown in the figure b. Hence pus is usually considered as a regularly organized body, consisting of a granular membrane envelop- ing transparent nuclei; being in fact a nu- cleated cell. The microscopic examination of a suspected purulent deposit is essential, for, as Ave have seen, phosphatic sediments -will sometimes so closely resemble pus, as to deceive a practised eye (259.)* 330. Pathological Indications.—Whenever pus occurs in urine, it generally indicates the existence of suppurative inflammation in some part of the urinary apparatus. It must, however, never be forgotten that an abscess from any adjoining viscus may discharge its contents by an ulcerated opening into the pelvis of a kidney or into the bladder. Suppuration in a more distant organ, will often, by bur- roAving under the peritoneum or through muscles, be discharged by the urinary apparatus. An empyema has thus been known to find its way to the kidney, emptying itself through an ulcerated opening, and be discharged with the urine. This is in all probability the mode in which the purulent contents of a diseased pleura have escaped, in the supposed cases of metastatic discharges of pus from the kidney, which have been repeatedly published on the Conti- nent (327). * Pus-casts have been already noticed. mucus. 293 The therapeutical indications of purulent urine will, of course, strictly depend upon the nature of the disease under which the patient labors, and the source of the suppuration. MUCUS. 331. The quantity of mucus present in healthy urine is very small, being merely sufficient to form a barely visible cloud. When collected on a filter it dries, forming a thin varnish-like layer. Characters of Urine containing an abnormal proportion of Mucus.—The quantity of mucus in urine may vary under the influence of different degrees of irritation or inflammation, from a mere flocculent cloud to the production of a fluid so viscid and tena- cious, as to be capable of being poured from one vessel to another in a long continuous rope. Urine containing a deposit of mucus is generally alkaline, and soon undergoes a putrefactive change, becoming ammoniacal even in the bladder, if long retained. If the urine itself be acid when first voided, the mucus it deposits will always restore the blue color of reddened litmus. Thus a specimen of urine will frequently redden litmus paper, and the blue color Avill be restored by allowing it to sink into the mucous deposit at the bottom of the vessel. Indeed, as a general rule, all mucous secretions exert an alkaline action on faintly reddened litmus paper, a condition which becomes better marked under the influence of inflammatory action, however slight. In common cynanche tonsillaris, in which the compound in- fusion of roses is often used as a gargle, nothing is more common than to observe the red mixture ejected from the mouth quite green, the Avliite fur on the tongue presenting a similar color, the quantity of alkali in the mucus covering the fauces and tongue, being sufficient to neutralize the sulphuric acid, and to change the red color of the roses to green. Providing the urine is even slightly acid, a deposit of pus and mucus may be readily distinguished, as the former will appear as a homogeneous opaque layer, readily miscible by agitation with the urine ; whilst the latter will appear gelatinous, and hang in irregular masses, often entangling large air-bubbles, and>no agitation, however violent, can completely mix it with the urine. There can never be any difficulty in distinguishing between purulent and mucous deposits 294 NON-CRYSTALLINE ORGANIC DEPOSITS. by simple inspection, unless the urine be alkaline (264); or a large quantity of earthy phosphates (262) be mixed with the mucus, which thus acquires great opacity, and may be readily mistaken for pus without microscopic examination. 332. The action of acetic acid on mucus is very characteristic, and is of great value in discriminating between that fluid and pus. "When a fluid containing the former is mixed with acetic acid, the fluid part of the mucus in which the particles float, coagulates into a thin, semi-opaque corrugated membrane, presenting an appear- ance so peculiar that once seen it can never be mistaken. Mucus contains no albumen in a state allowing of coagulation by heat or nitric acid. (317); hence simply mucous urine can never be albuminous like pus, unless the albumen be derived from some other source. Agitated with ether, mucus gives up but mere traces of fat, and in this respect also differs from pus. 333. Microscopic Characters of Mucus.—Mucus, like pus, is composed of granular round particles, floating in a fluid, which is viscid and glairy, and does not contain uncombined albumen. Un- der the microscope, it is nearly, if not quite, impossible to distin- guish between the pus and mucus particles—in fact, it may be questioned Avhether they are not identical.* Where mucus and pus essentially differ is not so much in the nature of the particles as in the fluid secreted Avith them, and in Avhich they float; the liquor puris being albuminous and coagulable by heat (328), the liquor muci not being affected by it. Treated with acetic acid, the mucus particle exhibits internal nuclei similar to those seen in pus (329). The particles are by no means so numerous as in the latter, and are perhaps not so distinctly granular ; a rather higher magnifying power being required to show satisfactorily the granular surface of the mucus, than of the pus particle. Even this slight distinction may depend rather upon the greater refractive power of the fluid part of the mucus, concealing the irregularities on the surface of the mucus particle from ready observation, than upon any real difference between them. 334. Pathological Indications of Mucous Deposits.—Their gene- ral indication, that of an irritated or inflamed state of the genito- * They are really identical, both being secreted by a membrane in a state of nflammation. MUCUS. 295 urinary mucous membrane, which may be excited by a variety of causes. Independently of idiopathic acute or chronic cystitis, cer- tainly rare affections, the mucus may be the result of the disease termed cystorrhcea, probably really a low form of chronic inflamma- tory action, in which a large quantity of secretion is poured out from the mucous membrane of the bladder, and gives great distress by producing much irritability of the viscus, and interfering Avith the free Aoav of urine. Mucous deposits are more generally symp- tomatic of some mechanical cause irritating the vesical mucous membrane, as the presence of a calculus, or the existence of a stric- ture in the urethra, or of some other mechanical obstruction to the free escape of urine. Cystorrhoea, accompanied by a copious se- cretion of phosphates by the vesical mucous membrane, has been already alluded to (296). 335. The treatment of mucous urine must strictly depend upon the nature of the exciting cause. It can never be treated as a special affection, except perhaps in cases of cystorrhoea or chronic cystitis, when much advantage is gained by the employment of cer- tain remedies which are supposed to exert a specific action over the secreting function of the mucous membrane of the bladder. This - specific action, after all, generally depends upon the astringent ele- ment of the drug reaching the urine, and thus acting nearly as directly as an injection of alum into the vagina does in leucorrhoea. Most of the vegetable astringents containing gallic acid are here available, but some have obtained a more especial reputation, "from their containing some elements which enable them to fulfil more than one indication, and hence become applicable in particular cases. Among these, the leaves of the arctostaphylos uva ursi, barosma cre- nata or buchu; chimaphila umbellata, and root of the pareira brava, are the most celebrated. Although these are often prescribed, as if they all acted in the same manner, in checking the. excessive mucous secretion, yet each fulfils a second indication, which never should be lost sight of. Thus we find in the— Uva ursi, a simple astringent, but slightly diuretic. Chimaphila, a less active astringent, but freely stimulating the kidneys. Buchu, a stimulating tonic, diuretic, and diaphoretic; AA'hose active principle (volatile oil) is excreted by the kidneys. Pareira, a narcotic (?) tonic diuretic. 296 NON-CRYSTALLINE ORGANIC DEPOSITS. 336. When a microscopic examination of the mucus has shoAvn that an excessh'e elimination of phosphates does not exist, the irri- tability of bladder and cystorrhoea are remarkably relieved by the administration of alkalies, especially of the bicarbonate of potass Oj) or liquor potassae (^xx—5j) Avith a sedative, as tinct. hyoscy- ami (5ss), in an infusion or decoction of one or other of the above drugs. When the earthy salts are copiously excreted, the dilute phosphoric acid (3ss) may be advantageously substituted for the alkalies, although it must not be supposed that the presence of a moderate quantity of phosphatic deposit with the mucus necessarily contraindicates the administration of alkalies. We have already seen that the alkaline state of urine and deposition of earthy salts is a result of the action of unhealthy mucus, secreted by the blad- der, upon the urine (275). When the administration of alkalies is capable of controlling the secretion of mucus, these remedies will lessen and even remove the earthy deposits instead of increasing them, by checking the formation of the substance which induced their precipitation. In several cases, I have seen marked relief follow the use of benzoic acid (gr. ix) given in dec. pareirae (§iss), Avith a minute dose of acetate of morphia (gr. ^—4J. In one very severe case, AA'hich was for some time under the joint care of my colleague, Mr. Cock, and myself, in which such an enormous quan- tity of alkaline purulent mucus Avas secreted from a chronically in- flamed bladder, that micturition was often quite prevented, from the urethra becoming temporarily blocked up with the secretion, so much temporary relief Avas afforded by this medicine that the patient de- clared he could not make water without it. The pareira indeed, as remarked by a high authority, Sir Ben- jamin Brodie,97 is of the greatest use, Avhere the mucus is copious and opaque, and the distress of the patient, from a constant desire to empty the bladder, considerable. In mild cases, where the nor- mal character of the mucus is scarcely changed, we may employ the uva ursi; the chimaphila being preferred if the kidneys are inactive. The buchu, from its free action on the skin, being of most service where a highly irritable state of kidney or bladder exists. 337. I cannot avoid alluding here to the very great advantage resulting from freely washing out the bladder with warm water in these cases as well as in phosphatic urine (297). By this treat- ment all the alkaline urine and portions of mucus generally left behind are washed out, and the bladder is placed in a much more ORGANIC GLOBULES. 297 satisfactory condition. The relief even temporarily given to the patient by injecting the bladder Avith Avarm Avater is so great, as to justify its frequent use even in cases Avhere the mucous membrane is so extensively diseased as to preclude all hope of ultimate recovery. I have found it of peculiar value in the treatment of cystorrhoea following lithotrity. In a very interesting case, which I recently saw with Mr. Hodgson, the irritability of bladder and secretion of mucus nearly ceased, after a few injections of warm Avater. Even in those most hopeless cases, paralysis of bladder from spinal paraplegia depending upon incurable disease of the spine, the relief obtained by this remedy is most remarkable. The comfort of the patient and of his attendant is not a little increased by the dis- appearance of the fetid urinous odor, which is too generally a seri- ous source of annoyance. ORGANIC OR EXUDATION GLOBULES. 338. There are tAvo other forms of globules allied to mucus occa- sionally found in urine, Avhich, for Avant of a better name, and until their true pathological relations are better understood, I proposed to name organic globules. The large organic globule much resembles the mucus particle or globule, being composed of a granular mem- brane investing a series of transparent nuclei, which become visible on the addition of acetic acid. In some, two nuclei of a crescentic shape, Avith their concavities opposed, are alone seen. I know of no character by which these bodies can be distinguished from pus or mucus, excepting that they are unaccompanied by the characteristic albuminous or glairy fluids (333) in Avhich the pus and mucus particles respectively float. The large organic globules seldom form a visible deposit, being free and floating in the urine, and are generally so scattered that not more than a dozen or two are visible at one time in the field of the microscope. They are abundant in the urine of pregnant Avomen, especially in the latter months, when there is a fre- quent desire to empty the bladder. They have existed in every case of ardor urinae I have examined, although irritability of bladder was not necessarily present, but when this does exist they abound. The globule under consideration occurs in the greatest abundance in the albuminous urine of confirmed morbus Brightii. I have seen them so abundant as to cause a drop of the urine to resemble, when micro- scopically examined, diluted pus, a resemblance rendered more close 298 NON-CRYSTALLINE ORGANIC DEPOSITS. by the albuminous character of the urine. Is it possible that these globules may here be indicative of subacute inflammatory action going on in the structure of the kidney ? I am not aware whether they are quite identical with Avhat have been termed the exudation or inflammatory globules of Gluge. The marginal figure, copied from one by Simon in his " Beitrage," accurately shoAvs the common microscopic appearance of deposits in the urine of morbus Brightii. The large dark bodies are organic globules ; mixed with them are seen altered blood-discs and epithelial cells, the latter, as shoAvn from some late researches of Dr. G. Johnson, fre- quently containing globules of fat (368), whilst a tubular mass of coagulated albumen, probably the cast of a uriniferous tubule (319), entangling granules and blood-discs, occupies the centre of the figure.* 339. In a most distressing class of cases which occasionally occur in practice, where all the symptoms of stone in the bladder exist, without any calculus being present, these globules are almost invaria- bly present. This is more especially the case when a roughened state of the interior walls of the bladder can be detected by the sound. A more intractable and distressing ailment hardly exists. I may add a remark of some practical interest, that it has occurred to me to meet with a case in which the operation for lithotomy Avas performed, but no stone found; the result Avas, that the patient consequently lost the symptoms Avhich had distressed him for years. My colleague, Mr. Bransby Cooper, has mentioned to me a similar case. 340. The small organic globules are very beautiful microscopic objects. These little bodies are very much smaller than the pus or mucus particles, and are essentially distinguished from them by the absolute smoothness of their exterior, no trace of granulation being visible even with a high magnifying power. I have never been able to detect a nucleus, or any other sign of definite structure, except their well-defined figure. In hot acetic acid they are quite un- changed. On the slightest agitation they roll over each other Avith the utmost facility, which their perfectly spherical figure readily permits. * These bodies are probably what Henle called cystoid corpuscles, which occur in lymph, as lymph-corpuscles ; in the blood, as colorless blood-cells; in the mucus of the mucous membranes, as mucus-corpuscles. (Lehmann.) i EPITHELIUM. 299 These globules form a visible white deposit, resembling, to the naked eye, a sediment of oxalate of lime. So rare are these curious little bodies, that comparatively few ex- amples of them have occurred to me ; in two, the urine was passed by Avomen during menstruation. It is just possible that they may really be nuclei of some larger nucleated cell, as pus or mucus, and have escaped by the bursting of the investing membrane or sac of the cell.* EPITHELIUM. 341. The epithelial covering of the genito-urinary mucous mem- brane is, like the external skin, constantly experiencing the effects of wear and tear, causing a more or less rapid exfoliation of epithelial cells. This structure is sometimes partly broken up, so as to appear like patches of membrane-like mucus, and its cells are irregularly lacerated. Most generally, however, a certain number are entire, and can be readily recognized by their microscopic characters ; when distended with fluid they are regularly oval cells, becoming irregularly angular and flat- tened when partially empty; when they are quite empty a Avell-marked central nu- cleus often appearing, if the focus be not properly adjusted, to project like the central boss of a shield (Fig. 70), is seen in each. These cells sometimes contain fat-globules, and when existing in any quantity, have been stated to be pathognomonic of some * Dr. Hassall has observed another kind of organic globule in several cases of catarrhus vesicae, and also in simple irritation of the mucous membrane of the bladder, the conse- quence of enlarged prostate or other cause, and accompanied .with an increased discharge of mucus. They vary in size, are circular, and many times larger than pus or mucus-corpuscles, and contain very distinct granular nuclei, clearly de- fined without the aid of acetic acid or other re- agent. The number of these nuclei is often very considerable, and are themselves almost as large as ordinary mucus or pus-corpuscles. Fi°-. 69. Large compound globules from a case of catarrhus vesica? with enlarged prostate^—Copied from Dr! Hassall's paper in the " British and Foreign Medico-Chirurgical Review, for July, 1853. Fig. 69. 300 NON-CRYSTALLINE ORGANIC DEPOSITS. varieties of morbus Brightii (369).* The exfoliation of epithelium sometimes is very considerable, so as to give rise to a copious deposit in the urine, which to the naked eye resembles mucus; but may be readily distinguished by the absence of all viscid qualities. Mixed Avith liquor potassae, such urine gelatinizes nearly as perfectly as Avhen pus is present. When oxalate of lime exists in the urine, an abun- dance of epithelium is generally found, and indeed has often, from its presence, induced me to make a careful investigation for the detec- tion of that salt (230). SPERMATOZOA. 342. Spermatozoa, the so-called spermatic animalcules, are by no means very unfrequent in urinary deposits; a feAV being occasionally found on examining microscopically the inferior portions of the urine of the male adult, after allowing it to repose for some time in a glass vessel. In some cases, hoAvever, a sufficient quantity of spermatic fluid is found mixed with the urine to form a visible cloud, and be- comes an important guide to the practitioner, in the investigation of a case perhaps previously obscure. Diagnosis of Spermatic Urine.—If a small quantity of spermatic fluid is present in urine, it may easily be passed over and mistaken for mucus, from which there is no character independent of micro- * Fig. 71, representing the epithelium of the pelvis of the kidney, is taken from Kolliker's work translated for the Sydenham Society. The epithelium is thick, measuring from 0'02—0'04/// Paris lines, or -0017—-0035 English inches, is lami- nated, and characterized by the variety of form and size of its elements, of which the most deeply seated also are rounded and small, and those in the middle cylin- drical or conical. It is a striking fact that the cells fre- quently contain two nuleci, as well as clear, darkish-colored, round granules, measuring *0008—-0017 English inches. The epithelial cells of the convoluted tubes have been alluded to. The epithe- lium of the bladder is both columnar and scaly; the former lines the mucous folli- cles, while the latter covers the general surface of the membrane. In the fundus the columnar epithelium is mixed with large oval cells. The urethral epithelium is mostly columnar, becoming scaly towards the orifice. The vaginal epithelium consists of large cells of the pavement variety. The different forms are well figured in Dr. Lionel Beale's work on the Microscope. SPERMATOZOA. 301 scopic examination, capable of distinguishing it. If, however, we have a specimen of urine passed by a man which is cloudy and opa- lescent, reddens litmus paper, and does not become clear on the ap- plication of heat or nitric acid, the presence of spermatic fluid may be at least suspected, especially if the characteristic odor of that secretion be perceptible. Should a larger quantity of the secretion be present, it subsides to the bottom of the vessel, and may be re- cognized by its physical character. If mere traces of spermatic liquor only are mixed with urine, they may easily be detected by vio- lently agitating the urine, and alloAving it to repose in a conical glass vessel for a feAV hours. On carefully decanting all the urine except the last few drops, the spermatozoa may be detected in the latter by the microscope. The addition of nitric acid will often produce a slight troubling in this urine. M. Lallemand106 describes spermatic urine as opaque and thick, as if mixed with gruel, with a fetid and nau- seous odor; the characters sufficiently common in ammoniacal urine (212), but certainly by no means, at least in this country, necessarily or generally characteristic of urine containing spermatozoa. In fact, an abundance of these little organisms may be present, without modi- fying materially the physical character of the urine. 343. Microscopic Characters of Spermatic Urine.—No character . can be assumed as distinctly diagnostic of the presence of semen in the urine, except the discovery of the spermatozoa. These minute structures never occur living in urine, unless protected by the pre- sence of a deposit of pus, in Avhich they retain their poAver of moving for a long period after emission. Urine appears, to be immediately fatal to their vitality, but exerts no further action upon them, as they may be detected scarcely changed even after it has become ammonia- cal. An object-glass of one-fifth or of one- eighth of an inch focus, should be used for FlS* 72* the detection of these minute bodies. The drop of urine chosen for examination should be taken from the bottom of the containing Aressel, placed on a slip of glass, and covered Avith a piece of mica or thin glass. The spermatozoa will be observed as minute ovate bodies, provided with a delicate bristle- like tail, which becomes more distinct on al- loAving the drop of urine to dry on the glass (Fig. 72). Mixed with these are generally found round granular 302 NON-CRYSTALLINE ORGANIC DEPOSITS. bodies, rather larger than the body of a spermatozoon, and nearly opaque from the numerous asperities on the surface of the investing membranes. These appear to be identical with the seminal granules described by Wagner107 and others. 344. Well-defined and often large octohedra of oxalate of lime (214) are of common occurrence in spermatic urine. The connection of this saline body with the presence of spermatozoa was first pointed out to me in a private communication with which I was favored by Professor Wolf, of Bonn. Very lately M. Donne has stated, as the result of his observations, that they frequently occur together, and that the presence of oxalate of lime is a constant indication of the existence of spermatorrhoea. This statement is quite opposed to my own experience, for although in the latter disease oxalate of lime often exists, yet this salt constantly occurs where no suspicion of an escape of semen can be entertained (248). 345. Pathological Indications.—Whenever spermatozoa, or sper- matic granules are detected in the urine, it is quite certain that the seminal secretion must have been mixed with it. The causes of this admixture are numerous, for it must be recollected that if the bladder be emptied even some time after a seminal emis- sion, a sufficient number of spermatozoa will remain in the urethra to be washed aAvay with the urine, and cause it to assume the ordi- nary microscopic character. A. certainly not unfrequent cause of the escape of semen is extreme constipation, for after the passage of hard and scybalous faeces, an oozing of fluid from the urethra, full of spermatozoa, is no#t uncommon. In some cases of stricture of the urethra, anterior to the orifices of the seminal ducts, an accumula- tion of semen may, upon sexual excitement, collect, and floAving into the bladder, be voided subsequently with the urine. An admixture of semen with the urine may occur occasionally in paraplegia, in persons reduced in health by excessive indulgence in intercourse, or by even less creditable modes of producing excitement of the sexual organs. 346. Therapeutical Indications.—The irritable state of the ner- vous system, the depressed general health, and in some cases the appearance of epilepsy, or of symptoms not unlike mild forms of deli- rium tremens, and characterized by the most abject melancholy and despondency, are familiar to all, as the effects of the too copious and frequent excretion of seminal fluid, whether excited or involuntary. To this ailment, spermatorrhoea, as it has been named, great atten- SPERMATOZOA. 303 tion has been drawn, especially by M. Lallemand, and by several writers in the English medical journals. That the detection of sper- matozoa in the urine Avill often enable the physician to detect a source of exhaustion previously concealed from him, and baffling his treatment, is unquestionable; but that this matter really merits all the verbose attention lately lavished upon it, is not so evident. I am quite sure that very great mischief has resulted from the publi- city given to the reported results of spermatorrhoea, in the moral effects produced on weak-minded young men, who too generally read these reports with avidity; no less than in the encouragement given to a most atrocious class of quacks and empirics. I hardly knoAv any state of mind more difficult to treat than that which is so often present in patients Avho believe themselves to be the subjects of spermatorrhoea. Although, perhaps, there may be no reason to believe that losses of this kind are actually going on, the patient's mind is too generally made wretched, and his happiness blasted, by the iniquitous pictures draAvn of the presumed results of spermatorrhoea by the miserable harpies Avho have so generally taken possession of this department of practice, and acquire the strongest hold over their victims by the threats and promises they alternately hold out. The patient's mind is so poisoned by the tales of misery and wretchedness poured into his ears by these persons, that it is often impossible to excite any hope of recovery, and they seem, indeed, to regard their imaginary impending fate with a sort of gloomy satisfaction. 347. In the treatment of spermatorrhoea it appears necessary to examine the therapeutic means to be employed in two points of view : as curative of the involuntary discharge, and of the habits keeping it up. The first indication is best fulfilled by attending to the general health, by cold hip-baths, or by dashing cold water over the genitals; by the use of astringent injections into the urethra, or the appli- cation of solid nitrate of silver to that part of the canal where the seminal ducts open, as recommended by Lallemand and Mr. B. Phillips. I may be permitted, hoAvever, to enter a strong protest against the reckless employment of this remedy. In the hands of experienced surgeons no injury is likely to follow its use, but unhap- pily this mode of practice has been adopted by the helots of our profession to whom I have before alluded. I have seen the most distressing results folloAV the use of the local application of the lunar caustic in the treatment of presumed spermatorrhoea. As an 304 NON-CRYSTALLINE ORGANIC DEPOSITS. example, I had under my care a case of intense cystitis occurring in the person of a previously healthy young farmer, Avho being about to be married, began to be anxious on account of his observing an involun- tary emission once in five or six weeks. His attention was arrested by one of the advertisements which too often disgrace our daily papers. He came up to town? consulted the quack, whose name he had then dis- covered. He was declared to be impotent—the nitrate of silver was applied, and the result was cystitis, which placed his life in peril, The use of iron, persisted in for some time, with a little quinine, and a careful use of purgatives, will greatly expedite the recovery of the patient. Marriage also becomes a very important curative agent. The second indication is fulfilled by an influence on the moral feel- ings of the person, and if these have no effect, the application of a blister, or croton oil, to the prepuce, or in some cases circumcision, will be found available in breaking through an iniquitous and inju- rious habit. CONFERVOID GROWTHS. A. Torulai Cerevisios. 348. It is well knoAvn that in all saccharine fluids undergoing the alcoholic fermentation, minute confervoid, or fungoid vegetations (to Avhich M. Turpin gave the name of Torulce cerevisios) appear and pass through certain definite stages of development. There is, indeed, considerable reason to believe that these vegetations, to a certain ex- tent, bear to fermentation the relation of cause and effect. The arguments lately advanced by Professor Liebig, in opposition to this opinion, do not, to my mind, afford a satisfactory answer to the observations previously made on this subject. When urine contains but very small portions of sugar, too little even to affect its specific gravity materially, or to cause it to assume a diabetic character, certain phenomena are developed connected with the production of the vegetation of the genus Torula or Saccha- romyces, which will at once point out the presence of sugar. These indications are of very great value as a guide to our treatment, as an occasional saccharine condition of the urine is, according to recent statements, not uncommon in some forms of dyspepsia in old age AA'hen the health begins to give way. 349. When saccharine urine is left in a warm place, a scum soon forms on its surface, as if a little flour had been dusted upon it. This consists of minute oval bodies, which soon enlarge from the development of minute granules visible in the interior. These con- SACCHARINE URINE. 305 tinue expanding, and dilate the oval vesicle containing them into a tubular form; soon afterwards the internal granules become larger and transparent, and project from the exterior of the parent vesi- cle-like buds. The Avhole then resembles a jointed fungoid or con- fervoid groAvth, Avhich ultimately breaks up; and a copious deposit of oval vesicles or spores fall to the bottom. All these stages of development (Fig. 73) require but a few hours for their completion. «If the deposited spores be placed in a solution of sugar, they ra- pidly germinate, and, exciting fermentation, produce a new crop of torulae. During the growth of the torulae, bubbles of carbonic acid gas are evolved, and the urine at length acquires a vinous odor, generally ac- companied by that of butyric acid. There are tAvo kinds of urine which may be mis- taken for saccharine, by the occurrence of a kind of fermentation, not unlike that of fluids really containing sugar. I refer to the form of viscous108 fermentation which occurs in urine, and ending in the appear- ance of much ropy mucus. This has occur- red to me repeatedly in specimens of urine containing cystine, the odor evolved being, however, disagreeable and sulphureous, quite distinct from the vinous odor of the alcoholic fer- mentation. Somewhat similar phenomena are occasionally presented by the urine of persons exhausted in health from scrofulous or syphi- litic cachexia.* * The two plates (Figs. 74 and 75) represent the growth of the torula; the first Fig. 74. Fig. 75. b 20 a 306 NON-CRYSTALLINE ORGANIC DEPOSITS. 350. Saccharine urine cannot be distinguished, by its appearance, from normal urine. Its specific gravity is generally high, and in consequence it becomes frothy on agitation ; its color is pale, its odor fragrant, and its taste sweet. It is also generally transparent. The presence of sugar, hoAYever, once suspected, may be easily proved by analysis or the application of tests.109 If a moderate quantity of sugar exists, the urine may be evaporated to an extract and digested in hot alcohol; Avhen cold, the tincture should be den canted and alloAved to evaporate spontaneously in a cylindrical vessel (a cupping-glass ansAvers very well). In this Avay white gra- nular masses of sugar will crystallize on the sides of the glass, whilst if the evaporation be expedited by heat, crystals are obtained with great difficulty, and often not at all, until the urea and other organic ingredients have been got rid of by a tedious process. 351. The most trustAvorthy tests for the detection of sugar in urine depend for their action upon the reducing action of sugar on salts of copper, or upon the decomposition of the sugar by alkalies. a. Trommer s test.—Add to the suspected urine in a large test- tube just enough of a solution of sulphate of copper to communicate a faint blue tint. A slight deposit of phosphate of copper gene- rally falls. Liquor potassae must then be added in great excess; a precipitate of hydrated oxide of copper first falls, which redissolves in excess of alkali if sugar be present; forming a blue solution like ammoniuret of copper. On gently heating the mixture to ebullition, a deposit of red suboxide of copper falls if sugar be present. Several objections have been made to this test, on the ground that mere uric acid is sufficient to reduce the copper, and thus introduce a serious source of fallacy. I confess that I have never met with any variety of urine which completely produced the above described phe- nomena with the test unless sugar existed. I believe the solubility of the precipitate first produced by liquor potassae in an excess of the precipitant, and its depositing a dense red cupreous precipitate by heat, not continued after the liquid has acquired the boiling tem- perature, to be quite characteristic of sugar. This dense red deposit is very different from the light orange-colored flocculent clouds Avhich slowly subside when non-saccharine urine is employed. (Fig. 74) is taken from Dr. Lionel Beale's work on the Microscope, and the latter from Dr. Otto Funke's beautiful Atlas ; a, a, shows the first or vesicular form • Fig. 74, b, the germination, and Fig. 75, b, the appearance assumed about the eighth day. SACCHARINE URINE. 307 Dr. Lionel Beale, in an excellent review on " Sugar in the Urine, and its Tests," in the ^British and Foreign Medico-Chirurgical Re- view,"* draws the following conclusions from many carefully per- formed experiments with reference to the practical application of the tartrate of potash and copper test, Barreswil, Fehling, and Trommer's tests. 1. That if the urine contain muriate of ammonia (even in very small quantities), lithate of ammonia (?), or other ammoniacal salts, suboxide of copper will not be thrown down if only a small quantity of sugar be present. 2. That unless there be a considerable quantity of the above salts present (in which case the blue color will remain), the mixture will change to a brownish color on boiling, but no precipitate of suboxide of copper Avill occur. Where only a small amount of sugar is pre- sent, we have been unable to obtain a precipitate, under these cir- cumstances, by the addition of potash to the solution, and prolonged boiling. By previous observationf it appears that a specimen of urine exhibiting this reaction may contain a large quantity of sugar, as ascertained by the yeast test. 3. That in many cases in Avhich the precipitation of the suboxide is prevented by the presence of ammoniacal salts, the addition of potash to the solution and subsequent boiling, will cause a precipitate with the evolution of ammoniacal fumes. Hence care should always be taken that there be a considerable excess of free alkali present. 4. When only small quantities of sugar are present, and the pre- cipitate of suboxide of copper is not decided, the fermentation test should be resorted to. b. Capezzuoli's test.™—Add a feAV grains of blue hydrated oxide of copper to urine contained in a conical glass vessel, and render the Avhole alkaline by the addition of liquor potassae. If sugar be present, * January, 1853. f This refers to the following experiment. Upon mixing a small quantity of grape sugar with a specimen of healthy urine, and boiling the mixture with the tartrate test, no precipitate, except what was owing to the presence of phosphates, was produced. About half an ounce of the same mixture of urine and grape sugar was placed in a test-tube, and mixed with six drops of yeast, and inverted over mercury. The whole was then placed in a temperature varying from 70° to 100° for about twelve hours, at the end of which time the tube was found quite filled with gas, and all the liquid was expelled into the vessel into which it had been placed. The specimen of urine with which the above experiment was tried, after cooling in a still place, gave an abundant precipitate of lithates. 308 NON-CRYSTALLINE ORGANIC DEPOSITS. the fluid assumes a reddish color, and in a feAV hours the edge of the deposit of oxide acquires a yelloAv color, Avhich gradually extends through the mass, from the reduction of the oxide to a metallic state (suboxide ?). c. Moore s test.m—This very easily applied and excellent test was proposed by Mr. Moore, of the Queen's Hospital, Birmingham, and depends for its action on the conversion of colorless diabetic (grape) sugar into brown melassic (or perhaps sacchulmic) acid under the influence of a caustic alkali. Place in a test-tube about two drachms of the suspected urine, and add nearly half its bulk of liquor potassae. Heat the Avhole over a spirit-lamp, and allow active ebullition to con- tinue for a minute or two; the previously pale urine will become of an orange-broAvn, or even bistre tint, according to the proportion of sugar present. The subsequent addition of an acid generally causes the evolution of an odor of boiling molasses. This test appears to be remarkably free from sources of fallacy, as boiling with liquor potassae rather tends to bleach non-saccharine urine than to deepen its color.* Dr. Rees has draAvn attention to an important error which may arise in the indications of this test from the solution of potass employed containing lead. When this is the case, the sulphur in the urinary excretion (99) produces a dark color Avith the lead, and might lead to a suspicion of the presence of sugar when none exists. Hence it is important to preserve the test solution in bottles of green glass free from lead. d. Maumene s test.—Another test has been recently proposed, which promises to be an important one. It is founded on the reducing power of sugar on salts of tin. To apply this, pieces of wdiite merino, or any other woollen tissue, are soaked in a solution of bichloride of tin, and carefully dried. On wetting a piece of this test-cloth Avith urine, and holding it over a spirit-lamp or before a fire, so as to become hot, a deep broAvn or black spot will appear if sugar be present. M. Maumene states that ten drops of diabetic urine in half a pint of Avater Avill afford a mixture in which the mere traces of sugar present may be thus detected. E. Pettenkofer's test.—This is founded on the production of a violet color when sulphuric acid and bile are mixed with a saccharine fluid. I believe it to be so far inferior both in facility of application and accuracy of its indication to the last-mentioned test that it is * I have observed that many specimens of urine containing oxalate of lime, but void of sugar, assume a darker shade, as of sherry, on being boiled with liquor potassae, and exhale a peculiar burnt odor. TESTS FOR SUGAR. 309 unnecessary to give any further account of it than has already been done when pointing out the diagnostic indications of bile (320). F. Chromate of Potash test.—This test has been proposed by Mr. Horsley of Cheltenham. It consists of equal parts of a solution of the neutral chromate of potash and liquor potassae. Mr. Horsley's description is as follows : If a freely alkaline solution of chromate of potash be mixed with urine supposed to contain sugar and boiled, the sugar will assume a deep sap-green color, arising from the decompo- sition of the chromic acid, the oxide of chromium being held in solu- tion by the potash. Such is the sensitiveness of this test that five or six drops only of saccharine urine, diffused through water, is sufficient to shoAv the effect, which is infinitely more striking than even Moore's potash, or Trommer's copper tests. When the quantity of sugar is very small, a piece of white paper should be placed at the back of the test-tube to render the color more distinct. The following experiments are easy, and illustrate the operation and value of the test: 1st experiment.—Take a small test-tube, and, having put into it ten or twelve drops of simple syrup (cane sugar), dilute with Avater, and add a few drops of the test. On the application of heat, no change Avill be produced. 2c? experiment.—Take another test-tube, and having put into it the same quantity of simple syrup diluted with Avater, add two or three drops of dilute sulphuric acid, and boil for a few minutes. This will convert the cane into grape sugar. If we noAV add a feAV drops of the test, and apply heat, the liquid assumes an intense green color. c. Fermentation test.—Mix ordinary yeast, or dried German yeast, with Avater. Fill a test-tube with the diabetic urine, and add a little of the solution on the tube with the thumb, and, having inverted it, place it in a saucer containing the urine. Be careful to exclude the entrance of air. The temperature should not be below 70° Fahren- heit. If sugar be present, minute air-bubbles will rise and occupy the upper part of the tube. According to Dr. Christison one cubic inch of carbonic acid indicates one grain of sugar. H. Luton s test*—This test is said to be easily prepared and un- alterable. Its action is immediate, no preliminary preparation of the urine is requisite, and it has often succeeded after the failure of other * " Gaz. Med. de Paris," Jan. 27th, 1855. Banking's " Abstract," vol. xxi, p. 87. 310 NON-CRYSTALLINE ORGANIC DEPOSITS. tests. The presence of uric acid, urea, or albumen lias no influence on the result. Add sulphuric acid in excess to a cold saturated solu- tion of bichromate of potash, so that after the liberation of all the chromic acid, free sulphuric acid may be present. It is, therefore, composed of water, chromic acid, bisulphate of potash, and an excess of sulphuric acid, and is of a beautiful red color. Add the test to the diabetic urine till you get a red color ; apply the spirit-lamp, and a brisk effervescence ensuing, the color changes from red to emerald- green. The chromic acid is an energetic oxidizing agent, especially when another acid is present. It yields oxygen to the sugar, and carbonic acid, water, and sesquioxide of chrome result, the last of which, uniting with the acid, forms a persulphate of the sesquioxide. I. Polarized light.—The apparatus for applying this test has been already described (52). PHYSIOLOGICAL AND PATHOLOGICAL ORIGIN OF SUGAR. Since the last edition of this work passed through the press, great light has been thrown upon the formation and destruction of sugar in the animal economy, more especially by the experiments and obser- vations of Bernard, in Paris, repeated and extended in this country by Dr. Pavy. The experiments of Bernard have established the fact that sugar is a natural constituent of the human body. It may be introduced as such into the stomach with the food, or it may be formed from the starch by the action of the pancreatic juice, or lastly it may originate in the liver itself. Of these modes of origin it is only requisite to notice the last. Dr. Pavy, in the first of his tAvo very interesting papers in " Guy's Hospital Reports,"* on the physiological relations of sugar in the animal economy, details the following experiment: A strong and healthy dog, which had been fed for three days on a strictly animal diet, was killed by pithing the medulla oblongata by means of a trocar inserted through the space between the occiput and atlas. The abdomen was opened, and a ligature placed on the portal trunk, and another on the abdominal vena cava, just above the entrance of the renal veins. The thorax was then opened and another ligature placed on the inferior vena cava, immediately above the entrance of the hepatic veins ; and portions of blood were separately collected * Second Series, vol. viii, p. 319 ; and Third Series, vol. i, p. 19. PATHOLOGICAL ORIGIN OF SUGAR. 311 from each of the above points, and submitted to chemical examina- tion. The blood removed from the portal vein, which was supplied by the veins of the alimentary canal and other abdominal viscera, did not yield the slightest indication of saccharine impregnation ; the blood from the abdominal vena cava below the hepatic veins also gave no trace of saccharine reaction, whilst that collected from the vena cava above the entrance of the hepatic veins, and likewise that squeezed from the hepatic veins themselves, strongly reacted both Avith the fermentation and copper tests. From this experiment it is manifest that the blood must have become impregnated with sugar during its transit through the liver, but to complete the experiment, Dr. Pavy analyzed the tissue of the several organs, and found that the tissue of the liver at once afforded evidence of the presence of sugar. The liver, hoAvever, not only itself produces the kind of sugar Avhich is called animal glucose, but also transforms into that sub- stance the sugar which the portal vein supplies from the results of digestion. In order to show this clearly, it is necessary to proceed a step further, and fallow the blood impregnated Avith saccharine mat- ter to the right side of the heart, and thence through the lungs to the left. The blood in the right ventricle gives abundant evidence of the presence of sugar, whilst that in the left ventricle contains com- paratively but a mere trace. Hence it appears that the sugar is principally destroyed within the lungs. But if blood impregnated with cane sugar be transmitted through the lungs no such change takes place, and the blood in the left and right ventricles evinces a similar reaction. Hence it may be safely concluded that the sugar in the portal vein is, during its passage through the liver, converted into some allied substance, which is known as animal glucose, and thus fitted for the change to be effected in its composition in the lungs, viz., conversion into lactic acid. But though the lungs are the prin- cipal seat of the destruction of the sugar, yet Dr. Pavy proved that the process of destruction was continued through the systemic capil- laries, and that the sugar was never entirely absent, except in blood taken from the capillaries of the chylopoietic viscera, and that only when no sugar had been introduced into the alimentary canal with the food, and the animal Avas not at the period of full intestinal digestion. Having noAV considered the seat of the destruction of the sugar, and the change Avhich it undergoes in order to its conversion, Ave may 312 NON-CRYSTALLINE ORGANIC DEPOSITS. revieAV the circumstances upon which the conversion seems to depend. Experiments, varied so as to exclude sources of error, have determined that blood impregnated Avith animal glucose taken from one animal and passed through the lungs of another Avill give scarcely any sac- charine reaction, provided it be not first deprived of its fibrin ; but if the same experiment be performed Avith defibrinated blood, no loss of sugar is observed. This change is not produced in pure blood alone, but is also observable in blood in a state of decomposition, especially if exposed to a current of oxygen. Hence it appears that a condi- tion of molecular change is necessary to the production of saccha- rine metamorphosis, in illustration of Avhich Dr. Pavy remarks that if "glucose or grape sugar be placed in contact Avith caseine in a state of decomposition (which implies molecular change) it is resolved by a process of fermentation into lactic acid." In the living system an identical transformation is induced by the molecular changes either of the assimilation or destruction of tissue. An alkaline condition of blood is also favorable to the process of metamorphosis. Dr. Pavy injected the dilute phosphoric acid into the jugular vein of a dog, and on examining the blood draAvn from the carotid arrtery, he found it largely impregnated with sugar. In another case, he injected one hundred grains of the crystallized carbonate of soda, dissolved in eleven drachms of water, into the jugular vein, and then examined the blood taken from the carotid artery; but in this latter case the blood evinced the same reaction as ordinary arterial blood. These experiments have also determined that an injury to the pneumogas- tric nerve in its point of origin in the fourth ventricle may produce an attack of diabetes, because such injury either increases the quantity of glucose secreted by the liver, or deprives the liver of its poAver of converting cane sugar into animal glucose, or so impairs the functions of the lung as to check or retard those molecular changes, which are requisite for converting animal glucose into lactic acid.* Dr. Bence. Jones has suggested that as gout arises from deficient oxidation of uric acid—nitrogenous compounds—so possibly diabetes * The weak point in the argument is that this acid can scarcely be detected in the blood ; but when we remember the close alliance in composition between sugar (C12H12012) and lactic acid (C6H606), also that on the completion of saccharine de- struction in decomposing blood, there is a decided acid reaction, also that lactic acid is separated from the capillaries in the stomach and muscular tissue we are I think, justified in predicting its existence in arterial blood. THERAPEUTICAL INDICATIONS. 313 may arise from deficient oxidation of the non-nitrogenous com- pounds. These conditions, therefore, appear to be requisite for the process of saccharine metamorphosis, viz., 1. Presence of molecular change. 2. Exposure to atmospheric air or oxygen. 3. Alkaline condition of blood. Therapeutical Indications.—The true therapeutical indications in diabetes can never be satisfactorily determined, unless first the cause and source of the mischief (fons et origo mali) be understood. We have already seen that sugar is a natural constituent of the human body; that if it be not introduced from without, the system has been supplied with means of manufacturing it Avithin; and also that certain conditions are necessary for the due completion of its meta- morphosis, and that these conditions are fully provided in the healthy body. Diabetes may originate from these conditions being interfered with in one of the folloAving modes : 1. A greater amount of sugar may reach the liver than that organ is capable of converting into animal glucose ; in Avhich case the excess passes unaltered through the lungs into the systemic circulation, and being useless for the purposes of combustion or nutrition, is ex- creted by the kidneys. This is probably the history of those very interesting cases of intermitting diabetes of old people, upon which Dr. B. Jones has ably written. The remedy is dietetic, with sto- machic alteratives, such as rhubarb, soda, and calumba, and small doses of pilula hydrargyri; but in most cases of this kind regulation of the diet is all that is necessary. 2. The liver may, through or by reason of irritation of the brain or pneumogastric nerve, secrete a larger quantity of sugar than can be metamorphosed in the lungs. 3. The lungs, through a similar injury or irritation, may be ren- dered unfit to fulfil their part of the process. In such cases, as Avell as those referred to in the preceding paragraph, we must allay the cerebral irritation, regulate the diet, and prescribe alteratives and purgatives. 4. The function of the liver may be so impaired as to be incapable of converting the cane sugar supplied to it through the portal vein into animal glucose. Consequently, the conversion into lactic acid is impeded or preA'ented, and the sugar is discharged as a foreign body through the kidneys. In the first class of cases I have referred to regulation of the diet 314 NO N -CRYSTALLINE ORGANIC DEPOSITS. as in most instances of itself sufficient to cure the disease. But at- tention to this point is no less necessary in the other classes. Before giving the chart which I generally prescribe, I will detail the compo- sition of the bread which forms a prominent part of it. Place one pound of bran in an oven, and bake for a quarter of an hour ; then, while still warm and crisp, transfer it to a pepper or fine coffee-mill, and rapidly grind it. Put the ground bran into a basin and mix Avith it half a pound of fresh butter, the yolks of six eggs, one drachm of bicarbonate of soda, and milk enough to make into a paste, then divide into thin cakes, and bake rapidly in a quick oven.* These cakes, with fresh butter or cheese, are much relished by the patient for lunch. The following is, perhaps, the best diet-table for diabetics: Breakfast.—Rasher of bacon, or chop, or eggs, with bran bread or slices of Avhite bread, cut rather less than a quarter of an inch thick, and toasted so as to be brown throughout, no Avhite unchanged bread being left in the middle. Coffee, tea, or cocoaf Avith milk. * Mr. Camplin has published, in the "Medical Times and Gazette," May 2d, 1857, the following formula for bran loaf which contains no starch. Take a suffi- cient quantity (say two or three quarts) of wheat bran, boil it in two successive waters for ten minutes, each time straining it through a sieve ; then wash it well with cold water, on the sieve, till the water runs off perfectly clear : squeeze the bran in a cloth as dry as you can, then spread it thinly on a dish, and place it in a slow oven ; if put in at night let it remain until the morning, when, if perfectly dry and crisp, it will be fit for grinding. The bran thus prepared must be ground in a fine mill,'' and sifted through a nice sieve of sufficient fineness to require the use of a brush to pass it through ; that which does not go through at first must be ground and sifted again, until the whole is soft and fine. ' Take of this bran 3 ounces troy, 3 fresh eggs, 1J ounces of butter, rather less than half a pint of milk; mix the eggs with part of the milk, and warm the butter with the other portion; then stir the whole well together, adding a little nutmeg and ginger, or any other agreeable spice. Immediately before putting into the oven, stir in the first 35 grains of sesquicarbonate of soda, and then 3 drachms of dilute hydrochloric acid. The loaf thus prepared should be baked in a basin, previously well buttered, for about an hour or rather more. Biscuits may be prepared as above, omitting the soda and the hydrochloric acid, and part of the milk, and making of proper consistence for moulding into shape. If properly baked, the loaves and biscuits may be preserved several days, but should always be kept in a dry place, and not be prepared in too large quantities at a time. fThe cocoa must be ground at home. a Made by Mr. White, of Holbovn. CONFERVOID GROWTHS. 315 Dinner at 1*30 p.m.—Fresh meat, poultry, or fish of any kind. All Vegetables freely, excepting potatoes, carrots, parsnips, celery, beet-root, and artichokes. "Omelettes aux fines herbes" for pud- dings or custards made without flour or sugar, bran bread and cheese, Avith lettuce or water-cresses. Tea.—Like breakfast, omitting the meat. Supper at 9 o'clock p.m.—Bran bread and butter, a basin of rice milk Avithout sugar, or sandAvich of meat and toasted bread. Plain Bordeaux claret is the best Avine. It contains no sugar, and relieves thirst, Alum whey is recommended, in Dr. Buchan's Medi- cine, as a drink, and I have found it useful in allaying thirst. Our treatment by medicine is either rational or empirical—the former embraces all those remedies Avhich have a tendency to favor the con- version of cane sugar into animal glucose, as yeast, pepsine, rennet, liquor potassae, sesquicarbonate of ammonia, &c, or to facilitate the metamorphosis of the animal glucose into lactic acid, as strychnia (?); the latter comprises a long list of remedies Avhich have been admi- nistered with the view both of stimulating and arresting the urinary secretion, or of preventing the formation of glucose. The treatment by rennet, aided by strict attention to diet, has, in many instances, proved successful; the liquor potassae, in half drachm doses, taken shortly after a meal, in favorable cases, has been very beneficial, espe- cially if in conjunction with treatment by rennet, yeast, oils, &c. Milk just turned sour is recommended by Dr. Headland, as it contains caseine in the process of decomposition, and we have already observed that the presence of decomposing caseine favors the metamorphosis of animal glucose into lactic acid. With all plans of treatment it is necessary, as far as possible, to restore the healthy action of the skin, liver, and boAvels. B. Fungoid {confervoid) Growths, apparently distinct from Torulos {Penicilium ?) 352. Heller described some vesicular growths evidently allied to the genera Torula or Penicilium in the urine of a patient laboring under typhus fever. He gave figures of them in a paper published in his "Archiv fur Physiologische Chimie" for 1846. During the autumn of 1849, similar growths Avere discovered by my friend Dr. Basham in the urine of dyspeptic patients. These observations Avere made quite independently of Heller's paper, of the existence of which 316 NON-CRYSTALLINE ORGANIC DEPOSITS. Dr. Basham was at that time not aware. He met with these bodies in the urine of a patient who was passing stellar crystals of uric acid. They consisted of oval cells arranged by their long diameters in a bead-like form, with minute granules or cellules developing them- selves from the surface and points of juncture of the parent cells (Fig. 76). Fig. 76. Fig. 77. 353. Another and apparently very different fungoid vegetation Avas discovered nearly at the same time by Dr. Basham, in the urine of a patient Avho Avas suffering from symptoms suspected to be dependent upon oxaluria. It had been passed twenty-four hours, and mixed with the crystals of oxalate of lime Avere numerous annular cells; some were furnished Avith minute nuclei. Most of them were more or less elliptical, some split in half like a horseshoe. They are shoAArn in Fig. 77, mixed Avith crystals of oxalate of lime. Their apparent annular structure is probably OAving to their being thicker at the margin than in the centre. And in this they bear no small resem- blance to dried specimens of uredo and puccinia, the former so common on wheat, the latter on rose-buds. The most interesting fact connected with these observations consists in their having been made at the very time Avhen great attention was directed to the fun- goid theory of cholera, which disease was then prevailing Avith fearful virulence; the annular bodies discovered by Dr. Basham in the urine of a dyspeptic patient, being apparently identical Avith those described by Dr. Brittan as existing in the serous dejections of cholera patients. On submitting some specimens of these intestinal fluids to careful microscopic obsen-ation, Dr. Basham discovered the very im- portant fact that the annular bodies were not to be detected in the very recently excreted fluids; four hours subsequently a few were found, and in fourteen hours they Avere abundant. ' It is hence im- VIBRIONES. 317 possible to regard these organisms as in any way constituting the exciting cause of the terrible disease of Avhich they had been stated to be the constant accompaniment. Dr. Hassall has made several very interesting observations on the subject of the growth of torulae in the urine, and confirms the opi- nion that the fungus of saccharine urine is really the yeast-plant, and differs materially from the fungus developed in non-saccharine urine, Avhich is identical with the penicilium glaucum: the former has been already noticed. The latter was traced through its three stages of sporule, thallus, and fructification, well represented by Figs. 78 and 79, taken from Dr. Lionel Beale's works on the micro- Fig. 78. ■ Fig. 79. scope. The conditions necessary for its growth were found to be animal matter, especially, but not exclusively, albumen, acidity, and the presence of oxygen (exposure to atmospheric air). The penici- lium glaucum, though distinct from the sugar-fungus, yet is not un- frequently found associated with it, as the conditions necessary for its growth are generally present in saccharine urine.* C. VIBRIONES. 354. Minute animalcules, belonging to the genus Vibrio (V. Li- neola ?1U), are occasionally developed in urine, so soon after passing as to lead to the idea that their germs must have existed in the urine whilst in the bladder. All the urine in which I have found these minute creatures has been pale, neutral, of low specific gravity, and rapidly undenvent the putrefactive fermentation. * "Medical Times and Gazette," Dec. 4th, 1852; and Ranking's "Abstract," vol. xvii, p- 88. 313 NON-CRYSTALLINE ORGANIC DEPOSITS. When a drop of such urine is examined under a microscope be- tween plates of glass with an object-glass of one-eighth inch focus, it will be found full of minute linear bodies hardly so long as the diameter of a blood-corpuscle (about g^ inch) moving AA'ith great animation! The motion is of an oscillating character, aiicl strong enough to excite tolerably rapid currents in the fluid. Even under a very high magnifying power, no satisfactory evidence of organi- zation can be detected in these minute beings. 355. I have only met with these animalcules in the urine of per- sons in an excessively low and depressed state. In cases of syphi- litic cachexia, where the prostration of the strength is extreme, as well as in mesenteric diseases, I have repeatedly found them abun- dantly developed, with remarkable rapidity. They appeared in great abundance in the urine of a patient under my care at Guy's Hospital two years ago. The subject of this case was a most miserable-look- ing young man, who entered the hospital half starved, and laboring under polydypsia, passing a very large quantity of urine of Ioav spe- cific gravity. He died of rapid phthisis in a few Aveeks. The urine became full of vibriones in active motion a few hours after being passed. MILK. 356. No satisfactory case is recorded by any observer of credit, in Avhich milk has been discovered in the urine; although there are feAV who have devoted themselves to investigations connected Avith the pathology of the urine but have met with urine rendered opaque by the fraudulent admixture of milk,—a piece of deception occasion- ally practised by persons who labor under the unintelligible delusion of wishing to appear the subjects of some marvellous disease. All the cases of milk-like urine, where no fraud has existed, are instances of phosphatic (258), purulent (328), or fatty (370) urine. Although milk itself does not occur in urine, yet there can be little doubt that some of its elements may be met with in it, by a kind of vicarious action of the kidnpys, in the same manner that bile is. It must be remembered that milk consists of globules of fatty or oily matter floating in a fluid or serum in which a peculiar protein-compound, casein, is dissolved. This substance is distinguished from other protein principles by the action of acetic acid, which immediately coagulates it, producing the well-knoAvn curd, the basis of cheese. MILK. 319 The most interesting subject connected with the supposed presence of this substance in the urine, is its apparent connection withutero- gestation ; and its temporary occurrence when an obstruction occurs to the ready escape of milk from the breast. 357. An account of the supposed discovery of a peculiar mucila- ginous principle in the urine of pregnant women appeared a few years ago in several of the British and foreign medical journals,99 and attracted much notice as a diagnostic sign of pregnancy. This new constituent of renal secretion, to which the name of Kiestein was applied, was stated to exist in the urine of the human female during utero-gestation, and to become visible Avhen the secretion Avas alloAved to repose in a cylindrical vessel, in the form of a cotton- like cloud, Avhich in a lapse of time, varying from the second to the sixth day of exposure, became resolved into a number of minute opaque bodies, Avhich rose to the surface, forming a fat-like scum, and remaining permanent for three or four days. The urine then became turbid, and minute flocculi detached themselves from the crust, and sank to the bottom of the vessel: this action continued until the AA'hole pellicle disappeared. This crust of kiestein was stated to be distinguishable from analogous pellicles Avhich occasionally form on the surface of urine, from its never becoming mouldy, or remaining on the surface beyond three or four days from the time of its com- plete formation. 358. This subject appeared of sufficient importance to justify a mi- nute investigation, the results of which were published in the " Guy's Hospital Reports" for 1840. As nothing has appeared since to in- duce me to modify the opinions I then made public, I noAV republish the most important part of these remarks. The first specimen of urine submitted to examination was some voided by C— S—, aged 28, a married Avoman, in the sixth month of pregnancy, admitted under my care at the Finsbury Dispensary, on October 17tJi, 1839, for a slight attack of bronchitis. The urine was passed immediately on rising from her bed ; it Avas tolerably copious, pale, acid, and rather opaque, of sp. gr. 1*020. About half a pint of it Avas placed in a glass cylinder, covered with paper. After tAvo days' repose, it became very much troubled; numerous globules, presenting a fatty or greasy aspect, appeared on its surface ; in tAvo days more the urine became completely covered with a pelli- cle, very closely resembling that Avhich forms on the surface of mutton- broth in the act of cooling; on the sixth day of exposure, this crust 320 NON-CRYSTALLINE ORGANIC DEPOSITS. broke up, and fell to the bottom of the vessel. On the 26th of Octo- ber, this patient, then conA'alescing from her bronchial affection, again sent me a specimen of the urine, voided as before, immediately after awaking from sleep ; and the very same results Avere obtained ; the pellicle of fat-like matter being, hoAvever, much thicker. On November 30th, the urine was again exposed, with precisely identical results. Although in this woman the phenomena presented by the urine were tolerably constant, yet it became an important matter to determine whether such appearances Avere not to be met Avith in the urine of Avomen Avho were not pregnant, and Avhether they Avere con- stant in every case of utero-gestation. To determine the latter ques- tion Avas, within certain limits, somewhat easier than the former; for this purpose every pregnant woman who came under my care at the Finsbury Dispensary, or among my out-patients at Guy's Hospital, was desired to furnish specimens of urine, passed after awaking from sleep ; this request was not in every instance complied Avith; but during the months of November and December, specimens from about thirty women, in the third to the last month of pregnancy, were obtained; and in every case, with but three exceptions (to Avhich I shall hereafter allude), copious fat-like pellicles were observed, after tAvo or three days' exposure. The three Avomen whose cases thus appeared to be exceptions to the general rule, were all affected Avith inflammatory fever accompanying severe catarrh. The urine Avas turbid Avith urates. On the disappearance of the latter by the con- valescence of the patients, the phenomena characteristic of preg- nancy appeared. 359. Whilst collecting these specimens of the urine of pregnant women, I directed several young women, who presented themselves to be treated for amenorrhoea, to bring specimens of their urine; AA-hich were exposed simultaneously with those furnished by the preg- nant Avomen; and in two instances only Avas any evidence of the presence of the peculiar matter manifested. In one, a servant girl of 18 years of age, I strongly suspected pregnancy, from the appear- ance of the areola around the nipple; but she was so much annoyed at my questioning her on this point, that she ceased to attend. The second case was more satisfactory: it was that of a stout, tall unmarried woman, a servant, aged 33, who came under my care November 7th, 1839, suffering from cough, apparently depending upon deranged digestive functions and relaxed uvula: she had not menstruated since the preceding May, and attributed the disappear- URINE OF PREGNANCY. 321 ance of the catamenia to exposure to cold. She had morning sick- ness, and the veins of her loAver extremities were varicose. On examining the abdomen, no evident enlargement of the uterus could be observed, in consequence of the parietes being loaded Avith fat; and on looking at the breasts, the nipples were found surrounded by a large purplish-broAvn areola. On being charged with preg- nancy, she obstinately denied it; but admitted having been the mo- ther of an illegitimate child eleven years previously. She declared that she had preserved absolute chastity since that period, and Avept bitterly at my (as she termed them) unjust suspicions. I procured a specimen of her urine, and exposed it in a lightly covered glass cylinder: in two days, a dense pellicle of fat-like matter formed on its surface: this increased in thickness during three days, and then evolved so powerful an odor of putrefying cheese, that I was obliged to throw it away. Five months later this woman was delivered of a male child. The odor of putrescent cheese remarked in this case, is by no means unfrequent in those specimens of urine in Avhich the pellicle is very thick. 360. None of the specimens of urine voided by pregnant women that I examined, were coagulable by heat, nitric acid, or, with but two or three exceptions, by acetic acid, and therefore could not con- tain any considerable portion of albuminous or caseous matter. The \ addition of ammonia almost invariably produced a dense deposit of earthy phosphates; and with the exception of this proof of the ex- istence of an excess of earthy phosphates in the secretion, no ap- preciable portion of any abnormal ingredients could be detected. Some of the fat-like pellicle was removed from the surface of urine in which it had formed, by plunging a plate of glass perpendicularly into the fluid, and withdrawing it adroitly, in a nearly horizontal position: an equable layer of the substance was thus procured; and, when carefully covered with another plate of glass, it could be very conAreniently submitted to examination. The pellicle thus procured, appeared glistening with a lustre like that of spermaceti; when placed under a microscope, and examined with an object-glass of a half-inch focal length, myriads of triangular prisms of triple phosphate (264) were seen imbedded in a mass of gra- nular matter, mixed Avith Avhich might here and there be seen patches of fat-globules. The prisms of triple phosphate were so beautifully distinct, and their angles so sharply defined, that the Avhole became 21 322 NON-CRYSTALLINE ORGANIC DEPOSITS. a most interesting microscopic object: some of the crystals were placed on end, and thus appeared like triangular plates.^ When the urine is kept so long that the pellicle begins to break up, it falls, in the form of a deposit, to the bottom of the vessel. If the supernatant fluid be decanted, and the deposit collected on a slip of glass, it is found to present the same appearance as the pellicle; excepting that the crystals are much more numerous, and all the animal matter present is entirely composed of amorphous granules, all trace of anything like a regular structure being lost. 361. A slip of glass, on which a portion of the pellicle, had been collected, was placed under the microscope, and covered with a few drops of acetic acid: the Avhole became opaque, the crystals were rapidly dissolved, and a white pultaceous mass resulted. On Avash- ing it with a few drops of water, and carefully drying the residue, the animal matter was left upon the glass in a white opaque layer, in which no trace of crystalline matter was perceptible, upon very minute microscopic investigation. Another portion of the pellicle, also collected on a glass plate, was placed under the microscope, and a few drops of strong liquid am- monia were added: the crystals underwent no change, but became much more distinct from the opaque matter, in which they were im- bedded, undergoing solution. In the course of half an hour, the glass was carefully washed with a little water, and again examined, when every trace of animal matter was found to have disappeared, and the crystals of the triple phosphate were alone left. 362. From these investigations, it is evident that the greasy aspect of the pellicle of the so-called Kiestein arises less from the presence of fat, than from the numerous crystals of triple phosphate, which, from their brilliancy, produce this glistening appearance. Some fatty matter is, however, present, and Lehmann,100 in repeating these observations, discovered that on digesting the pellicle in ether and allowing the ethereal solution to evaporate, a fat was obtained which closely resembled butter, and when saponified with potass, yielded butyric acid (100) on the addition of sulphuric acid. Dr. Rees137 has also detected genuine fat-globules, precisely like those found in milk. With regard to the nature of the animal matter soluble in ammonia, mixed with these crystals, it is difficult, in the present state of phy- siological chemistry, to give a positive opinion. It is not mere albu- men or casein, although much more closely allied to the latter than to any other product of organization I am acquainted with, especially URINE OF PREGNANCY. 323 when Ave connect with its chemical characters the powerful cheese- like odor so frequently evolved, during its development in the urine, in the form of a pellicle. To this view may be objected the circum- stance that the urine yielding it does not coagulate on the addition of acetic acid; this, however, is by no means an important objection, as milk, Avhen very much diluted with a saline solution, or even water, is not perceptibly troubled by acids. The pellicle may be regarded as possibly constituted of an imperfect caseous matter, mixed Avi/;h traces qf butter and crystals of the ammoniacal phosphate of mag- nesia. It has been proposed, indeed, to dignify the animal matter present in this mixture with the name of gravidine, but we are not justified in considering it as constituting a neAv organic principle. There are few products formed during repose in urine which can be readily confounded Avith this caseous pellicle, if it be borne in mind that the secretion remains faintly acid up to the moment of the crust breaking up; Avhich phenomenon seems to depend upon the de- velopment of ammonia in the urine, as at that time it acquires dis- tinct alkaline properties. The crust of earthy phosphate, which forms on the surface of all urine by long repose, cannot be mistaken for the pellicle under consideration; as that Avhich destroys the latter, viz., putrefaction, causes the production of the former. 363. If it be granted that we possess sufficient evidence of the pre- sence of certain ingredients of the milk, as an imperfect caseous mat- ter, and abundance of earthy phosphates, in the urine of pregnant Avomen, it might be suggested as a probable explanation, opposed to no physiological views that I am acquainted with, that during utero- gestation, certain ingredients of the milk are eliminated from the blood by the mammary glands, and, as is very well known, often ac- cumulate in the breasts, in sufficient abundance to escape from the nipple on pressing it between the fingers. This imperfectly formed secretion, not having a ready exit by the mammae, is taken up into the circulating mass, is separated by the kidneys, and eventually escapes with the urine. This view is certainly sanctioned by the statements of a high authority, Professor Burdach,101 of Konigsberg, and although not quite consonant with the opinion of M. Rayer,102 yet it is in accordance with what we find occurring, under certain circumstances, in the bile, in the cases of obstruction of the biliary ducts; and more rarely in the urine, when, from the presence of calculi or other causes, the ureters are completely obstructed. 364. At a late meeting of the Academy of Science of Paris, MM. 324 NON-CRYSTALLINE ORGANIC DEPOSITS. Grullot and Leblance announced their discovery of casein in the blood during lactation. They examined the serum of blood obtained from two persons'who Avere nursing infants. After coagulating the albumen by heat, and separating it by filtration, they found that the addition of acetic acid produced an abundant precipitate of casein. The quantity of this substance present seemed to bear a direct ratio to the proportion of albumen in the blood. These observations ren- der the excretion of casein by the kidneys, in accordance Avith the law of Wohler, at least a probable circumstance (383). 365. Although it is extremely probable that similar pellicles, which I have assumed to be characteristic of the presence of certain ele- ments of milk in the urine, may be met with in the renal secretion of nurses Avhilst suckling, yet I have never met with an instance of this kind: indeed the following interesting case appears rather opposed to this view: Oct. 26, 1839, I was consulted by Mrs. T----, then in the third month of utero-gestation, on the case of her child, a boy sixteen months old, whom, notwithstanding her pregnancy, she was then suckling. This little patient had a severe attack of pneumonia fol- lowing measles, from which he was recovering, when, a few days, before I was called in, from imprudent exposure to cold, he contracted bronchitis; and when I saw him he Avas evidently dying: he had, however, sufficient strength to take the breast. As it was evident that the child would in all probability expire in a few hours, I was anxious to ascertain whether the urine of the mother contained any of the supposed caseous matter; and if not, how long after the death of the boy it would appear. Some of her urine was collected ; and, after six days' repose, it underwent no particular change. Putre- factive decomposition then commenced, and it was thrown away. She continued to suckle her child until within a few hours of its death, which took place forty-eight hours after my first visit; and on the following day I procured another specimen of the mother's urine. This, after two days' repose, had a thin caseous pellicle on its surface. In the course of a week, a third specimen was procured; and this in three days became covered with a complete creamy layer, evolving a strong cheese-like odor. This case certainly appears to justify the idea that, whilst suck- ling, the milk being got rid of almost as quickly as it is secreted, none of its elements find their way into the urine; but as soon as the milk ceases to be removed in this way, indications of it are to be URINE OF PREGNANCY. 325 met with in the urine, providing pregnancy exists. The following case appears to support the position I have assumed: E— C----, aged 24, suckling her first child, five months old, admitted under my care, at the Finsbury Dispensary, in December, 1839, complaining of symptoms generally referable to asthenia lactan- tium. She was a tall, thin, delicate-looking woman, and had lost a mother and some collateral relations from consumption. She had little or no cough ; on examining her chest, I detected tubercular deposit at the apices of both lungs, with evidence of commencing softening on the left side. Her urine was pale, and free from any appearance of caseous pellicle. I desired her to wean her infant; but this she did not do until January 27th, 1840. When she sent her child aAvay, her breasts became painful and hard. She was com- pelled to have them draAvn ; and in a Aveek they became flaccid, and the secretion of milk stopped. On January 30th, the breasts being still turgid, and three days after the cessation of suckling, some of her urine was collected, and exposed in a glass cylinder. In the course of four days a cream-like pellicle, eArolving a cheese-like odor, was observed. On collecting some of it on a slip of glass, and ex- amining it under the microscope, it Avas found to resemble the usual pellicle Avhich forms, by repose, on the urine of pregnant Avomen in every respect, except in the extreme paucity of the crystals of triple phosphate; the entire portion of the pellicle examined being nearly entirely composed of the animal matter, insoluble in acetic acid. A feAV days afterwards the urine was again examined, but with negative results ; no evidence of caseous matter, as indicated by the formation of a pellicle, could be detected. 366. It is not known hoAV soon after conception the urine assumes the properties characteristic of pregnancy. In one case, that of a woman Avho considered herself to be at the end of the second month of her pregnancy, the urine yielded a Avell-marked pellicle ; but I do not place much confidence in this observation, as the woman might very likely err in calculating hoAV far she was advanced in utero- gestation. Kleybolte,138 Avho, in common with many others, considers the presence of kiestein as quite indicative of pregnancy, has asserted that he detected it in the urine on the fifth day after conception. As a test for the existence of pregnancy, the formation of the case- ous pellicle, especially if accompanied by a cheese-like odor, will be an extremely valuable corroborative indication ; but it would be unsafe to found on it alone any positive opinion, because, as a suffi- 326 NON-CRYSTALLINE ORGANIC DEPOSITS. cient number of observations have not yet been made on this subject, we have no right to assume, however probable it may be, that a case- ous pellicle can appear only when pregnancy exists. This opinion I feel still inclined to maintain, notwithstanding the very opposite opinion advanced by different observers, some of whom have declared the kiestein to be pathognomonic of pregnancy, and others have ex- pressed a conviction of its utter worthlessness. Whilst the sheets of the third edition of this work were passing through the press, a very interesting case, in which the urinary diag- nosis of pregnancy proved to be of great importance, occurred in the practice of my colleague, Dr. Gull. I prefer giving an account of it in his own words, on account of the many points of interest in this curious case: My dear Dr. Bird, At your request, -I send you the particulars of the following case of mole pregnancy, which illustrates the importance of examining the urine as a means of diagnosis. The age of the patient and the other circumstances of the case made it somewhat difficult to determine with certainty the state of the patient, but the presence of the caseous substance in the urine was so indicative, as you have pointed out, of that physiological state which occurs only in pregnancy, that I felt very confident in the opinion it led to, and the result of the case showed that its importance had not been overrated. In the autumn of 1849, I was consulted by a lady in her fiftieth year, the mother of a large family, who informed me that the cata- menia, which had been previously regular, had ceased for four months, and that for three months^she supposed herself pregnant, when, after being much excited by the misconduct of a servant, her symptoms changed; the breasts became flaccid, the abdomen did not enlarge, and a slight vaginal discharge, of a reddish-brown color, and faint acid odor, had since troubled her. I found the papillae about the nipple prominent, and there was a distinct fulness at the lower part of the abdomen, but no uterine sounds could be heard. Having set apart a few ounces of her urine, for several days, a large amount of kiestein separated, and this, together with her history, led me to regard it as one of pregnancy with threatened abortion. For three successive weeks the urine contained kiestein, but after this no traces of it could be discovered. For the folloAving two months, the case went on without any change the discharge continuing; but all symp- URINE OF PREGNANCY. 327 toms of pregnancy had disappeared, and the abdomen did not enlarge. Seven months having now elapsed from the beginning of the symp- toms, it was thought prudent to expel the contents of the uterus, and for this purpose Dr. Lever, who was consulted, advised the use of the ethereal tincture of ergot, and within twenty-four hours a large mole was expelled, consisting of degenerated chorion, partly vesi- cular. No traces of a foetus could be found. From this time the ute- rine discharge ceased, and the patient was soon in her usual health. I am yours, faithfully, William W. Gull. Guy's Hospital, Nov. 14th, 1850. FATTY MATTER. 367. A very minute trace of fatty matter is not unfrequently pre- sent in urine, and in some rare instances it increases in quantity, so as to become an important element of the secretion. The majority of cases of this kind hitherto recorded have not been very satisfactory, in consequence of the general dearth of detail respecting both the chemical and microscopical characters of the supposed fatty fluid. In some cases oil has been said .to have been seen floating on the surface of the urine in large drops, even to the extent of ounces ;103 but no instance of this kind has ever occurred to me, and I suspect that certainly, in most of such cases, a fraud has been practised by the patient. An oil-like pellicle, often observed on the surface of urine, from the formation of a pellicle of earthy phosphates, may have been mistaken for true fat. It has been lately shown, that during preg- nancy a portion of butter-like fat may form part of the pellicle which forms on the urine by repose (362). All genuine specimens of fatty urine that have occurred to me have been opaque, like diluted milk, and in the majority of instances have spontaneously gelatinized, like so much blanc mange, on cooling. To these the term of chylous urine has been applied by Dr. Prout.104 368. Great interest has become attached to the existence of fat in the urine, from the researches of Dr. Dichholz, and of Dr. G. John- son, who have stated that fatty matter not only exists in abundance in the urine in granular disease of the kidneys, but is even pathogno- monic of that affection. According to Dr. Johnson, fat or oil-globules naturally exist in the epithelial cells of the tubular structure of the 328 NON-CRYSTALLINE ORGANIC DEPOSITS. kidneys; and in the disease in question the fat increases so rapidly as to press on the venous capillary plexuses on the exterior of the tubuli, so as to interfere with the return of blood from the organs. On the cells giving way or escaping from the tubuli, their fatty con- tents become mixed with the urine. 369. The quantity of fatty matter thus mingled with the urine is far too small to cause it to assume any appearance by which its pre- sence can be detected by the naked eye. It is generally only to be detected by ex- amining the deposit which subsides from such urine by repose, and the epithelial cells (Fig. 80, a) filled Avith fat-globules, and sometimes even casts of tubes con- taining them (Fig. 80, b) may be observed. Dr. Johnson does not assume that this evidence of fatty degeneration is essen- tially present in every case of Bright's disease, but that it is pathognomonic of one of the most frequent forms of that most serious disease.* Chemical Characters of Opaque Fatty Urine {chylous urine ?). 370. On agitating the fresh urine with an equal bulk of ether in a tube, the fat is dissolved, and by repose a yelloAv ethereal solution of it Avill float on the top of the urine, which, by thus losing the fat, be- comes nearly transparent. On decanting the solution, and allowing it to evaporate in a Avatch-glass, the fat is left in 'little yellow glo- bules, like butter, and having a rancid odor. This fat readily melts by a gentle heat into a yellow oil, and slowly solidifies on cooling. Albumen often exists in chylous urine in its spontaneously coagu- lable form (fibrin), so that on cooling it readily assumes the figure of the vessel. In this respect the urine often remarkably varies, some- times losing its poAver of spontaneous coagulation for days together. Albumen is, however, even then present, and readily coagulates on the application of heat and nitric acid (317). In some cases which occurred to Dr. Prout, the albumen did not coagulate by heat, although it did by nitric acid; he hence considered it to be in an imperfect or * This point has been more fully noticed in connection with the subject of renal easts, p. 280. FATTY (CHYLOUS?) URINE. 329 hydrated state, like the albumen of the chyle. If a large proportion of fat exists, the fibrin, if present, is often prevented by its presence from coagulating; in this case, after agitation with ether, so as to dissolve out the fat, a delicate tremulous transparent coagulum of fibrin will form on the surface of the urine, and beneath the ethereal solution of fat. 371. Microscopic Characters.—Cases have been reported in which globules of fat, like those existing in milk, were detected by the mi- croscope. In all the specimens I have examined, the fat appeared to form a most intimate mixture or emulsion with the albumen, so that under the microscope nothing could be detected except myriads of infinitely minute particles floating in the fluid, generally unmixed with the slightest appearance of a globule of oil. More rarely, how- ever, the oily matter was readily to be observed in distinct globules, resembling those seen in milk. 372. Pathological Indications.—These can scarcely be said to be accurately knoAvn. In the feAV instances I have witnessed of fatty urine, the patients have (with one exception, occurring some years ago in a lady, a native of China, remarkable for her emaciated con- dition, under the care of Dr. Protheroe Smith) shown a remarkable disposition to obesity. The continued presence of albumen coexisting with the fat, must, hoAvever, excite our alarm, for fear of the proba- ble termination of the ailment in diseased kidney and resulting in dropsy, especially if the recent statements of Dr. G. Johnson (369) are corroborated by more extended observations. In these cases there can be no question, notwithstanding the occasionally repeated assertion that albuminous urine is not ahvays connected with renal mischief, that our most serious apprehensions must be entertained for the welfare of our patient. The more extended our experience be- comes, the more correct does the laAV laid down by Dr. Bright, of the almost necessary connection between persistently albuminous urine and diseased kidney, appear. 373. I Avas indebted for the opportunity of investigating a Avell- marked case «f this affection to the kindness of the late Mr. Montague Gossett, in whose practice it occurred. This case was peculiarly in- teresting on account of several curious anomalies it presented, as well as from its affording an opportunity of correcting the account gene- rally given of the microscopic characters of urine containing fat. The first specimens of the urine from the patient to which I have referred Avere given to me on April 14th, 1814, with an inquiry as to their nature; one specimen was of specific gravity 1*018, someAvhat 330 NON-CRYSTALLINE ORGANIC DEPOSITS. paler than usual, and was perfectly transparent, with the exception of a slight mucous cloud. The other specimens, stated to have been passed some hours before the former, resembled milk in color and general appearance, and was quite free from any urinous odor. It was faintly acid, of specific gravity 1*020 ; the addition of either nitric or hydrochloric acid produced a considerable curdling. By re- pose, a cream formed on the surface of the urine, forming a layer one-tenth the thickness of the whole volume of fluid. When a drop of this milky urine was placed under the microscope, no oily globules could be seen when examined with an excellent object-glass of one- eighth of an inch focus, by PoAvell; the turbidity appears to have depended upon an immense number of particles, so minute that under a magnifying power of 800 diameters they resembled mere points. I confess that I could not help suspecting that some addition had been made to the urine by the patient after its being passed ; an idea that at first gained some support from the fact that when the bladder was emptied by means of the catheter, the urine removed was found to be quite transparent and healthy. On April 22d, I saw Mrs. T----in bed. She was an extremely fat, flabby woman, about 35 years of age, the mother of several chil- dren. She expressed herself as quite well with regard to her general health, and only complained of the occasional milky state of the urine as possibly indicative of some threatening ailment. She stated to me that for several years she had been accustomed to pass milky urine, especially during part of her pregnancies. On several occasions the urine, although not milky, had gelatinized on cooling so as to assume the form of the vessel like so much ordinary jelly. The appearance of the milky urine was exceedingly capricious, sometimes being con- stant for weeks together, and then disappearing for some time. She could trace no apparent connection betAveen its appearance and any obvious exciting cause; it bore no evident relation to the quality, quantity, or hours of her meals, nor to the periods of menstruation. The only general rule she had observed regarding its appearance was that it most frequently appeared when she first voided tyine on rising from bed, and hence she fancied it was produced by lying on her back all night. It had become most frequent in its appearance since she had begun to grow fat. My visit was made about 2 p. m. ; Mrs. T— had not risen, except to pass water, since the preceding evening. Three specimens of urine were shown to me as having been passed since an early hour in the morning. FATTY URINE. 331 The first specimen was like ordinary urine; contained an abun- dance of pinkish urates, Avhich disappeared by heat; it was acid, and not coagulable ; contained no albumen. The second specimen was as pale as water, subacid, and, on heat- ing it, clouds formed in it from the coagulation of albumen. The third specimen was of a healthy amber color; it appeared natural, and was free from albumen. The examination of these specimens certainly gave no satisfactory explanation of the nature of the milky urine she had previously passed, and she declared that this was the first occasion on which she had failed to pass that kind of urine for some Aveeks. I intro- duced a catheter into the bladder, and a pint of fluid escaped, pos- sessing the odor, color, and general appearance of hot milk and water; in fact, having none of the physical characters of urine. The specimen thus obtained was of specific gravity 1*010, slightly acid ; by repose a cream-like layer formed on its surface, leaving the loAver portion of the fluid nearly transparent. I may remark that Mrs. T— had not partaken of any food since breakfast. This milk-like urine presented the following chemical characters. A. When exposed to heat, a large and tremulous coagulum of albu- men formed, becoming firmer and more solid on raising the tempe- rature to ebullition. B. About four ounces of the urine were agitated with half an ounce of pure ether, and the mixture set aside in a carefully-closed bottle. On the following day the mixture had lost all its opacity, and pre- sented three Avell-defined layers. The lowest, forming the great bulk of the urine, was transparent, and consisted of urine deprived of the ingredients Avhich had produced its previous opacity. On the surface of this rested a perfectly transparent and tolerably firm coagulum of fibrin, about a quarter of an inch thick, of a pale yellowish color. The superior layer consisted of an ethereal solution of fatty matter; this fluid was of a fine golden yellow color. C. The ethereal solution was decanted and allowed to evaporate spontaneously; a large proportion of yellow fat, closely resembling butter in color and odor, was left. It differed from some specimens of fatty matter obtained by an analogous process from milky serum of blood, in not presenting any tendency to crystallize. This yellow fat readily fused by heat into a perfectly transparent oil, which slowly solidified by cooling, and it has undergone no change by keeping, up to the present period. 332 NON-CRYSTALLINE ORGANIC DEPOSITS. D. A portion of the urine left to itself for some time underwent no further change than the formation of a thin creamy layer on its surface: not the slightest tendency to the formation of a fibrous coagulum appeared. E. A portion of the milky fluid was evaporated at a boiling tem- perature to dryness, and digested with hot water. The fluid was filtered, and after concentration, treated with nitric acid, when crys- tals of nitrate of urea slowly formed. . 374. I carefully examined the urine under the microscope, but riot the slightest appearance of oil-globules, blood-discs, or pus- granules, could be detected; the opacity appearing, as in the first specimen given me by Mr. Gossett, to depend upon the presence of particles so minute as to present no defined form; appearing like mere irregular points when examined with a linear power of 800 under an excellent achromatic microscope. The result of this exa- mination is completely opposed to the few statements recorded by Continental observers on the optical characters of fatty urine. Thus, M. L'Heritier has stated that oily globules can always be detected in fatty urine; and a similar remark was made by the late Dr. Simon, of Berlin. The latter has indeed stated, that he has met with three varieties of fatty urine: one in which the fat is merely diffused through it, and collects on its surface by repose, as in the cases recorded by Dr. Elliotson ; the other in which the fat was combined with albumen; and a third in which the fatty matter ex- isted with casein as an emulsion, forming, in fact, true milky urine. In all these Simon states that fat-globules could be seen by the microscope. 375. This curious state of the urine is epidemic in the Mauritius, and accompanies a form of irritative fever. Mr. Rogers, surgeon to the police establishment in that island, has been kind enough to put into my possession some information respecting this curious ail- ment, and I have selected one of the cases he placed in my hands for illustrating this affection as it occurs there. Madame B—, residing in the Mauritius, nursing an infant six months old, first suffered from dysentery four months previously On its disappearance in three weeks, she became the subject of fever, pain in the back, sense of weight in the loins, and the secretion of milk quite stopped. The urine gradually became of a light ochre-color, thick and opaque, like urine mixed with milk. On visiting her (July, 1846), Mr. Rogers found her laboring under severe fever, with thick, full, and hard pulse of 96, the pain in the right lumbar region aggravated by pressure. Bowels confined, but had been FATTY URINE. 333 acted on by small doses of castor oil. The urine was acid, free from odor, specific gravity 1015; a microscopic examination discovered in it myriads of minute irregular globular masses. When 'agitated with ether, the urine soon became clear, a yellow fluid separating and floating on its surface. The urine, thus freed from fat, deposited albumen both by heat and nitric acid. After separating the albumen by heat and filtration, the concentrated urine yielded crystals of nitrate of urea on the addition of nitric acid. During this evaporation, the fluid evolved the urinous odor, which had been pre- viously absent. The urine consisted of Water,..... 943* u Matter separated by ether, 20* a Albumen, .... 6* a Urea,..... 23* (i Extractive matter, . 2- u Saline matter, 6* 1000* A second specimen was collected a week or two later (July 22); it was less opaque, specific gravity 1010, acid. It contained an abundance of ovoid particles, about the size of pus-globules, quite smooth, mixed with epithelial cells and blood-discs. Agitated with ether, it separated into three layers by repose; the uppermost was a white woolly matter (coagulated albumen), the next a yellow solution of fat, floating on the now clear urine. By a violent agitation, the two upper layers became mixed and floated on the urine, form- ing a loose coagulum. The composition of this urine was— Water,.......909-4 Matter separated by ether, .... 7'0 Albumen,....... 2*0 Urea, Extractive matter, ^ .... 81*6 Salts, 1000* A third specimen was obtained August 8th. It was much less milky, pale yellow, specific gravity 1-013, nearly neutral, under the microscope numerous blood-discs were visible; with a few pus-like globules with serrated margins. It consisted of— Water,.......963-44 Matter separated by ether, .... 6-00 Albumen,....... 2-00 Urea, Extractive, }......28*56 Salts, 1000* 334 NON-CRYSTALLINE ORGANIC DEPOSITS. 376. Dr. Bence Jones, to whose zeal in these inquiries we are so much indebted, has recently published the result of his observations on this form of urine, and I must refer to his papers for a full account of his results. The following, however, are the most important con- clusions at which he arrived. 1. The fat on which the milky aspect of the urine depends, ap- pears after the absorption of chyle, but the albumen, fibrin, blood, and alkaline salts, may be found even when no food has been taken, and consequently no chyle formed. 2. During absolute rest, albumen disappears from the urine, and does not reappear in any quantity, even after taking food, unless active exercise is employed. A short time before rising early, the urine gelatinizes by repose, but is free from fat. 3. This state of urine does not depend upon the presence of an excess of fat in the blood, as proved by actual analysis. 4. The seat of this disease is probably some slight alteration in the structure of the kidneys, by which, when the circulation through these organs is most active, one or more of the constituents of the blood exude from the capillaries and escape into the urine. 377. Dr. G. R. Bouyun, of Georgetown, Demerara, has de- scribed some cases of this disease, which seems to be often epidemic there, especially among the Creoles and negroes. The appearance of the so-called chylous state of the urine appears to be in his cases always accompanied by attacks of irritative fever and emaciation like that of diabetes. Dr. Bouyun is inclined to refer this disease to some lesion of the assimilative functions, and has been successful in curing it by the free administration of a decoction of the Mangrove bark (Rhizophora racemosa). This remedy seems to act freely on the skin, increases the secretion, and alters the character of the urine, and improves the general health. URO-STEALITH. 378. A peculiar form of fatty matter has been lately discovered by Dr. Florian Heller,136 who has described it under the name of uro- stealith. The patient Avas a weaver, 24 years of age, admitted into the Vienna Hospital, in February, 1844, under the care of Dr. Bittner, for calculus. He labored under all the symptoms of stone in the bladder, and passed some small concretions, which on examina- URO-STEALITH. 335 tion proved to be composed of a peculiar fatty matter. He was, therefore, treated with carbonate of potass, in doses of 3ij daily, and in fourteen days he lost nearly all the symptoms for which he entered the hospital. 379. Diagnosis of Uro-stealith.—When small concretions of this substance are passed, they may be recognized by the following cha- racters. When fresh, they are soft, becoming, when dry, hard, yel- low, wax-like, brittle, and amorphous ; and by transmitted light, pre- senting a greenish-yellow color. By heat, this substance melts, puffs up, inflames, emitting a peculiar pungent odor between that of shel- lac and benzoin, and leaving a voluminous ash. In hot water it softens, but does not dissolve; slightly soluble in alcohol, readily in ether ; the latter solution, on evaporation, leaves a residue, which as- sumes a violet-color by a gentle heat. Nitric acid dissolves it with slight effervescence, forming a colorless substance. 380. Characters of the Urine.—The urine, in the only case in which uro-stealith has been hitherto found, was quite destitute of uric acid, but contained 12*63 grains of urea in 1000 of urine, was quite neutral, contained an abnormally large proportion of chloride of sodium, and deposited crystals of triple phosphate, mixed with fat- globules. Specific gravity 1*017, inodorous, color light yellow and whey-like. It was not rendered turbid by nitric acid. After the administration of the alkaline carbonate to this patient, the fatty matter appeared in the urine completely saponified, and then the ad- dition of ammonia, which previously scarcely affected the urine, pro- duced a reddish-broAvn color. 381. Pathological Indications.—Unknown, from our experience being limited to the single case here related. The successful treat- ment by carbonate of potass will be a useful hint as to the treatment to be pursued if another case should fall under our notice. CHAPTER XIII. REMARKS ON THE THERAPEUTICAL EMPLOYMENT OF REMEDIES INFLUENCING THE FUNCTIONS OF THE KIDNEYS. Assumed Capricious Influence'of these Remedies, 382—First Law regulating Them, 383—Apparent Exception to, 384—Second Law, 385—Conditions for the Entrance of the Remedy into Circulation, 386—Time required for Absorption of Salts, 387—For Decomposition, 388—Illustrated in Alkaline Salts, 389—In Mineral Waters, 389—Diuresis opposed by Irritable Gastro-intestinal Mucous Membrane, 391—By Obstructive Diseases of the Heart or Liver, 392—Dr. Bar- low's Researches, 393—Applied to the Explanation of Irregular Action of Reme- dies, 394—Practical Conclusions, 395. 382. It has been long stated by writers on therapeutics, and as generally admitted by the profession, that few remedies are so capri- cious in their action as those which directly or indirectly influence the functions of the kidneys: in some patients, a diuretic effect being obtained by the first remedy prescribed in a most satisfactory manner; whilst in other apparently parallel cases, all medicines have failed in stimulating the secreting functions of the renal capillaries. When we refer to the writings of authors on this subject, Ave find the remedies Avhich are supposed to excite the urinary secretion arranged according to their presumed modes of action; and although there is always included a class of direct diuretics, or, in other Avords, of drugs which are supposed really to reach the capillary circulation of the kidneys, and stimulate the vessels by actual contact: yet daily ex- perience proves that even these, too frequently, entirely fail in ex- citing the medicinal influence which has been accredited to them. As much importance has been attributed, in the preceding pages, to the impregnation of the urine with solvents for deposits, so as to prevent the formation of a concretion, it becomes a matter of especial interest to devote a little space to the consideration of the question, whether by any means we can insure the exertion of a therapeutical effect upon the secreting functions of the kidneys, and whether the LAWS OF ABSORPTION. 337 apparently uncertain results of our diuretics and other analogous reme- dies are really as capricious as has been supposed. In a word, Avhether it is not in almost every case possible to predict, with tolerable cer- tainty, from the knowledge of a few general laws, what will really be the effect of a remedy destined to act upon the kidneys. 383. To save any unnecessary circumlocution, I may be permitted to state that I take it for granted that independently of absorption by the lymphatics, fluids can find their way into the various capilla- ries by direct imbibition: and further, that living membrane is obe- dient, quoad imbibition and exudation, or endosmosis and exosmosis, to the same physical laws as when dead and removed from the body. A consideration of facts recorded by observers of credit in all modern works on physiology114 will afford ample data for admitting these several assumptions. It will then be necessary to consider, seriatim, the laws which appear to be fairly deducible from recorded experience. Law 1st.—All therapeutical agents intended to reach the kidneys must either be in solution when administered, or capable of being . dissolved in the fluids contained in the stomach or small intestines, after being swallowed. No one in the present state of physiological science can dissent from this law; not the slightest evidence exists of the kidneys ever allowing a body not in solution to pass their capillaries without posi- tive breach of surface. It has, indeed, been stated that metastatic discharges of pus have occurred from the kidneys; that the purulent effusion of an empyema has been absorbed, and finally excreted, by those organs. Such statements, however, admit, as we have already seen, of a much more direct explanation. The capillary and lym- phatic vessels can be readily submitted to microscopic examination, and no visible pores can be detected in their walls. How then is it possible that organized cells, consisting each of an investing granular membrane, with several distinct nuclei, can find their way through the walls of a vessel in which no visible pores can be detected, and permeate, without breach of •'surface, other capillary vessels in the kidney similarly organized ? In the same way, it has been loosely said, that exudations of blood-corpuscles occur from the renal vessels in some cases of haematuria. To this statement a similar objection applies. All experience goes to prove that no escape of blood-cor- puscles or pus-particles can possibly occur from a capillary without 22 338 THERAPEUTICAL CONSIDERATIONS. actual solution of continuity. Where urine really contains haemato- sine without actual lesion of vessels, the corpuscles must have burst in the capillaries, and allowed the oozing out of their contents, as often occurs, in purpura and scurvy. The researches of Wohler115 have proved to a demonstration that for a body to be excreted by the kidneys it must be actually in solution, and indeed they have shown that the function of these organs is strictly limited to the elimination alone of substances in solution. 384. I am quite aware that an objection may be urged against these conclusions, founded on the presumed metastasis of purulent formations from their original seat and their subsequent deposition in the structure of distant organs, especially of the liver. To the ma- jority of such cases, when really accredited and free from fallacy, the coexisting presence of phlebitis will generally afford a sufficient answer. In some rarer cases, pus may escape from a deep-seated abscess by ulceration into a blood-vessel. In either case, if the pus- particles enter the current of the circulation, they would be hurried along with it, to be entangled in the capillary ramifications through which their size presents an insuperable obstacle to their escaping. Still, although such cases are by no means sufficiently numerous, nor in many instances sufficiently accredited, yet we are not justified in refusing to admit the possibility of a purulent deposit being occasion- ally absorbed. But this admission by no means implies that the pus- particles really enter the vascular system from the sac of the abscess. The process of absorption here is almost indubitably one of metamor- phosis, by which the elements of the pus are partly rearranged to constitute a soluble compound. The presence of oxygen, or saline matters, or of an alkaline salt, conveyed in the arterial blood, will be amply sufficient to explain this reduction of the pus-particle to a solu- ble form, without supposing its ultimate metamorphic change into the elements of bile and urine to occur, as in the case of absorption of muscle (39). The liquor puris of pus contains tritoxide of protein in solution (the pyin of some chemists), and the accession of oxygen would soon be able to convert the solid pus-particles into a similar state, whilst the action of salts and alkalies in breaking up the par- ticle has been before explained (328). Pus thus dissolved and ab- sorbed may readily be deposited in its original form by the removal of its solvent, and thus we are enabled to avoid admitting the neces- sity of a nearly physical impossibility, viz., the absorption of a pus- particle through the parietes of a vein or absorbent. ABSORPTION OF REMEDIES. 339 Law 2d.—Bodies intended to reach the kidneys must, to insure their absorption, have their solutions so diluted as to be of considerably lower density than either the liquor sanguinis or serum of blood (i. e. below 1*028). 385. Peculiar attention to this important law has been directed by the published remarks of Professor Liebig already referred to. It is founded upon the well-known phenomena described by Dutrochet,116 under the terms of endosmosis and exosmosis, or imbibition and exu- dation. They may be thus briefly described. Let a glass tube, open at both extremities, have a piece of animal membrane, as bladder, &c, tied firmly over one end. Partly fill the tube with syrup, and im- merse it in a glass of distilled water. In a short time the fluid will rise in the tube, the water having permeated the membrane and di- luted the syrup; this is an example of imbibition or endosmosis. Empty the tube, partly fill it Avith water, and immerse it in syrup; the fluid will now fall in the tube, exuding through the membrane, and diluting the syrup in the external vessel by exosmosis. As a general law, it may, as far as living tissues are concerned, be sufficient to state that when two different fluids, capable of mixture, be separated by an animal membrane, the fluid lowest in specific gravity will per- meate the membrane, to dilute the denser fluid. In dead animal membrane, whilst imbibition goes on, a certain amount of exudation occurs, but to a much smaller extent, and vice versd; whether this also occurs in living tissue there are no facts before us to enable us to decide. 386. When, therefore, saline substances, especially, are intended to be absorbed and ultimately to reach the kidneys, it is necessary that the density of their solutions should be much below 1*028; the proportion of solids dissolved in the aqueous vehicles prescribed being ahvays less than five per cent. Daily experience in the em- ployment of remedies will show the importance of this law in a thera- peutical sense. Thus, a tolerably strong solution of the tartrate, or acetate of potass, will altogether escape the absorbents; indeed, so far from being imbibed by the capillaries, it will actually excite an exudation of water.from these vessels in the stomach and small intes- tines, thus becoming diluted by exosmosis, and a sensation of thirst is excited, by Avhich the patient is compelled to drink for the pur- pose of supplying the water removed from the blood by exudation. 340 THERAPEUTICAL CONSIDERATIONS. In strong solutions, the salts alluded to stimulate the bowels and purge. They are, moreover, said to act as hydragogue purgatives, producing watery motions,—a fact also capable of ready explanation on physical laws ; exudation of water from the exhalents (capillaries) occurring, on account of the density of the saline solution traversing the intestines, just as exosmosis was produced in the experiment of the tube of water immersed in syrup. We can hence readily per- ceive why half an ounce of acetate or tartrate of potass will purge, and a scruple of either excite diuresis. This statement has been lately called in question by Mr. F. W. Headland, in his elaborate and valuable Essay on the " Action of Medicines" (a work none can read without instruction), but a long and careful observation has quite convinced me of its accuracy and practical importance. 387. The rapidity with which even properly adjusted doses of saline bodies reach the urine is liable to great variation from many causes, but from none more than from the influence of the preceding meal. As a general rule, the substance finds its way to the kidneys with the greatest rapidity when the stomach is empty. Some very interesting experiments, performed by Mr. Erichsen,139 throw great light on this subject. This gentleman had under his care a lad who had been the subject of congenital extroversion of the bladder; the abdominal parietes and anterior wall of the bladder being deficient above the pubes to a considerable extent, so that the orifices of the ureters were visible. On ten different occasions a solution of ferro- cyanide of potassium was given to this lad, and the urine carefully allowed to drop from the ureters into a solution of sulphate of iron, so that the instant at which the salt appeared in the urine it was readily detected. The following table shows the results of the expe- riments : When last meal taken. 2 minutes. 2 « 24 a 1 hour. 1* 2 u a 4 a 4* 11 a a 11* a Time required for the detection of the salt in the urine. 27 minutes. 39 u 16 a 14 ii 6* a 12 a 2 it 2* a 1 a 2 a ABSORPTION OF REMEDIES. 341 388. When alkaline citrates and tartrates were administered, the time required for their appearing as carbonates (162) in the urine was found to vary considerably. This admits of a ready explana- tion, not only in the influence of the previous meal, but in the per- fection at the time of the process of assimilation. For, as has been already stated, the salts of vegetable acids undergo decomposition only when the digestive functions are in a state of tolerable integrity, escaping metamorphosis when the assimilating powers are much de- pressed. Mr. Erichsen obtained the following results in his experi- ments on this patient: Time since the last meal. Salt given. Time elapsing before the occurrence of an alkaline condition of the urine. 3£ hours, . Citrate of soda, . . 28 minutes. 5 " . . . Citrate of potass,. . 40 " 12 " . . . Tartrate of soda, . . 34 " 2 " . . Ditto. . 47 " In the first two of these experiments the urine remained alkaline for several days after the administration of the salts. 389. These facts are of the utmost importance to the success of our practice in the treatment of uric acid deposits, or gravel, by saline remedies, especially by phosphate of soda. This salt readily finds its way into the kidneys when administered in a diluted solu- tion ; but if prescribed in a saturated solution or in large quantities, it, like the tartrate and acetate of potass, excites exosmosis instead of endosmosis, and acts as a mild hydragogue cathartic. A similar remark applies to the majority of salts, of alkalies, and of earths. Most neutral salts are therefore diuretic, if properly administered so as to insure their absorption into the circulation; once being absorbed, it is the duty of the kidneys to filter them off from the blood, and hence they exert a diuretic influence, merely by giving the kidneys an extra amount of Avork to perform. 390. All the natural waters are diuretic, and if drunk in equal quantities are nearly so in the ratio of their levity and consequent purity. Thus the nearly pure water of the Malvern springs, rapidly and readily enters the blood by endosmosis, and escapes by the kid- neys, whilst sea-water in equal doses causes the exosmosis of water from the .intestinal capillaries; hence exciting thirst and purging with fluid motions, scarcely inducing an}T diuretic action. On the contrary, sea-Avater, like all moderately strong solutions, diminishes the bulk of the urine, and causes it to escape in a more concentrated 342 THERAPEUTICAL CONSIDERATIONS. form, simply from its inducing an efflux of water from the blood through the walls of the capillaries of the intestines, Avhich Avould otherwise have escaped by the capillaries of the kidney. 391. In diseases in Avhich an extremely irritable condition of the gastro-intestinal mucous membrane exists, diuresis is often excited with great difficulty, and it is scarcely possible to cause any remedy to reach the urine by direct absorption. Where there is any consi- derable diarrhoea, and copious watery motions are excreted from the bowels, the urine is always scanty and high-colored, a condition necessarily arising from its concentration: Avater freely exuding through the intestines from the blood, and hence but little is left to escape by the kidneys. An extreme instance of this state of things is found in malignant cholera ; here, water is so rapidly pumped off, through the intestinal exhalents, that the blood is left absolutely viscid and thick. Hence the nitrogenized elements, which it is the duty of the kidneys to excrete, cannot be removed by the intestines in consequence of the escape of the Avater which would normally have washed them from the circulation; and the patient dies from a retention of a poison in his system, which the kidneys are unable to remove. 392. The laws just illustrated must be regarded as obtaining only when the entrance of water into the capillaries of the intes- tines is unobstructed ; and when no serious obstacle presents itself to the transit of the water with the blood from the intestinal capil- laries to the vena porta, through the liver to the ascending cava, thence through the lungs and heart to the aorta, and finally to the emulgent arteries. When any obstacle materially interferes Avith the route thus taken by the blood, in any part of its course, a smaller supply of water must reach the kidneys, and the urine will become diminished in bulk and increased in density. To take a familiar illustration : a patient labors under a contracted condition of either of the auriculo-ventricular openings of the heart, and drop- sical effusions occur. In consequence of the impediment opposed to the current of blood, the kidneys excrete but a small quantity of urine. The very dropsical effusions may be regarded as a sort of vicarious effort to relieve the congested state of the veins by allow- ing the Avatery elements of the blood to filter through the Avails of the smaller vessels. Again, if a patient has a cirrhose or hobnail condition of the liver, the portal circulation will be materially ob- structed, and some effects analogous to those produced by a con- THERAPEUTICAL CONSIDERATIONS. 343 tracted ventricular orifice are the result, viz.', dropsical effusions and diminished secretion of urine. In cases of this kind, no benefit can accrue from goading the kidneys by diuretics, unless the obstruction can possibly be lessened or removed. They may be irritated by stimulants like cantharides, copaiba, or squills, until congestion or something worse occurs, without increasing the secretion of urine, simply because the fluid elements are prevented from reaching the kidneys. In cases of this kind, the physician at once sees that all direct diuretics are comparatively useless, and he wisely endeavors to remove the dropsical effusion by remedies which, like elaterium, exert a hydragogic action on the intestines. 393. The attention of the profession has been especially drawn to these conditions by the researches of my friend and colleague, Dr. Barlow. He has, morever, announced the very interesting fact, that whenever a stricture or other obstruction exists in the course of the small intestines, sufficient to prevent fluids readily passing along them, the urine will be diminished in bulk in the direct ratio of the proximity of the obstruction to the pylorus ; nearly absolute suppres- sion of urine occurring when the stricture is so high up as to allow but a small quantity of the fluid contents of the intestines to be exposed to the absorbing influence of the portal capillaries. So absolutely does this obtain," that the observation of the bulk of urine secreted has been proposed by Dr. Barlow as a means of diagnosticating the seat of obstruction in cases of insuperable constipation. The pro- position laid down by the discoverer of these facts may properly be assumed for a third law governing the influence of remedies intended to excite the action of the kidneys. I give it in Dr. Barlow's own words: Law 3d. " If a sufficient quantity of water cannot be received into the small intestines, or the circuit through the portal system in the vena cava ascendens, or thence through the lungs and heart into the systemic circulation, be obstructed, or if there be extensive dis- organization of the kidneys, the due secretion of urine cannot be effected." 394. I think, then, that the so-called capricious effects of most diuretics, or the entrance of any remedy into the renal circulation,, may all be explained by one or other of the foregoing laAvs, and that the supposed uncertainty attending their action is, in most instances, 344 THERAPEUTICAL CONSIDERATIONS. to be traced rather to a want of discrimination on the part of the practitioner, than to any fault in the remedy. An example or two of this kind will be sufficient. Bitartrate of potass is regarded as a diuretic; if a drachm of it be administered with a little fluid, or in a confection, it irritates the inteetines, produces fluid motions, and the kidneys are scarcely affected. Let the same quantity of the drug be dissolved in water and then given; it is imbibed by the capillaries, and causes an increased excretion of water by the kid- neys, in accordance with the first law. Sufficient examples of the second law have been given already. Of the third we have an ex- cellent illustration in the action of mercury and other cholitic drugs in " directing," as it has been termed, the action of a diuretic. Thus let us suppose we are called to a patient in whom a sluggish state of the portal circulation exists, the liver being congested or even myristicated, and from some dropsical effusion, or other symptoms, we are anxious to stimulate the action of the kidneys. It is notorious that in these cases the acetate of potass, nitric ether, squill, and other active diuretics, may be prescribed in vain ; but as soon as moderate frequently repeated small doses of pil. hydrar- gyri, or hydrarg c. creta, or even aloetic remedies, have been admi- nistered, and the liver disgorged of its contents by a free secretion of bile, the kidneys begin to act as the almost nece'ssary result of a readier circulation of portal blood. Experience has shown that there is perhaps no diuretic so valuable in dropsy connected with congested or even contracted liver, as a combination of the squill with a little blue-pill. Many remedies regarded as diuretic, probably really act in this manner; thus colchicum appears to influence the secretion of urine by its stimulating the mucous membrane of the duodenum, and thus by irritating the orifice of the common choledic duct, produces an increased secretion of bile and pancreatic juice, and indirectly relieves a loaded state of liver. Taraxacum, a popu- lar cholagogue, owes its diuretic action, in all probability, to a similar cause. Aloes in small doses, and other remedies, may be referred to this category. Again, in heart-disease, especially when from a contracted mitral orifice, or from dilatation of the organ, a loss of relation between its cavities and their orifices exists, and dropsy results, the exhibition of stimulant diuretics is nearly valueless. Here, the guarded employ- ment of the infusion of digitalis, by soothing the irritability of the heart, and calming the irregular circulation, virtually diminishes the THERAPEUTICAL CONSIDERATIONS. 345 congested state of the vascular system, and acts indirectly as an excellent and efficient diuretic* 395. From the above observations the following practical con- clusions may be drawn: 1. Whenever it is desirable to impregnate the urine with a salt, or to excite diuresis by a saline combination, it must be exhibited in solution, so diluted as to contain less than five per cent, of the remedy, or not more than about twenty-five grains in an ordinary draught. The absorption of the drug into the capillaries will be insured by a copious draught of water, or any diluent, immediately after each dose. 2. When the urine contains purpurine (187), or presents other evidence of portal obstruction, the diuretics or other reme- dies employed should be preceded or accompanied by the ad- ministration of mild mercurials,—taraxacum, hydrochlorate of ammonia, or other cholitic remedies. By these means, or by local depletion, especially by leeches to the anus, the portal vessels will be unloaded, and a free passage obtained to the general circulation. 3. In cases of valvular or other obstructions existing in the heart and large vessels it is next to useless to endeavor to excite diuretic action, or appeal to the kidneys by remedies intended to be excreted by them. The best diuretic will in such cases be found in whatever tends to diminish the congested state of the vascular system, and to moderate the action of the heart; as digitalis, colchicum, and other sedatives, with mild mercurials. * I cannot avoid alluding to the extreme value of a combination of iron with this important drug, in the dropsical effusion arising from contracted mitral orifice. The benefit resulting from tinct. ferri sesquichloridi, TtJJxv, with infusi digitalis ^ij, every five or six hours, the bowels being kept freely acting, is really very remark- able. This combination of a direct sedative with the haematic tonic is not so unphilosophical as may at first sight appear. The digitalis obviously allays the morbid irritability of the diseased organs, whilst the iron supports the vital powers, and enables the blood to act as a healthier stimulant to the heart itself. CHAPTER XIV. BLOOD DEPURATION BY THE KIDNEYS AS A REMEDY IN DISEASE. Blood Depuration by the Kidneys, 396—Crisis by Urine, 397—Elimination of Poi- sons, 398—Evidence of Blood Depuration in Ague, 399, 400—In Acute Rheu- matism, 402—Aided by Remedies, 403—Diuretics, 404—Renal Hydragogues, 405—Renal Depurants, 406—Their Influence in Disease, 408—Persistence of Miasmatic Poison, 409—Therapeutical Value of Acetate of Potass, 410—In Con- junction with Mercurials in Ague, 411—Successful Treatment of Rheumatism by the Acetate, 413—Use of Nitrate of Potass, 414—Renal Depurants as Substi- tutes for Mercurial Alterants, 415—Superiority of Acetate, Citrate, and Tartrate, over Carbonates of Alkalies, 416. 396. Enough has been advanced in the earlier chapters of this work, to prove that the function performed by the kidneys is far more exalted than that popularly assigned to these organs. It is true that they do act as pumps, and remove from the blood a con- siderable quantity of water (51), and hence the bulk of the fluid they excrete is often most erroneously assumed to be a measure of the perfection of their office. This is, however, as Ave have seen, but a small part of the renal function (32); and, indeed, by no means in many animals, especially birds, reptiles, and insects, is it even a ne- cessary one (87). But in all classes of animals, the kidneys, by act- ing as blood-depurants, are ever active in preserving life by remov- ing from the circulating mass, containing, as it does, part of the sewage of the body (40, 45), certain matter, which, if retained, would produce, not merely inconvenience, but death. Every animal de- velops, in its own organism, during the process of metamorphosis of tissue (38), a series of nitrogenized substances, which are, if allowed to accumulate in the blood, as poisonous to it as the deadly secretion of the puff-adder is to a person into whose blood its fatal bite has conveyed it. Hence, although the influence of the skin, the lungs, and the liver, in preserving the blood in a state fit for the nutrition BLOOD DEPURATION IN AGUE. 347 of the body is well recognized, and its importance admitted, we can hardly attribute sufficient consequence to the depurating influence of the kidneys. 397. We have seen how remarkably the kidneys act in depurating the blood of bile when the hepatic functions are impaired (187); and how, by this remarkable compensation of function, life is preserved for a very long period after the liver has ceased to excrete anything. We have also noticed the application of Wohler's law to the function of the kidney, and have seen that the urine holds in solution a very large number of bodies, whose retention in the blood would be in- jurious to health (383), although they generally appear in the excre- tion in a metamorphosed state; thus benzoic acid, hydruret of sali- cyle, and sulphuret of potassium, when taken into the stomach, ap- pear in the urine respectively as hippuric acid, salicylic acid, and sulphate of potass. In the lectures I had the honor of delivering before the Royal College of Physicians, in the spring of 1848, I entered at some length into this subject, especially in relation to the observations of the old physicians, who watched Avith the utmost attention the critical changes occurring in disease as eAridenced by certain changes in the urine. The crisis by urine, indeed, a term as old as the father of physic himself, was always looked for as an indication of the depuration of the blood from the " deleterium quid," which was assumed to be, by acting as a ferment, the exciting cause of disease. Indeed, the modern zymotic theory of disease is but the revived hypothesis of Sydenham, Morton, Willis, and their contemporaries, and the study of the works of the latter physician especially is of great interest in connection with this subject. I am quite aware that many, in com- mon with myself, have often wondered that this crisis by urine was so seldom discovered now, at the bedside, especially in cases of fever. But this does, I think, admit of some explanation ; for on referring to the history of fevers earlier than the last century, it is impossible to avoid noticing the remarkable tendency to well-marked periodicity they all exhibit. It might, indeed, almost be doubted Avhether a genuine continued fever was ever then met with. The greater pre- valence of malaria and marsh-miasm in this country, from the exis- tence of larger tracts of unreclaimed and undrained marshes, will, to some extent, explain the marked periodicity then observed in fever. That a critical change in the urine (by which I mean a change syn- chronous Avith alterations in the phase of disease) does exist in peri- 348 BLOOD DEPURATION odical fevers or agues, and can readily be detected, has been, I hope, sufficiently proved in the lectures referred to. 398. It is hardly necessary to say that I do not mean to assert that the materies morbi does escape by the kidneys unchanged, and that these organs can really separate from the blood the actual miasmatic poison of ague or other zymotic disease. But I am anxious to express my belief in our being able by remedies to decompose or modify such poison, and enable the kidneys to remove it in a metamorphosed state. We have, however, some evidence that certain organic matters easily decomposed, are really occasionally excreted from the kidneys un- changed ; thus quinine, daturine, and some other of the vegetable alkaloids are thus carried off in the urine. The Kamschatdale debauch on the Amanita muscaria is a good illustration of the kidneys receiv- ing a poison from the blood unchanged. A party of men will eat this fungus and luxuriate in the sensual excitement of its intoxicating influence, and when this has passed off, the further supply of Amanita being exhausted, they can keep up the revel by drinking the urine they excrete. 399. In watching disease, we must not hope to obtain evidence of critical depuration of the blood by merely looking at the urine. This can alone be detected by carefully collecting the urine of each twenty- four hours, measuring and taking the specific gravity of the Avhole. Then, as we have already seen, a close approximation to the amount of solids contained in the urine can be obtained by a single calcula- tion (59). From a very careful set of observations carried on during several years in the wards of Guy's Hospital, in which I have been aided most zealously by my clinical reporters for the time, we have determined the fact that in every case of ague, a remarkable relation was observed to exist between the accession of each paroxysm, and the diminished excretion of solids in the urine, and consequently less perfect depuration of blood. The following cases, being two of the earlier ones on which this observation was made, will illustrate this statement; they were reported by Dr. Robert Finch, now of Green- wich : Owen S—, aet. 27, by occupation a bricklayer's laborer, admitted into Lazarus ward, May 21st, 1845, under Dr. Golding Bird. His last residence was at Bankside; before that, for some time at Gravesend. Previous health good; said that he had lived temperately, and once suffered from syphilis. Five months ago, at Gravesend, he first had a shivering fit, followed by the usual hot and sweating stages; he entered Guy's Hospital under the care of Dr. Barlow, and left in three weeks well. On April 1st, the first attack IN AGUE. 349 appeared rather irregular in its stages, and, to use his own expression, he did not ** shake out." The paroxysm returned every alternate day, at about three o'clock in the afternoon. In the previous illness they appeared at noon. On admission, aspect sallow and melancholy; complained of frequent giddiness, with a sensation of dulness and stupor. Abdomen flatulent, pain- less; no appetite; bowels confined; tongue clean and moist. No evidence of enlarged spleen or liver. Urine, sp. gr. 1-028, depositing pink urates, and containing a little biliary coloring matter, but no albumen. Hyd. c. Creta, Ipecacuanhse, aa. gr. j; Ext. Conii, gr. iij, t. d. s. May 22d.—Had a paroxysm yesterday at 3 o'clock, lasting about four hours; complained of "cold creeping" down his back.—P. 23d.—A paroxysm at 3 A. M., lasting not much more than two hours; bowels act freely; dejections pale.—P. 24th.—Felt better; in good spirits.—P. 27th.—No return of ague; aspect improved and less sallow; urine depo- siting urates, stained pink with purpurine; bowels acted freely; skin rather hot and inactive.—P. 29th.—Improving in health and spirits; complained of shivering between the scapulae. Urine pink from purpurine, but not letting fall a deposit. Beeberinse Sulphatis, gr. j, ter in die. June 2d.—Yesterday at noon had a severe paroxysm; shivered severely for three hours, followed by a long and severe hot and sweating stage; bowels confined for two days.—P. Pil. Cal. c. Hyd. iij, hfic nocte. 3d.—Another paroxysm, but not so severe; urine alkaline. Beeberinse Sulphatis, gr. j; Pil. Hyd., gr. j, t. d. s. 5th.—Another attack this morning; urine acid; perspiration neutral.—P. 7th.—Quite well yesterday; this morning had a slight shivering at 10 A.M., but no hot and sweating stage; seemed dull and stupid. Beeberinae Sulphatis, gr. j, ter in die. 10th.—No return of ague; appetite good.—P. 13th.—Progressing favorably; had a healthy tint of the whole surface of the body. 16th.—Complained of a little giddiness, otherwise quite well. 17th.—Convalescent. Made an out-patient, and remained free from ague as long as he was kept under notice. The following is a tabular view of the examination of the urine of this patient: 350 BLOOD DEPURATION Fluid-ounces Weight of Date. of urine in 24 hours. Specific Gravity. Action on Litmus. solids present in grains. May 23 12 1*028 Acid, pink deposits. 352 " 26 40 1-020 a 828 " 28 35 1020 Acid, no deposit. 725 " 30 48 1*020 a 1054 " 31 45 1*016 u 743 June 2 35 1-014 Alkaline. 514 " 4 30 1-028 Acid, pink deposits. 879 " 6 27 1-034 a 1036 » Y 35 1013 Acid, no deposit. 436 " 9 40 1-028 it 1172 " 11 45 1-016 u 742 " 13 40 1-022 ii 916 «■ 14 43 1-022 ii 984 " 16 37 1*027 ii 1041 The proportion of solids excreted in a given time, is calculated from the specific gravity, according to the table before alluded to, and therefore must be regarded as approximately, not absolutely, correct (59). 400. In this case we had to treat a patient who had been long im- mersed in malaria, who had suffered from a previous attack of ague, and whose portal circulation was interfered with. Although no en- largement of the liver or spleen could be detected by "palpation," still the jaundiced urine and sallow miasmatic melancholic aspect sufficiently attest the torpid mode in which the liver was carrying on its functions. On looking to the table of the urine, it must be admitted that there exists, to say the least, some curious coincidences between the free action of the kidneys, quoad the excretion of the solids, and the im- provement of the patient. The unusually large quantity of solid constituents removed by the kidneys of this patient is remarkable, and certainly very unfrequent. Whether this was owing to any idiosyncrasy, I have no means of knowing. On referring to the table, we find that on May 23d, but 352 grains of solids were removed by the kidneys in twenty-four hours; the patient's disease not having then shown any tendency to yield to our remedies, and bile existed in the urine; the quantity of solids in- creased to the 30th, on which day it reached the remarkable quantity of 1054 grains; on the 31st, it suddenly fell to 743 grains; and in the succeeding twenty-four hours, the paroxysm, absent for several days, returned. On the following day, June 2d, the urine was alka- line for the first time, and contained less than half the quantity of IN AGUE. 351 solids which existed four days previously, and he had a most severe attack on the next day ; the kidneys became more active, and a less severe attack appeared on the 7th, when the solids again fell to a minimum; after this time they were again copiously excreted, and the ague finally vanished. Mary H----, aet. 13 years, admitted May 23d, 1845, into Martha ward, under Dr. Golding Bird. She was born at Sheerness, and had lately re- moved to Deptford ; had scarcely suffered from any illness ^before the pre- sent one. Although well developed for her age she had never menstruated. Three years ago she first suffered from ague of the quartan type, two clear days elapsing between the attacks; the paroxysm then commencing at noon, and appearing pretty regularly in spite of treatment for two years. She then left Sheerness, and came to Deptford, and shortly after attended Guy's Hospital, as an out-patient, under Dr. G. Bird. She was cupped over the spleen, and took quinine, so that in a month she appeared cured, and re- mained well for eight months. Lately she had become emaciated; a month ago, ague again appeared; still quartan in type. On admission, the skin was active, although cold; aspect not very sallow, but dull and stupid ; pulse quick, although small and regular ; no appetite ; complained of thirst, and occasional bilious vomitings. There was consider- able pain across the forehead, and from her mother's account she was light- headed at night. On examining the abdomen, the spleen could be felt de- cidedly enlarged. Urine stated to be high-colored during the paroxysm; pale in the intermissions. May 24th.—Had a paroxysm to-day, lasting from noon to six in the evening. * Hyd. c. Creta, gr. ij ; Ipecac, gr. j, ter in die. 27th.—Paroxysm came on at noon, as usual, and continued seven hours. Beeberinaa Sulphatis, gr. j, 4ta quaque hora. Paroxysms absent. 29th.—Pretty well, but the skin hot and dry.—P. 31st.—No ague yesterday; skin acting freely; bowels confined. Rep. Beeberinae Sulphatis. Pil. Hydrarg. gr. iij ; Ex. Coloc. Co., gr. vj, alt. nocte. June 3d.—No return of ague; too much heat of skin; the tongue had a white fur with elongated marginal papillae (strawberry.tongue). Augeatur dosis Beeberinae ad gr. ij. 7th.—Going on well; tongue the same; cheeks flushed, but the skin per- spirable.—P. 14th.—Progressing favorably during the week; the tongue had cleaned. She seemed very well.—P. 17th.—Not so well; some gastric disturbance, owing to some irregularity in food. Zinci Sulphatis, 3j, statim. 352 BLOOD DEPURATION 20th.—Was well after the emetic. 27th.—Convalescent. The following table presents a view of the patient's urine whilst under treatment: Fluid-ounces Specific Weight of Date. in 24 hours. Gravity. Action on Litmus. Solids in grains. May 24 35 1*008 Acid. 280 " 26 28 1*013 a 375 " 28 26 1020 u 538 " 30 25 1*024 a 625 " 31 20 1*022 u 458 June 2 30 1-017 a 528 " 6 35 1018 Alkaline. 651 a 1 30 1*020 Acid. 621 A glance at this table shows that pari passu with the patient's improvement, a gradual increase occurred in the solids excreted by the kidneys. No ague appeared after the blood had been depurated of 538 grains of effete matter, on the 28th of May. In this case, unlike the last, although the patient had long been exposed to the poison of marsh malaria, she did not suffer any relapse, and she re- mained Avell during two years, when she again came under my care as an out-patient, with a very slight attack of ague. 401. I hope that I shall not be misunderstood in the line of argu- ment I have adopted. Although believing most completely that ague is primarily excited by the influence of a peculiar septic poison derived from marsh malaria, I do not for a moment assert that this particular poison is excreted in the urine during the recovery of the patient (398). The great influence of the malarious poison is in all proba- bility essentially and primarily exerted upon the nervous system, especially on the organic or ganglionic structures, which preside so importantly over the function of secretion. Thus, all the secretions elaborated in a body become affected; and, as is well known, a re- markable tendency to congestion is observed in the portal circulation destined most particularly for the depuration of matters rich in carbon. There can be no doubt that the unhealthy secretions thus formed become active agents in keeping up in the body the impression of the disease. One of the great elements of successful treatment must of necessity be the depuration of the blood, and thus, by freeing the system from the depressing influence of these vitiated matters, allow IN AGUE. 353 the vital powers to throAV off the influence of the poison which for a time oppressed them. The influence of small doses of mercury in the treatment of ague is well known; by a gentle but persistent appeal of this kind to the liver, the patient is immensely relieved, and his ultimate cure expedited. Contemporaneously with this, the aspect generally becomes less sallow, a sufficient indication of the liver be- coming active in depurating the blood of carbon. Then, under the influence of that very curious class of remedies, the anti-periodic tonics, the paroxysms become less, or quite vanish, whilst ample evi- dence is afforded of the kidneys performing the important duty of filtering from the blood highly nitrogenized substances, in the rapidly increasing amount of solids existing in the urine. 402. It is not in ague alone that this remarkable critical increase in the excreted solids of the urine is observed; the same thing is, if possible, still more marked in cases of some other diseases, especially acute rheumatism. In every case of this affection in which the urine was carefully collected, and the quantity of the contained solids cal- culated, we invariably found that whenever the patient improved, the quantity of solid urinary excreta steadily and considerably increased; any relapse being attended with as remarkable a diminution. These observations were neither small in number, nor hastily made; they extended over several years, and amounted to upwards of four hun- dred in different diseases. 403. Having thus accumulated sufficient evidence to prove that the old idea of washing away a materies morti from the blood, by the urine, was at least based on truth, the next question for conside- ration Avas hoAV far it was possible to aid this function of blood-depu- ration ; and thus, by expediting the removal of noxious matters from the system, hasten the cure of the patient. That we do possess such means, I am as convinced as I am of the existence of the function of blood-depuration itself; but before alluding to the proposed plan for effecting this, it is requisite to point out a very important distinction to be made in the different remedies commonly employed to stimulate the kidneys. 404. The class of direct diuretics, therapeutically distinguished from those which act indirectly, by modifying the supply of blood to the kidneys, or by otherAvise influencing the capillary circulation in these organs, although limited to remedies which are supposed to stimulate the structure of the kidneys by actual contact, contain nevertheless a very heterogeneous collection of substances. Thus can- 23 354 RENAL DEPURANTS. tharides and nitrate of potass are both regarded as direct diuretics, and yet their influence is really of the most opposite kind. In a word, some diuretics are alone active in increasing, nearly exclusively, the water discharged by the kidneys; Avhilst others, as I have proved I hope beyond all doubt, increase the excretion of solids from the blood. Even independently of any chemical explanation of this dif- ference of their action, the researches of Mr. BoAvman enable us to suggest a probable physiological solution of this curious fact, by sup- posing that the vascular tufts of the kidneys are especially stimulated by one series of diuretics to induce the exudation of more water from the blood, whilst the other series especially increase the formation of epithelial structure. 405. With the value of ordinary diuretics, or renal hydragogues, every practitioner is familiar; their utility in carrying off undue ac- cumulations of fluid in the system is well known and appreciated. But I am anxious to claim for the depurating or chemical diuretics, or renal depurants, the careful consideration of the physician, be- lieving that they constitute a class of agents now almost completely neglected, and indeed hardly recognized, and yet of the highest value in the treatment of disease. To the class of renal hydragogues belong all those agents which out of the body exert no chemical effect on animal matter, as squill, copaiba, broom, juniper, guaiac, lytta, &c. All these, in the absence of any opposing cause connected with mechanical obstructions to the free course of the circulation, will, it is well known, increase the dis- charge of fluid by the kidneys, and become often valuable agents in enabling us to successfully treat dropsical accumulations. If the urine secreted under the influence of these diuretics be examined, the quantity of solids present will not be found to much exceed the nor- mal quantity, unless a considerable quantity of water or other bland fluid be taken at the same time. After I had fully satisfied myself of the general truth of the facts now mentioned, I was much gratified by meeting with a paper by Professor Kramer,156 on this subject. He administered to persons in health different diuretic agents, and having collected and analyzed the urine secreted, he found the proportion of solids seldom exceeded, and was often rather less than the normal average; and hence concluded that these agents had no physiological action on the system; at least, so far as the excretion of solids was concerned: "Dass die gewohnlich sogenannten Diuretica ohne alle physiologische Wirkung sind." I adduce Kramer's observations in RENAL DEPURANTS. 355 preference to my own, as they were evidently not made under the influence of any preconceived vieAV, as it is evident from his paper that he had no knowledge whatever of the facts I have alluded to. I have calculated the* following table from his experiments: Medicine given. Solids in the urine of twenty-four hours. Combustible (animal) matter in. Saline matters in. None, .... Juniper, Venice turpentine, Squill, .... Digitalis, Guaiac, Colchicum, 2-4 ounces. 2*12 " 1*94 " 2-25 " 2*45 " 2-43 " 2*32 " 1-28 ounces. 0-94 " 1*11 " 1-04 " 1*28 " 1-38 " 1*36 " 1-13 ounces. 1*18 " 0-83 " 1-21 " 1*17 " 1-05 " 0-96 " Remedies, then, which exert no chemical action on organic matter out of the body, appear to be incapable of augmenting the quantity of solids in the urine, and hence are only of use in increasing the elimination, of water ; they may, and do act as renal hydragogues, but not as renal depurants. 406. We have next to notice those remedies among the reputed diuretics which exert the influence I have alluded to, and which, ac- cording to my own observation, act as renal depurants by increasing the metamorphoses of tissue, and act as depurating agents. This class includes the alkalies, their carbonates, and their salts, with such acids as in the animal economy are capable of being converted into carbonic acid, including the acetates, tartrates, citrates of soda and potass.* These remedies all act alike, actively stimulating the ex- creting function of the kidneys, and generally augment the bulk of the urine; but they do more, they actually increase the metamor- phoses of tissue by, in all probability, a direct chemical action on the elements of worn-out and exhausted tissues, or other matter in the capillary laboratory of the body. It is well known that alkalies and their carbonates readily dissolve albumen out of the body, and even break it up into various secondary products. Thus, digested with an alkali, albumen yields leucine, protid, and erythro-protid (bodies allied * Among these ought to be specially mentioned liquor potassae, the action of which has been so carefully and ingeniously determined by Dr. Parkes. When given while food is in the stomach, it acts merely as an antacid; but when given on an empty stomach, it passes into the blood, facilitates the decomposition of pro- tein compounds, and thus liberates sulphur, which, combining first with oxygen and then with the potass, is eliminated by the kidney, as sulphate of potass. 356 RENAL DEPURANTS. to gelatine), formic acid, and other compounds. In like manner casein is broken up into tyrosin, leucine, valerianic acid, and other elements. It is exceedingly probable that some such changes occur in the living organism itself, and we should almost expect to find the chemical diuretics effecting important changes. This I have repeat- edly confirmed by absolute experiment. But one illustration, one I have already published, may be taken as an example of the rest. A young lady was for some time under my care, laboring, among other things, under a condition of the orifice of the urethra AA'hich prevented her passing water without the aid of a catheter; thus ad- mitting a very accurate examination of the quantity secreted in twenty-four hours. This, when no medicine was exhibited, was col- lected and examined; and afterwards three drachms of acetate of potass being administered in the course of twenty-four hours, the urine secreted in that time was collected and analyzed. The results are shown in this table: uantity of urine in twenty-four hours, pecific gravity of, . Solids in Uric acid, . . . Without medicine. After 5iij pot. acet • f^xvj. . . fgxlvj. . 1-025 . . 1*017 . 416 grs. . 782 grs. 2*6 . 3*45 Urea, . Soluble salts, • 130-5 72-0 . 202*40 . 248-40 Insoluble salts, 21*6 32-25 Organic matters the above, not incl ided in l 189*3 . 225-50 416 782 407. The results of these analyses show that, after deducting the excess in the amount of soluble salts, arising from the conversion of acetate of potass into carbonate in its transit from the stomach to the kidneys, the solids of the urine, separated from the blood under the influence of the chemical diuretic, exceed those excreted without its aid by 190 grains. We further learn, that although a large propor- tion of matter was metamorphosed into both uric acid and urea after the administration of the acetate, still that the greatest increase Avas in that mixture of organic products set down as extractive, and which, as we have seen, consisted chiefly of creatine, creatinine, uroxanthin, and matter rich in sulphur (103). In the example adduced, not only did the patient lose an excess of 30 ounces of water in twenty-four hours, but she wasted to the extent of 190 grains more than if no BLOOD DEPURATION. 357 remedy had been given, and to this extent had the blood been depu- rated of those elements which yielded easiest to the influence of the alkaline salt. As it cannot be denied that vital force is ever active in opposing the chemical changes to which all living fibres are ob- noxious, it is fair to assume that this resistance will increase Avith the vital endowments of a part, or, in other Avords, that the elements of our frames resist chemical influences in the ratio of their vitality. It would follow that such constituents of our body as present the greatest departure from health are less highly vitalized, and thus would be expected to yield the easiest to the influence exerted by the alkaline diuretics or renal depurants. As a result of this view*, we should expect that when Ave cause an alkaline carbonate to circulate through the blood, it exerts an influence on the nascent elements of those matters less highly influenced by life, resembling that which it exerts on dead matter, aiding their resolution into substances allied to those produced out of the body, and actually causes the matter to assume so soluble a form as to alloAv of its ready excretion. This remarkable effect of the alkaline diuretics (although noAV demonstrated by actual experiment, and the results of their chemical influence de- tected in the stream by which they are washed from the body), was not overlooked by the observing physicians of former years. It was, indeed, acted upon by the old physicians—Avitness the host of apo- zems, diuretic decoctions, and diet-drinks, in. Avhich renal stimulants abound; and let us not shut our eyes to the success of the practice, for unless we deny all credence to the statements of the painstaking practitioners of past times, those who will read their quaint records of cases Avill learn how generally they succeeded in curing the effects of a caco-osmia, an unhealthy blood, as evidenced in various eruptive affections, cellular membranous sores, furunculi, and very many such ailments. It is true that in looking at some of their prescriptions we do not generally obserAre remedies which have noAV much confidence placed in them as trustAvorthy diuretics, but then an important ele- ment of their potions is most undoubtedly the water of the decoction employed, not in doses of tablespoonfuls, but, as was common in former days, of pints. A most important truth here demands our attention. It may be said that it is true that if a patient takes a pint or tAvo extra of Avater he will, supposing that no organic lesion exists, excrete a large bulk of urine, from the necessity there exists for pumping off the excess of diluent partaken of. In this way a pint or two of water becomes a diuretic. This every one's experience will 358 BLOOD DEPURATION. enable him to admit; but Avhat is this, it may be asked, but the mere draAving off of excess of Avater,—where is the proof of blood-depura- tion ? This proof is afforded by calculating the amount of the solid constituents of the urine. It will then be found that the excess of water does not escape alone, but there is really Avashed away Avith it a certain, although not very large quantity, of solid debris. To Ed- mund Becquerel must be accorded the credit of this observation; and any one may satisfy himself of its accuracy by collecting all the urine he passes in twenty-four hours, and determining the quantity of solids it contains ; and repeating this process next day, while throwing into his system three or four bottles of aerated—the so- called soda—water. This observation affords a key to many of the undoubted.cures effected by the use of many of the mineral springs. Some of them are, like that of Malvern, remarkable only for the posi- tive purity of their water. Setting aside (Avhatwe must never forget) the influence of change of scene and association, the diminution of the Avear and tear of mind by relaxation from business, healthy air and exercise, amusement of mind and excitement of renewed hopes, we cannot help recognizing in the increased action of the kidneys, exerted by the so-called mineral Avater, a most important agent. A man laboring under some chronic ailment, which, perhaps, like old rheumatism, is the direct result of unhealthy constitution of the blood, starts for one of the Brunnens or Spas, and with fearful devotion SAvalloAvs the enormous quantity of ten or fourteen beakers of the warm and bubbling water. In a few minutes he begins to secrete abundance of urine, and is engaged alternately drinking and mictu- rating for part of the morning—active exercise, when possible, being enjoined the Avhole time. By this exercise the waste of tissue is in- creased, and the copious water-bibbing positively aids the metamor- phosis of tissue, and washes its results from the body. 408. The results of these researches have now been tested by some years' close observation at the bedside of the sick, as it is obvious that nothing but clinical experience can determine the value of any class of remedies as agents in the treatment of disease. From all that has occurred to me I can most confidently repeat the statement I ventured to make more than four years ago in my lectures at the College of Physicians: " I would earnestly beg those who are now doing me the honor of listen- ing to my remarks, to give a careful and steady trial to the depurating or chemical diuretics, especially the salts of potass with vegetable acids, Avhen DUMB AGUE. 359 they are called upon to treat a chronic affection in which the exciting cause, or existing disease, depends upon the presence of some product of less vita- lity or imperfect organization. I fully believe that in many instances such matters will be often found to yield, whether they present themselves as albuminous deposits in glands, furuncular disease of cellular tissue, or incrus- tations on the skin, as in some of the squamous and tubercular cutaneous diseases. That they will succeed in increasing the waste of matter, is, from my observation, beyond all doubt; that the lowest vitalized matter will yield to the solvent the readiest is most probable, and that an important and pow- erful addition to our supply of therapeutic weapons is certain. "lam not anxious, so soon after the observation of the fact I have announced, to appeal too soon to the results of my own practice in support of it, as I know full well how deceptive are often the results of experience unless largely extended; and the whole history of medicine is one great commentary on the errors arising from observation on results which the mind of the observer has anticipated—an obedience to those idola specus, against the influence of which Lord Bacon long ago warned us. I will not dare to do more than state that it has occurred to me to see the periodicity of ague broken through, the paroxysm lessened and made more distant, and the sallow dirty aspect of malaria exchanged for the cleaner and brighter com- plexion of returning health, under the influence of the agents I am advo- cating. The disease has thus been rendered readily amenable to the subse- quent administration of the anti-periodic whose previous influence it had resisted, or, at least, not satisfactorily obeyed. Jaundice, connected with a large, sluggish, congested liver, has certainly better yielded to setting up a complementary function on the part of the kidneys by a diuretic alterant, than by goading the liver with remedies whose influence it refused to obey; and in more than a single instance a strumously enlarged cervical gland has yielded to the persistent use of an analogous remedy, even after resisting the iodide of potassium." 409. In ague, nothing is more easy, as every one is aware, than to check the paroxysms by means of anti-periodics, especially qui- nine, and in many cases the patient is really cured by the remedy. But any one who has had an opportunity of seeing much of the effects of marsh miasmata, is perfectly aware that if a patient has been long exposed to their influence, although paroxysms of ague may be for a time checked with quinine or arsenic, the unhealthy state of the blood is not removed. The sallow aspect—the depressed health—the visceral engorgement—all indicate that the poison re- mains in the system and is continuing its work, although its influence has been blunted by our remedies. After a time, however, imperfect paroxysms, the " dumb ague," as they are often graphically called by the patient, appear again, requiring the anti-periodic to check their further development. This is a common history, and many persons are thus not really absolutely freed from miasmiatic poison for months or years. 360 BLOOD DEPURATION. 410. I do not claim for the acetate of potass the virtues of an anti-periodic, but I do unhesitatingly declare that it will effect that which quinine and its allies cannot do. It will enter the blood, and as a nascent carbonate (possessing a far higher state of " chemical tendency"* than ready formed carbonate of potass) in the capillary netAvork of the body aid the metamorphosis and excretion of the unhealthy elements of the blood, and their consequent elimination by the kidneys. When to a person suffering from the effects of marsh malaria, this drug has been administered to the extent of 3\j iQ tne course of twenty-four hours largely diluted, and continued for two or three weeks, not only is no injury effected by the remedy, but the most marked benefits are observed to result. The patient's skin-becomes less dusky, the expression more healthy, the dull aspect of the eyes changed for one of cheerfulness, the engorgement of liver and spleen lessens, and the paroxysms of " dumb ague" disappear, or merely require a few doses of arsenic for their complete cure, and thus to effect the complete restoration of the patient. Even in recent ter- tian ague, in -which the paroxysms are well marked and even violent, I have hardly ever administered the acetate of potass without ob- serving a diminution in the intensity of the attacks, and a consider- able prolongation of the intermissions. Indeed, when quinine has been administered for the purpose of at once checking the ague fit, the subsequent administration of the acetate will not only prevent a relapse, but greatly improve the patient's general health. 411. Every practitioner is aware of the value of mercurial purga- tives, as Avell as of the administration of small doses of pilula hydrar- gyri to patients suffering from ague, in consequence of the remoATal of visceral congestion, and resulting in increased depuration of blood by the liver. But I believe the most successful practice, especially in the treatment of cases of ague which have resisted long courses of anti-periodics, consists in the administration of minute doses of a mild mercurial contemporaneously with the acetate of potass. The folloAving case, taken from one of our clinical report books, will illustrate this: {Reported by Mr. Bayes.) Patrick L—, set. 27, admitted into Spare Ward, under Dr. Goldin°" Bird, May 1st, 1850. A muscular, well-proportioned man, of light com- * "Medical Gazette," 1848, vol. i, page 1018. CASE OF AGUE. 361 plexion, a native of Cork, having resided in England during nine years. Always intemperate when earning good wages as a laborer, and sober only when deprived of the means to be otherwise. He scarcely remembered to have been previously ill since childhood. In the preceding August he was employed in harvest-work, in the fenny districts of Norfolk and Cambridge- shire, where his wife took ague. In October he went to Woolwich, and was employed in unloading barges, until two months ago; since which he had been similarly engaged at Billingsgate. After being thus constantly exposed to miasmatic influences for nine months, he was attacked, three weeks ago, with an ague paroxysm, recurring each morning about five o'clock. About a fortnight before admission, he had a most violent attack; the shivering in the cold stage was so severe that he was obliged to be held in bed, as he stated, by two men. The hot and sweating stage which fol- lowed lasted the whole day. Since then the disease assumed a regular tertian type. During the first twenty-four hours of his residence in the hospital, he passed 58 ounces of urine of specific gravity 1023. A warm bath was ordered, as his skin was exceedingly dirty, and Pil. Cal. c. Col. ij, h. s. s. May 3d.—Pil. Hydrarg. gr. i; Ex. Conii, gr. iii, fiat pilula, t. d. s. Potass. Acetatis, gss. ex Mist. Camphorae, f .^ij, t. d. s. During the next four or five days, the paroxysms diminished remarkably in severity, and the urine on the 6th, amounted to 72 ounces of 1018, and on the 9th, to 90 ounces of 1-017. By this time a most remarkable improve- ment had taken place in his countenance, the malarious aspect having nearly disappeared. May 13th.—He became as bad as ever; the paroxysm of to-day was more severe than any he had experienced since his admission. On the 15th, diarrhoea appeared. It was then discovered that he had been privately sup- plied with black-pudding, and had voraciously devoured a considerable quantity of this mixture of coagulated blood, fat, and oatmeal. The urine had fallen to 50 ounces of 1-016. A brisk cathartic of calomel and colocynth was ordered, and the acetate of potass to be afterwards continued without any mercurial. 17th.—Very much improved, ague fits much less severe, general health apparently good between the slight paroxysms. Rep. Mist. c. Liq. Potass. Arse nit., ^ v. 20.—Ague fits much slighter. June 2d.—Ague fits absent since last report. 412. The remarkable improvement in the patient's condition, after the use of his remedies for a feAV days, and the diminution of the par- oxysm in intensity before any anti-periodic was given, attracted the attention of all who saw him. Yet his case was by no means so remarkable as that of many others under treatment at the same time. I do not doubt that the arsenic or quinine, if given at first, might have checked the disease, but I am quite sure they could not have effected—which the other remedies did—the conversion of a sallow, \ 362 BLOOD DEPURATION. malarious aspect into one of really ruddy health—nor do I believe he would have been left so free from tendency to relapse. 413. It is, however, in that really formidable disease, acute rheu- matism, a malady which merits the most careful and jealous watch- ing, on account of its too frequently leaving behind disease of the cardiac valves and pericardium, that the effects of the acetate are most remarkable. I would not Avillingly use language Avhich AA*as not completely compatible Avith experience, but I do not still hesitate to declare that I have never seen the disease in question yield with so much facility to any other remedy. In the severest cases Avhich have been admitted into the hospital under my care (and I prefer alluding to them in preference to cases in private practice, as they have the advantage of being watched by many, and less chance of error arising in the reports of the progress of the patient), I have seen the cure to be more rapid, and the immediate relief to the patient more marked by the use of the acetate of potass in quantities of half an ounce, administered, largely diluted, in divided doses, in tAventy- four hours, than by any other treatment. In three days I have re- peatedly found the exquisite pain of the joints nearly absent, the patient comparatively comfortable, and able to bear with greater ease the helpless state in which the still swollen state of the joints place him. In no case has any ill effect followed the use of the remedy, and whilst the cure has been far more expeditious, the ill effects of colchicum and mercury have been avoided. The pain remarkably and suddenly lessens, as soon as the urine becomes alkaline and rises in specific gravity. I can, indeed, unhappily attest my experience in my own person on the marked alleviation and rapid cessation of the pains of rheumatic fever from the use of the drug, and can grate- fully compare its influence with the tedious and painful results of mercurial treatment in a former attack. It is difficult to decide on the comparative immunity from pericarditis in acute rheumatism under particular modes of treatment, but the impression on my mind is very deep, that the tendency to this fearful complication is very much lessened as soon as the urine is rendered alkaline by the acetate. I could quote a large number of cases from our clinical report books to demonstrate the efficacy of this plan of treatment. This would, however, be quite useless, as the above remarks convey all the infor- mation I can offer. The treatment is as uncomplicated as pos- sible, the acetate being usually administered in some aromatic water, or what is far more grateful, in plain water, to which a few drops of USE OF NITRATE OF POTASS. 363 oil of lemons have been added. The only addition to this treatment has generally been a mercurial laxative if constipation existed, and a full dose of Dover's powder on the first day or two of treatment if the pains be severe. The joints being wrapped in sheets of wadding, a plan I have invariably followed since noticing the comfort it afforded to myself in a severe attack ten years ago. 414. In connection with this subject I would especially draw at- tention to the undoubted benefit resulting from the treatment of acute rheumatism by large doses of one of our most certain diuretics, nitrate of potass, in doses of §ss or Ij, dissolved in two or three pints of any diluent in the tAventy-four hours. An enormous amount of urine re- places the scanty excretion generally noticed, and the cure of the patient is considerably expedited. This practice, really of British origin, has been popular in the Parisian hospitals for some years, and has attracted notice here. My friend Dr. Basham has especially drawn attention to this practice in a valuable paper read before the Royal Medical and Chirurgical Society. The quantity of solids re- moved from the system by the nitrate of potass is, however, far less than that which is carried off under the solvent influence of those agents which act more energetically on animal matters. It must not, however, be supposed that nitre, or, indeed, any other of the neutral salts, are destitute of influence. It has been long shown that the salt in question will readily dissolve coagulated albumen and fibrin; and it thus, when circulating in the capillaries, may probably exercise no mean influence in aiding the metamorphosis of .tissue. 415. I would most anxiously urge upon my professional brethren the importance of giving a fair and patient trial to the acetate of potass in a large class of ailments where the blood is obviously in an unhealthy state, especially where glandular engorgements and furun- culous eruptions exist. Indeed, in many of these forms of chronic indisposition in which there is no evidence of organic mischief, but where the general health is depressed, the face salloAv, the urine colored by purpurine, constituting the condition in which the patient is popularly said to be " bilious," the advantage gained by the use of this remedy is remarkable. Hitherto, whenever a remedy influencing the general health, through the capillary circulation, is required in chronic disease, we generally fall back upon mercury, indeed, a mer- curial and an alterative are nearly convertible terms. Instead, then, of trusting to mercurials nearly exclusively, or after they have been administered without benefit, or in the strumous diathesis, where for 364 BLOOD DEPURATION. the most part they are not well tolerated, I would advocate the use of renal depurants, especially of acetate of potass. 416. Although in these remarks I have especially alluded to the acetate of potass, yet I have merely selected it as a type of a large class of remedies, many of which equal it in their remedial effects. The citrates and tartrates of potass and soda constitute remedies of probably equal value. Indeed, the utility of the popular " saline draughts" of these salts is in all probability to be explained by their influence as renal depurants. The solutions of potass and soda, as well as their carbonates, are most useful remedies of their class, but decidedly of much less value than the acetates and citrates. Two reasons may be given for this,—first, they are very likely to become neutralized whilst in the primos vice by acids, which, like the hydro- chloric and phosphoric, are not decomposed Avhilst passing through the circulation ; secondly, the Conversion of acetates and citrates into carbonates takes place in the blood, and thus they, in the nascent state, when their chemical tendencies are the highest, come in contact with those matters which it is important to eliminate ffom the blood. It is well known that a considerable quantity of liquor potassae (160) is required to render the urine even neutral, whilst a few grains of an acetate or tartrate will rapidly render it alkaline (162). 417. Having thus explained my reasons for believing in the exis- tence of an important class of remedies, the renal depurants, capable of replacing with advantage in many cases mercurial alteratives/ I dare not trespass further, as the very introduction of this chapter demands an apology, as being somewhat foreign to the design of this volume. The only excuse I can offer is the unwillingness that the results of some very tedious and protracted, but I hope not useless observations, should be lost, and the too well-grounded belief that I may never be permitted to make them known, as I had once hoped, in another and more extended form. APPENDIX. CATALOGUE OF THE URINARY CALCULI CONTAINED IN THE MUSEUM OF guy's HOSPITAL. In the year 1817, when Dr. Marcet published his Essay, the Museum of Guy's Hospital contained but 228* calculi. During the last twenty-seven years, this number has been augmented to 374; all of which have been divided so as to exhibit their internal structure, with the exception of 21. The great majority of the calculi added since Dr. Marcet's publication have been analyzed at different periods, as they were placed in the Museum, by Dr. Babington, Dr. Rees, and myself ;f and in every instance, the exami- nation has not been limited to the composition of the external crust, but has been particularly directed to the chemical constituents of the ingredients composing each layer. Attention has in each specimen been directed to the composition of the nucleus, in contradistinction to that of the body of the concretion. This is of very great importance; for when once a few solid particles of any substance aggregate and form a mass in the bladder, they very readily induce a crystallization of oxalate of lime, uric acid, or triple phosphate; or a deposition of urate of ammonia, phosphate of lime, or other amorphous ingredient, according to the lesion of function and state of irrita- bility or enervation present. Hence, if ever, by medical treatment, we shall be enabled to prevent the formation of a calculous concretion, or remove one already formed, it will, in all probability, be by means directed by the cha- racter of the matter which there is a tendency to deposit as a nucleus. On this account I have adopted a classification of the calculi in Guy's Hospital Museum, founded not upon the number of alternating layers, but upon the character and composition of the nuclei. In the following table, it must be borne in mind, that all the distinct constituents present in each concretion have not been mentioned; those only being inserted which were present in such quantity as to constitute a considerable portion of either body, nucleus, or crust of the concretion. Those ingredients, which existed in mere traces, or in very minute quantities, have been omitted; as they are rather to be re- garded as accidental contaminations, than as essential elements of the calculus. No urinary concretion, indeed, ever exists perfectly pure and unmixed; for * Including 142 removed from one patient. f Still more recently Mr. Bransby Cooper has continued these investigations, and added largely to the collection of calculi in the Museum. 366 APPENDIX. there are very few in which some traces of uric acid, or phosphates, are not observable : and even if these be absent, the coloring matter of urine or blood prevents the calculus being regarded as perfectly pure. CALCULI IN GUY'S HOSPITAL MUSEUM, OF WHICH SECTIONS HAVE BEEN MADE, ARRANGED ACCORDING TO THE CHEMICAL COMPOSITION OF THE NUCLEI. Genus I.—Nucleus, Uric Acid, 250. Species 1. Calculi nearly entirely composed of Uric Acid or Urates. , Nearly all uric acid,......... Uric acid, nearly pure,........*° Stained with purpurine,........2 Contained urate of lime, ........^ " " and ammonia,.....3 " urate of soda and lime,......2 " oxalate of lime,.......2 " phosphate of lime,.......1 •' triple phosphate,.......2 32 B. Body consisting chiefly of urates, . Contained urate of soda, . " '* and lime, " urate of lime, . " uric acid in the body, 32 170 142* 22 4 2 170 Species 2. Bodies differing in composition from Nuclei A. Bodies consisting of oxalate of lime, Oxalate of lime and uric acid alternating, Uric acid in the body, with an outer layer of carbonate of lime, Oxalate, chiefly confined to external layer, Oxalate of lime in the bodies nearly pure, 2 1 1 7 11 11 B. Bodies consisting chiefly of earthy phosphates, Bodies composed of fusible calculus, . •• phosphate of lime, " triple phosphate, . C. Body consisting of carbonate of lime, 24 D. Body compound, . Body: Urate of ammonia, Crust: Fusible, 16 3 5 24 1 1 12 * From the same patient. APPENDIX. 367 Oxalate of lime, . . . Uric acid, . . . .3 " ... Fusible, .... 3 " ... Triple, .... 1 ** ... Phosphate of lime, . . 3 Fusible,.....Uric acid, ... 1 12 Genus II.—Nucleus, Urates op Ammonia or Lime, 19. Species 1. Calculi nearly all compound of Urate of Ammonia, . 8 Urate of ammonia, nearly pure,.......6 Uric acid, in tubercular patches on crust, ..... 1 Traces of urate of soda and phosphate of lime, .... 1 8 Species 2. Bodies differing from Nuclei,..... 10 Body: Crust: Uric acid and fusible, . . .As body, .... 2 Urate of ammonia, . . . Uric acid, .... 1 " " ... Oxalate of lime,. . . 1 " " ... Phosphate of lime, . . 1 " •* and oxalate \ Uric acid with oxalate and) . of lime, j phosphate of lime, j Urate of ammonia and fusible, . As body, .... 1 Urate and phosphate of lime, . Ditto,.....1 Oxalate of lime, .... Fusible, .... 1 Fusible,.....As body, .... 1 10 Species 3. Nucleus Urate of Lime. A. Body fusible,..........1 Genus III.—Nucleus, Uric Oxide, 1. Species 1. All Uric Oxide,*.......1 Genus IV.—Nucleus, Oxalate of Lime, 47. Species 1. Calculi nearly all of Oxalate,...... 19 Uric acid in nucleus, ......... 1 Crust, covered with opaque octohedral crystals, .... 1 •• " transparent, ....... 3 " not covered with crystals, . . . . . • .14 19 Species 2. Bodies differing from Nuclei. A. Bodies consisting of uric acid or urates, ..... 8 * A portion of the calculus removed by Langenbeck, at Hanover, and analyzed by Wohler and Liebig. 368 APPENDIX. Uric acid, nearly pure, . . ._.....' " covered with urate of ammonia,.....1 8 B. Bodies consisting of phosphates,....... 14 Phosphate of lime,.........6 Triple phosphate,..........5 Fusible mixture,..........3 14 C. Body compound,.........• 6 Body: . Crust: Uric Acid, .... Fusible, _.....2 " .... Oxalate of lime, .... 1 Urate of ammonia, . . Phosphate of lime, ... 1 1. Uric acid, . . . ) 2. Oxalate of lime, . > Oxalate of lime, .... 1 3. Uric acid, . . . j Cystine,...........1 6 Genus V.—Nucleus, Cystine. Species 1. All Cystine, ......... 11 Color, greenish-blue, ......... 1 " dirty greenish-gray, ........ 9 " fawn brown, ......... 1 11 Genus VI.—Nucleus, Earthy Phosphates, 22. Species 1. All Phosphates of Lime,.......2 2 Species 2. All Triple Phosphates, .......1 1 Species 3. All Fusible Mixed Pliosphates,......19 19 Genus VII.—Ingredients op Calculi mixed, with no evi- dence of arrangement, in concentric layers, 3. A. Uric acid and triple,......... 1 B. " phosphate of lime, ....... 1 C. '* urates of soda and ammonia, with oxalate and phos- phate of lime, ......... 1 3 ABSTRACT VIEW OF THE NUCLEI. Nuclei, consisting of uric acid or urates,.....269 " *' oxide,........1 " " cystine,.......11 " " oxalate of lime,......47 " " phosphates,.......22 350 Mixed calculi,..........3 353 Calculi undivided,.........21 374 APPENDIX. 369 I have not included in the above Tables the fibrinous calculus of Dr. Mar- cet, in consequence of its differing so totally from other concretions; as it must be regarded as a portion of dried inspissated albuminous matter exuded from an irritated kidney, rather than as a calculus produced under circum- stances at all analogous to those of other concretions. Several specimens exist in the Museum, of the pelves of kidneys and ureters being obstructed by clots of fibrin ; but none of them present the hard, concrete condition of the calculus described by Dr. Marcet. I am not aware of this variety having been mentioned by any other except Brugnatelli, who, in his Litologia Umana, described some calculi as consisting of crystallized albumen (di ma- teria albuminosa cristallizata di colore d'ambra): they were passed by one individual, and each was about the size of a nut. These pseudo-calculi were supposed to consist of dried coagulated albumen, which not unfrequently presents considerable lustre, and a vitreous fracture, although scarcely suffi- cient to justify its being regarded as crystallized. I confess I have a strong suspicion that the calculi described by Brugnatelli really consisted of cystine. Among the other ingredients existing in calculi in very minute quantities, and not enumerated in the Table, are hydrochlorate of ammonia, oxide of iron, and carbonate of lime. The former has been described by Dr. Yellowly as a frequent ingredient, generally, however, existing in mere traces of cal- culi; the second was discovered by Professor Wurtzer, and is often present in uric acid calculi; and the third is frequently present in phosphatic and oxalic concretions. None of these ingredieuts are so generally present as to merit their being regarded as presenting much interest in a pathological sense. Calculi present the greatest possible variety in appearance; generally, however, having more or less of an ovoid figure. Of those in Guy's Museum, the urate of ammonia and urio acid concretions are the most regular, nearly all being ovoid or circular,1 a few only reniform;b this species never pre- senting any very prominent processes or projections, unless fresh centres of deposition occur on their surfaces, as when crystals of uric acid are deposited on an ovoid urate of ammonia concretion.0 The cystic oxide concretions vary considerably in outline; when large, being generally oval and smooth;d and when smaller, often presenting projections from their surface's, as if they were made up of crystals radiating from a common centre;3 sometimes being moulded to the figure of the organ which secreted it, as shown in the curious ear-drop-like concretion/ The oxalate of lime is generally most irregular, as far as the surface is concerned, although its outline is generally tolerably de- fined, either bearing a close approximation to an elliptic or even a rectangular figure. The most contorted and irregularly figured calculus is the triple or fusible, it being often a complete cast of the pelvis and calyces of the kidney;8 occasionally, however, it is almost regularly oval, and sometimes circular;1* this variation, in all probability, depending upon the position occupied by the calculus, and upon whether it had been retained in the kidney, or passed down the ureter before it had become of any considerable size. The mixed calculi, or those not presenting any regular concentric arrangement or a dis- tinct nucleus, are often moulded to the kidney.' The phosphate of lime calculus is generally smooth externally, and conchoidal in fracture, sometimes Reference to Calculi in the Museum. » No. 2118. bNo. 2119. c No. 2125. -"No. 2143. eNo. 2145. f No. 2145.35 b No. 2163. h No. 2161. • No. 2136. 24 370 APPENDIX. appearing as if made up of several cohering portions.k The triple phosphate1 and fusible mixturem are not unfrequently found deposited on one side of a previously formed calculus, as if one surface only had been exposed to the urine containing the earthy salt in solution, which is generally found under the form of elegant white vegetations. The nucleus is usually found in the geometric centre of the calculus, or nearly so; sometimes, however, being remarkably eccentric, as in some reni- form concretions -,11 and in a few, several distinct nuclei or centres of depo- sition are met with.0 In some rare instances, the concretion which forms the nucleus is found loose within the body of the entire calculus; a circum- stance in all probability arising from a laye* of blood or mucus having con- creted around the nucleus, and on which the matter forming the body of the calculus became deposited.«* In this case, on the whole becoming dry, the mucus or blood would be diminished to a very thin layer, and the calculus would appear to contain loose matter in it. In a few instances, calculi appear to possess no nucleus, the centre being occupied by a cavity, full of stalactitic or mammillated projections, giving the idea of the external layer having been first formed, and the mammillated portions subsequently formed in the inte- rior. This state occurs only, so far as I have seen, in uric acid calculi.q In one specimen in the collection the central cavity is lined with fine crystals of triple phosphate, resembling the crystals of quartz so often found lining cavities in flints." Brugnatelli describes one of a similar kind. Sometimes calculi present very remarkable appearances, as if they had been divided into segments. This, in some cases, can be explained by the attrition of calculi* against each other, where several exist at once. In some, they actually appear as if they had been di\'ided by a fine cutting instrument; and in one, in the Museum, the apparently divided portions seem as if they had again become cemented and framed in by a subsequent deposit.* An American physician, Dr. Peters, has submitted to a very elaborate exa- mination the calculi contained in the Museum of the medical department of the Transylvania University, and the results of his researches offered a very interesting comparison with the above details of my own. ABSTRACT VIEW OP THE COMPOSITION OF CALCULI IN TRANSYLVANIA UNIVERSITY MUSEUM. . 32 . 26 . 2 . 7 . 7 . 4 78 . 34 . 2 . 2 . 16 kNo. 2148. 'No. 2198. mNo. 2154.3 "No. 2119. "No. 2158. p No. 2133. 'No. 2113. 'No. 2154. ■No. 2218.88 'No. 2136.50 Nuclei consisting of uric acid nearly pure, " " urate of ammonia, . " " cystine, . " " oxalate of lime, " " phosphates, " " foreign substances, . The bodies were composed of uric acid chiefly in, " " urate of ammonia, '• " cystine, •• " oxalate of lime, . APPENDIX. 371 The bodies were composed of mixed phosphates, » " triple phosphates, 66 4 124 The cortical portion was composed of uric acid in, . . . 34 urate of ammonia with phosphates, I cystine, ..... 2 oxalate of lime, ... 9 mixed phosphates, ... 37 triple phosphates, ... 2 86 LIST OF PREFERENCES. N.B.—In the first reference to any work its title is given in full, in the subsequent, the name only of the author or work is mentioned. 1. Dr. Prout, Nature and Treatment of Stomach and Urinary Affections, 3d edition. London, 1840, p. xviii. 2. Professor Liebig, Animal Chemistry, translated by Dr. Gregory. Lon- dop, 1842, p. 103. 3. Dr. Prout, p. xl. 4. Annalen der Chemie und Pharmacie, B. 47, s. 306. 5. Ed. Becquerel, Semeiotique des Urines. Paris, 1841, p. 7. 6. Dr. Kemp's Letter to Professor Liebig, &c. London, 1844, p. 37. 7. 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Sir B. Brodie's Lectures on Diseases of the Urinary Organs, p. 108. 98. Guy's Hospital Reports, vol. vii, p. 336. 99. Medico-Chirurgical RevieAV, 1839, p. 223, and Journal de Chimie Medi- cale, 1839. 100. Physiologische Chemie, 1842, B, i, s. 252. 101. Burdach, Traite de Physiologie. Paris, 1839, T. vii. 102. Rayer, T. i, p. 162. 103. Medico-Chirurgical Transactions, Part xviii, p. 80. 104. Dr. Prout, p. 112. 105. Journal de Chimie Medicale, 1840, p. 68. 106. Lallemand, des Pertes Seminales. Paris, 1834. 107. Miiller's Elements of Physiology, translated by Dr. Baly, 1842, vol. ii, p. 1472. 108. Elements of Chemistry, by Professor Graham. London, 1842, p. 808. 109. Dr. Golding Bird, in Medical Gazette, November 24, 1843. 110. Journal de Chimie Medicale, 1844, p. 359. 111. Pritchard's History of Infusoria. London, 1842, p. 134. 112. Poggendorff's Annalen der Physik, V. 1844, and copied into the Chemist for 1844, p. 363. 113. The Lancet for September, 1844, p. 751. 114. Midler's Physiology, by Baly. London, 1840, vol. i, p. 5. 115. Tiedemann's Zeitschrift. Band 1—quoted in Midler's Physiology. 376 APPENDIX. 116. Nouvelles Recherches sur l'Endosmose. Paris, 1828. 117. Medical Gazette, March, 1836. • 118. Lecon sur la Statique Chimique des Stres organises. Paris, 1841, p. 39. 119. Poggendorff's Annalen, 1845, p. 114. 120. Heller's Archiv., 1844, p. 132. 121. Journal de Pharmacie, February, 1845. 122. Mellon, Annuaire de Chimie, 1845, p. 509. 123. Poggendorff's Annalen, 1845, p. 118. 124. Dr. Golding Bird in Phil. Mag , June, 1845, p. 532. 125. Midler's Physiology, vol. i, p. 638. 126. Practical Treatise on the Human Skin. London, 1845. 127. Medical Gazette, 1845, p. 1286. 128. Journal de Chimie et Pharmacie, November, 1845, p. 370. 129. Annalen der Chimie und Pharmacie, March, 1845. 130. Medical Gazette, 1844, October, p. 49. 131. Heller's Archiv., 1845, p. 266. 132. Mulder's Versuch einer AUgemeinen Physiologischen Chemie, 1844, s. 385. 133. Bouchardat, Annuaire, 1843, p. 138. 134. Journal de Chimie Medicale, 1845, p. 302. 135. Medical Gazette, 1845, p. 235. 136. Heller's Archiv., 1845, p. 1, and 1844, p. 97. 137. Analysis of Blood and Urine, 2d edition, p. 217. 138. Caspar's Wochenschrift, April 26th, 1845. 139. Philosophical Transactions, 1845, p. 335. 140. Medical Gazette, 1845, pp. 363, 410. 141. Liebig's Annalen, February, 1846, and Chemical Gazette, May, 1846. 142. Lectures on the Urine, 1846, p. 11. Dublin, 1846. 143. Medical Gazette, 1846, p. 324. 144. Liebig's Researches on the Chemistry of Food, 1847, p. 88. 145. Chemical Gazette, 1850, p. 181. 146. Medical Gazette, 1850, September. 147. Medico-Chirurgical Transactions, vol. xxx, p. 186. 148. Animal Chemistry. London, 1450, p. 41. 149. Chemical Gazette, 1850, p. 182. 150. Medico-Chirurgical Transactions, vol. xxxi, p. 83. 151. Philosophical Transactions, 1846, p. 463. 152. Harnsaure in Blut, &c. Berlin, 1848, s. 112. 153. American Journal of Medical Science, April, 1851, p. 297. 154. " " « for July, 1850. 155. Entwurf einer AUgemeinen Untersuchungsmethode der Safte und Excrete. Leipzig, 1846, p. 63. 156. Heller's Archiv., December, 1847. 157. Quarterly Journal of Microscopic Science, 1852, p. 26. 158. British and Foreign Medico-Chirurgical Review. 159. Odling's Practical Chemistry. 160. Philosophical Magazine, January, 1854, and Medico-Chirurgical Re- view, October, 1854. 161. Lehmann, Physiological Chemistry, translated for the Cavendish Soci- ety, by Dr. Day 162. Dr. Day's Contributions to Urology. 163. Lancet, June 12, 1852. ALPHABETICAL INDEX. Abnormal pigments, 269. tints of urine, 79. Absorption of remedies, 337, 338. pus, 291, 338. Acetate of potass, therapeutic properties of, 356, 359. Acidity of urine, 84. Acids, Butyric, 113. Hippuric, 37, 111. Lactic, 107. Marcet's, 39. Melanic, 273. Oxalic, -204. Phosphoric, 118, 229. Sulphuric, 121. Uric, 95. Age, influence of, in depositing phosphates, 245. Ague, cases of, 349. 350, 360. urine in, 349. Albumen, composition of, 121. in urine, 277. in pus, 291. in leucorrhoeal discharge, 292. Albuminuria after scarlatina, 287, 289. Alkaline urine, 94, 245. from fruit, 158, 246. from use of citrates, 157, 341. from decomposition of urea, 94, 246. from fixed alkali, 250. following injuries to the back, 247. Allantoin, 208. Amanita muscaria, 348. Ammonia in urine, 117. Analysis of urine, 40, 86. of urates, 97. of Brighton waters, 155. Anaxagoras, theory of, 67. Ashes of blood, 121. faeces, 121. urine, 39. Assimilation of food, 58. Average bulk of urine, 83. density of urine, 73. • Bacon, Dr., his researches on oxalate of lime, 198. Balance of secretions, 67. Barlow, Dr., on absorption, 343. Barral, Mr., on chloride of sodium, 123. Basham, Dr., on fungoid growths in urine, 315. Beale, Dr., on chloride of sodium in pneu- monia, 124. on tests for saccharine urine, 307. Becquerel, Ed., researches, 72. on water as a remedy, 358. analysis of urine, 86. formula for solids, 75. uric acid in urine, 145. Begbie, Dr., on oxaluria, 218. Benzoic acid, 159, 260. Bile in urine, 284. composition of, 61. pigment, 170. Biot, M., on circular polarization, 81. Birds, urine of, 104, 106. Bischojfs table of the relative quantities of urinary constituents at different ages, 92. Black deposits, 273. Blood, uric acid in, 141. oxalate of lime in, 207. casein in, 324. in urine, 276, 283. Blood-casts, 282. Blood-depurations, 346. in ague, 349, 350. in acute rheumatism, 362. Blue deposits, 272. Borax in lithi-uria, 158. Bouchardat, M., on circular polarization, 81. Boussingault, 31., on excretion of lactic acid, 108. uric acid, 104. Butter in urine, 322. Butterflies, urine of, 106. Butyric acid, 113. Brett, Dr.. on deposition of phosphates, 234. Brighton waters, analysis of, 155. I 378 ALPHABETICAL INDEX. Brights Dr., disease, 277, 287. Calculi in Guy's Museum, 365. Transylvania Museum, 370. pisiform, 136,162. Camplin, Mr., receipt for diabetic bread, 314. Carbonate of ammonia, 95. lime, 265. Carbonic acid, excretion of, 62. Carnivora, urine of, 103. Casein in blood, 324. urine, 322. Cases of fatty urine, 330, 322. hippuria, 181. lithi-uria, 153. mole-pregnancy, 326. oxaluria, 219. phosphuria, 239, 241, 255, 257, 261, 263. Caterpillars, urine of, 209. Cells, oxalate of lime in, 210. Chloride of sodium, microscopic characters of, 38, 176. Chlorine in urine, 37, 44, 123. Christison, Dr., formula for solids, 76. Cholera, urine in, 316. Chromate of potash test for sugar, 309. Chylous urine, 330. Citrates, decomposition of, 157. Clinical examination of urine, 46. Coloring matter of urine, 36, 114. physiology of, 114. pathology of, 167. tests for, 114. Colors of urine, 79, 80. VogeVs table of, 80. Compensation of functions, 67. Composition of urine, 86. influenced by food, 87,211. Concretions, glandular, 306. Confervoid growths in urine, 305, 306,315, 317. "Constitution water," 161. Creatine, 36, 108. Creatinine, 36, 108. physiology of, 110. Crisis by urine, 347. detections of, 348, 352. Curling, Mr., on alkaline urine, 249. Cyanourine, 269. Cyanate of ammonia, 272, 307. Cystine, 172. microscopic characters of, 175. pathology of, 177. Cystitis, phosphatic, 263. Cystorrhoea, 295. Davy, Dr., on determining the amount of urea, 42. Day, Dr., on solids in urine, 75. Density of urine, 09. Deposits, general rule for recognizing 50, 51, 52. formation of, 125. Depurants, renal, 354, 355. Diabetes, pathology of, 310. treatment of, 313. Diabetic diet, 314. Diabetic urine, 304. Diagnosis of bloody urine, 283. cystine, 172. hippuric acid, 180. mucus, 294. oxalate of lime, 191. phosphates, 230. pus, 292. spermatic urine, 300. sugar, 304. Diagnosis of urates, 136. uric acid, 128. uric oxide, 164. Direct diuretics, 353. Diuretics, laws governing, 339, 345. cautions respecting, 289, 290. Ducks, uric acid excreted by, 105. Dulk, Professor, on cases of dark urine, 273. Dumas, M., on alkaline urine, 248. Dumb ague, 359. Dumb-bell deposits, 136, 195. traced to oxalurate of lime, 197. oxalate of lime, 199. in urine of the horse, 267. Dr. Bacon's researches on, 198. mistaken for uric acid, 198. Dyspepsia, phosphatic, 242, 255. Earthy phosphates, 37, 118. Enderlin, on phosphates, 119. Endosmosis, 339. Epithelial casts, 280. Epithelium co*htaining oxalate of lime, 210. deposits of, 203, 299. Erichsen, Mr., on absorption, 340. Extractive, urinary, 46, 115. sulphur, 116. Exudation globules, 297. Faeces, phosphates in, 121. Faraday, Dr., on exhalation of nitrogen, 143. Fatty casts, 281. urine, 327. Fermentation of cystinic urine, 174. saccharine urine, 304. test for sugar, 309. Ferrocyanide of potassium, absorption of, 340. Fever, deposition of phosphates, 245. Fibrin, composition of, 122. Fibrinous casts of tubules, 280, 281, 282, 283, 328. Fluids, absorption of, 336. Food, assimilation of, 58. influencing urea, 90. ALPHABETICAL INDEX. 379 Food, influencing uric acid, 103. phosphates, 119. 'oxalate of lime, 211. Formulae for solids in urine, 76. Gallic acid in haematuria, 288. Garrod, Dr., on uric acid in blood, 141. oxalate of lime in blood, 206. Gelatinous urine, 277. Glycocoll, 64. Gout, urine in, 141. Granular casts, 280. Gravel, uric, 134. Gravimeter, 69. errors of, compensated, 69. Griffith, Dr., on dumb-bell crystals, 199. Guano, 106, 208. Guanine, 164. Gull, Dr., case of mole-pregnancy, 326. Guy's Museum, calculi in, 365. Haemaphaein, 114. Haematosine, 283. Haematuria, 276, 288. Halophyle, 114. Hassall, Dr., on indigo deposits, 271. on organic prostatic globules, 299. his case of sarcinae ventriculi, 240. his views on the nature of the urates, 97. on penicilium glaucum, 317. Heintz, detection of urea, 93. Heller, on urinary pigments, 114. Henry, Dr., formula for solids, 75. Herbivora, urine of, 111. Hippuria, 180. Hippuric acid, detection of, 37, 180. physiology of, 111. pathology of, 182. Horse, oxalate of lime in urine of, 211. Horsley, Mr., on chromate of potash as a test for sugar, 309. Hour-glass uric acid, 130, 133, 136. Hughes, Dr., his cases of black urine, 273. Hyaline casts, 282. Hydrated albumen, 279, 328. Hydrochloric acid in the stomach, 150. Hydrometer, 69. Hypoxanthine, 66, 164. Indications of urine, 55. Indigo deposits, 270. Dr. HassalVs analysis of, 271. Inosinic acid, 66. Inosite, 66. Insects, urine of, 106, 209. Iron, in lithi-uria, 154. Jaundice, urine in, 171. Johnson, Dr., on fatty urine, 327. renal casts, 280. Jones,Dr. B.,on acidity of urine, 84. ■ alkaline urine, 250. fatty urine, 328. phosphates in urine, 121, 234, 251. the want of relation be- tween the specific gra- vity and solid residue of the urine, 78. uric acid in urine, 95, 105. Kemp, Dr., on bile, 62. Kiestein, its nature, 319. diagnosis in pregnancy, 324. in mole-pregnancy, 326. Kramer's researches, 354. Lactate of zinc, 35. Lactic acid, 107. Laskowski on protein, 60. Laws of absorption, 342. phosphatic deposits, 251. uric deposits, 101, 147. Lecanu, on urea and uric acid, 91. Lehmann on urea, 90. on uric acid, 103. views on the nature of the urates, 97. Letheby, Dr., his analysis of urates, 97. his analysis of Brighton wa- ters, 155. his analysis of urine con- taining phosphate of. mag- nesia, 240. Lever, Dr., on albuminuria of pregnancy, 287. Liebig, Baron, theory of assimilation, 58,61. uric acid, 144. method for determining amount of urea, 43. test for cystine, 172. Lime, phosphate of, 232, 251. carbonate, 265. Liquor muci, 294. ' puris, 292. sanguinis, 376. Lithi-uria, 128. treatment of, 151. Lucretius, criticisms on corpuscular theory, 67. Luton's test for sugar, 309. Magnesia, triple salts of, 232. Magendie on influence of food, 104. Marcet, Dr., his account of two new acids in the urine, 39. his cases of black urine, 273. on the relation of skin to kid- neys, 144. 380 ALPHABETICAL INDEX. Maumene, diabetic test, 308. Melanourine, 273. Metamorphosis of tissue, 58, 63. Microscope, 52. pocket, 53. Microscopic form of alkaline phosphates, 238, 239. blood, 286. Microscopic form of carbonate of lime, 266. creatine, 36. creatinine, 36. chloride of sodium, 38, 39,176. cystine, 175. dumb-bell crystals, 195. earthy phosphates, 37, 236, 237. epithelial casts, 280. epithelium cells, 299, 300. fatty casts, 281. fibrinous casts, 280, 261, 282. fungoid vegetations, 315, 317. granular casts, 280. hippuricacic), 181, 182. hyaline or waxy casts, 282. lactate of zinc, 35. Marcet's acids, 39. organic globules. 297. organic prostatic glo- bules, 299. oxalate of lime, 192,197. penicilium glaucum, 317. pus, 292. phosphate, of magne- sia, 239. phosphates of soda, 238, 239. renal cells, 280. spermatozoa, 301. torulae, 305, 306. urate of soda, 141. urates, 138-140. nitrate of urea, 34. uric acid, 34, 130, 132-136. Milk in the urine, 318. Mitral valve, disease of, 344. Modifications of urine, 57. Moore, Mr., diabetic test, 308. Mucus, 34, 293. oxalate of lime in, 211. Mulder, Professor, on piotein, 59. on tannin, 288. Muscle, metamorphpsis of, 62. Nitrate of potass in rheumatism, 363. Nitrogen, excretion of, by the kidney, 90. skin, 142. Nitric acid tests for albumen, 278. bile, 79. Nitro-hydrochloric acid, 216. Oil in urine, 282, 327. Organic globules, 297. prostatic globules, 299. Oxalate of lime, frequency of, 191. diagnosis of, 191. chemical properties of, 196, 199. dodecahedral form of, 192. dumb-bel.ls, 195. in urine of caterpillars, 209. in urine of the horse, 211. urine containing, 200. pathology of, 204. physiology of, 210. Oxalurate of lime, 195. Oxaluria, symptoms, 212. arguments in support of the ex- istence of, 187. treatment, 215. cases of, 219. with excess of urea, 212. without excess of urea, 213. Oxidation theory, 61, 101. Pavy, Dr., on the physiological relations of sugar 310. Perspired fluid, 143. Pelouze on lactic acid, 108. Peters, Dr., list of calculi, 370. Pettenkofer's test, 285. Pigments, abnormal, 269. Pigeon's urine, 139. Pisiform calculi, 136, 162. Phosphates, alkaline, in urine, 39, 119. earthy, in urine, 37, 117, 235. detection of, 37, 235. normal, 118. in food, 118. Phosphate of lime, 232. secreted by the bladder. 252. secreted by the glands, 253. Phosphates, triple, composition of, 231. microscopic forms of, 236. of magnesia in cases of sar- cinae ventriculi, 240. of soda in urine, 238. Phosphate of soda in lithi-uria, 159. Phosphatic cystitis, 263. dyspepsia, 253. Phosphuria, 229. deposits in, 232. urine in, 233. treatment of, 253. Physiological origin of urine, 56. ALPHABETICAL INDEX. 381 Pink deposit, 168. Pneumonia, chloride of sodium in, 124. Polarizing power of urine, 81. Porphyuria, 167. Pregnancy, urine of, 287, 319. Primary assimilation, 58. Protein, 59. Prussian blue, 272. Purpurine', pathology of, 168. composition of, 170. relation to bile, 170. Pus in urine, 290. absorption of, 292. casts, 282. Queket.t, Mr., on oxalate of lime in cells, 210. Ratio of solids to density, 76. Redtenbacher on taurine, 122. Renal depurants, 354, 355. cells, 280. hydragogues, 354. Rees, Dr., on fat in urine, 322. on deposition of phosphates, 234. Rheumatic fever, treatment of, 353. Rigby, Dr., on oxaluria"*2l5. • Robin and Verdeil on urinary- phosphates of soda, 238. Rogers, Mr., case of chylous urine, 352. Rose, Mr., on oxalate of lime, 211. Saccharine urine, 304. Saline draughts, 364. Salts of urine, 38,45. absorption of, 339. of vegetable acids, decomposition of, 157, 340. Sarcosin, 64. Sarcinae ventriculi, urine in cases of, 240. Scarlatinal dropsy, 287. Scherer, Professor, on urinary extractive, 115, 170. Schweig, Dr., speculations, 72. Schmidt, Dr., on uric acid, 133. Secondary assimilation, 58. Sediments, formation of, 125. classification of, 126. Seguin, on perspiration, 143. Seminal granules, 301. Serpents, urine of, 103. Shearman, Dr., on cystine, 174. Silicic acid, 267. Simon on urine of fever, 245. Skin, exhalation from, 143. Snow, Dr., on alkaline urine, 249. Solid residue of urine not indicated by spe- cific gravity, 78. Solids in urine, 74. Solubility of uric acid, 95. Specific gravity, 69. of urine not a measure of amount of solid residue 78. Spermatozoa, 300. Spiders, urine of, 106. Spine, diseased, urine in, 246. Sugar, detection of, 306. physiological and pathological origin of, 310. Sulphur in cystine, 172. taurine, 122. urine, 116. Sulphuric acid, 37. Sulphocyanogen, 90. Table of" relative quantities of constituents of urine at different ages, 92. Tables, color of urine, 79, 80. density of urine, 75. examining urine, 50, 51, 52. ratio of density to solids, 75, 76. Taurine, 122. Tests for sugar, 306. Therapeutical laws, 337. Torulae in urine, 304, 305. Transition elements in urine, 111. Triple phosphate, neutral, 236. bibasic, 237. Trommels diabetic test, 306. Tubuli, fibrinous casts of, 280-282, 328. Urates, 136. Lehmann's views on the nature of, 97. Dr. Hassall's views on the nature of, 97. Dr. Letheby's analysis, 97. Urate of soda in blood, 141. microscopic form of, 142. Urea, artificial, 93. detection of, 35, 41, 88. Dr. Davy's method for determining its amount, 42. excess of, in oxaluria, 205. influenced by food, 90. Liebig's method for determining its amount, 43. physiology of, 88. relation of, to carbonate of ammonia, 93. cyanate of ammonia, 93. Uric acids, causes of deposits of, 144, 147. crystals of, 35, 130, 131-136. deposit of, 128. detection of, 128. in blood, 142. pathology of, 128. physiology of, 95. preparation of, 45. treatment of, 151. Uric oxide, 163. excreted by spiders, 106, 166. Urine, acid, 84. density of, 71. alkaline, 245. 382 ALPHABETICAL INDEX. Urine, fetid, 245. non-sedimentary, 47. normal composition of, 86. quantity of, 73. ratio of, to food, 58. ratio of, to fluids, 72. sources of, 56. sedimentary, 48. Urinometer, 69. corrections for, 69. Uro-stealith, 334. Uroxanthine, 114. Vapor bath, 151. Vegetable acids, decomposition of, 157. Vibriones in urine, 317. Vichy water, analysis of Brighton artificial, 156. .Vogel's scale of urinary colors, 80. 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It A-ill thus be seen that for the small sum of FIVE DOLLARS, paid in advance, the subscriber w.ll obtain a Quarterly and a Monthly periodical, EMBRACING A30UT FIFTEEN HUNDRED LARGE OCTAVO PAGES. Those subscribers who do not pay in advance will bear in mind that their subscription of Five Dollars will entitle them to the Journal only, without the News. The advantage of a remittance when orderiig the Journal will thus be apparent. Remittances of subscriptions can be mailed at our risk, when a certificate is taken from the Post- master that the money is duly inclosed and forwarded. Address BLANCHARD & LEA, Pmi.Ai)KLPiitA. ■ AND SCIENTIFIC PUBLICATIONS. 3 ASHTON (T. J.), Surgeon to the Blenheim Dispensary, &c. ON THE DISEASES, INJURIES, AND MALFORMATIONS OF THE RECTUM AND ANUS; with remarks on Habitual Constipation. From the third and enlarged London edition. With handsome illustrations. of about 300 pages, extra cloth. $3 00. The most complete one we possess on the subject. Medico-Chirurgical Review. We are satisfied, after a careful examination of the volume, and a comparison of its contents witn those of its leading predecessors and contemporaries, that the best way for the reader to avail himself of In one very beautifully printed octavo volume, the excellent advice given in the concluding para- graph above, would be to provide himself with a c >py of the book from which it lias been taken, and diligently to con its instructive pages. They may secure to him miny a triumph and fervent blessing.— Am. Journal Med. Sciences. ALLEN (J. M.), M. D., Professor of Anatomy in the Pennsylvania Medical College, Ac. THE PRACTICAL ANATOMIST; or, The Student's Guide in the Dissecting. PtOOM. With 266 illustrations. In one handsome royal 12mo. volume, of over 600 pages,extra cloth. $2 00. We believe it to be one of the most useful works upon the subject ever written. It is handsomely illustrated, well printed, and will be found of con- venient size for use in the dissecting-room.—Med. Examiner. However valuable may be the " Dissector's Guides" which we, of late, have had occasion to notice, we feel confident that the work of Dr. Allen is superior to any of them. We believe with the iuthor, that none is so fully illustrated as this, and the arrangement of the work is such as to facilitate the labors of the student. We most corditlly re- commend it to their attention.— Western Lancet. ANATOMICAL ATLAS. By Professors H. H. Smith and W. E. Horner, of the University of Pennsyl- vania. 1 vol. 8vo., extra cloth, with nearly 650 illustrations. H5F"' See Smith, p. 26. ABEL (F. A.), F. C. S. AND C. L. BLOXAM. HANDBOOK OF CHEMISTRY, Theoretical, Practical, and Technical; with a Recommendatory Preface by Dr. Hofmann. In one large octavo volume, extra cloth, of 662 pages, with illustrations. $4 25. ASHWELL (SAMUEL), M.D., Obstetric Physician and Lecturer to Guy's Hospital, London. A PRACTICAL TREATISE ON THE DISEASES PECULIAR TO WOMEN. Illustrated by Cases derived from Hospital and Private Practice. Third American, from the Third and revised London edition. In one octavo volume, extra cloth, of 528 pages. $3 50. The most useful practical work on the subject in I The most able, and certainly the most standard the English language. — Boston Med. and Surg, andpractical, work on female diseases that we hav« Journal. I yetseen.—Medico-Chirurgical Review. ARNOTT (NEILL), M.O. ELEMENTS OF PHYSICS; or Natural Philosophy, General and Medical. Written for universal use, in plain or non-technical language. A new edition, by Isaac Hays, M. D. Complete in one octavo volume, leather, of 484 pages, with about two hundred illustra tions. $2 25. __________________ BIRO (GOLDING), A. M., M. D., ice. URINARY DEPOSITS: THEIR DIAGNOSIS, PATHOLOGY, AND THERAPEUTICAL INDICATIONS. Edited by Edmund Lloyd Birkett, M.'D. A new American, from the last and enlarged London edition. With eighty illustrations on wood. In one handsome.octavo volume, of about 400 pages, extra cloth. $3 00. It can scarcely be necessary for us to say anything to the extension and satisfactory employment of our of the merits of this well-known Treatise, which so therapeutic resources. In the preparation of this admirably brings into practical application the re- newedition of his work, it isobvious that Dr. Gold- suits of those microscopical and chemical re- ing Bird has spared no pains to render it a faitufut starches regarding the physiology and pathology representation of the present state of sciencific of the urinary secretion, which havecontributed so knowledge on the subject it embraces.—British and much to the increase of our diagnostic powers, and Foreign Med.-Chir. Review. BARLOW (GEORGE H.), M.D. Physician to Guy's Hospital, London, &c. A MANUAL OF THE PRACTICE OF MEDICINE. With Additions by D F. Condie, M. D., author of" A Practical Treatise on Diseases of Children," &c. In one hand- some octavo volume, extra cloth, of over 600 pages. $2 50. We recommend Dr. Barlow's Manual in the warm- I found it clear, concise, practical, and sound__Bos- tit, manner as a most valuable vade-mecum. We ton Med. and Surg. Journal. have had frequent occasion to consult it, and have | BUCKLER ON THE ETIOLOGY,PATHOLOGY AND TREATMENT OF FIBRO-BRONCHI- TIS AND RHEUMATIC PNEUMONIA. In one 8vo. volume, extra cloth, pp.150. 8125. BRODIE'S CLINICAL LECTURES ON SUR GERY. 1 vol.8vo. cloth. 350pp. 8125. BLOOD AND URINE (MANUALS ON). BY JOHN WILLIAM GRIFFITH, G. OWEN REESE, AND ALFRED MARKWICK. One thick volume, royal l2mo., extra cloth, with. plates, pp.460. 81 25. 4 BLANCHARD & LEA'S MEDICAL BUDD (GEORGE), M. D., F. R. 3., Professor of Medicine in King's College, London. ON DISEASES OF THE LIVER. Third American, from the third and enlarged London edition. In one very handsome octavo volume, extra cloth, with four beauti- fully colored plates, and numerous wood-cuts. pp. 500. $3 75. Has fairly established for itself a place among the classical medical literature of England.—British and Foreign Medico-Chir. Review. Dr. Budd's Treatise on Diseases of the Liver is now a standard work in Medical literature, and dur- ing the intervals which have elapsed between the successive editions, the author has incorporated into the text the most striking novelties which have cha- racterized the recent progress of hepatic physiology ind pathology: so thatalthoughthe size of the book is not perceptibly changed, the history of liver dis- eases is made more complete, and is kept upon a level with the progress of modern science. It is the best work on Diseases of the Liver in any language.— London Med. Times and Gazette. BUCKNILL (J. C), M. D., and DANIEL H. TUKE, M. D., Medical Superintendent of the Devon Lunatic Asylum. Visiting Medical Officer to the York Retreat. A MANUAL OF PSYCHOLOGICAL MEDICINE; containing the History, Nosology, Description, Statistics, Diagnosis, Pathology, and Treatment of INSANITY. With a Plate. In ore handsome octavo volume, of 536 pages, extra cloth. $4 00. The increase of mental disease in its various forms, and the difficult questions to which it is constantly giving rise, render the subject one of daily enhanced interest, requiring on the part of the physician a constantly greater familiarity with this, the most perplexing branch of his profes- sion. Yet until the appearance of the present volume there has been for some years no work ac- cessible in this country, presenting the results of recent investigations in the Diagnosis and Prog- nosis of Insanity, and the greatly improved methods of treatment which have done so much in alleviating the condition or restoring the health of the insane. BENNETT (HENRY), M. D. A PRACTICAL TREATISE ON INFLAMMATION OF THE UTERUS, ITS CERVIX AND APPENDAGES, and on its connection with Uterine Disease. Sixth American, from the fourth and revised English edition. In one octavo volume, of about 500 pages, extra cloth. $3 75. (Just Ready.) This standard work, which has done so much to introduce the modern and improved treatment of female diseases, has received a very careful revision at the hands of the author In his preface he states : " During the past two years this revision of former h bors has been my principal occupa- tion, and in its present state the work may be considered to embody the matured experience of the many years I have devoted to the study of uterine disease." BROWN (ISAAC BAKER), Surgeon-Accoucheur to St. Mary's Hospital, Ice. ON SOME DISEASES OF WOMEN ADMITTING OF SURGICAL TREAT- MENT. With handsome illustrations. One vol. 8vo\, extra cloth, pp. 276. $160. Mr. Brown has earned for himself a high reputa- tion in the operative treatment of sundry diseases and injuries to which females are peculiarly subject. We can truly say of his work that it is an important addition to obstetrical literature. The operative suggestions and contrivances which Mr. Brown de- scribes, exhibit much practical sagacity and skill, and merit the careful attention of every surgeon - accoucheur.—Association Journal. We have no hesitation in recommending this book to tli'e careful attention of all surgeons who make female complaints a part of their study and practice. —Dublin Quarterly Journal. BOWMAN (JOHN E.), M.D. PRACTICAL HANDBOOK OF MEDICAL CHEMISTRY. Edited by C. L Bloxam. Third American, from the fourth and revised English Edition. In one neat volume, royal 12mo., extra cloth with numerous illustrations, pp.351. $200. (Now Ready, May, 1863.) ject in view lucidly detailed and explained. And this new edition is not merely a reprint of the last. With a laudable desire to keep the book up to the scientific mark of the present age, every improve- ment in analytical method has been introduced. In conclusion, we would only say that, familiar from long acquaintance with each page of the former issues of this little book, we gladly place beside them another presenting so many acceptable im- provements and additions.—Dublin Medical Press. Of this well-known handbook we may say that it retains all its old simplicity and clearness of ar- rangement and description, whilst it has received from the able edit jr those finishing touches which the progress of chemistry has rendtredneeesBary.— London Med. Times and Gazette, Nov. 29, 1862. Nor is anything huiried-over, anything shirked ; open the book where you will, you find the same careful treatment of the subject manifested, ana the best process for the attainment of the particular ob- BY THE SAME AUTHOR. INTRODUCTION TO PRACTICAL CHEMISTRY, INCLUDING ANA- LYSIS. Third American, from the third and revised London edition. With numerous illus- trations. In one neat vol., royal 12mo.. extra cloth. S3 00. (Just Ready.) This favorite little manual has received a very thorough and careful revision at the hands of a competent editor, and will be found fully brought up to the present condition of chemical science. Many portions have been rewritten, the subjects of the blow-pipe and volumetric analysis have re- ceived special attention, and an additional chapter has been appended. Students of practical chem- istry will therefore find it, as hereiofore, a most convenient »nd condensed text-book and guide in the operations of the laboratory. _^________ BEALE ON THE LAWS OF HEALTH IN RE- LATION TO MIND AND BODY. A Series of Letters from an old Practitioner to a Patient. In one volume, royal l2mo, extra cloth, pp. 296. B0 cents. iUSHNAN'S PHYSIOLOGY OF ANIMAL AND VEGETABLE LIFE; a Popular Treatise on the Functions and Phenomena of Organic Life. In one handsome royal 12mo. volume, extra cloth, with over 100 illustrations, pp.234. 80 cents AND SCIENTIFIC PUBLICATIONS. BUMSTEAD (FREEMAN J.) M. D., Lecturer on Venereal Diseases at the College of Physicians and Surgeons, New York, &c. THE PATHOLOGY AMD TREATMENT OF VENEREAL DISEASES, including the results of recent investigations upon the subject. Second edition, thoroughly re- vised and much improved. With illustrations on wood. In one very handsome octavo volume, of about 700 pages. $4 75 (Now Ready.) By far the most valuable contribution to this par- ticular branch of practice that has seen the light within the last score of years. His clear and accu- rate descriptions of the various forms of venereal disease, and especially the methods of treatment he proposes, are worthy of the highest encomium. In these respects it is better adapted for the assistance of the every-day practitioner than any other with which we are acquainted. In variety of methods proposed, in minuteness of direction, guided by care- ful discrimination of varying forms and complica- tions, we write down the book as unsurpassed. It is a work which should be in the possession of every practitioner.— Chicago Med. Journal. Nov. 1861. The foregoing admirable volume comes to us, em- bracing the whole subject of syphilology, resolving many a doubt, correcting and confirming many an entertained opinion, and in our estimation the best, completest, fullest monogjaph on this subject in our language. As far as the author's labors themselves are concerned, we feel it a duty to say that he has not only exhausted his subject, but he has presented to us, without the slightest hyperbole, the best di- gested treatise on these diseases in our language He haB carried its literaturt down to the present moment, and has achieved his task in a manner which cannot but redound to his credit.—British American Journal, Oct. 1861. We believe this treatise will come to be regarded as High authority in this branch of medical practice, and we cordially commend it to the favorable notice of our brethren in the profession. For our own part, we candidly confess that we have received n.any new ideas from its perusal, as well as modified many views which we have long, and, as we now thinK. erroneously entertained on the subject ol syphilis. To sum up all in a few words, this book is one which no practising physician or medical student can very well afford to do without.—American Med. Times, Nov. 2, 1861. The whole work presents a complete history of venereal diseases, comprising much interesting and valuable material that has been spread through med- ical journals within the last twenty years—the pe- riod of many experiments and investigations on the subject—the whole carefully digested by the aid of the author's extensive personal experience, and offered to the profession in an admirable form. Its completeness is secured by good plates, which are especially full in the anatomy of the genital organs. We have examined it with great satisfaction, and congratulate the medical profession in America on the nationality of a work that may fairly be called original.—Berkshire, Med. Journal, Dec. 1861. One thing, however, we are impelled to say, that we have met with no other book on syphilis, in the English language, which gave so full, clear, and impartial views of the important subjects on wnich it treats. We cannot, however, refrain from ex- pressing our satisfaction with the full and perspicu- ous manner in which the subject has been presented, and the careful attention to minute details, so use- ful—not to say indispensable—in a practical treatise. In conclusion, if we may be pardoned the use of a phrase now become stereotyped, butwhich we here employ in all seriousness and sincerity, we do not hesitate to express the opinion that Dr. Bumstead's Treatise on Venereal Diseases is* " work without which no medical library will hereafter be consi- dered complete."—Boston Med. and Surg. Journal, Sept. 5, 1861. BARCLAY (A. W.), M. D., , Assistant Physician to St. George's Hospital, &c. A MANUAL OF MEDICAL DIAGNOSIS; being an Analysis of the Signs and Symptoms of Disease. Third American from the second and revised London edition. In one neat octavo volume, extra cloth, of 451 pages. 83 50. {Just Ready.) The demand for a second edition of this work shows that the vacancy which it attempts to sup- ply has been recognized by the profession, and that the efforts of the author to meet the want have been successful. The revision which it has enjoyed will render it better adapted than before to afford assistance to the learner in the prosecution of his studies, and to the practitioner who requires a convenient and accessible manual for speedy reference in the exigencies of his daily duties. For this latter purpose its complete and extensive Index renders it especially valuable, offering facilities for immediately turning to any class of symptoms, or any variety of disease. The task of composing such a work is neither an easy nor a light one j but Dr. Barclay has performed it in a manner which meets our most unqualified approbation. He is no mere theorist; he knows his work thoroughly, and in attempting to perform it, has not exceeded his powers.—British Med. Journal. We venture to predict that the work will be de- servedly popular, and soon become, like Watson's Practice, an indispensable necessity to the practi- tioner.—N. A. Med. Journal. An inestimable work of reference for the young practitioner and student.—Nashville Med. Journal. We hope the volume will have an extensive cir- culation, not among students of medicine only, but practitioners also. They will never regret a faith- ful study of itspages.—CincinnatiLancet. An important acquisition to medical literature. It is a work of high merit, both from the vast im- portance of the subject upon which it treats, and also from the real ability displayed in ;ts elabora- tion. In conclusion, let us bespeak for this volume that attention of every student of our art which it so richly deserves — that place in every meuical library whicn it can so well adorn.-- Peninsular Medical Journal. BARTLETT (ELISHA), M. D. THE HISTORY, DIAGNOSIS, AND TREATMENT OF THE FEVERS OF THE UNITED STATES. A new and revised edition. By Alonzo Clark , M. D., Prof. of Pathology and Practical Medicine in the N. Y. College of Physicians and Surgeons, &c. In one octavo volume, of six hundred pages, extra cloth. Price $4 00. stood deservedly high since its first publication. It It is a work of great practical value and interest. containing much that is new relative to the several diseases of which it treats, and, with the additions of the editor, is fully up to the times. Thedistinct- ive features of the different forms of fever are plainly and forcibly portrayed, and the lines of demarcation carefully and accurately drawn, and to the Ameri- can practitioner is a more valuable and safe guide than any work on fever extant.—Ohio Med. and Surg Journal. This excellent monograph on febrile disease, has will be seen that it has now reached its fourth edi- tion under the supervision of Prof. A. Clark, a gen- tleman who, from the nature of his studies and pur- suits, is well calculated to appreciate and discuss the many intricate and difficult questions in patho- logy. His annotations add much to the interest of the work, and have brought it well up to the condi- tion of the science as it exists at the present day in regard to this class of diseases.—Southern Med. and Surg. Journal. b BLANCHARD & LEA'S MEDICAL BRANDE(WM. TJD.C. L., and ALFRED S. TAYLOR, M. D., F. R. S. Of her Majesty's Mint, &c. Professor of Chemistry and Medical Jurisprudence in Guy's Hospital. CHEMISTRY. In one handsome 8vo. volume of 696 pages, extra cloth. $1 25. " Having been engaged in teaching Chemistry in this Metropolis, the one for a period of forty, and the oiher for a period of thirty years, it has appeared to us that, in spite of the number of books already exiting, there was room for an additional volume, which shi uld be especially adapted tor the use of students. In preparing such a volume for the press, we have endeavored to bear in mind, that the student in ihe present day has much to learn, and but a short time at his disposal for the acquisition of this learning."—Authors' Preface. In reprinting this volume, its passage through the press has been superintended by a competent chemist, who has sedulously endeavored to secure the accuracy so necessary in a work of this nature. No notes or additions have been introduced, but the publishers have been favored by the authors with some corrections and revisions of the first twenty-one chapters, which have been duly inserted. In so progressive a science as Chemistry, the latest work always has the advantage of presenting the subject as modified by the results of the latest investigations and discoveries. That this advan- tage has been made the most of, and that the work possesses superior attractions arising from its clearness, simplicity of style, and lucid arrangement, ~are manifested by the unanimous testimony of the English medical press. It needs no great sagacity to foretell that this book will be, literally, the Handbook in Chemistry of the student and practitioner. For clearness of language, accuracy of description, extent of information, and freedom from pedantry and mysticism of modern chemistry, no other text-book comes into competition with it. The result is a work which for fulness of matter, for lucidity of arrangement, for clearness of style, is as yet without a rival. And long will it be without a rival. For, although with the necessary advance of chemical knowledge addenda will be re- quired, there will be little to take away. The funda- mental excellences of the book will remain, preserv- ing it for years to come, what it now is, the best guide to the study of Chemistry yet given to the world.— London Lancet, Dec. 20, 1S62. Most assuredly, time has not abated one whit of the fluency, the vigor, and the clearness with which they not only have composed the work before us, but have, bo to say, cleared the ground for it, by hitting right and left at the affectation, mysticism, and obscurity which pervade some late chemical treatises. Thus conceived, and worked out in the most sturdy, com- mon sense method, this book gives, in the clearest and most summary method possible, all the facts and doc- trines of chemistry, with more especial reference to the wants of the medical student.—London Medical Times and Gazette, Nov. 29, 1862. If we are not very much mistaken, this book will occupy a place which none has hitherto held among chemists; for, by avoiding the errors of previous au- thors, we have a work which, for its size, is certainly the most perfect of any in the English language. There are several points to be noted in this volume which separate it widely from any of its compeers— its wide application, not to the medical student only, nor to the student in chemistry merely, but to every branch of science, art, or commerce which is in any way connected with the domain of chemistry.—Lon- donMed. Review, Feb. 1863. BARWELL (RICHARD,) F. R. C. S., Assistant Surgeon Charing Cross Hospital, &c. A TREATISE ON DISEASES OF THE JOINTS. Illustrated with engrav- ings on wood. In one very handsome octavo volume, of about 500 pages, extra cloth; $3 00. At the outset we may state that the work is worthy of much praise, and bears evidence of much thoughtful and careful inquiry, and here and there of no slight originality. We have already carried tnie notice further than we intended to do, but not to the extent the work deserves. We can only add, that the perusal of it has afforded us great pleasure. The author has evidently worked very hard at his subject, and his investigations into the Physiology and Pathology of Joints have been carried on in a manner which entitles him to be listened to with attention and respect. We must not omit to men- tion the very admirable plates with which the vo- lume is enriched. We seldom meet with such strik- ing and faithful delineations of disease.—London Med. Times and Gazette, Feb. 9, 1861. This volume will be welcomed, as the record of much honest research and careful investigation into the nature and treatment of a most important class of disorders. We cannot conclude this notice of a valuable and useful book without calling attention to the amount oi bona fide work it contains. It is no slight matter for a volume to show laborious inves- tigation, and at the same time original thought, on the part of its author, whom w e may congratulate on tne successful completion of his arduous task.— London Lancet, March 9, 1861. CARPENTER (WILLIAM B.), M. D., F. R. S., &.C., Examiner in Physiology and Comparative Anatomy in the University of London. THE MICROSCOPE AND*ITS REVELATIONS. With an Appendix con- taining the Applications of the Microscope to Clinical Medicine, &c. By F. G. Smith, M. D. Illustrated by four hundred and thirty-four beautiful engravings on wood. In one large and very handsome octavo volume, of 724 pages, extra cloth, $5 25. The great importance of the microscope as a means of diagnosis, and the number of microsco- pists who are also physicians, have induced the American publishers, with the author's approval, to add an Appendix, carefully prepared by Professor Smith, on the applications of tne instrument'to clinical medicine, together with an account of American Microscopes, their modifications and accessories. This portion of the work is illustrated with nearly one hundred wood-cuts, and, it is hoped, will adapt the volume more particularly to the use of the American student. Those who are acquainted with Dr. Carpenter's previous writings on Animal and Vegetable Physio- logy , will fully understand how vast a store of know- ledge he is able to bring to bear upon so comprehen- sive a subject as the revelations of the microscope j and even those who have no previous acquaintance with the construction or uses of this instrument, will find abundance of information conveyed in clear tad simple language— Med. Times and Gazette. The additions by Prof. Smith give it a positive claim upon the profession, for which we doubt not he will receive their sincere thanks. Indeed, we know not where the student of medicine will find such a complete and satisfactory collection of micro- scopic facts bearing upon physiology and practical medicine as is contained in Prof. Smith's appendix; and this of itself, it seems to us, is fully wortli the cost of the volume.—Louisville Medicat Review. AND SCIENTIFIC PUBLICATIONS. 7 CARPENTER (WILLIAM B.), M. D., F. R. S., Examiner in Physiology and Comparative Anatomy in the University of London. PRINCIPLES OF HUMAN PHYSIOLOGY; with their chief applications to Psychology, Pathology, Therapeutics, Hygiene, and Forensic Medicine. A new American, from the last and revised London edition. With nearly three hundred illustrations. Edited, with addi- tions, by Francis Gurney Smith, M. D., Professor of the Institutes of Medicine in the Pennsyl- vania Medical College, &c. In one very large and beautiful octavo volume, of about nine hundred large pages, handsomely printed, extra cloth, if 5 25. For upwards of thirteen years Dr. Carpenter's work has been considered by the profession gene- rally, both in this country and.England, as the most valuable compendium on the subject of physiology in our language. This distinction it owes to the high attainments and unwearied industry of its accom- plished author. The present edition (which, like the >aBt American one, was prepared by the author him- self), is the result of such extensive revision, that it may almost be considered a new work. We need hardly say, in concluding this brief notice, that while the work is indispensable to every student of medi- cine in this country, it will amply repay the practi- tioner for its perusal by the interest and value of its contents.—Boston Med. and Surg. Journal. This is a standard work—the text-book used by all medical students who read the English language. tt has passed through several editions in order to keep pace with the rapidly growing science of Phy- siology. Nothing need be said in its praise, for its merits are universally known ; we have nothing to Bay of its defects, for they only appear where the science of which it treats is incomplete.—Western Lancet. The most complete exposition of physiology which any language can at present give.—Brit, and For. Med.-Chirurg. Review. The greatest, the most reliable, and the best book oa the subject which we know of in the English language.—Stethoscope. To eulogize this great work would be superfluou s. We should observe, however, that in this edition the author has remodelled a large portion of the former, and the editor has added much matter of in- terest, especially in the form of illustrations. We may confidently recommend it as the most complete work on Human Physiology in our language.— Southern Med. and Surg. Journal. The most complete work on the science in our language.—Am. Med. Journal. The most complete work now extant in our lan- guage.—JV. O. Med. Register. The best text-book in the language on this ex- tensive subject.—London Med. Times. A complete cyclopaedia of this branch of science. —N. Y. Med. Times. The profession of this country, and perhaps also of Europe, have anxiously and for some time awaited the announcement of this new edition of Carpenter's Human Physiology. His former editions have for many years been almost the only text-book on Phy- siology in all our medical schools, and its circula- tion among the profession has been unsurpassed by any work in any department of medical science. It is quite unnecessary for us to speak of this work as its merits would justify. The mere an- nouncement of its appearance will afford the highest pleasure to every student of Physiology, while its perusal will be of infinite service in advancing physiological science.—Ohio Med. and Surg. Journ BY THE SAME AUTHOR. ELEMENTS (OR MANUAL) OF PHYSIOLOGY, INCLUDING PHYSIO- LOGICAL ANATOMY. Second American, from a new and revised London edition. With one hundred and ninety illustrations. In one very handsome octavo volume, leather, pp. 566. 84 00. In publishing the first edition of this work, its title was altered from that of the London volumei by the substitution of the word " Elements" for that of " Manual," and with the author's sanction the title of "Elements" is still retained as being more expressive of the scope of the treatise. BY THE SAME AUTHOR. PRINCIPLES OF COMPARATIVE PHYSIOLOGY. New American, from the Fourth and Revised London edition. In one large and handsome octavo volume, with over three hundred beautiful illustrations, pp.752. Extra cloth, $5 00. This book should not only be read but thoroughly studied by every member of the profession. None are too wise or old, to be benefited thereby. But especially to the younger class would we cordially commend it as best fitted of any work in the English language to qualify them for the reception and coin- prehension of those truths which are daily being de- veloped in physiology.—Medical Counsellor. Without pretending to it, it is an encyclopedia of the subject, accurate and complete in all respects— a truthful reflection of the advanced state at which the science has now arrived.—Dublin Quarterly Journal of Medical Science. A truly magnificent work—in itself a perfect phy- siological study.—Ranking's Abstract. This work stands without its fellow. It is one few men in Europe could have undertaken j it is one no man, we believe, could have brought to so suc- cessful an issue as Dr. Carpenter, ft required for its production a physiologist at once deeply read in the labors of others, capable of taking a genera'.. critical, and unprejudiced view of those labors, and of combining the varied, heterogeneoub materials at his disposal, so as to form an harmonious whole, We feel that this abstract can give the reader a very imperfect idea of the fulness of this work, and no idea of its unity, of the admirable mar ner in which material has been brought, from the most various sources, to conduce to its completeness, of the lucid- ity of the reasoning it contains, or of the clearness of language in which the whole is clothed. Not the profession only, but the scientific world at large, must feel deeply indebted to Dr. Carpenter for this great work. It must, indeed, add lirgelyeven to his high reputation.—Medical Times. BY the same author. (Preparing.) PRINCIPLES OF GENERAL PHYSIOLOGY, INCLUDING ORGANIC CHEMISTRY AND HISTOLOGY. With a General Sketch of the Vegetable and Animal Kingdom. In one large and very handsome octavo volume, with several hundred illustrations. BY THE SAME AUTHOR. A PRIZE ESSAY ON THE USE OF ALCOHOLIC LIQUORS IN HEALTH AND DISEASE. New edition, with a Preface by D. F. Condie, M. D., and explanations of •cientific words. In one neat 12mo. rolume, extra cloth, pp. 178 60 cents. 8 BLANCHARD & LEA'S MEDICAL CONDIE (D. F.), M. D., «tc A PRACTICAL TREATISE ON THE DISEASES OF CHILDREN. Fifth edition, revised and augmented. In one large volume, 8vo., extra cloth, of over 750 pages. 84 00. In presenting a new and revised edition of this favorite work, the publishers have only to state that the author has endeavored to render it in every respect "a complete and faithful exposition of the pathology and therapeutics of the maladies incident to the earlier stages of existence—a full and exact account of the diseases of infancy and childhood." To accomplish this he has subjected the whole work to a careful and thorough revision, rewriting a considerable portion, and adding several new chapters. >In this manner it is hoped that any deficiencies which may have previously existed have been supplied, that the recent labors of practitioners and observers have been tho- roughly incorporated, and that in every point the work will be found to maintain the high reputation it has enjoyed as a complete and thoroughly practical book of reference in infantile affections. A few notices of previous editions are subjoined. Dr. Condie's scholarship, acumen, industry, and practical sense are manifested in this, as in all his numerous contributions to science.—Dr. Holmes's Report to the American Medical Association. Taken as a whole, in our judgment, Dr. Condie's Treatise is the one from the perusal of which the practitioner in this country will rise with the great- est satisfaction.—Western Journal of Medicine and Surgery. One of the best works upon the Diseases of Chil- dren in the English language.—Western Lancet. We feel assured from actual experience that nc physician's library can be complete without a copy of this work.—IV. Y. Journal of Medicine. A veritable pediatric encyclopaedia, and an honor to American medical literature.—Ohio Medical and Surgical Journal. Wefeel persuaded thatthe American medical pro- fession will soon regard it not only as a very good, but as the vert best "Practical Treatise on the Diseases of Children."—American Medical Journal In the department of infantile therapeutics, the work of Dr. Condie is considered one of the best which has been published in the English language. — The Stethoscope. We pronounced the first edition to be the best work on the diseases of children in the English language, and, notwithstanding all that has ht-en published, we still regard it in that light.—Medical Examiner. The value of works by native authors on the dis- eases which the physician is called upon to combat, will be appreciated by all; and the woTkof Dr. Con- die has gained for itself the character of a safe guide for students, and a useful work for consultation by those engaged in practice.—iV. Y. Med. Times. This is the fourth edition of this deservedly popu- lar treatise. During the interval since the last edi- tion, it has been subjected to a thorough revision by the author; and all new observations in the pathology and therapeutics of children have been included in the present volume. As we said btfore, we do not know of a better book on diseases of chil- dren, and to a large part of its recommendations we yield an unhesitating concurrence.—Buffalo Med. Journal. Perhaps the most full and complete work now be- fore the profession of the United States; indeed, wo may say in the English language. It is vastly supe- rior to most of its predecessors.—Transylvania Med. Journal CHRISTISON (ROBERT), M. D., V. P. R. S. E., &.C. A DISPENSATORY; or, Commentary on the Pharmacopoeias of Great Britain and the United States; comprising the Natural History, Description, Chemistry, Pharmacy, Ac- tions, Uses, and Doses of the Articles of the Materia Medica. Second edition, revised and im- proved, with a Supplement containing the most important New Remedies. With copious Addi- tions, and two hundred and thirteen large wood-engravings. By R. Eglesfeld Griffith, M. D. In one very large and handsome octavo volume, extra cloth, of over 1000 pages. $3 50. COOPER (BRANSBY BJ, F. R. S. LECTURES ON THE PRINCIPLES AND PRACTICE OF SURGERY. In one very large octavo volume, extra cloth, of 750 pages. $2 00. COOPER ON THE ANATOMY AND DISEASES OF THE BREAST, with twenty-five Miscellane- ous and Surgical Papers. One large volume, im- perial 8vo., extra cloth, with 252 figures, on 36 plates. $3 00. COOPER ON THE STRUCTURE AND DIS- EASES OF THE TESTIS, AND ON THE THYMUS GLAND. One vol. imperial Hvo., ex- tra cloth, with 177 figures on 29 plates. $2 50. CLYMER ON FEVERS; THEIR DIAGNOSIS, PATHOLOGY, AND TREATMENT. In ona octavo volume, leather, of 600 pages. SI 75. C%.°5fJ?.4T DE L'ISERE ON THE DISEASES Ob FEMALES, and on the special Hygiene of their Sex. Translated, with many Notes and Ad- ditions, by C. D. Meigs, M. D. Second edition, revised and improved. In one large volume, oc- tavo, leather, with numerous wood-cuts. pp. 720 CARSON (JOSEPH), M. D., Professor of Materia Medica and Pharmacy in the University of Pennsylvania SYNOPSIS OF THE COURSE OF LECTURES ON MATERIA' MFDTP a AND PHARMACY, delivered in the University of Pennsylvania Whh ihr£ it,, the Modus Operandi of Medicines. Third edition, revised In one ha!d on J „„ "TS 0" (Now Ready.) $2 50. °ne handson'e octavo volume. CURLING (T. B.), F. R.S., Surgeon to the London Hospital, President of the Hunterian Society fcc A PRACTICAL TREATISE ON DISEASES OF THE TESTIS SPERM A TIC CORD, AND SCROTUM. Second American, from the second and enlacedIEn*£hedi" Hon. In one handsome octavo volume, extra cloth, with numerous illustrations pp. 420. $2 00~ AND SCIENTIFIC PUBLICATIONS. 9 CHURCHILL (FLEETWOOD), M. D., M. R. I. A. ON THE THEORY AND PRACTICE OF MIDWIFERY. A new American from the fourth revised and enlarged London edition. With Notes and Additions, by D. Francis Condie, M. D., author of a "Practical Treatise on the Diseases of Children," &c. With 194 illustrations. In one very handsome octavo volume, of nearly 700 large pages, extra cloth, $4 00. This work has been so long an established favorite, both as a text-book for the learner and as a reliable aid in consultation lor the practitioner, that in presenting a new edition it is only necessary to call attention to the very extended improvements which it has received. Having had the benefit of two revisions by the author since the last American reprint, it has been materially enlarged, and Dr. Churchill's well-known conscientious industry is a guarantee that every portion has been tho- roughly brought up with the latest results of European investigation in all departments of the sci- ence and art of obstetrics. The recent date of the last Dublin edition has not left much of novelty for the American editor to introduce, but he has endeavored to insert whatever has since appeared, together with such matters as his experience has shown him would be desirable for the American student, including a large number of illustrations. With the sanction of the author he has added in the form of an appendix, some chapters from a little "Manual for Midwives and Nurses," re- cently issued by Dr. Churchill, believing that the details there presented can hardly fail to prove of advantage to the junior practitioner. The result of all these aaditions is that the work now con- tains fully one-half more matter than the last American edition, with nearly one-half more illus- trations, so that notwithstanding the use of a smaller type, the volume contains almost two hundred pages more than before. No effort has been spared to secure an improvement in the mechanical execution of the work equal to that which the text has received, and the volume is confidently presented as one of the handsomest that has thus far been laid before the American profession; while the very low price at which it is offered should secure for it a place in every lecture-room and on every office table. Were we reduced to the necessity of having but me work on midwifery, and permitted to choose, gve would unhesitatingly take Churchill.—Western Med. and Surg. Journal. It is impossible to conceive a more useful ana slegant manual than Dr. Churchill's Practice of "flidwifery.—Provincial Medical Journal. Certainly, in our opinion, the very best work on he subject which exists.—N. Y. Annalist. A better book in which to learn these important' points we have not met than Dr. Churchill's. Every page of it is full of instruction; the opinion of all writers of authority is given on questions of diffi- culty, as well as the directions and advice of the learned author himself, to which he adds the result of statistical inquiry, putting statistics in their pro per place and giving them their due weight, and no more. We have never read a book more free from professional jealousy than Dr. Churchill's. It ap- pears to be written with the true design of a book on medicine, viz: to give all'that is known on the sub- ject of which he treats, both theoretically and prac- tically, and to advance such opinions of his own as he believes will benefit medical science, and insure the safety of the patient. We have said enough to convey to the profession that this book of Dr. Chur- chill's is admirably suited for a book of reference for the practitioner, as well as a text-book for the Btudent, and we hope it may be extensively pur- chased amongst our readers. To them we most strongly recommend it. — Dublin Medical Press. To bestow praise on a book that has received such marked approbation would be superfluous. We need only say, therefore, that if the first edition was thought worthy of a favorable reception by the medical public, we can confidently affirm that this will be found much more so. The lecturer, the practitioner, and the student, may all have recourse to its pages, and derive from their perusal much in- terest and instruction in everything relating to theo- retical and practical midwifery.—Dublin Quarterly Journal of Medical Science. A work of very great merit, and such as we can eonfidently recommend to the study of every obste- tric practitioner.—London Medical Gazette. Few treatises will be found better adapted as s text-book for the student, or as a manual for th« frequent consultation of the young practitioner.- American Medical Journal. No work holds a higher position, or is more de- serving of being placed in the hands of the tyro, the advanced student, or the practitioner.—Medical Examiner. Previous editions have been received with mark- ed favor, and they deserved it; but this, reprinted from a very late Dublin edition, carefully revised and brought up by the author to the present time, does present an unusually accurate and able expo- sition of every important particular embraced in the department of midwifery. * * The clearness, directness, and precision of its teachings, together with the great amount of statistical research which its text exhibits, have served to place it already in the foremost rank of works in this department of re- medial science.—IV. O. Med. and Surg. Journal. In our opinion, it forms one of the best if not the very best text-book and epitome of obstewic scienca which we at present possess in the English lan- guage.—Monthly Journal of Medical Science. The clearness and precision of style in whiehit is written, and the greatamountof statistical researeh which it contains, have served to place it in the first rank of works in this departmentof medical science. —N. Y. Journal of Medicine. This is certainly the most perfect system extant. It is the best adapted for the purposes of a text- book, and that which he whose necessities confine lim to one book, should select in preference to all jthers.—Southern Medical and Surgical Journal. BY the same author. (Lately Published.) ON THE DISEASES OF INFANTS AND CHILDREN. Second American Edition, revised and enlarged by the author. Edited, with Notes, by W. V. Keating, M. D. In one large and handsome volume, extra cloth, of over 700 pages. $4 00. In preparing this work a second time for the American profession, the author has spared no labor in erivinl it a very thorough revision, introducing several new chapters, and rewriting others, while every portion of the volume has been subjected to a severe scrutiny. The efforts of the American editor have been directed to supplying such information relative to matters peculiar to this country as might have escaped the attention of the author, and the whole may, there- fore be safely pronounced one of the most complete works on the subject accessible to the Ame- rican Profession. By an alteration in the size of the page, these very extensive additions have been accommodated without unduly increasing the size of the work. BY THE SAME AUTHOR. ESSAYS ON THE PUERPERAL FEVER, AND OTHER DISEASES PE- CULIAR TO WOMEN. Selected from the writings of British Authors previous to the close of the Eighteenth Century. In one neat octavo volume, extra cloth, of about 450 pages. $2 50. 10 BLANCHARD & LEA'S MEDICAL CHURCHILL (FLEETWOOD), M. D., M. R. I. A., «Yc ON THE DISEASES OF WOMEN; including those of Pregnancy and Child- bed. A new American edition, revised by the Author. With Notes and Additions, by D Fran- cis Condie, M. D., author ol "A Practical Treatise on the Diseases of Children." With nume- rous illustrations. In one large and handsome octavo volume, extra cloth, of 768 pages. $4 00. This edition of Dr. Churchill's very popular treatise may almost be termed a new work, so thoroughly has he revised it in every portion. It will be found greatly enlarged, and completely brought up to the most recent condition of the subject, while the very handsome series of illustra- tions introduced, representing such pathological conditions as can be accurately portrayed, present a novel feature, and afford valuable assistance to the young practitioner. Such additions as ap- peared desirable for the American student have been made by the editor, Dr. Condie, while a marked improvement in the mechanical execution keeps pace with the advance in all other respects which the volume has undergone, while the price has been kept at the former very moderate rate. extent that Dr. Churchill does. His, indeed, is tha It comprises, unquestionably, one of the most ex- act and comprehensive expositions of the present state of medical knowledge in respect to the diseases of women that has yet been published.—Am. Journ. Med. Sciences. This work is the most reliable which we possess on this subject; and is deservedly popular with the profession.—Charleston Med. Journal, July, 1857. We know of no author who deserves that appro- bation, on "the diseases of females," to the same only thorough treatise we know of on the subject; and it may be commended to practitioners and stu- dents as a masterpiece in its particular department. —Tht Western Journal of Medicine and Surgery. As a comprehensive manual for students, or a work of reference for practitioners, it surpasses any other that has ever issued on the same subject from the British press.—Dublin Quart. Journal. DICKSON (S. H.), M. D., Professor of Practice of Medicine in the Jefferson Medical College, Philadelphia. ELEMENTS OF MEDICINE; a Compendious View of Pathology and Thera- peutics, or the History and Treatment of Diseases. Second edition, revised. In one large and handsome octavo volume: of 750 pages, extra cloth. $3 75. The steady demand which has so soon exhausted the first edition of this work, sufficiently shows that the author was not mistaken in supposing that a volume of this character was needed—an elementary manual of practice, which should present the leading principles of medicine with the practical results, in a condensed and perspicuous manner. Disencumbered of unnecessary detail and fruitless speculations, it embodies what is most requisite for the student to learn, and at the same time what the active practitioner wants when obliged, in the daily calls of his profession, to refresh his memory on special points. The clear and attractive style of the author renders the whole easy of comprehension, while his long experience gives to his teachings an authority every- where acknowledged. Few physicians, indeed, have had wider opportunities for observation and experience, and few, perhaps, have used them to better purpose. As the result of a long life de- voted to study and practice, the present edition, revised and brought up to the date of publication, will doubtless maintain the reputation already acquired as a condensed and convenient American text-book on the Practice of Medicine. DRUITT (ROBERT), M.R. C.S., Sec. THE PRINCIPLES AND PRACTICE OF MODERN SURGERY. A new and revised American from the eighth enlarged and improved London edition. Illustrated with four hundred and thirty-two wood-engravings. In one very handsomely printed octavo volume of nearly 700 large pages, extra cloth, $4 00. A work which like Druitt's Surgery has for so many years maintained the position of a lead- ing favofite with all classes of the profession, needs no special recommendation to attract attention to a revised edition. It is only necessary to state that the author has spared no pains to keep the work up to its well earned reputation of presenting in a small and convenient compass the latest condition of every department of surgery, considered both as a science and as an art; and that the services of a competent American editor have been employed to introduce whatever novelties may have escaped the author's attention, or may prove of service to the American practitioner. As several editions have appeared in London since the issue of the last American reprint, the volume has had the benefit of repeated revisions by the author, resulting in a very thorough alteration and improvement. The extent of these additions may be estimated from the fact that it now contains about one-third more matter than the previous American edition, and that notwithstanding the adoption of a smaller type, the pages have been increased by about one hundred, while nearly two hundred and fifty wood-cuts have been added to the former list of illustrations. A marked improvement will also be perceived in the mechanical and artistical execution of the work, which, printed' in the best style, on new type, and fine paper, leaves little to be desired as regards external finish; while at the very low price affixed it will be found one of the cheapest volumes accessible to the profession. This popular volume, now a most comprehensive work on surgery, has undergone many corrections improvements, and additions, and the principles and the practice of the art have been brought down to the latest record and observation. Of the operations in su rgery it is impossible to speak too highly. The descriptions are so clear and concise, and the illus- trations so accurate and numerous, that the student can have no difficulty, with instrument in hand, and book by his side, over the dead body, in obtaining a proper knowledge and sufficient tact in this much neglected depart ment of medical education.—British and Foreign Medico-Chirurg. Review, Jan. 1960. In the present edition the author has entirely re- written many of the chapters, and has incorporated the various improvements and additions in modern surgery. On carefuhy going over it, we find that nothing of real practical importance has been omit- ted ; it presents a faithful epitome of everything re- lating t) surgery up to the present hour. It is de- servedly a popular manual, both with the student and practitioner.—London Lancet, Nov. 19, 1859. In closing this brief notice, we recommend as cor- dially as ever this most useful and comprehensive hand-book. It must prove a vast assistance, not only to the student of surgery, but also to the busy practitioner who may not have the leisure to devote himself to the study of more lengthy volumes.— London Med. Times and Gazette, Oct 22, 1859. In a word, this eighth edition of Dr. Druitt's Manual of Surgery is all that the surgical student or practitioner could desire. — Dublin Quarterly Journal of Med. Sciences, Nov. 1859. AND SCIENTIFIC PUBLICATIONS. 11 DALTON, JR. (J. C), M. D. Professor of Physiology in the College of Physicians, New York. A TREATISE ON HUMAN PHYSIOLOGY, designed for the use of Students and Practitioners of Medicine. Third edition, revised, with nearly three hundred illustrations on wood. In one very beautiful octavo volume, of 700 pages, extra"cloth, $5 00. (Just Ready, 1864.) The rapid demand for another edition of this work sufficiently shows that the author has suc- ceeded in his efforts to produce a text-book of standard and permanent value, embodying within a moderate compass all that is definitely and positively known within the domain of Human Physiology. His high reputation as an original observer and investigator, is a guarantee that in again revising it he has introduced whatever is necessary to render it thoroughly on a level with the advanced science of the day, and this has been accomplished without unduly increasing the size of the volume. No exertion has been spared to maintain the high standard of typographical execution which has rendered this work admittedly one of the handsomest volumes as yet produced in this country. It will be seen, therefore, that Dr. Dalton's best j own original views and experiments, together with efforts have been directed towards perfecting his a desire to supply what he considered some deficien- work. The additions are marked by the same fea tures which characterize the remainder of the vol- ume, and render it by far the most desirable text- book on physiology to place in the hands of the student which, so far as we are aware, exists in the English language, or perhaps in any other. We therefore have no hesitation in recommending Dr. Dalton's book for the classes for which it is intend- ed, satisfied as we are that it is better adapted to cies in the first edition, have already made the pre- sent one a necessity, and it will no doubt be even more eagerly sought for than the first. That it is not merely a reprint, will be seen from the author's statement of the following principal additions and alterations which he has made. The present, like the first edition, is printed in the highest style of the printer's art, and the illustrations are truly admira- ble tor their clearness in expressing exactly what their use than any other work of the kind to which i their author intended.—Boston Medical and Surgi cal Journal, March 28, 1861. It is unnecessary to give a detail of theadditions; suffice it to say, that they are numerous and import- ant, and such as will render the work still more they have access.—American Journal of the Med Sciences, April, 1861. It is, therefore, no disparagement to the many books upon physiology, most excellent in their day, to say that Dalton's is the only one that gives us the j valuable and acceptable to the profession as a learn- science as it was known to the best philosophers ed and original treatiseon this all-important branch throughout the world, at the beginning of the cur- of medicine. All that was said in commendation rent year. It states in comprehensive but concise | of the getting up of the first edition, and the superior diction, the facts established by experiment, or ' style of the illustrations, apply with equal force to other method of demonstration, and details, in an J this. No better work on physiology can be placed understandable manner, how it is done, but abstains i in the hand of the student.—St. Louis Medical and from the discussion of unsettled,or theoretical points. Herein it is unique; and these characteristics ren der it a text-book without a rival, for those who desire to study physiological science as it is known to its most successful cultivators. And it is physi- ology thus presented that lies at the foundation of correct pathological knowledge; and this in turn is the basis of rational therapeutics; so that patholo- gy, in faet, becomes of prime importance in the proper discharge of our every-day practical duties. —Cincinnati Lancet, May, 1861. Dr. Dal ton needs no word of praise from us. He Surgical Journal, May, 1861. These additions, while testifying to the learning and industry of the author, render the book exceed- ingly useful, as the most complete expose of a sci- ence, of which Dr. Dalton is doubtless the ablest representative on this side of the Atlantic.—Neio Orleans Med. Times, May, 1861. A second edition of this deservedly popular work having been called for in the short space of two years, the author has supplied deficmjtcies, which existed in the former volume, and tos thus more completely fulfilled his design of presenting to the is universally recognized as among the first, if not ' profession a reliable and precise text-book, and one the very fii st, of American phvsiologists now living, j which we consider the best, outline on the subject The first edition of his admirable work appeared but of which it treats, in any language__N. American two years since, and the advance of science, his < Medico-Chirurg. Review, May, 1861. DUNGLISON, FORBES, TWEEDIE, AND CONOLLY. THE CYCLOPEDIA OF PRACTICAL MEDICINE: comprising Treatises on the Nature and Treatment of Diseases, Materia Medica, and Therapeutics, Diseases of Women and Children, Medical Jurisprudence, York Med. Gazette. The great learning of the author, and his remark- able industry in pushing his researches into every source whence information is derivable,have enabled him to throw together an extensive mass of facts and statements, accompanied by full reference to authorities; which last feature renders the work practically valuable to investigators who desire to examine the original papers.—The American Journal of Pharmacy. ELLIS (BENJAMIN), M.D. THE MEDICAL FORMULARY: being a Collection of Prescriptions, derived from the writings and practice of many of the most eminent physicians of America and Europe. Together with the usual Dietetic Preparations and Antidotes for Poisons. To which is added an Appendix, on the Endermic use of Medicines, and on the use of Ether and Chloroform. The whole accompanied with a few brief Pharmaceutic and Medical Observations. Eleventh edition, carefully revised and much extended by Robert P. Thomas, M. D., Professor of Materia Me- dica in the Philadelphia College of Pharmacy. In one volume, 8vo., of about 350 pages. $2 75. (Just Issued.) On no previous edition of this work has there been so complete and thorough a revision The extensive changes in the new United States Pharmacopoeia have necessitated corresponding alter- ations in the Formulary, to conform to that national standard, while the progress made in the materia medica and the arts of prescribing and dispensing during the last ten years have been care- fully noted and incorporated throughout. It is therefore presented as not only worthy a continuance of the lavor so long enjoyed, but as more valuable than ever to the practitioner and pharmaceutist. Those who possess previous editions will find the additional matter of sufficient importance to warrant their adding the present to their libraries. 14 BLANCHARD & LEA'S MEDICAL ERICHSEN (JOHN), Professor of Surgery in University College, London, Ac. THE SCIENCE AND ART OF SURGERY; being a Treatise on Surgical Injuries, Diseases, and Operations. New and improved American, from the second enlarged and carefully revised London edition. Illustrated with over four hundred engravings on wood. In one large and handsome octavo volume, of one thousand closely printed pages, extra cloth, $6 CO. The very distinguished favor with which this work has been received on both sides of the Atlan- tic has stimulated the author to render it even more worthy of the position which it has so rapidly attained as a standard authority. Every portion has been carefully revised, numerous additions have been made, and the most watchful care has been exercised to render it a complete exponent of the most advanced condition of surgical science. In this manner the work has been enlarged by about a hundred pages, while the series of engravings has been increased by more than a hundred, rendering it one of the most thoroughly illustrated volumes before the profession. The additions of the author having rendered unnecessary most of the notes of the former American editor, but little has been added in this country; some few notes and occasional illustrations have, however, been introduced to elucidate American modes of practice. It is, in our humble judgment, decidedly the best book oi the kind in the English language. Strange that just such books are notoftener produced by pub- lic teachers of surgery in this country and Great Britain Indeed, it is a matter of great astonishment. but no less true than a«lonishing. that of the many works on surgery republished in this country within the last fifteen of twenty years as text-books for medical students, this is the only one that even ap proximate? to the fulfilment of the peculiar wants of youngmen just enienngupon the study of this branch of the profession.— Western Jour.of Med. awl Surgery. Its value is greatly enhanced by a very copious well-arranged index. We regard this as one of the most valuable contributions to modern surgery. To one entering his novitiate of practice, we regard ii the mos; serviceable guide which he can consult. He will find a fulness of detailleadinghim through every step of the operation, and not deserting him until the final issue of the case is decided.—Sethoscope. Embracing, as will be perceived, the whole surgi- cal domain, and each division of itself almost com- plete and perfect, each chapterfull and explicit, each subject faithfully exhibited, we can only express out estimate of it in the aggregate. We consider it an excellent contribution to surgery, as probably the best single volume now extant on the subject, and with great pleasure we add it to our text-books.— Nashville Journal of Medicine and Surgery. Prof. Erichsen's work, for its size, has not been surpassed j his nine hundred and eight pages, pro- fusely illustrated, are rich in physiological^ patholo- gical, and operative suggestions, doctrines, details, and processes ; and will prove a reliable resource for information, both to physician and surgeon, in the hour of peril.—JV. 0. Med. and Surg. Journal. FLINT (AUSTIN), M. D., Professor of the Theory and Practice of Medicine in the University of Louisville, A;c. PHYSICAL EXPLORATION AND DIAGNOSIS OF DISEASES AFFECT- ING THE RESPIRATORY ORGANS. In one large and handsome octavo volume, extra cloth, 636 pages. $4 00. A work of original observation of thehighest merit We recommend the treatise to every one who wishei to become a correct auscultator. Based to a very large extent upon cases numerically examined, il carries the evidence of careful study and disorimina tion upon every pa completing the work from p. 431 to end, with Index, Title Matter, &c, may be had separate, cloth backs and paper sides. Price $3 00. From Prof. E. N. Horsford, Harvard College. It has, in its earlier and less perfect editions, been familiar to me, and the excellence of its plan and the clearness and completeness of its discussions, have long been my admiration. No reader of English works on this science can afford to be without this edition of Prof. Graham's Elements.—Silliman's Journal, March, 1858. From Prof. Woleott Gibbs, N. Y. Free Academy. The work is an admirable one in all respects, and its republication here cannot fail to exert a positive influence upon the progress of science in this country. A.ND SCIENTIFIC PUBLICATIONS. 15 FOWNES (GEORGE), PH. D., &.c. A MANUAL OF ELEMENTARY CHEMISTRY; Theoretical and Practical. With one hundred and ninety-seven illustrations Edited by Robert Bridges, M. D. In one large royal 12mo volume, of 600 pages, extra cloth, $2 00. The death of the author having placed the editorial care of this work in the practised hands of Drs. Bence Jones and A. W. Hoffman, everything has been clone in its revision which experience could suggest to keep it on a level with the rapid advance of chemical science. The additions requisite to this purpose have necessitated an enlargement of the page, notwithstanding which the work has been increased by about fifty pages. At the same time every care has been used to maintain its distinctive character as a condensed manual for the student, divested of all unnecessary detail or mere theoretical speculation. The additions have, of course, been mainly in the depart- ment of Organic Chemistry, which has made such rapid progress within the last few years, but yet equal attention has been bestowed on the other branches of the subject—Chemical Physics and inorganic Chemistry—to present all investigations and discoveries of importance, and to keep up the reputation of the volume as a complete manual of the whole science, admirably adapted for the learner. By the use of a small but exceedingly clear type the matter of a large octavo is compressed within the convenient and portable limits of a moderate sized duodecimo, and at the very low price affixed, it is offered as one of the cheapest volumes before the profession. Dr. Fownes'excel lent work has been universally recognized everywhere in his own and this country, as the best elementary treatise on chemistry in the English tongue, and is very generally adopted, we believe, asthestandardtextbookin all* ur colleges, both literary and scientific.—Charleston Med. Journ. and Review. A standard manual, which has long enjoyed the reputation of embodying much knowledge in a small apace. The author has achieved the difficult task of condensation with masterly tact. His book is con- cise without being dry, and brief without being too dogmatical or general.— Virginia Med. and Surgical Journal. The work of Dr. Fownes has long been before the public, and its merits have been fully appreci- ated as the best text-book on chemistry now in existence. We do not, of course, place it in a rank superior to the works of Brande, Graham, Turner, Gregory, or Gmelin, but we say that, as a work for students, it is preferable to any of them.—Lon- don Journal of Medicine. A work well adapted to the wants of the student. It is an excellent exposition of the chief doctrines and facts of modern chemistry. The size of the work, and still more the condensed yet perspicuous style in which it is written*, absolve it from the charges very properly urged against most manuals termed popular.—Edinburgh Journal of Medical Science FISKE FUND PRIZE ESSAYS —THE EF- FECTS OF CLIMATE ON TUBERCULOUS DISEASE. By Edwin Lee, M. R. C. S , London, and THE INFLUENCE OF PREGNANCY ON THE DEVELOPMENT OF TUBERCLES By Edward Warren, M. D, of Edenton,N. C. To- ■ eether inoneneat 8vo volume, extracloth. $1 00. FRICK ON RENAL AFFECTION:?; their Diag- nosis and Pathology. With illustrations. One volume, royal 12mo., extra cloth. 75 cents FERGUSSON (WILLIAM), F. R. S., Professor of Surgery in King's College, London, &e. A SYSTEM OF PRACTICAL SURGERY. Fourth American, from the third and enlarged London edition. In one large and beautifully printed octavo volume, of about 700 pages, with 393 handsome illustrations, leather. $3 50. GRIFFITH (ROBERT E.>, M. D., &c. A UNIVERSAL FORMULARY", containing the methods of Preparing and Ad- ministering Officinal and other Medicines. The whole adapted to Physicians and Pharmaceu- tists. Second Edition, thoroughly revised, with numerous additions, by Robert P. Thomas, M. D., Professor of Materia Medica in the Philadelphia College of Pharmacy. In one large and handsome octavo volume, extra cloth, of 650 pages, double columns. $3 75. It was a work requiring much perseverance, and | This is a work of six hundred and fifty-one pages when published was looked upon as by far the best work of its kind that had issued from the American press. Prof Thomas has certainly "improved," as well as added to this Formulary, and has rendered it additionally deserving of the confidence of pharma- ceutists and physicians.—Am. Journalof Pharmacy We are happy to announce a new and improved edition of this, one of the most valuable and useful works that have emanated from an American pen. It would do credit to any country, and will be found of daily usefulness to practitioners of medicine; it is better adapted to their purposes than the dispensato- ries.— Southern Med. and Surg. Journal. Itis one of the most useful books a country practi tio ler can possibly have.—Medical ChronicU. embracing all on the subject of preparing and admi- nistering medicines that can be desired by the physi- Bian and pharmaceutist.— Western Lancet The amountof useful, every-day matter,for a prac- ticing physician, is really immense.—Boston Med and Surg. Journal. This edition has been greatly improved by-the re- vision and ample additions of Dr. Thomas, and is now, we believe, one of the mosi complete works of its kind in any language. The additions amount to about seventy pages, and no effort has been spared to include in them all the recent improvements. A work of this kind appears to us indispensable to the physician, and there is none we can more cordiallv recommend—IV. Y. Journal of Medicine. GROSS (SAMUEL D.), M. D. Professor of Surgery in the Jefferson Medical College of Philadelphia, &c. ELEMENTS OF PATHOLOGICAL ANATOMY. Third edition, thoroughly revised and greatly improved. In one large and very handsome octavo volume, with about three hundred and fifty beautiful illustrations, of which a large number are from original drawings, extra cloth. H 00. ,.,,/.. The very rapid advances in the Science of Pathological Anatomy during the last few years have rendered essential a thorough modification of this work, with a view of making it a correct expo- nent of the present slate of the subject. The very careful manner in which this task has been executed, and the amount of alteration which it has undergone, have enabled the author to say that " with the many changes and improvements now introduced, the work may be regarded almost as a new treatise," while the efforts of the author have been seconded as regards the mechanical execution of the volume, rendering it one of the handsomest productions of the American press. 16 BLANCHARD & LEA'S MEDICAL GROSS (SAMUEL D.), M. D., Professor of Surgery in the Jefferson Medical College of Philadelphia, to. Enlarged Edition. Now Ready. A SYSTEM OF SURGERY: Pathological, Diagnostic, Therapeutic, and Opera- tive. Illustrated by over Thirteen Hundred Engravings. Third edition, much enlarged and carefully revised In two large and beautifully printed royal octavo volumes, of 2200 pages; leather. $15 00. (Now Ready.) The exhaustion within five years of two large editions of so elaborate and comprehensive a work as this is the best evidence that the author was not mistaken in his estimate of the want which existed of a complete American System of Surgery, presenting the science in all ita necessary details and in all its branches. That he has succeeded in the attempt to supply this want is shown not only by the rapid sale of the work, but also by the very favorable manner in which it has been received by the organs of the profession in this country and in Europe, and by the fact that a translation is now preparing in Holland—a mark of appreciation not often bestowed on any scien- tific work so extended in size The author has not been insensible to the kindness thus bestowed upon his labors, and in revising the work for a third edition he has spared no pains to render it worthy of the favor with which it has been received. Every portion has been subjected to close examination and revision; any defi- ciencies apparent have been supplied, and the results of recent progress in the science and art of surgery have been everywhere introduced; while the series of illustrations has been still further enlarged, rendering it one of the most thoroughly illustrated works ever laid before the profession. To accommodate these very extensive additions, the form of the work has been altered to a royal octavo, so that notwithstanding the increase in the matter and value of the book, its size wi 1 be found more convenient than before. Every care has been taken in the printing to render the typographical execution unexceptionable, and it is confidently expected to prove a work in every way worthy of a place in even the most limited library of the practitioner or student. Has Dr. Gross satisfactorily fulfilled this object? A careful perusal of his volumes enables us to give an answer in the affirmative. Not only has he given to the reader an elaborate and well-written account of his o ivn vast experience, but he has not failed to embody in his pages the opinions and practice of surgeons in this and other countries of Europe. The result has been a work of such completeness, that it has no superior in the systematic treatises on sur- gery which have emanated from English or Conti- nental authors. It has been justly objected that these have been far from complete in many essential particulars, many of them having been deficient in some of the most important points which should characterize such works Some of them have been elaborate—too elaborate—with respect to certain diseases, while they have merely glanced at, or given an unsatisfactory account of, others equally important to the surgeon. Dr. Gross has avoided this error, and has produced the most complete work that has yet issued from the press on the science and practice of surgery. It is not, strictly speaking, a Dictionary of Surgery, but it gives to the reader all the information that he may require for his treatment of surgical diseases. Having said so much, it might appear superfluous to add another word; but it is only due to Dr. Gr03s to state that he has embraced the opportunity of transferring to his pages a vast number of engravings from English and other au- thors, illustrative ol the pathology and treatment of surgical diseases. To these are added several hun- dred original wood-cuts. The work altogether com- mends itself to the attention of British surgeons, from whom it cannot fail to meet with extensive patronage.—London Lancet, Sept. 1, 1860. Of Dr. Gross's treatise on Surgery we can say no more than that it is the most elaborate and com- plete work on this branch of the healing art which ■has ever been published in any country. A sys- tematic work, it admits of no analytical review; but, did our space permit, we should gladly give some extracts from it, to enable our readers to j udge of the classical style of the author, and the exhaust- ing way in which each subject is treated.—Dublin Quarterly Journal of Med. Science. The work is so superior to its predecessors in matter and extent, as well as in illustrations and style of publication, that we can honestly recom- mend it as the best work of the kind to be taken home by the young practitioner__Am. Med. Journ. With pleasure we record the completion of this long-anticips ted work. The reputation which the author has for many years sustained, both as a sur- geon and as a writer, had prepared us to expect a treatise of great excellence and originality; but we confess we were by no means prepared for the 'work which is before us—the most complete treatise upon surgery ever published, either in this or any other country, and we might, perhaps, safely say, the most original. There is no subject belonging pro- perly to surgery which has not received from the authoTa due share of attention. Dr. Groes has sup- plied a want in surgical literature which has long been felt by practitioners; he has furnished us with a complete practical treatise upon surgery in all its departments As Americans, we are proud of the achievement; as surgeons, we are most sincerely thankful to him for his extraordinary labors in our behalf.—N.Y. Review and Buffalo Med Journal. The great merit of the -work may be stated as follows. It presents surgical science as it exists at the latest date, with all its improvements ; and it discusses every topic in due proportion. No- thing is omitted, nothing is in excess.— Chicago Med. Examiner, May, 1860. AVe cannot close this brief notice* of Dr. Gross's most valuable and excellent compendium of Sur- gery without again drawing attention to it, as we did in our notice of his first edition, as an evidence of the progress our American brethren are making towards establishing a literature of their own.— Dublin Quarterly Journal, Feb. 1863. It has been characterized by the representative press and by individual surgeons of the highest eminence, both at home and abroad, as " the best systematic work on surgery ever published in the English language;" and that tlje profession at large have given substantial proofs of their agree- ment to this verdict, is sufficiently evident from the fact that translations into European languages have been called for, and that go shortly after its first appearance, and at a time most unfavorable to literary " enterprise," the Philadelphia publishers have found it pay to issue a " second edition, much enlarged and carefully revised."—American Med. Monthly, May, 1862 We are much gratified to be able to announce a new edition of this Cyclopaedia of Surgery. Con- sidering the large size of the work and its expen- siveness, the extremely rapid sale and exhaustion of an entire edition, not only proves the value of the work, and its adaptation to the wants of the profession, but it speaks well for the intelligence of American surgeons.—American Medical Times. May, 1862. A valuable and even necessary addition to every surgical library.—Chicago Med. Journ., Dec. 1859. A system of Burgery which we think unrivalled in our language.—British American Journal. BY THE SAME AUTHOR. A PRACTICAL TREATISE ON FOREIGN BODIES IN THE AIR-PAS- SAGES. In one handsome octavo volume, extra cloth, with illustrations, pp.468. $2 75. AND SCIENTIFIC PUBLICATIONS. 17 GROSS (SAMUEL D.), M. D., Professor of Surgery in the Jefferson Medical College of Philadelphia, &c. A PRACTICAL TREATISE ON THE DISEASES, INJURIES, AND MALFORMATIONS OF THE URINARY BLADDER, THE PBOSTATE GLAND, AND THE URETHRA. Second Edition, revised and much enlarged, with one hundred and eighty- four illustrations. In one large and very handsome octavo volume, of over nine hundred pages, extra cloth, $4 00. Philosophical in its design, methodical in its ar- rangement, ample and sound in its practical details, it may in truth be said to leave scarcely anything to be desired on so important a subject.—Boston Med. und Surg Journal. Whoever will peruse the vast amount of valuable practical information it contains, will, we think, agree with us, that there is no work in the English language which can make any just pretensions to be its equal.—N. Y. Journal of Medicine. A volume replete with truths and principles of tha utmost value in the i n vestigation of these diseases.— American Medical Journal. GRAY (HENRY), F. R. S., Lecturer on Anatomy at St. George's Hospital, London, &c. ANATOMY, DESCRIPTIVE AND SURGICAL. The Drawings by H. V. Carter, M. D.,late Demonstrator on Anatomy at St. George's Hospital; the Dissections jointly by the Author and Dr. Carter. Second American, from the second revised and improved London edition. In one magnificent imperial octavo volume, of over 800 pages, with 388 large and elaborate engravings on wood.•Price in extra cloth, $7 00. The speedy exhaustion of a large edition of this work is sufficient evidence that its plan and exe- cution have been found to present superior practical advantages in facilitating the study of Anato- my. In presenting it to the profession a second time, the author has availed himself of the oppor- tunity to supply any deficiencies which experience in its use had shown to exist, and to correct any errors of detail, to which the first edition of a scientific work on so extensive and complicated a science is liable. These improvements have resulted in some increase in the size of the volume, while twenty-six new wood-cuts have been added to the beautiful series of illustrations which form so distinctive a feature of the work. The American edition has been passed through the press under the supervision of a competent professional man, who has taken every care to render it in all respects accurate, and it is now presented, without any increase of price, as fitted to maintain and extend the popularity which it has everywhere acquired. With little trouble, the busy practitioner whose knowledge of anatomy may have become obscured by want of practice, may now resuscitate his former anatomical lore, and be ready for any emergency. It is to this class of individuals, and not to the stu- dent alone, that this work will ultimately tend to be of most incalculable advantage, and we feel sat- isfied that the library of the medical man will soon be considered incomplete in which a copy of this work does not exiBt.— Madras Quarterly Journal of Med. Science, July,'186l. This edition is much improved and enlarged, and contains several new illustrations by Dr. Westma- cott. The volume is a complete companion to the dissecting-room, and saves the necessity of the stu dent possessing a variety of" Manuals."—The Lon- don Lancet, Feb. 9, 1861. The work before us is one entitled to the highest praise, and we accordingly welcome it as a valu- able addition to medical literature. Intermediate in fulnesR of detail between the treatises of Snar- pey and of Wilson, its characteristic merit lies in the number and excellence of the engravings it contains. Most of these are original, of much larger than ordinary size, and admirably executed. The various parts are also lettered after the plan adopted in Holden's Osteology. It would be diffi- cult to over-estimate the advantages offered by this mode of pictorial illustration. Bones, ligaments, muscles, bloodvessels, and nerves are each in turn figured, and marked with their appropriate names; thus enabl ing the student to comprehend, at a glance, what would otherwise often be ignored, or at any rate, acquired only by prolonged and irksome ap- plication. In conclusion, we heartily commend the work of Mr. Gray to the attention of the medical profession, feeling certain that it should be regarded as one of tne most valuable contributions ever made to educational literature.—N. Y. Monthly Review. Dec. 1859. In this view, we regard the work of Mr. Gray as far better adapted to the wants of the profession, and especially of the student, than any treatise on anatomy yet published in this country. It is destined, we believe, to supersede all others, both as a manual of dissections, and a standard of reference to the student of general or relative anatomy. — N. Y. Journal of Medicine, Nov. 1859. In our judgment, the mode of illustration adopted in the present volume cannot but present many ad- vantages to the studentof anatomy. To the zealous disciple of Vesalius, earnestly desirous of real im- provement, the book will certainly be of immense value; but, at the same time, we must also confess that to those simply desirous of "cramming" it will be an undoubted godsend. The peculiar value of Mr. Gray's mode of illustration is nowhere more markedly evident than in the chapter on osteology, and especially in those portions which treat of the bones of the head and of their development. The study of these parts is thus made one of comparative ease, if not of positive pleasure; and those bugbears of the student, the temporal and sphenoid bones, are shorn of half their terrors. It is, in our estimation, an admirableandcompletetext-bookfor the student, and a useful work of reference for the practitioner; its pictorial character forming a novel element, to which we have already sufficiently alluded.—Am. Journ. Med. Sci., July, 1859. GIBSON'S INSTITUTES AND PRACTICE OF SURGERY". Eighth edition, improved and al- tered. With thirty-four plates. In twohandsome octavo volumes, containing about 1,000 pages, leather, raised bandi. $6 50. GARDNER'S MEDICAL CHEMISTRY, for the use of Students and the Profession. In one royal l2mo. vol., cloth, pp. 396, with wood-cuts. 81. J SLUGE'S ATLAS OF PATHOLOGICAL HIS- TOLOGY Translated, with Notes and Addi- tions, by Joseph Leidy, M. D. In one volume, very large imperial quarto, extra cloth, witl 320 copper-plate figures, plain and colored, $4 00. HUGHES' INTRODUCTION TO THE PRAC- TICE OF AUSCULTATION AND OTHER MODES OF PHYSICAL DIAGNOSIS, IN DIS- EASES OF THE LUNGS AND HEART. Se- cond edition 1 vol. royal 12mo., ex. cloth, pp. 304 8100. HOLLAND'S MEDICAL NOTES AND RE- FLECTIONS. From the third London edition. In one handsome octavo volume, extra cloth. S3 50. HORNER'S SPECIAL ANATOMY AND HIS- TOLOGY. Eighth edition. Extensively revised and modified. In two large octavo volumes, ex- tra cloth, of more than 1000 pages, with over 30(1 illustrations. $6 00. IS BLANCHARD & LEA'S MEDICAL HAMILTON (FRANK H.), M. D., Profrssor of Sufgery in the Lung Island College Hospital. A PRACTICAL TREATISE ON FRACTURES AND DISLOCATIONS. Second edition, revised and improved. In one large and handsome octavo volume, of over 750 pages, with nearly 300 illustrations, extra cloth, $5 00. (Just Ready, May, 1S63.) v The early demand for a new edition of this work shows that it has been successful in securing the confidence of the profession as a standard authority for consultation and reference on its import- ant and difficult subject. In again passing it through the press, the author has taken the opportu nity to revise it carefully, and introduce whatever improvements have been suggested by further experience and observation. An additional chapter on Gun-shot Fractures will be found to adapt it still more fully to the exigencies of the time. Among the many good workers at surgery of whom Amerioa may now boast rot the least is Frank Hast- ings Hamilton; and the volume before us is (we say it with a pang of wounded patriotism) the best and handiest book Qn the subject in the Erglish lan- guage. It is in vain to attempt a review of it; nearly as vain to seek for any sins, either of com- mission or omission. We have seen no work on practical surgery which we would sooner recom- mend to our brother surgeons, especially those of " the services," or those whose practice lies in dis- tricts where a man has necessarily to rely on his own unaided resources. The practitioner will find in it directions for nearly every possible acjident, easily found and comprehended ; and much pleasant reading for him to muse over in the after considera- tion of his cases.—Edinburgh Med. Journ. Feb.lS61. This is a valuable contribution to the surgery of most important affections, and is the more welcome, inasmuch as at the present time we do not possess a single complete treatise on Fractures and Dislo- cations in the English language. It has remained for our American brother topToduce a complete treatise upon the subject, and bring together in a convenient form those alterations and improvements that have been made from time to time in the treatment of these affections. One great and valuable feature in the work before us is the fact that it comprises all the improvements introduced into the practice of both English and American surgery, and though far from omitting mention of our continental neighbors, the author by no means encourages the notion—but too prevalent in some quarters—that nothing is good unless imported from France or Germany. The latter half of the work is devoted to the considera- tion of the various dislocations and their appropri- ate treatment, and its merit is fully equal to that of the preceding portion__The London Lance*, May 5, 1860. It is emphatically the book upon the subjects of which it treats, and we cannot doubt that it will continue so to be for an indefinite period of time. When we say, however, that we believe it will at once take its place as the best book for consultation by the practitioner; and that it will form the most complete, available, and reliable guide in emergen- cies of every nature connected with its subjects; and also that the student of surgery may make it his text- book with entire confidence, and with pleasure also, from its agreeible and easy style—wethink our own opinion may be gathered as to its value.— Roston Medical and Surgical Journal, March 1, i860. The work is concise, judicious, and accurate, and adapted«o the wants of the student, practitioner, and investigator, honorable to the author and to the profession.—Chicago Med. Journal, March, 1860. We regard this work as an honor not only to its author, but to the profession of our country. Were we to review it thoroughly, we could not convey to the mind of ihe reader more forcibly our lmntst opinion expressed in the few words—wethink it the best, book of its kind extant. Every man interested in surgery will soon have this work on his desk. He who does not, will be the loser.—New Orleans Medical News, March, 1860. Dr. Hamilton is fortunate in having succeeded in filling the void, so long felt, with what cannot fail to be at once accepted as a model monograph in some respects, and' a work of classical authority. We sincerely congratulate the profession of the United States on the appearance of such a publication from one of their number. We have reason to be proud of it as an original work, both in a literary and sci- entific point of view, and to esteem it as a valuable guide in a most difficult and important branch of study and practice. On every account, therefore, we hope that it may soon be widely known abroad as an evidence of genuine progress on this side of the Atlantic, and further, that it may be still more widely known at home as an authoritative teacher from which every one may profitably learn, and as affording an example of honest, well-directed, and untiring industry in authorship which every surgeon may emulate.- Am. Med. Journal y April, 1860. HODGE(HUGH L.), M.D., Professor of Midwifery and the Diseases of Women and Children in the University of Pennsylvania, &c. ON DISEASES PECULIAR TO WOMEN, including Displacements of the Uterus. With original illustrations. In one beautifully printed octavo volume, of nearly 500 extra cloth. $3 50. recur—these, taken in connection -with the entire competency of the author to render a correct ac- count of their nature, their causes, and their appro- priate management—his ample experience, his ma- tured judgment, and his perfect conscientiousness— invest this publication with an interest and value to which few of the medical treatises of a recent date can lay a stronger, if, perchance, an equal claim.— Am. Journ. Med. Sciences, Jan. 1861. Indeed, although no part of the volume is not emi- nently deserving of perusal and study, wethink that the nine chaptt rs devoted to this subject, are espe- cially so, and we know of no more valuable mono- graph upon the symptoms, prognosis, and manage- ment of these annoying maladies than is conttituted by this part of the work. We cannot but regard it as one of the most original and m jst practical works of the day ; one which every accoucheur and physi- cian Bhould most carefully read; for we are per- Biiaded that he will arise from its perusal with new ideas, which will induct him into a more rational practice in regard to many a suffering female, who may have placed her health in his hands.—British American Journal, Feb. 1661. We will say at once that tne work fulfils its object capitally well j and we will moreover venture the assertion that it will inaugurate an imnroved prac- tice throughout this whole country. The secrets of the author's success are so clearly revealed that the attentive student cannot fail to insure a goodly por- tion of similar success in his own practice. It is a credit to all medical literature; and we add, that the physician who does not place it in his library, and who does not faithfully con its pages, will lose a vast deal of knowledge that would be most useful to himself and beneficial to his patients. It is a practical work of the highest order of merit; and it will take rank as such immediately.—Maryland and Virginia Medical Journal, Feb. 1661. This contribution towards the elucidation of the pathology and treatment of some Of the diseases peculiar to women, cannot fail to meet with a favor able reception from the medical profession. The character of the particular maladies of which the work before us treats; their frequency, variety,and obscurity: the amount of malaise and even of actual suffering by which they are invariably attended; their obstinacy, the difficulty with which they are overcome, and their disposition again and again to The illustrations, which are all original, are drawn to a uniform scale of one-half the natural size. AND SCIENTIFIC PUBLICATIONS. 19 HODGE (HUGH L.), M. D., Late Professor of Midwifery, &c, in the Unb nr-ity of Pennsylvania. PRINCIPLES AND PRACTICE OF OBSTETRICS. In one large quarto volume of o/er 550 pages, with one hundred and fifty-eight figures on thirty two beautifully exe- cuted lithographic plates, and numerous wood-cuts in the text. $14 00. (Now Ready.) This work, embodying the results of an extensive practice for more than forty years, cannot fail to prove of the utmost value to all who are engaged in this department of medicine. The author's position as one of the highest authorities on the subject in this country is well known, and the fruit of his ripe experience and long observation, carefully matured and elaborated, must serve as an invaluable text-book for theSstudent and an unfailing counsel for the practitioner in the emergencies which so frequently arise in obstetric practice. The illustrations will form a novel feature in the work. The lithographic plates are all original, and to insure their absolute accuracy they have all been copied from photographs taken expressly for the purpose. In ordinary obstetrical plates, the positions of the fcetus are represented by dia- grams or sections of the patient, which are of course purely imaginary, and their correctness is scarcely more than a matter of chance with the artist. Their beauty as pictures is thereby increased without corresponding utility to the student, as in practice he must for the most part depend for his diagnosis upon the relative positions of the foetal skull and the pelvic bones of the mother. It is, therefore, desirable that the points upon which he is in future to rely, should form the basis of his instruction, and consequently in the preparation of these illustrations the skeleton has alone been used, and the aid of photography invoked, by which a series of representations has been secured of the sfrictest and most rigid accuracy. It is easy to recognize the value thus added to the very full detais on the subject of the Mechanism of Labour with which the work abounds It may be added that no pains or expense will be spared to render the mechanical execution of the volume worthy in every respect of the character and value of the teachings it contains. HABERSHON (S. O.), M. D., Assistant Physician to and Lecturer on Materia Medica and Therapeutics at Guy's Hospital, &c. PATHOLOGICAL AND PRACTICAL OBSERVATIONS ON DISEASES OF THE ALIMENTARY CANAL, CESOPHAGUS, STOMACH, CAECUM, AND INTES- TINES. With illustrations on wood. In one handsome octavo volume of 312 pages, extra cloth $2 y one who has accurately observed and retained the experience of many years.—Dublin Quarterly Journal. Full of important matter, conveyed in a ready and agreeable manner.—St.Louis Med. and Surg. Jour. There is an off-hand fervor, a glow, and a warm- heartedness infecting the effort of Dr. Meigs, which is entirely captivating, and which absolutely hur- ries the reader through from beginning to end. Be- sides, the book teems with solid instruction, and it shows the very highest evidence of ability, viz., the clearness with which the information is pre- sented. We know of no better test of one's under- standing a subject than the evidence of the power of lucidly explaining it. The most elementary, as well as the obscurest subjects, under the pencil of Prof. Meigs, are isolated and made to stand out in such bold relief, as to produce distinct impressions upon the mind and memory of the reader. — The Charleston Med. Journal. 22 BLANCHARD & LEA'S MEDICAL MEIGS (CHARLES D.) M. D., Lately Professor of Obstetrics, <5*c., in Jefferson Medical College, Philadelphia. ON THE NATURE, SIGNS, AND TREATMENT OF CHILDBED FEVER. In a Series of Letters addressed to the Students of his Class. In one handsome octavo volume, extra cloth, of 365 pages. $2 OO. lectable book. * * * This treatise upon child- bed fevers will have an extensive sale, being des- tined, as it deserves, to find a place in the library of every practitioner who scorns tolag in the rear.— Nashville Journal of Medicine and Surgery. The instructive and interesting author of this work, whose previous labors have placed his coun- trymen under deep and abiding obligations, again challenges their admiration in the fresh and vigor- ous, attractive and racy pages before us. It is a de- BY the same author ; with colored plates. A TREATISE ON ACUTE AND CHRONIC DISEASES OF THE NECK OF THE UTERUS. With numerous plates, drawn and colored from nature in the highest style of art. In one handsome octavo volume, extra cloth. $6 00 MACLISE (JOSEPH), SURGEON. SURGICAL ANATOMY. Forming one volume, very large imperial quarto, With sixty-eight large and splendid Plates, drawn in the best style and beautifully colored. Con- taining one hundred and ninety Figures, many of them the size of life. Together with copious and explanatory letter-press. Strongly and handsomely bound in extra cloth, being one of the cheapest and best executed Surgical works as yet issued in this country. $13 00. Gentlemen preparing for service in the field or hospital will find these plates of the highest practical value, either for consultation in emergencies or to refresh their recollection of the dissecting room. *,* The size of this work prevents its transmission through the post-office as a whole, but those who desire to have copies forwarded by mail, can receive them in five parts, done up in stout wrappers. Price $ 11 00. One of the greatest artistic triumphs of the age in Surgical Anatomy.—British American Medical Journal. No practitioner whose means will admit should fail to possess it.—Banking's Abstract. Too much cannot be said in its praise; indeed, we have not language to do it justice.—Ohio Medi- tal and Surgical Journal. The most accurately engraved and beautifully colored plates we have ever seen in an American book—one of the best and cheapest surgical works ever published.—Buffalo Medical Journal. It is very rare that so elegantly printed, so well illustrated, and so useful a work, is offered at so moderate a price.—Charleston Medical Journal. Its plates can boast a superiority which places them almost beyond the reach of competition.—Medi- cal Examiner. Country practitioners will find these plates of im- mense value.—N. Y. Medical Gazette. A work which has no parallel in point of accu- racy and cheapness in the English language.—N. Y. Journal of Medicine. We are extremely gratified to announce to th« profession the completion of this truly magnificent work, which, as a whole, certainly stands unri- valled, both for accuracy of drawing, beauty of coloring, and all the requisite explanations of tha subject in hand.—The New Orleans Medical and Surgical Journal. This is by far the ablest work on Surgical Ana- tomy that has come under our observation. Wt know of no other work that would justify a stu- dent, in any degree, for neglect of actual dissec- tion. In those sudden emergencies that so often arise, and which require theinstantaneouscommand of minute anatomical knowledge, a work of this kind keeps the details of the dissecting-room perpetually fresh in the memory.—The Western Journal of Medi- cine and Surgery. MILLER (HENRY), M. D., Professor of Obstetrics and Diseases of Women and Children in the University of Louisville. PRINCIPLES AND PRACTICE OF OBSTETRICS, &c. ; including the Treat- ment of Chronic Inflammation of the Cervix and Body of the Uterus considered as a frequent cause of Abortion. With about one hundred illustrations on wood. In one very handsome oc- tavo volume, of over 600 pages, extra cloth. $3 75. We congratulate the author that the task is done. We congratulate him that he has given to the medi- cal public a work which will secure for him a high and permanent position among the standard autho- rities on the principles and practice of obstetrics. Congratulations are not less due to the medical pro- fession of this country, on the acquisition of a trea- tise embodying the results of the studies, reflections, and experience of Prof. Miller.—Buffalo Medical Journal. In fact, this volume must take its place among the standard systematic treatises on obstetrics ; a posi- tion to which its merits justly entitle it.—The Cin- cinnati Lancet and Observer. A most respectable and valuable addition to our home medical literature, and one reflecting credit alike on the author and the institution to which he is attached. The student will find in this work a most useful guide to his studies; the country prac- titioner, rusty in his reading, can obtain from its pages a fair resume of the modern literature of the science; and we hope to see this American produc- tion generally consulted by the profession.— Vm. Med. Journal. MACKENZIE (WJ, M. D., Surgeon Oculist in Scotland in ordinary to Her Majesty, ice. Ice. A PRACTICAL TREATISE ON DISEASES AND INJURIES OF THE EYE. To which is prefixed an Anatomical Introduction explanatory of a Horizontal Section oi the Human Eyeball, by Thomas Wharton Jones, F. R. S. From the Fourth Revised and En- larged London Edition. With Notes and Additions by Addinell Hewson, M. D., Surgeon to Wills Hospital, &c. &c. In one very large and handsome octavo volume, extra cloth, with plates and numerous wood-cuts. $6 00. The treatise of Dr. Mackenzie indisputably holds the firstplace, and forms, in respect of learning and research, an Encyclopaedia unequalled in extent by any other work of the kind, either English or foreign. —Dixon on Diseases of the Eye. We consider it the duty of eveTy one who has the love of his profession and the welfare of his patient at heart, to make himself familiar with this the most complete work in the English language upon the dis- eases of the eye.—Med. Times and Gazette. AND SCIENTIFIC PUBLICATIONS 23 MILLER (JAMES), F. R. S. E., Professor of Surgery in the University of Edinburgh, A.C. PRINCIPLES OF SURGERY. Fourth American, from the third and revised Edinburgh edition. In one large and very beautiful volume, extra cloth, of 700 pages, with two hundred and forty illustrations on wood. $3 75. BY THE SAME AUTHOR. ±11U ^KAUTICE OF SURGERY. burgh edition. Revised by the American edit engravings on wood. In one large octavo volu No encomium of ours could add to the popularity of Miller's Surgery. Its reputation in this country is unsurpassed by that of anyother work, and, when taken in connection with the author's Principles of Surgery, constitutes a whole, without reference to which no conscientious surgeon would be willing to practice his art.—Southern Med. and Surg. Journal It is seldom that two volumes have ever made so profound an impression in so short a time as the " Principles" and the " Practice" of Surgery by Mr. Miller—or so richly merited the reputation they have acquired. The author is an eminently sensi- ble, practical, and well-informed man, who knows exactly what he is talking about and exactly how to talk it.—Kentucky Medical Recorder. By the almost unanimous voice of the profession, MORLAND (W Fellow of the Massachusc DISEASES OF THE URINARY ORG Pathology, and Treatment. With illustrations. about 600 pages, extra cloth. $3 50. Taken as a whole, we can recommend Dr. Mor- land's compendium as a very desirable-addition to the library of every medical or surgical practi- tioner.— Brit.and For. Med.-Chir. Rev., April, 1859. Every medical practitioner whose attention has been to any extent attracted towards the class of diseases to which this treatise relates, must have often and sorely experienced the want of some full, yet concise recent compendium to which he could BY THE SAIV THE MORBID EFFECTS OF THE THE ELEMENTS OF THE URINARY SE Fiske Fund Prize was awarded, July 11, 1861 cloth. 75 cents. MONTGOMERY (W. F.), Professor of Midwifery in the King and <4u< AN EXPOSITION OF THE SIGNS A With some other Papers on Subjects connected English edition. With two exquisite colored handsome octavo volume, extra cloth, of nearly A book unusually rich in practical suggestions.— Am. Journal Med. Sciences, Jan. 1857. These several subjects so interesting in them- selves, and so important, every one of them, to the most delicate and precious of social relations, con- trolling often the honor and domestic peace of a \ family, the legitimacy of offspring, or the life of its parent, are all treated with an elegance of diction, fulness of illustrations, acutenessand justice of rea- soning, unparalleled in obstetrics, and unsurpassed in medicine. The reader's interest can never flag, so MOHR (FRANCIS), PH. D., AN! PRACTICAL PHARMACY. Compris Manipulations of the Pharmaceutical Shop and by Prof. William Procter, of the Philadelp printed octavo volume, extra cloth, of 570 page MORLAND (W. W.), M. D., Fellow of the Massachusetts Medical Society, &c. DISEASES OF THE URINARY ORGANS; a Compendium of their Diagnosis, Pathology, and Treatment. With illustrations. In one large and handsome octavo volume, of about 600 pages, extra cloth. $3 50. Taken as a whole, we can recommend Dr. Mor- land's compendium as a very desirable-addition to the library of every medical or surgical practi- tioner.— Brit.and For. Med.-Chir. Rev., April, 1859. Every medical practitioner whose attention has been to any extent attracted towards the class of diseases to which this treatise relates, must have often and sorely experienced the want of some full, yet concise recent compendium to which he could refer. This desideratum has been 'supplied by Dr. Morland, and it has been ably done. He has placed before us a full, judicious, and reliable digest. Each subject is treated with sufficient minuteness, yet in a succinct, narrational style, such as to retder the wors one of great interest, and one which will prove in the highest degree useful to the general practitioner.—N. Y. Journ. of Medicine, BY THE SAME AUTHOR. THE MORBID EFFECTS OF THE RETENTION IN THE BLOOD OF THE ELEMENTS OF THE URINARY SECRETION. Being the Dissertation to which the Fiske Fund Prize was awarded, July 11, 1861. In one small octavo volume, 83 pages, extra cloth. 75 cents. MONTGOMERY (W. F.), M. D., M. R. I. A., Sec, Professor of Midwifery in the King and Queen's College of Physicians in Ireland, &c. AN EXPOSITION OF THE SIGNS AND SYMPTOMS OF PREGNANCY. With some other Papers on Subjects connected with Midwifery. From the second and enlarged English edition. With two exquisite colored plates, and numerous wood-cuts. In one very handsome octavo volume, extra cloth, of nearly 600 pages. $3 75. A book unusually rich in practical suggestions.— Am. Journal Med. Sciences, Jan. 1857. These several subjects so interesting in them- selves, and so important, every one of them, to the most delicate and precious of social relations, con fresh, and vigorous, and classical is our author's style; and one forgets, in the renewed charm of every page, that it, and every line, and every word has been weighed and reweighed through years of preparation; that this is of all others the book of t'rofling' oTtenThYhonor" "and domes tic 'peace of "a { Obstetric Law, on each of its several topics; on all family, the legitimacy of offspring, or the life of its parent, are all treated with an elegance of diction, fulness of illustrations, acutenessand justice of rea- soning, unparalleled in obstetrics, and unsurpassed in medicine. The reader's interest can never flag, so points connected with pregnancy, to be everywhere received as a manual of special jurisprudence, at once announcing fact, affording argument, establish- ing precedent, and governing alike the juryman, ad- vocate, and judge. — N. A. Med.-Chir. Review. MOHR (FRANCIS), PH. D., AND REDWOOD (TH EOPH I LUS). PRACTICAL PHARMACY. Comprising the Arrangements, Apparatus, and Manipulations of the Pharmaceutical Shop and Laboratory. Edited, with extensive Additions, by Prof. William Procter, of the Philadelphia College of Pharmacy. In one handsomely printed octavo volume, extra cloth, of 570 pages, with over 500 engravings on wood. £4 00.. MAVNE'S DISPENSATORY AND THERA- PEUTICAL REMEMBRANCER. With every Practical Formula contained in the three British Pharmacopoeias Edited, with the addition of the Formulas of the U. S. Pharmacopoeia, by R. E. Sriffith.AI.D 1 12mo. vol. ex. cl.,300 pp. 75 c. Fourth American from the last Edin- or. Illustrated by three hundred and sixty four ime, extra cloth, of nearly 700 pages. $3 75. his works, both on the principles and practice of surgery have been assigned the highest rank. If we were limited to but one work on surgery, that one should be Miller's, as we regard it as superior to all others.—St. Louis Med. and Surg. Journal. The author has in this and his " Principles," pre- sented to the profession one of the most complete and reliable systems of Surgery extant. His style of writing is original, impressive, and engaging, ener- getic, concise, and lucid. Few have the faculty of condensing so much in small space, and at the same time so persistently holding the attention. Whether as a text-book for students or a book of reference for practitioners, it cannot be too strongly recom- mended.—Southern Journal of Med. and Physical Sciences. MALGAIGNE'S OPERATIVE SURGERY, based on Normal and Pathological Anatomy. Trans- lated from the French by Frederick Brittan, A- B.,M.D. Wi thnumerous illustrations on wood! In one handsome octavo volume, extra cloth, of nearly six hundred pages. $250. 24 BLANCHARD & LEA'S MEDICAL NEILL (JOHN), M. D., Surgeon to the Pennsylvania Hospital, &.c.; and FRANCIS GURNEY SMITH, M.D., Professor of Institutes of Medicine in the Pennsylvania Medical College. AN ANALYTICAL COMPENDIUM OF THE VARIOUS BRANCHES OF MEDICAL SCIENCE; for the Use and Examination of Students. A new edition, revised and improved. In one very large and handsomely printed royal 12mo. volume, of about one thousand pages, with 374 wood-cuts, extra cloth, $3 50. Strongly bound in leather, with raised bands. S4 50. This work is again presented as eminently worthy of the favor with which it has hitherto been received. As a book for daily reference by the student requiring a guide to his more elaborate text-books, as a manual for preceptors desiring to stimulate their students by frequent and accurate examination, or as a source from which the practitioners of older date may easily and cheaply acquire a knowledge of the changes and improvement in professional science, its reputation is permanently established. The best work of the kind with which we are acquainted.—Med. Examiner. Having made free use of this volume in our ex- aminations of pupils, we can speak from experi- ence in recommending it as an admirable compend for students, and as especially useful to preceptors who examine their pupils. It will save the teacher much labor by enabling him readily to recall all of the points upon which his pupils should be ex- amined. A work of this sort should be in the hands of every one who takes pupils into his office with a view of examining them; and this is unquestionably the best of its class.—Transylvania Med. Journal. In the rapid course of lectures, where work for the students is heavy, and review necessary for an examination, a compend is not only valuable, but it is almost a sine qua non. The one before us is, in most of the divisions, the most unexceptionable of all books of the kind that we know of. The newest and soundest doctrines and the latest im- provements and discoveries are explicitly, though concisely, laid before the student. There is a class to whom we very sincerely commend this cheap book as worth its weight in silver—that class is the gradu- ates in medicine of more than ten years' standing. who have not studied medicine since. They will perhaps find out from it that the science is not exactly now what it was when they left it off.—The Stetho- scope. NEL1GAN (J. MOORE), M. D., M. R. I. A., &c. ATLAS OF CUTANEOUS DISEASES. In one beautiful quarto volume, extra cloth, with splendid colored plates, presenting nearly one hundred elaborate representations of disease. $5 50. This beautiful volume is.intended as a complete and accurate representation of all the varieties of Diseases of the Skin. While it can be consulted in conjunction with any work on Practice, it has especial reference to the author's " Treatise on Diseases of the Skin," so favorably received by the profession some years since. The publishers feel justified in saying that few more beautifully exe- cuted plates have ever been presented to the profession of this country. Neligan's Atlas of Cutaneous Diseases supplies a long existent desideratum much felt by the largest clasB of our profession. It presents, in quarto size, 16 plates, each containing from 3 to 6 figures, and forming in all a total of 90 distinct representations of the different species of skin affections, grouped together in genera or families. The illustrations have been taken from nature, and have been copied with sueh fidelity that they present a striking picture of life; in which the reduced scale aptly serves to give, at a coup d'eeil, the remarkable peculiarities of each individual variety. And while thus the dis- ease is rendered more definable, there is yet no loss of proportion incurred by the necessary concentra- tion. Each figure is highly colored, and so truthful has the artist been that the most fastid'ous observer could not justly take exception to the correctness of the execution of the pictures under his scrutiny.— Montreal Med. Chronicle. BY THE SAME AUTHOR. A PRACTICAL TREATISE ON DISEASES OF THE SKIN. Fourth American edition. In one neat royal 12mo. volume, extra cloth, of 334 pages. $1 50. OWEN ON THE DIFFERENT FORMS OF THE SKELETON, AND OF THE TEETH. One vol. royal 12mo., extra cloth with numerous illustrations. SI 25 PI RRIE (WILLIAM), F. R. S. E., Professor of Surgery in Hie University of Aberdeen. THE PRINCIPLES AND PRACTICE OF SURGERY. Edited by John Neill, M. D., Professor of Surgery in the Penna. Medical College, Surgeon tothe Pennsylvania Hospital, &c. In one very handsome 8vo. volume, extra cloth, of 780 pages, with 316 illustrations $3 75. We know of no other surgical work of a reason- rately discussed the principles of surgery, and a able size, wherein there is so much theory and prac tice, or where subjects are more soundly or clearly taught.—The Stethoscope. Prof. Pirrie, in the work before us, has elabo- safe and effectual practice predicated upon them. Perhaps no work upon this subject heretofore issued is so full upon the science of the art of surgery.__ Nashville Journal of Medicine and Surgery. PARKER (LANGSTON), Surgeon to the Queen's Hospital, Birmingham. THE MODERN TREATMENT OF SYPHILITIC DISEASES, BOTH PRI- MARY AND SECONDARY; comprising the Treatment of Constitutional and Confirmed Syphi- lis, by a safe and successful method. With numerous Cases, Formulae, and Clinical Observa- tions. From the Third and entirely rewritten London edition. In one neat octavo volume extra cloth, of 316 pages. «2 50. * ' AND SCIENTIFIC PUBLICATIONS. 25 PARRISH (EDWARD), Professor of Materia Medica in the Philadelphia College of Pharmacy. A TREATISE ON PHARMACY. Designed as a Text-book for the Student, and as a Guide for the Physician and Pharmaceutist. With many Formulae and Prescriptions. Third edition, greatly improved. In one handsome octavo volume, of 850 pages, with several hundred Illustrations, extra cloth. $5 00. (Just Ready.) Though for some time out of print, ihe appearance of a new edition of this work has been de- layed for the purpose of embodying in it the results of the new U. S. Pharmacopoeia. The pub- lication of this latler has enabled the author to complete his revision in the most thorough manner. Those who have been waiting for the work may therefore rely on obtaining a volume completely on a level with the most advanced .condition of pharmaceutical science. The favor with which the work has thus far been received shows that the author was not mis- taken in his estimate of the want of a treatise which should serve as a practical text-book for all engaged in preparing and dispensing medicines. Such a guide was indispensable not only to the educated pharmaceutist, but also to that large class of practitioners throughout the country who are obliged to compound their own prescriptions, and who during their collegiate course have no opportunity of obtaining a practical familiarity with the necessary processes and, manipulations. The rapid exhaustion*of two large editions is evidence that the author has succeeded in thoroughly carrying out his object. Since the appearance of the last edition, much has been done to perfect the science **the new Pharmacopoeia has introduced many changes to which the profession must conform ; and the author has labored assiduously to embody in his work all that physicians and pharmaceutists can ask for in such a volume. The new matter alone will thus be found worth more than the very moderate cost of the work to those who have been using the previous editions. edition, containing the added results of his recent and rich experience as an observer, teacher, and practic ±1 operator in the pharmaceutical laboratory. The excellent plan of the first is more thoroughly, —Peninsular Med. Journal, Jan. I860. Of course, all apothecaries who have not already All that we can say of it is that to the practising physician, and especially the country physician, who is generally his own apothecary, there is hard- ly any book that might not betteT be dispensed with. It is at the same time a dispensatory and a pharma- cy.—Louisville Review. A careful examination of this work enables us to speak of it in the highest terms, as being the best treatise on practical pharmacy with which we are acquuinted, and an invaluable vade-mecum, not only to the apothecary and to those practitioners who are accustomed to prepare tleir own medicines, but to every medical man and medical student.—Boston Med. and Surg. Journal. This is altogether one of the most useful books we have seen. It is just what we have long felt to be needed by apothecaries, students, and practition- ers of medicine, most of whom in this country have to put up their own prescriptions. It bears, upon every page, the impress of practical knowledge, conveyed in a plain common sense manner, and adapted to the comprehension of all who may read it.—Southern Med. and Surg. Journal. That Edward Parrish, in writing a book upon practical Pharmacy some few years ago—one emi- nently original and unique—did the medical and pharmaceutical professions a great and valuable ser- vice, no one, we think, who has had access to its pages will deny; doubly welcome, then, is this new a copy of the first edition will procure one of this; it is, therefore, to physicians residing in the country and in small towns, who cannot avail themselves of the skill of an educated pharmaceutist, that we would especially commend this work. In it they will find all that they desire to know, and should know, but very little of which they do really snow in reference to this important collateral branch of their profession; for it is a well established fact, that, in the education of physicians, while the sci- ence of medicine is generally well taught, very little attention is paid to the art of preparing them for use, and we know not how this defect can be so well remedied as by procuring and consulting Dr. Parrish's excellent work.—St. Louis Med. Journal. Jan.1860. We know of no work on the subject which would be more indispensable to the physician or student desiring information on the subject of which it treats. With Griffith's " Medical Formulary" and this, the practising physician would be supplied with nearly or quite all the most useful information on the sub- ject.—Charleston Med. Jour.and Review, Jan. I860. PEASLEE (E. R.), M. D., Professor of Physiology and General Pathology in the New York Medical College. HUMAN HISTOLOGY, in its relations to Anatomy, Physiology, and Pathology; for the use of Medical Students. With four hundred and thirty-four illustrations. In one hand- some octavo volume, extra cloth, of over 600 pages. $3 75. It embraces a library upon the topics discussed within itself, and is just what the teacher and learner need. We have not only the whole subject of His- tology, interesting in itself, ably and fully discussed, but what is of infinitely greater interest to the stu- dent, because of greater practical value, are its re- lations to Anatomy, Physiology, and Pathology, which are here fully and satisfactorily set forth.— Nashville Journ. of Med. and Surgery. We would recommend it as containing a summary of all that is known of the important subjects which it treats; of all that is in the great works of Simon and Lehmann, and the organic chemists in general. Master this one volume, and you know all that is known of the great fundamental principles of medi- cine, and we have no hesitation in saying that it is an honor to the American medical profession.__ St. Louis Med. and Surg. Journal. ROKITANSKY Curator of the Imperial Pathological Museum, A MANUAL OF PATHOLOGICAL bound in two, extra cloth, of about 1200 pages. king, C. H. Moore, and G. E.Day. $7 00. The profession is too well acquainted with the re- putation of Rokitansky's work to need our assur- ance that this is one of the most profound, thorough. and valuable books ever issued from the medical press. It is sui generis, and has no standard of com- parison, it is only necessary to announce that it is issued in a form as cheap as is compatible with its (CARL), M. D., and Professor at the University of Vienna, &c. ANATOMY. Four volumes, octavo, Translated by W. E. Swaine, Edward Sieve- size and preservation, and its sale follows as a matter of course. No library can be called com- plete without it.—Buffalo Med. Journal. An attempt to give our readers any adequate idea of the vast amount of instruction accumulated in these volumes, would be feeble ana hopeless.— Western Lancet. ROYLE'S MATERIA MEDICA AND THERAPEUTICS; including the Preparations of the Pharmacopoeias of London, Edinburgh, Dublin, and of the United States. With many new medicines. Edited by Joseph Carson, M. D. With ninety-eight illustrations. In one large octavo volume, extra cloth, of about 700 pages. $3 00. \ 26 BLANCHARD & LEA'S MEDICAL RIGBY (EDWARD), M.D., Senior Physician to the General Lying-in Hospital, Ac A SYSTEM OF MIDWIFERY. With Notes and Additional Illustrations. Second American Edition. One volume octavo, extra cloth, 422 pages. $2 50. BY THE SAME AUTHOR. ON THE CONSTITUTIONAL TREATMENT OF FEMALE DISEASES. In one neat royal 12mo. volume, extra cloth, of about 250 pages. $1 00. RAMSBOTHAM (FRANCIS H.), M.D. THE PRINCIPLES AND PRACTICE OF OBSTETRIC MEDICINE AND SURGERY, in reference to the Process of Parturition. A new and enlarged edition, thoroughly revised by the Author. W ith Additions by W. V. Keating, M. D., Professor of Obstetrics, &c, in the Jefferson Medical College, Philadelphia. In one large and handsome imperial octavo volume, of 650 pages, strongly bound in leather, with raised bands; with sixty-four beautiful Plates, and numerous Wood-cuts in the text, containing in all nearly 200 large and beautiful figures. $7 00. From Prof. Hodge, of the University of Pa. To the American public, it is most valuable, from its intrinsic.undoubted excellence, and as beirg the best authorized exponent of British Midwifery. Its circulation will, I trust, be extensive throughoiit our country. It is unnecessary to say anything in regard to the utility of this work. It is already appreciated in our country for the value of the matter, the clearness of its style, and the fulness of its illustrations. To the physician's library it is indispensable, while to the student as a text-book, from which to extract the material for laying the foundation of an education on obstetrical science, it has no superior.—Ohio Med and Surg. Journal. The publishers have secured its success by the SOLLY ON THE HUMAN BRAIN; its Structure, Physiology, and Diseases. From the Second ana much enlarged London edition. In one octave volume, extra cloth, of 500 pages, with 120 wood- cuts. 82 50. SKEY'S OPERATIVE SURGERY. In one very truly elegant style in which they have brought it out, excelling themselves in its production, espe- cially in its plates. It is dedicated to Prof. Meigs, and has the emphatic endorsement of Prof. Hodge, as the best exponent of British Midwifery. We knr,w of no text-book which deserves in all respects to be more highly recommended to students, and we could wish to see it in the hands of every practitioner, foT they will find it invaluable for reference.—Med. Gazette. handsome octavo volume, extra cloth, of over 650 pages, with about one hundred wood-cuts. 83 25 SIMON*:* liENERAl. PATHOLOGY, as conduct ive to the Establishment of Rational Principles for the prevention and Cure of Disease. In on« octavo volume, extra cloth, of 212 page*. 91 25 RICORD (P.), M. D. A TREATISE ON THE VENEREAL DISEASE. By John Hunter, F. R. 8. With copious Additions, by Ph. Ricord, M.D. Translated and Edited, with Notes, by Freeman J. Btjmstead. M.D., Lecturer on Venereal at the College of Physicians and Surgeons, New York. Second edition, revised, containing a resume of Ricord's Recent Lectures on Chancre. In one handsome octavo volume, extra cloth, of 550 pages, with eight plates. $4 00. BY THE SAME AUTHOR. RICORD'S LETTERS ON SYPHILIS. Translated by W. P. Lattimore, M. D- In one neat octavo volume, of 270 pages, extra cloth. $2 00. SMITH (HENRY H.), M. D., AND HORNER (WILLIAM E.), M.D. AN ANATOMICAL ATLAS, illustrative of the Structure of the Human Body. In one volume, large imperial octavo, extra cloth, with about six hundred and fifty beautiful figures. $4 50. of the kind that has yet appeared ; and we must add, the very beautiful manner in which it is " got up'* The plan of this \tlas, which renders it so pe- culiarly convenient for the student, and its superb artistical execution, *>.ave been already pointed out. We must congratulate the student upon the comple- tion of this Atlas, as it is the most convenient work is so creditable to the country as to be flattering to our nations 1 pride.—American Medical Journal. SMITH (EDWARD), M.D., LL.D., F.R.S. Assistant Physician to the Hospital,for Consumption and Diseases of the Chest, Brompton, &c. CONSUMPTION; ITS EARLY AND REMEDIABLE STAGES. In one neat octavo volume of 254 pages, extra cloth. $2 25. (Now Ready.) One-half of Dr. Smith's work is devoted to the than to drugs in the treatment of the disease In treatment of Tuberculosis. We find in this portion taking leave of the work, we would express the of the work no occasion to join issue with the au- hope that the author will furnish occasions for the thor ; but, on the contrary, much which we would renewal of our intercourse as a reader if not as a commend to the reader's attention. Dr. Smith at- leviewer.—Am. Med. Journal, Jan. 1863 taches far greater importance to hygienic measures SHARPEY (WILLIAM), M.D., JONES QUAIN, M.D., AND RICHARD QUAIN, F. R. S., &c. HUMAN ANATOMY. Revised, with Notes and Additions, by Joseph Leidy M. D., Professor of Anatomy in the University of Pennsylvania. Complete in two large octavo volumes, extra cloth, ol about thirteen hundred pages. With over 500 illustrations. $6 00. AND SCIENTIFIC PUBLICATIONS. 27 STILLE (ALFRED), M. D., Professor of the Theory and Practice of Medicine in the University of Pennsylvania. THERAPEUTICS AND MATERIA MEDICA; a Systematic Treatise on the Action and Uses of Medicinal Agents, including their Description and History. Second Edition, revised and enlarged. In two large and handsome octavo volumes, extra cloth. $10 00. (Now Ready.) This work is designed especially for the student and practitioner of medicine, and treats the various articles of the Materia Medica from the point of view of the bedside, and not of the shop or of the lecture-room. While thus endeavoring to give all practical information likely to be useful with respect to the employment of special remedies in special affections, and the results to be anticipated from their administration, a copious Index of Diseases and their Remedies renders the work emi- nently fitted for reference by showing at a glance the different means which have been employed, and enabling the practitioner to extend his resources in difficult cases with all that the experience of the profession has suggested. The speedy demand for another edition of this work shows that it has acceptably filled an acknow- ledged want No exertion of the author has been wanting to render it worthy a continuance of the favor with which it has been received, while an alteration in the typographical arrangement has accommodated the additions without increasing unduly the size of the volumes. tioned, Stille. His great, work on " Materia Medi- Rarely, indeed, have we had submitted to us a work on medicine so ponderous in its dimensions as that now before us, and yet so fascinating in its contents. It is, therefore, with a peculiar gratifi- cation that we recognize in Dr. Stille the posses- sion of many of those more distinguished qualifica- tions which entitle him to approbation, and which justify him in coming before his medical brethren as an instructor. A comprehensive knowledge, tested by a sound and penetrating judgment, joined to a love of progress —which a discriminating spirit of inquiry has tempered sons to accept nothing new because it is new, and abandon nothing old because it is old, but which estimates either according to its relations to a just logic and experience—manifests itself everywhere, and gives to the guidance of the author all 'he assurance of safety which the diffi- culties of his subject can allow. In conclusion, we earnestly advise our readers to ascertain for them- selves, by a study of Dr. Stille's volumes, the great value and interest of the storeB of knowledge they present. We have pleasure in referring rather to the ample treasury of undoubted truths, the real and assured conquest of medicine, accumulated by Dr. Stille in his pages ; and commend the sum of his la- bors to the attention of our readers, as alike honor- able to our science, and creditable to the zeal, the candor, and the judgment of him who has garnered the whole so carefully.—Edinburgh Med. Journal. The most recent authority is the one last men- ca and Therapeutics," published last year, in two octavo volumes, of some sixteen hundred pages, while it embodies the results of the labor of others up to the time of publication, is enriched with a great amount of original observation and research. We would draw attention, by the way, to the very convenient mode in which the Index is arranged in this work. There is firstan " Index of Remedies ;' next an "Index of Diseases and their Remedies." Such an arrangement of the Indices, in our opinion, g reatly enhances the practical val ue of books of this kind. In tedious, obstinate cases of disease, where we have to try one remedy after another until our stock is pretty nearly exhausted, and we are almost driven to our wit's end, such an index as the second of the two just mentioned, is precisely what we want.—London Med. Times and Gazette, April, 1861. We think this work will do much to obviate the reluctance to a thorough investigation of this branch of scientific study, for in the wide range of medical literature treasured in the English tongue, we shall hardly find a work written in a style more clear and simple, conveying forcibly the facts taught, and yet free from turgidity and redundancy. There isa fas- cination in its pages that will insure to it a wide popularity and attentive perusal, and a degree of usefulness not often attained through the influence of a single work. SIMPSON (J. Y.), M. D., Professor of Midwifery, f°r a very 'ong period, be acknowledged as the chief standard work on dermatology. The principles of an enlightened and rational therapeia are introduced on every ap- propriate occasion.—Am. Jour. Med Science. When the first edition of this work appeared about fourteen years ago, Mr Erasmus Wilson had already given some yeais to the study of Diseases of the Skin, and he then expressed his intention of devoting his future life to the elucidation of this branch of Medical Science In the present edition Mr. Wilson presents us with the results of his ma- tured experience, and we have now before us not merely a reprint of his former publications, but an entirely new and rewritten volume. Thus, the whole .history of the diseases affecting the skin, whether they originate in that structure or are the mere mani- festations of derangement of internal organs, is brought under notice, and the book includes a mass of information which is spread over a great part of the domain of Medical and Surgical Pathology. We can Bafely recommend it to the profession as the best work on the subjectnow in existence in the En- glish language.—London Med. Times and Gazette. No matter what other treatises may.be in the libra- ry of the medical attendant, he needs the clear and suggestive counsels of Wilson, who is thoroughly posted up on all subjects connected with cutaneous pathology. We have, it is very true, other valuable works on the maladies that invade the skin; but, compared with the volume under consideration, they are certainly to be regarded as inferior lights in guid- ing the judgment of the medical man.—Boston Mad. and Surg. Journal, Oct. 1857. The author adopts a simple and entertaining style. He strives to clear away the complications of his subject, and has th«is produced a book filled with a vast amount of information, in a form so agreeable as to make it pleasant reading, even to the uninitiated. More especially does it deserve our praise because of its beautiful and complete atlas, which, the American publishers have successfully imitated from the origi- nal plates. We pronounce them by far the best imi- tations of nature yet published in our country. With the text-book and atlas at hand, the diagnosis is ren- dered easy and accurate, and the practitioner feels himself safe in his treatment. We will add that this work, although it must have been very expensive to the publishers, is not high priced. There is no rea- son, then, to prevent every physician from obtaining a work of such importance, and one which will save him both labor and perplexity.— Va. Med. Journal. As a practical guide to the classification, diagnosis, and treatment of the diseases of the skin, the book is complete. We know nothing, considered in this as- pect, better in our language; it is a safe authority on all the ordinary matters which, in this range of dis- eases, engage the' practitioner's attention, and pos- sesses the high quality — unknown, we believe, to every older manual, of being on a level with science's high-watermark; a sound book of practice.—London Med. Times. ALSO, NOW READY, A SERIES OF PLATES ILLUSTRATING WILSON ON DISEASES OF THE SKIN; consisting of twenty beautifully executed plates, of which thirteen are exquisitely colored, presenting the Normal Anatomy and Pathology of the Skin, and containing accurate re- presentations of about one hundred varieties of disease, most of them the size of nature. Price in cloth. $5 50. In beauty of drawing and accuracy and finish of coloring these plates will be found equal to anything of the kind as yet issued in this country. The value of the new edition is enhanced by an additional colored plate. We have already expressed our high appreciation of Mr. Wilson's treatise on Diseases'of the Skin. The plates are comprised in a .separate volume, which we counsel all those who possess the text to purchase. It is a beautiful specimen of color print- ing, and the representations of the various forms of skin disease are as faithful as is possible in plates of the size.—Boston Med. and Surg. Journal, April 8, 1853. The plates by which this edition is accompanied leave nothing to be desired, so far as excellence of delineation and perfect accuracy of illustration are concerned.— Medico-Chirurgical Review. Ot these plates it is impossible to speak too highly. The representations of the various forms of cutane- ous disease are singularly accurate, and the color- ing exceeds almost anything we have met with.— British and Foreign Medical Review. Also, the TEXT and PLATES done up in one handsjme volume, extra cloth, price $9 50. BY THE SAME AUTHOR. THE DISSECTOR'S MANUAL; or, Practical and Surgical Anatomy. Third American, from the last revised and enlarged English edition. Modified and rearranged, by William Hunt, M. D., Demonstrator of Anatomy in the University of Pennsylvania. In one larsre and handsome royal 12mo. volume, extiacloth, of 582 pages, with 154illustrationa, $2 00. BY THE SAME AUTHOR. HEALTHY SKIN; A Popular Treatise on the Skin and Hair, their Preserva- tion and Management. Second American, from the fourth London edition. One neat volume, royal 12mo., extra cloth, of about 300 pages, with numerous illustrations. $1 00. 32 BLANCHARD «fe LEA'S MEDICAL PUBLICATIONS. WINSLOW (FORBES), M.D., D. C. L., 8ec ON OBSCURE DISEASES OF THE BRAIN AND DISORDERS OF THE MIND; their incipient Symptoms, Pathology, Diagnosis, Treatment, and Prophylaxis. In one handsome octavo volume, of nearly 600 pages, extra cloth. $4 00. We close this brief and necessarily very imperfect notice of Dr. Winslow's great and classical work, by expressing our conviction that it is long since so important and beautifully written a volume has is- sued from the British medical press.—Dublin Med. Press, July 25,1860. We honestly believe this to be the best book of the season.— banking's Abstract, July, 1860. The latter portion of Dr. Winslow's work is ex- clusively devoted to the consideration of Cerebral Pathology. It completely exhausts the subject, in the same manner as the previous seventeen chapters relating to morbid psychical phenomena left nothing unnoticed in reference to the mental symptoms pre- monitory of cerebral disease. It is impossible to overrate the benefits likely to result from a general perusal of Dr. Winslow's valuable and deeply in- teresting work.—London Lancet, June 23,1660. It contains an immense mass of information.— Brit, and For. Med.-Chir. Review, Oct. 1860. WEST (CHARLES), M. D., Accoucheur to and Lecturer on Midwifery at St. Bartholomew's Hospital, Physieian to the Hospital for Sick Children, &c. LECTURES ON THE DISEASES OF WOMEN. Second American, from the second London edition. In, one handsome octavo volume, extra cloth, of about 500 pages; price $3 25. *^.* Gentlemen who received the first portion, as issued in the "Medical News and Library," can now complete their copies by procuring Part II, being page 309 to end, with Index, Title matter, &c, 8vo., cloth, price $1 25. We mustnow conclude this hastily written sketch with the confident assurance to our readers that the work will well repay perusal. The conscientious, painstaking, practical physician is apparent on every page.—N. Y. Journal of Medicine. We know of no treatise of the kind so complete and yet so compact.—Chicago Med. Jour. A fairer, more honest, more earnest, and more re- liable investigator of the many diseases of women and children is not to be found in any country.— Southern Med. and Surg. Journal. We have to say of it, briefly and decidedly, that it is the best work on the subject in any language ; and that it stamps Dr. West as the facile princeps of British obstetric authors.—Edvnb. Med. Journ. We gladly recommend his Lectures as in the high- est degree instructive to all who are interested in obstetric practice.—London Lancet. Happy in his simplicity of manner, and moderate in his expression of opinion, the author is a sound reasoner and a good practitioner, and his book is worthy of the handsome garb in which it has ap- peared.— Virginia Med. Journal. . We must take leave of Dr. West's very useful work, with our commendation of the clearness of its style, and the incustry and sobriety of judgment ' of which it gives evidence.—London Med Times. Sound judgment and good sense pervade every chapter of the book. From its perusal we have de- rived unmixed satisfaction.— Dublin Quart. Journ. BY THE SAME AUTHOR. LECTURES ON THE DISEASES OF INFANCY AND CHILDHOOD. Third American, from the fourth enlarged and improved London edition. In one handsome octavo volume, extra cloth, of about six hundred and fifty pages. $3 25. The three former editions of the work now before i diseases it omits to notice altogether. But those us have placed the author in the foremost rank of who know anything of the present condition of those physicians who have devoted special attention paediatrics will readily admit that it would be next to the diseases of early life. We attempt no ana- * lysis of this edition, but may refer the reader to some of the chapters to which the largest additions have been made—those on Diphtheria, Disorders of the Mind, and Idiocy, for instance—as a proof that the work is really a new edition; not a mere reprint. In its present shape it will be found of the greatest possible service in the every-day practice of nine- tenths of the profession.—Med. Times and Gazette, London, Dec. 10,1859. All things considered; this book of Dr. West is by far the best treatise in our language upon such modifications of morbid action and disease as are witnessed when we have to deal with infancy and childhood. It is true that it confines itseif to such disorders as come within the province of the phy- sician, and even with respect to these it is unequal as regards minuteness of consideration, and some to impossible to effect more, or effect it better, than the accoucheur of St. Bartholomew's has done m a single volume. The lecture (XVI.) upon Disorotrs of the Mind in children is an admirable specimen of the value of the later information convened in the Lectures of Dr. Charles West.—London Lancet, Oct. 22, 1859. ' Since the appearance of the first edition, about eleven years ago, the experience of the author has doubled; so that, whereas the lectures at first were founded on six hundred observations, and one hun- dred and eighty dissections made among nearly four- teen thousand children, they now embody the Results of nine hundred observations, and two hundred and eigh y-eight post- mortem examinations made amone nearly- thirty thousand children, who, during the P18.'*'? y«»™> have been under his care.- British Med. Journal, Oct. 1, 1859. BY THE SAME AUTHOR. AN ENQUIRY INTO THE PATHOLOGICAL IMPORTANCE OF TTLPFR ATION OF THE OS UTERI. In one neat octavo volume, extra cloth. $1 25. V^XV" WHITEHEAD ON THE CAUSES AND TREAT- I Second American Edition. In one volume MENT OF ABORTION AND STERILITY.! vo, extra cloth, pp. 308 $3 00. ' r