FOOTNOTES
[1] Ewart, discussing the antiquity of gout, observes that it is “certainly as ancient as civilisation,” and as far as we can identify them in the accounts handed down from remote ages, the etiology, the leading symptoms, the outward characters of the articular gout of the ancients were practically the same as belong to gout in our own times! But of its relative prevalence in antiquity we have no means of judging. Continuing, he holds that “the ultimate lesions of gouty arthritis and its pathology are presumably as immutable as those of osteoarthritis.” This may be so, but such objective evidence as we possess certainly points to the greater antiquity of osteoarthritis as the following quotation from our work, “Arthritis Deformans,” testifies:—
“During the course of some excavations undertaken by the Survey Department of the Egyptian Government in that tract of Nubia lying immediately south of the First Cataract, over 6,000 bodies were brought to light, comprising among them representatives of all periods from early pre-dynastic times down to the fifth century after Christ. As the result of their examination of this vast accumulation of human débris, Professor Elliot Smith, in the Nubian Survey Bulletin, states that “The disease which shows itself with by far the greatest frequency in the bodies of all periods is rheumatoid arthritis” (Osteoarthritis).
[2] 920 (S. Eng. Leg.), “There cam a goute In is knee, of Anguische gret.... So longue, that is kneo to-swal.”
1310 (In Wright Lyric), “A goute me hath ygreythed so, Ant other eveles monye mo.”
1377 (Langl., P. Pl.), “He ... gyued me in goutes, I may noughte go at large.”
1400 (Lanfranc’s Cirurg.), “A man that hath arteticam, that is as myche to seie as a goute.”
1450 (M.E. Med. Bk., Heinrich), “Here wyth anoynte the goutes.”
1566 (J. Alday, tr. Baoystuau’s Theat. World), “Their legges full of gouts.”
1579 (Langham, Gard. Health, 1633), “For all goutes, seethe Leekes and Otemeale with sheepes tallow, and apply them hot.”
1590 (Spenser, F. Q.), “And eke in foote and hand A grievous gout tormented him full sore.”
1697 (Dryden, Virg. Georg.), “From Winter keep Well fodder’d in the Stalls, they tender Sheep.... That free from Gouts thou mayst preserve thy Care.”
1704 (Fuller, Med. Gymn.), “There have been some Gouts ... which nothing could remove but a very low Diet.”
1732 (Pope, Ess. Man.), “So, when small humours gather to a gout The Doctor fancies he has driv’n ’em out.”
1822 (Ld. Eldon, in Twiss Life), “I found the King in bed yesterday. He has had a pretty severe gout.”—New English Dictionary, Oxford, 1901. (Ed. Sir James Murrary.)
[3] Pitt, in one of his last letters to the Marquess Wellesley, deplores his slow recovery from severe attacks of gout with which, by the bye, the statesman Fox was likewise affected.
[4] Both Norman Moore and Bowlby subsequently upheld Ord’s view that uratic deposits only occur in tissues already degenerated. “Ebstein’s view has been modified by Von Noorden, who holds that a special ferment leads to the tissue change, to which the deposit of the urate is secondary.”
[5] Physiognomy of the Goutily Disposed.—Taking the principles as laid down by Laycock, the peculiarities of those thus affected fall under the head of the sanguine arthritic diathesis. (That careful observer did not fail to note the modifying influences of gout upon struma and other cachexia.) Thus may be compared the physiognomy of the diathesis and its associated cachexia (developed in time):—
Blood-vessels numerous; heart large and powerful; blood-corpuscles numerous; skin over malar bones highly vascular (florid complexion); skin fair, firm, oleaginous, perspirable; eyes blue; hair thick, not falling easily; teeth massive, well-enamelled, regular, even, undecayed in advanced life; malar bones flattened; head symmetrical; nasal bones well-formed, nose aquiline or of mixed form; lower jaw massive; lips symmetrical.
Form.—Figure for the most part tall; thorax broad at the summit; ribs well-curved; abdomen full; muscles firm, large; limbs large, robust; gait erect, well-poised. Nutrition active; digestion vigorous; appetite great for animal food and alcoholic stimuli. Respiration deliberate, deep; circulation vigorous; animal heat abundant; locomotion active; aptitude for exercise and outdoor amusements. Reproductive powers active; innervation abundant, the mental powers vigorous and enduring.
Physiognomy of the Sanguine Gouty Cachexia.—Blood-vessels largely developed over the malar bones and varicose; skin oily, yellow from subcutaneous deposit of fat; hair thick and white; teeth numerous, discoloured, crusted with tartar; lips bluish, nose reddish, hypertrophied; arcus senilis; abdomen pendulous; limbs thick; joints nodose; nodosities on the ends of the fingers, lobes of ears, fascia of muscles, and tendons; respiration hurried, wheezing; pulse intermittent, irregular; stomach flatulent; digestion acid; urine loaded with lithates; temper irritable; mind sometimes enfeebled.
The local diseases of the arthritic cachexia are principally seen in adult males past the age of forty-five. They consist especially in chronic inflammation of the muscular and articular tissues; in calcification of the basilar and coronary arteries, and of the cardiac valves. These changes give rise to hæmorrhagic apoplexy, angina pectoris, cardiac hypertrophy and dilation; and to secondary pulmonary affections, as emphysema, pulmonary apoplexy, and asthma. Irritation of the mucous surfaces may give rise to nephritis, pharyngeal and laryngeal coughs, and diarrhœa.—Med. Observation and Research, 2nd edition, pp. 96-98.
[6] According to Fischer the protein molecule can be split up into amino-acids, di-amino-acids, aromatic-amino-acids, nitrogenous derivatives of the benzene ring, pyrimidine bases, pyrrolidine derivatives, cystin, and ammonia. During proteolysis the amino-acids exist in groups, e.g., glycine and leucine (glycyl-leucine), two leucine radicles (alanyl-leucine), etc.—which combinations Fischer termed polypeptides, and some of which he has been able to produce synthetically. Furthermore, Fischer proved that nitrogen equilibrium can be maintained in animals by feeding them upon these polypeptide products of proteolytic digestion which no longer gives the biuret reaction. The derivation of amino-acids, etc., from peptone is the outcome of the action of a special intestinal ferment—erepsin. This enzyme is found not only in the alimentary tract, but in all tissues of the body, its action being especially developed in the renal tissues.
[7] Glycocoll in solution dissociates more H-ions than OH-ions. In the presence of alkalies this acid character is more marked, so that it tends to throw the uric acid salts out of solution. The inhibitory influence of the urea upon the precipitation of uric acid from solutions is due to its basic nature.
[8] Recent researches by S. R. Benedict show that uric acid, in the blood of most mammals, exists in combination, but not in that of the bird. Fresh ox-blood (Folin method) contains only 0·30005 gram, free uric acid per 100 grams of blood. But after boiling the protein-free blood filtrate with hydrochloric acid the uric acid content was about ten times as high. Moreover, this same augmented uric acid content was found to exist “in whole blood that had been allowed to stand for some time, indicating that the uric acid compound can be split by means of an enzyme.” The compound exists, not in the plasma, but in the corpuscles. MacLeod, to whose work on bio-chemistry we are indebted, remarks that “It is of some significance that after thus setting free the uric acid, there should be about 50 per cent. more of it present in the blood of the ox than in that of the bird, where most exists in a free state in the serum, although the urine of the ox contains only the smallest trace of uric acid, and that of the blood is loaded with it. Investigation of the condition of uric acid in human blood is at present in progress.”
[9] According to Sir William Roberts, there are three compounds of uric acid (H₂U)—the neutral urate, M₂U, in which the metal replaces all the displaceable hydrogen, the biurate, MHU, in which half the displaceable hydrogen is replaced by the metal, and the quadriurate H₂UMHU, in which one-fourth of the displaceable hydrogen of two molecules is replaced by the metal.
Hutchison and Tidy suggest “that if Roberts’ salt be considered as NaHU. MH₂U instead of Na. HU, his hypothesis remains unaltered, whilst much of the criticism urged against it is nullified. The possibility of such a substance is shown by the existence of the compound LiHU₄HU. Roberts’ theory, or such a modification, is not inconsistent with Von Noorden’s views if these intermediate salts be regarded as within the tabernacle of organic combinations from which the kidneys can split off and excrete the uric acid.”
[10] “If further investigations yield facts which sustain such an idea, it may be more easy to comprehend the types of the demands which are made upon the renal functions.... One of the next stages of research will be the determination of the behaviour of renal tissue to the various purin isomers. This may lead on to the identification of the types of nuclein derivations and their precise cellular origin. Perhaps this in turn may reveal whether there are any differences between the nucleotides of normal and gouty tissues. To this end progress in the technics of the cultivation of tissues in vitro may furnish a means for the elucidation of some of these questions.”—Walker Hall.
[11] As a further illustration of the differences which may exist in the purin metabolism in different kinds of animals, in man and the anthropoid apes the quantity of purin bases in the urine is small in proportion to the quantity of uric acid. In the pig, which is included among the animals that form allantoin from uric acid, the purin bases exceed the uric acid in amount, whereas in the dog, which likewise excretes allantoin, the purin bases exist in very small amount compared with the uric acid.—Stewart’s “Manual of Physiology.”
[12] The findings of Soetbeer and Ibrahim also indicate that 50 per cent. of the exogenous purin bodies undergo oxidation to uric acid, and 50 per cent. undergo further disruption and are excreted as urea or intermediate bodies.
[13] The subject of the experiments—a healthy male (M. S. D.), 22 years of age and 58 kilos in weight—was placed for over six months upon a meat-free low protein diet, free also from purin-containing beverages. This with the exception of a few meals in the holidays, during which a small amount of meat was taken. “No attempt was made to secure a quantitative uniformity of the diet.” On the evening preceding the day of an experiment a light supper was eaten, and no further food was ingested until the completion of the day’s experiment, save the substance whose influence on uric acid excretion was to be studied. The urine was collected hourly, 200 c.c. of water being ingested hourly throughout the experimental period.—“Uric Add Metabolism,” 11—H. B. Lewis, M. S. Dunn, and E. A. Doisy, “Journal of Biological Chemistry,” 1918.
Two other men also served as subjects. Many of the experiments were duplicated, and similar results obtained with these other subjects, but inasmuch as the experiments with M. S. D. were more comprehensive and extended over a longer period of time, the data of these experiments alone are presented.
[14] Quoting from the same article, Journal of Biological Chemistry, 1918, by Lewis, Dunn and Doisy, these authorities observe that—re glycocoll and alanine, Lusk concluded that “the chemical stimulation of protoplasm which is responsible for the phenomena of increased heat production (specific dynamic action) results from the action of their intermediary products, glycocollic and lactic acids, rather than from the amino-acids themselves. The phenomena of the stimulation of uric acid metabolism by amino-acids run parallel to those of the specific dynamic action of the amino-acids (except in the case of the dicarboxylic amino-acids), and it is possible that the same chemical factors are responsible for both.”
[16] Experimenting on a Dalmatian coach-hound, Gideon Wells was able to confirm Benedict’s observation that it excretes large quantities of uric acid. But inasmuch as the liver of this same dog was able to destroy uric acid in vitro, the inference is that the presence of uric acid in the urine of the Dalmatian is not attributable to the absence of uricase in its tissues. “The kidney did not exhibit uricolytic activity. Neither the liver nor spleen converted xanthine into uric acid, but the liver deaminised both guanine and adenine.”—Journal of Biological Chemistry, 1918.
[17] Wells, in his “Chemical Pathology,” observes that the amount of uric acid that appears in the urine depends upon a variety of factors which may be summarised as follows:—
(1) The amount of purin bodies taken in the food upon which chiefly depends the amount of exogenous uric acid.
(2) The amount of destruction of tissue nucleo-proteins.
(3) The amount of purin bases formed in the muscle tissue.
(4) The amount of conversion of purin bases into the uric acid.
(5) The amount of destruction of uric acid, if any, occurring in the body.
(6) Possibly upon the capacity of the tissues to synthesize uric acid; and in case such power to synthesize uric acid exists upon the presence of the precursors of uric acid in the body.
(7) The retention of uric acid in the blood and tissues.
(8) The power of the kidney to excrete uric acid.
(9) The solubility of uric acid in urine—dependent upon the amount of neutral phosphates present, the temperature, reaction and concentration thereof.
Effect of Atophan on Exogenous Purins. (McLester, in “Archives of Internal Medicine.”)
| Date. | R. E. | Blood Mg. U in 100 Gm. | Twenty-four Hour Urine. | |||
|---|---|---|---|---|---|---|
| Amt. c.c. | U. Gm. | NH. Gm. N. | N. Gm. | |||
| 5/28 | —— | 2·9 | 1,150 | ·46 | ·58 | 10·26 |
| 5/29 | 7 a.m.: 500 grams thymus. 2 p.m.: Blood | 3·2 | 900 | ·66 | ·69 | 10·96 |
| 5/31 | 7 a.m.: 500 grams thymus. 9 a.m.: Atophan, 2 p.m.: Blood | 1·1 | 1,280 | ·75 | ·76 | 11·16 |
[19] Walker Hall states that: “Taking the total volume of blood at three and a half litres, and the volume passing through the lungs as four and a half litres per minute, and through the kidneys as one litre per minute, and the solubility of lactim-urate as 0·1 grm. per 4,000 c.c. of blood, it would seem that the average daily output of 0·5 grm. could be suspended in the quantity of blood passing through the lungs in five minutes or through the kidneys in twenty minutes normal.”
[20] Criticising the colorimetric method on the ground that “different workers obtain on the same blood samples results which vary considerably,” L. J. Curtman and A. Lehrman have devised a new volumetric method for the determination of uric acid in blood. The following is the summary of their researches:—
(1) An experimental study of a number of metallic salts as precipitants for uric acid in a solution alkaline with sodium carbonate was made. The results showed that nickel is the best of those tried.
(2) A 0·0004 N iodine solution was found suitable for the estimation of small amounts of uric acid provided certain conditions are adhered to.
(3) Based upon the above considerations, a new method has been developed for the determination of uric acid in blood, the chief features of which are (a) the precipitation of the uric acid by means of nickel acetate in a solution alkaline with sodium carbonate. (b) The estimation of the uric acid in the precipitate by means of a dilute solution of iodine.
(4) The method was applied with good results to aqueous solutions of uric acid as well as to blood serum to which known amounts of uric acid were added.
(5) Low and inconsistent results were obtained when the method was applied to sheep’s blood to which known amounts of uric acid were added. This was shown to be due to the inadequacy of the procedure generally employed, for the coagulation and preliminary treatment of the blood. The colorimetric method when used in the analysis of samples of the same blood also gave low and inconsistent results for the same reason.
(6) Comparison tests show that the volumetric method is fully as accurate as the colorimetric method, and possesses the advantage of requiring no special apparatus.
Uric Acid Estimation in Normal Individuals
(McLester, “Archives of Internal Medicine.”)
Milligrams Uric Acid in 100 grams Blood.
| J. C. | 0·5 |
| H. D. | 0·6 |
| M. D. | 0·6 |
| A. B. | 0·8 |
| R. C. | 0·9 |
| H. D. | 0·9 |
| J. G. | 0·0 |
| S. M. | 1·1 |
| R. D. | 1·3 |
| L. S. | 1·4 |
| L. H. | 1·7 |
| R. O. | 2·1 |
| H. H. | 2·5 |
| J. M. | 2·5 |
| R. E. | 2·9 |
Uric Acid of Blood in Disease. (McLester, “Archives of Internal Medicine.”)
Milligrams in 100 grams Blood.
| Mitral lesion | 0·5 |
| Rheumatic fever | 0·6 |
| Acute syphilis | 0·8 |
| Chronic tuberculous pleurisy | 0·8 |
| Pneumonia | 1·2 |
| Pneumonia | 1·3 |
| Sciatica | 1·3 |
| Typhoid fever | 1·4 |
| Ulcer of stomach | 1·5 |
| Pneumonia | 1·6 |
| Amœbic dysentery | 1·6 |
| Neurasthenia (?) | 1·7 |
| Acute tuberculous pleurisy | 1·7 |
| Chronic interstitial nephritis | 1·8 |
| Malaria | 1·8 |
| Pneumonia | 1·9 |
| Uremia | 2·1 |
| Polycythemia | 2·2 |
| Graves’ disease | 2·5 |
| Pneumonia | 2·7 |
| Gout | 3·3 |
| Arterial hypertension | 3·3 |
| Intermittent gastric supersecretion | 3·7 |
| Gout | 4·5 |
[22] However, as Walker Hall reminds us, Taylor, writing in 1912, stated, “That the margin of safety with regard to renal excretion is an exceedingly narrow one, that the kidney excretes uric acid slowly, and that its powers are soon overstepped.”
[23] Magnus Levy and McClure have also noted that the excretion of exogenous purin is not invariably retarded or diminished.
[24] When experimentally injected, the urates are absorbed slowly by phagocytic leucocytes and giant cells.—Gideon Wells.
[25] Because the gouty tophi do not suppurate, even when ulcerated, through the skin, it has been suggested that the urates have antiseptic properties. Bendix (Zeit. klin. Med., 1902 (44), 165), however, could not demonstrate such antiseptic properties experimentally.—Gideon Wells.
[26] Levinthal, in a personal experiment, injected half a gram of xanthin dissolved in piperazine into his cubital vein. A few days later, after a moderate strain upon the limbs through dancing, he was suddenly seized with a fairly acute painful attack in one of his knees, attended with some swelling and local heat.
[27] “Tophi sometimes precede by some years ... the development of gouty attacks in joints. The same is true also of auricular tophi.”—Duckworth: “A Treatise on Gout.”
[28] “While, however, tophaceous concretions generally show themselves after attacks of articular gout, cases occur, as I have already told you, in which the secretion of calcareous matter takes place irrespective of any arthritic attack. This sort of cutaneous gravel, if I may employ a comparison based on the great analogy between the composition of urinary gravel and tophaceous concretions, gravel of the skin, constitutes the sole manifestation of the diathesis, and is accompanied merely by a slight feeling of pain, of pricking unattended by any disturbance of the general health.”—Trousseau’s “Clinical Medicine.”
[29] Redness of the skin overlying a developing tophus is not invariable. In a case recently under my care, the dorsum of the mid-phalangeal joints was the seat of small soft localised swellings. The superjacent skin was unchanged in colour. Aspiration of the contents by a hypodermic syringe disclosed the presence of a turbid white fluid, which, when microscopically examined, was found loaded with the acicular crystals of sodium biurate.
[30] “Quod in omnibus podagricorum paroxysmis solemne est, insignior intumescentia venerum membro vexato intertextarum se in conspectu dat.”—Sydenham.
[31] Sydenham’s classical description: “Towards the end of January or the beginning of February suddenly, and with scarcely any premonitory feelings, the disease breaks out. Its only forerunner is indigestion and crudity of the stomach, which troubles the patient for some weeks previous to the attack. His body also feels swollen, heavy, and windy—symptoms which increase from day to day until the fit breaks out. But a few days before this torpor comes on, and a feeling of flatus along the legs and thighs. Besides this, there is a spasmodic affection, whilst the day before the fit the appetite is unnaturally hearty. The victim goes to bed in good health and sleeps. About two o’clock in the morning he is awakened by a severe pain, generally in the great toe, more rarely in the heel, ankle, or instep. This pain is like that of a dislocation of the bones of these parts, and is accompanied by a sensation as of chilly water poured over the membranes of the suffering joint. Then follow chills and shivers and a little fever. The pain, which was at first moderate, becomes gradually more intense, and while it increases the chills and shivers die out. Every hour that passes finds it greater, until at length at night-time it reaches its worst intensity, and insinuates itself with most exquisite cruelty among the numerous small bones of the tarsus and metatarsus, in the ligaments of which it is lurking. Now it is a violent stretching and tearing of the ligaments, now it is gnawing pain, and now a pressure and tightening. So exquisite and lively meanwhile is the feeling of the part affected that it cannot bear the weight of the bedclothes nor the jar of a person walking in the room. Hence the night is passed in torture and a restless rolling first to one side, then to the other, of the suffering limb, with perpetual change of posture, the tossing about of the body being as incessant as the pain of the tortured joint, and being at its worst as the fit is coming on. Hence the vain efforts by change of posture, both in the body and the limb affected, to obtain an abatement of the pain.
“This comes only towards the second or third hour of the morning (a whole day and night after the first outbreak of the fit), such time being necessary for the moderate digestion and dispersion of the peccant matter. The patient then has a sudden respite, which he falsely attributes to the last change of position. A gentle perspiration is succeeded by sleep. He wakes freer from pain and finds the part recently swollen. Up to this time the only visible swelling has been that of the veins of the affected joint. Next day (perhaps for the next two or three days), if the generation of the gouty matter have been abundant, the part affected is painful, getting worse towards evening and better towards morning. A few days after the other foot swells, and suffers the same pains. The pain in the latter regulates the state of the one first attacked, for the more acutely it is tortured the more perfect is the abatement of suffering and the return of strength in the other. Nevertheless, there is a repetition in the second case of all the misery of the first both as regards intensity and duration. Sometimes during the first days of the disease the peccant matter is so exuberant that one foot is insufficient for its discharge. It then attacks both, and that with equal violence. Generally, however, it takes the feet in succession. After it has attacked each foot the fits become irregular both as to the time of their coming and as to their duration. One thing, however, is constant—the pain increases at night and abates in the morning. Now a series of lesser fits like these constitute a true attack of gout, long or short, according to the age of the patient. To suppose that an attack two or three months in length is all one fit is erroneous. It is rather a series of minor fits. Of these the latter are milder and more limited in their extent than the former, so that the peccant matter is discharged by degrees, and recovery follows. In strong constitutions, when the previous attacks have been few, a fortnight is the length of an attack. With age and impaired habits gout may last two months. With very advanced age, and in constitutions very much broken down by previous gout, the disease will hang on till the summer is far advanced. For the first fourteen days the urine is high-coloured, has a red sediment, and is loaded with gravel. Its amount is less than a third of what the patient drinks. During the same period the bowels are confined. Want of appetite, general chills towards evening, heaviness, and a troublesome feeling even in the parts which are free from the attack, attend the fit throughout. As it goes off the foot itches intolerably, mostly between the toes; the cuticle scales off, and the feet desquamate, as if venomed. The disease being disposed of, the vigour and appetite of the patient return, and this in proportion to the violence of the last fits. In the same proportion the next fit either comes on or keeps off. Where one attack has been sharp, the next will take place that time next year, not earlier.”—Sydenham.
[32] “Pain is better borne by the poor man, as I have had opportunities of seeing, than by the man who acquired or promoted his gout with two or three bottles of port wine daily, with the surroundings which such luxury implies.”—Longstreth, “On Gout.”
[33] “The pain is altogether disproportionate to the other signs of inflammation, and, even more, to the consequent structural changes in the inflamed part.”—Paget.
As to the peculiar character of the pain, Duckworth states: “Nothing at all like it occurs in any other joint disease.”
[34] Sydenham noted that “sometimes the morbific matter is thrown upon the elbows and occasions a whitish swelling, almost as large as an egg, which becomes gradually inflamed and red.”
[35] “Regular gout may supervene suddenly, and be chronic; that is to say, its outbreak need not have been preceded by paroxysms in any way characteristic of acute gout.”—Trousseau, “On Gout.”
[36] As Trousseau puts it: “Regular chronic gout, in respect of the frequency of the recurrence of the paroxysms, resembles acute gout with successive paroxysms, there being this capital difference, however, that its attacks are longer and during the intervals are not entirely absent.”
[37] Mr. James Moore, surgeon to the Second Regiment of Life Guards (Medico-Chirurgical Transactions, 1809, Vol. I.):—
“This effusion” (meaning the milky fluid containing the urate of soda) “occurs not only during fits of gout, but likewise in the intervals; and as the extremities, particularly the hands and feet, are the principal seat of gout, it is there the greatest accumulation of chalk takes place. Though this process is usually preceded and accompanied by inflammation, the chalk is never inclosed in a cyst, like pus in an abscess. It lies usually in the cellular membrane, in the bursæ mucosæ, or in the cavities of the joints. I have even seen it thrown out between the cutis and the cuticle. But, as the gouty inflammation is of the erythematous kind, there is no extravasation of coagulable lymph, and no new-formed covering surrounding the chalk. This point is of the first importance, and explains many of the peculiarities of gout, which is generally considered as a phlegmon. But the absence of coagulable lymph in the inflamed parts I consider as full evidence of the inflammation being erythematous.
“The chalky liquid when first secreted gives to the finger the feeling of fluctuation, and cannot be distinguished from the ordinary serous effusion of gout. But unfortunately the absorbents cannot suck up the chalky particles. The consistence of the liquid therefore becomes thicker and thicker, till at last nothing remains but a hard mass. When even a considerable effusion of this kind occurs, the quantity of chalk which ultimately remains is comparatively small, as by far the greater quantity is merely serum. It therefore usually requires repeated effusions to form any great mass of chalk, and the consistency depends upon its age and the activity of the absorbents. The quantity at last accumulated by repeated paroxysms is in some instances immense, which augments very seriously the sufferings of the gouty. The distress, however, is not owing to any irritating quality in the chalk, but to its obstructing the motion of the tendons and joints, occasioning often complete anchylosis, and pressing and distending the surrounding parts by its bulk. It acts, therefore, by mechanically embarrassing the machine of the body, and not upon the living principle, for it will often remain for years in parts highly sensible without exciting the slightest pain or inflammation. Although these concretions are of so mild a nature, they often are the cause of extensive mischief, bursting externally, occasioning ulcers very difficult to heal. When a violent fit of the gout attacks a chalky tumour, the appearance is frequently very alarming, the new paroxysm being accompanied with a fresh serous and chalky effusion, which, added to the old deposit of chalk, occasions a prodigious swelling; the cutis when distended to the utmost opens, yet sometimes the cuticle remains entire. The chalky or serous liquid may then be seen through the semi-transparent epidermis. The surrounding integuments appear of a deep red, or of a purple hue, threatening mortification, while the pain is excruciating.
“At length the cuticle gives way, a discharge of serum and chalk takes place, and a remission of all the symptoms usually follows. During the whole of this alarming process suppuration never occurs; but soon after the opening has taken place suppuration commences, and pus and chalk are then discharged from the ulcer. There are several unexpected occurrences in the progress of such ulcerations. When an opening is formed, the whole of the chalk never escapes, and its complete evacuation is often a very tedious process; this is owing to its being diffused through the cellular membrane, as in the cells of a sponge. One cell must sometimes give way after another, and small portions of chalk are successively thrown out, so that months and even years pass away before the whole is discharged. It also frequently happens that the orifice contracts and closes over, leaving portions of chalk underneath. This kind of cicatrix sometimes stands its ground, but more commonly breaks out again and again to discharge chalk. Even openings into joints, which are so dangerous when occasioned by other extraneous bodies, are often attended with no serious symptoms when the joint is filled with chalk. On such an accident happening a surgeon unacquainted with these peculiarities might be tempted to propose large openings, or even amputation, as the only resource for hindering extensive inflammation and carious bones. But if he treats the disease mildly, he will find that no such severe plans are requisite, for the parts will probably fall into a very tranquil or indolent state; a sore will continue for a certain period, discharging pus, and occasionally a bit of chalk, till at last the orifice will close up. Independent of the opening formed by a fit of the gout, the skin, stretched over a mass of chalk, is sometimes thinned, absorbed, and pierced by mere pressure. At other times this is effected by common inflammation and suppuration. When openings take place in these milder ways, a less quantity of chalk is usually evacuated; but this depends entirely upon the degree of inflammation. When the suppuration is great, it naturally detaches and washes out a greater quantity of chalk.
“The last peculiarity is the rarest, namely, that a dry, hard piece of chalk shall pierce the skin, and remain like an excrescence, without exciting either inflammation or suppuration.”
[38] According to Adler, about one-tenth as much uric acid is excreted in the sweat as in the urine, sweat containing 0·1 mg. per cubic centimetre.
[39] In this connection the tendency of gouty glycosurics to exhibit boils and sometimes carbuncles should not be forgotten.
[40] Max Strunsky, of New York, discussing the frequency with which by the older physicians gouty forms of arthritis were confused with gonorrhœal, syphilitic, and other undifferentiated forms of infective arthritis, makes the following observation: “Also flatfeet must have added herds of cases, for this pathological entity was as yet unknown. The rich man in pursuit of his pleasure and the poor man from prolonged standing at his labour strained their arches then as they do now, and women by their ultra-fashionable shoes, which fashion decreed upon them in certain periods of history, produced painful feet which were undoubtedly mistaken for gout. That patients with local foot trouble were treated for gout the writer can speak from experience. A typical case is of a woman who came to his office two years ago. She had broken-down anterior arches. Hallux valgus, hammer-toes, and bunions were present, and the heels were small and undeveloped. Her feet were one mass of pain, and they looked infantile, reminding one of a Chinese woman. All her adult life she wore high-heeled, narrow, pointed, tight shoes. She said that for twenty years she had been treated for gout.”
[41] In support of this contention, I would note that Charcot, while he gives us an inimitable account of the tophaceous variety of gout, introduces also another variant, as he deems it, of chronic articular gout. The joint changes in this latter are marked by what he terms “a thorough atrophy,” including the superjacent skin, which “is pale, shining and polished.” With this are associated ankyloses, angular deflections, and partial dislocations. The joints, he states, “may be absolutely free from swelling, for example when the extra-articular urate deposits either do not exist at all, or only mere traces of them, or when only the articular cartilages are invaded by the urate of soda.” It cannot, we think, be doubted that the clinical content of this group is largely made up of rheumatoid or atrophic arthritis. The evidence that these examples, quâ uratic deposits, are of “gouty” nature, is obviously very slender.
Reverting to Sir Dyce Duckworth, this authority also recognises two varieties of chronic articular gout: (a) tophaceous gout; (b) chronic deforming gout, with as its synonym arthritis deformans uratica. As to the clinical content of this latter group he writes: “The fingers, hands, and wrists show various deformities depending on over-growth of articulating ends of bone, cartilage, ligaments, and bursæ. These may be complicated with visible or invisible tophaceous deposits.” As to these anatomical alterations, Duckworth regards them as “similar to, but not the same as, those induced by rheumatic disease.” But he adds: “It is very rare for the deformities of true gout to attain the gross characters peculiar to chronic rheumatic arthritis; they are altogether of lesser degree in the majority of the worst instances.” From a careful study of their anatomical characters, I cannot avoid the conclusion that they were in the main examples of the hypertrophic variety of arthritis deformans, viz., osteoarthritis.
[42] As Sir W. Hale White has pointed out, “pads” not uncommonly develop on the dorsal aspects of the mid-phalangeal joints. They range in size from a split pea to a hazel nut. Histologically they are the outcome of an excessive overgrowth of fibrous tissue beneath the corium. They in no way involve the joints, but, according to Hale White, they have been confused with osteoarthritis. Their frequent association with Dupuytren’s contracture might conceivably lead to their confusion with gout also, inasmuch as that deformity is so widely attributed to a “gouty” habit.
[43] Sir Spencer Wells in his “Practical Observations on Gout and its Complications and on the Treatment of Joints stiffened by Gouty Deposits.”
“Of the many cases related by authors as anonymous disease by far the greater portion were connected with a gouty diathesis, as indicated both by the formation of calculi, by the occurrence of regular paroxysms of gout, and by the descent of the individual from gouty ancestors; they are cases, in fact, which would have been better understood and better treated if they had been termed ‘anomalous gout’; but as the subjects are young females, they are of course set down as ‘anomalous hysteria.’”—Laycock: “Nervous Diseases of Women.”
[44] “Diseases of the Eye” (1918), p. 258.
[45] “Diseases of the Eye” (1919).
[46] “Diseases and Injuries of the Eye” (1913).
[47] Kruckmann, Med. Klinik., 1910, No. 38.
[48] Proc. Roy. Soc. Med., Ophth. Section, 1914, p. 66.
[49] Ophth. Hosp. Reps., VII., p. 287, 1873.
[50] “Diseases of the Eye” (1854), p. 558.
[51] Brit. Med. Journ., 1885, R. Clement Lucas.
[52] Lancet, 1920, Vol. I., p. 500, Browning.
[53] Archives d’Ophtalmologie, Vol. XII., p. 623.
[54] A very rare form of iritis was described by the late Mr. Doyne as guttate iritis (Trans. Ophth. Soc., Vol. XXX., p. 91) because the appearances resembled drops of lymph on the margin of the pupil. In his view it was a true form of gouty iritis, but the diagnosis does not seem to have been confirmed by other observers. Even if we grant that his view is possibly correct, we must beware how we generalise on a basis of exceptions and freaks.
[55] Brit. Med. Journ., 1903, Vol. II., p. 138.
[56] “Gout” (1876), p. 450.
[57] Clin. Soc. Trans., Vol. XI., p. 132, 1898.
[58] “Medical Ophthalmoscopy,” 3rd edition, p. 267.
[59] Practitioner, 1909, Vol. II., p. 61.
[60] Sydenham, discussing a milk diet, observes that “it has done good as long as it has been rigidly attended to. The moment, however, that the patient swerves from it a hair’s breadth, and the moment he betakes himself to the diet of a healthy man (no matter how mild and simple), the gout returns worse than ever.”
[61] “The lighter beers of Germany, Austria, and Scandinavia, appear to be harmless for the gouty unless taken immoderately. Residents in towns goutily disposed, leading sedentary lives, are seldom long tolerant even of light laager beer.”
[62] Sir Archibald Garrod has suggested that guaiacum has a distinct effect in reducing the amount of uric acid excreted, i.e., it was thought that the uric acid is eliminated in some other form, possibly hippuric acid. Accordingly Martindale and Westcott conducted investigations to determine whether this resin increases or decreases the elimination of uric acid from the human body.
A normal individual took guaiacum resin in 5-grain doses daily in the morning, and the uric acid was estimated in the urine the same afternoon. Hippuric acid was also estimated in specimens of the same urine by the method given by Allen, “Chemistry of Urine,” p. 186. After a day’s interval the acids were estimated on several days without administration of the drug. The two series were then repeated on the same lines after an interval. Seeing that the diet of the individual could not well be controlled in weighed amounts of food, as would strictly be necessary for an investigation of this kind, it was thought that to express the results in percentage ratios of uric acid to excess of solids (R.U.A.) over water might yield more comparable results.
Joulie employs this method of indicating the constituents of urine by ratios; cf. Vol. I., p. 736. Thus, taking a specimen of urine with the following “normal” factors in grams per litre:—
| Specific gravity | 1017·8 |
| Excess of solids over water | 17·8 |
| Physiological acidity in terms of H₂SO₄ | 0·849 |
| Total P₂O₄ | 2·083 |
| Cl | 6·865 |
| Urea | 18·75 |
| Uric acid | 0·416 |
| Hippuric acid | 1·3 |
| (mean). |
One may express the constituents as the following percentage ratios:—
| Normal. | |||||
|---|---|---|---|---|---|
| “R.A.”—Ratio of physiological acidity to excess of solids over water | 4·77 |
| |||
| “R.P.”—Ratio of total P₂O₄ to excess of solids over water | 11·17 | ||||
| “R.U.”—Ratio of urea to excess of solids over water | 100·53 | ||||
| “R.U.A.”—Ratio of uric acid to excess of solids over water | 2·33 | ||||
| “R.H.A.”—Ratio of hippuric acid to excess of solids over water | 7·3 | ||||
| “R.P./R.A.”—Ratio of phosphoric acid to ratio of acidity (Joulie’s factor, cf. Vol. I., p. 737) | 2·45 | ||||
| Ratio of uric acid, for example, is arrived at thus |
| = 2·33 | |||
The results which we obtained are given in the following table:—
Effects of Guaiacum Resin on the Urine of a Normal Individual.
| Date. | Sp. Gr. | Urea. | Uric Acid. | Hippuric Acid. | “R.U.A.” | “R.H.A.” | |
|---|---|---|---|---|---|---|---|
| With guaiacum | 28/12/11 | 1·0107 | 2·29 | 0·09 | 0·09 | 4·43 | 4·34 |
| With guaiacum | 29/12/11 | 1·0247 | 1·29 | 0·08 | 0·1 | 3·34 | 4·04 |
| With guaiacum | 1/1/12 | 1·0215 | 2·56 | 0·015 | 0·15 | 4·88 | 6·97 |
| With guaiacum | 2/1/12 | 1·0141 | 2·82 | 0·10 | 0·2 | 4·2 | 8·20 |
| Without guaiacum | 4/1/12 | 1·0229 | 2·42 | 0·06 | 0·1 | 2·62 | 4·36 |
| Without guaiacum | 5/1/12 | 1·0249 | 2·42 | 0·08 | 0·2 | 3·16 | 8·03 |
| Without guaiacum | 8/1/12 | 1·0255 | 3·09 | 0·10 | 0·225 | 4·11 | 8·12 |
| With guaiacum | 11/1/12 | 1·0233 | 2·56 | 0·09 | 0·1 | 3·7 | 4·29 |
| With guaiacum | 12/1/12 | 1·0213 | 1·88 | 0·075 | 0·1 | 3·05 | 4·69 |
| Without guaiacum | 24/1/12 | 1·0239 | 2·42 | 0·08 | 0·038 | 3·45 | 1·57 |
| Without guaiacum | 25/1/12 | 1·0229 | 2·15 | 0·06 | 0·05 | 2·61 | 2·18 |
| Average uric acid ratio under guaiacum resin | = | 3·39 |
| Average uric acid ratio without guaiacum resin | = | 3·19 |
| Average hippuric acid ratio under guaiacum resin | = | 5·43 |
| Average hippuric acid ratio without guaiacum resin | = | 4·49 |
The quantity of hippuric acid normally found is known to vary enormously, e.g., between 0·02 and 0·25 per cent. From this we deduced, for purpose of this investigation, a mean normal R.H.A. of 7·3. A number of other investigations were conducted on analogous lines, but need not be recorded.
From the results of these experiments one notices an average increase of uric and hippuric acids during the “+ guaiacum” periods. It is not possible to draw a conclusion without further corroboration. The amount of each acid from day to day is seen to be erratic, and the process of estimation of hippuric acid is not accurate.
[63] “Weakly mineralised thermal muriated waters, such as those of Baden-Baden in Germany, and Bourbon-Lancy in France, which in character and action approach the simple thermal group, may also show great radio-activity. In fact, the Büttquelle of Baden-Baden in this respect rivals some of the most radio-active springs of Gastein. Of Bourbon-Lancy springs, according to A. Piatot, the least mineralised are the most radio-active.”—“Climato-therapy and Balneo-therapy,” by Sir Hermann Weber.
Sir William Ramsay’s Analysis of the Bath Waters.
| Density of the water from King’s Well | 1·0166 | |
| Osmotic pressure equivalent to that of a salt solution containing per litre | 1·09 | grams NaCl. |
Volume of gas in twenty-four hours from—
| Litres. | ||
|---|---|---|
| King’s Well | 4,927 | |
| Cross Spring | 218 | |
| Hetling Spring | 218 | (estimated). |
| 5,363 |
Analysis of gas (King’s Well)—
| Parts per 10,000. | |
|---|---|
| Carbon dioxide | 360 |
| Nitrogen, etc. | 9,640 |
| No oxygen, no hydrogen, no marsh gas. | |
The nitrogen contains—
| Argon | 73·63 |
| Neon | 23·34 |
| Helium | 2·97 |
From all three wells in twenty-four hours—
| Litres. | |
|---|---|
| Argon | 39 |
| Neon | 12½ |
| Helium | 1½ |
Gases dissolved in Pump-room Water.—This water contains 18·5 volumes of gas per 1,000 of water. Its composition is—
| Carbon dioxide | 6·9 |
| Nitrogen | 11·6 |
It had become somewhat aerated on drawing, but allowance has been made for that.
| Milligrams per million litres. | |
|---|---|
| Radium in the water of the King’s Well | 0·1387 |
| Niton (radium emanation) in the water of King’s Well | 1·73 |
| ” ” ” ” of Cross Bath | 1·19 |
| ” ” ” ” of Hetling Bath | 1·70 |
| ” ” ” in the gas from King’s Well | 33·65 |
[65] Bickel in a series of experiments in which the acid contents as well as the total amount of gastric juice were considered obtained the following results: simple gaseous waters (Apollinaris, Giesshübl), muriated waters (Rakoczy spring of Kissingen, Wiesbaden, Kochbrunnen), and muriated alkaline waters (Ems, Selters), all of them, as compared to distilled water and ordinary tap water, rather increased than decreased the specific secretory activity of the gastric mucous membrane, whereas simple alkaline waters (Vichy) and sulphated alkaline waters (Karlsbad) had a slight tendency to diminish, and the sulphated “bitter” waters (Hunyadi Janos water) decidedly diminished, the gastric secretory activity, although “bitter” waters sometimes induced a watery flow from the gastric mucosa, which increased the fluid contents of the stomach.
[66] Bain, of Harrogate, from his observations on a man with permanent cutaneous biliary fistula, found that the old sulphur spring of Harrogate increased both the quantity of bile and the bile solids. This, he thinks, may “fairly be taken as an index of the degree to which it stimulates the liver, and is, in fact, the most reliable indication of the value of a cholagogue.”